Infectious Diseases

To the Editor:

Lichenoid drug eruptions are lichen planus–like hypersensitivity reactions induced by medications. These reactions are rare but cause irritation to the skin, as extreme pruritus is common. One review of 300 consecutive cases of drug eruptions submitted to dermatopathology revealed that 12% of cases were classified as lichenoid drug reactions.¹ Lichenoid dermatitis is characterized by extremely pruritic, scaly, eczematous or psoriasiform papules, often along the extensor surfaces and trunk.² The pruritic nature of the rash can negatively impact quality of life. Treatment typically involves discontinuation of the offending medication, although complete resolution can take months, even after the drug is stopped. Although there have been some data suggesting that topical and/or oral corticosteroids can help with resolution, the rash can persist even with steroid treatment.²

The histopathologic findings of lichenoid drug eruptions show lichen planus–like changes such as hyperkeratosis, irregular acanthosis, and lichenoid interface dermatitis. Accordingly, idiopathic lichen planus is an important differential diagnosis for lichenoid drug eruptions; however, compared to idiopathic lichen planus, lichenoid drug eruptions are more likely to be associated with eosinophils and parakeratosis.^1,3 In some cases, the histopathologic distinction between the 2 conditions is impossible, and clinical history needs to be considered to make a diagnosis.¹ Drugs known to cause lichenoid drug reactions more commonly include angiotensin-converting enzyme inhibitors, beta blockers, thiazides, gold, penicillamine, and antimalarials.² Lichenoid drug eruptions also have been documented in patients taking the second-generation nonsteroidal androgen receptor antagonist enzalutamide, which is used for the treatment of prostate cancer.⁴ More recently, the newer second-generation nonsteroidal androgen receptor antagonist apalutamide has been implicated in several cases of lichenoid drug eruptions.^5,6

We present a case of an apalutamide-induced lichenoid drug eruption that was resistant to dose reduction and required discontinuation of treatment due to the negative impact on the patient’s quality of life. Once the rash resolved, the patient transitioned to enzalutamide without any adverse events (AEs).

A 72-year-old man with a history of metastatic prostate cancer (stage IVB) presented to the dermatology clinic with a 4-month history of a dry itchy rash on the face, chest, back, and legs that had developed 2 to 3 months after oncology started him on apalutamide. The patient initially received apalutamide 240 mg/d, which was reduced by his oncologist 3 months later to 180 mg/d following the appearance of the rash. Then apalutamide was held as he awaited improvement of the rash.

One week after the apalutamide was held, the patient presented to dermatology. He reported that he had tried over-the-counter ammonium lactate 12% lotion twice daily when the rash first developed without improvement. When the apalutamide was held, oncology prescribed mupirocin ointment 2% 3 times daily which yielded minimal relief. On physical examination, widespread lichenified papules and plaques were noted on the face, chest, back, and legs (Figure 1). Dermatology initially prescribed triamcinolone ointment 0.1% twice daily. A 4-mm punch biopsy specimen of the upper back revealed a lichenoid interface dermatitis with numerous eosinophils compatible with a lichenoid hypersensitivity reaction (Figure 2). Considering the clinical and histologic findings, a diagnosis of lichenoid drug eruption secondary to apalutamide treatment was made.

To the Editor:

Lichenoid drug eruptions are lichen planus–like hypersensitivity reactions induced by medications. These reactions are rare but cause irritation to the skin, as extreme pruritus is common. One review of 300 consecutive cases of drug eruptions submitted to dermatopathology revealed that 12% of cases were classified as lichenoid drug reactions.¹ Lichenoid dermatitis is characterized by extremely pruritic, scaly, eczematous or psoriasiform papules, often along the extensor surfaces and trunk.² The pruritic nature of the rash can negatively impact quality of life. Treatment typically involves discontinuation of the offending medication, although complete resolution can take months, even after the drug is stopped. Although there have been some data suggesting that topical and/or oral corticosteroids can help with resolution, the rash can persist even with steroid treatment.²

The histopathologic findings of lichenoid drug eruptions show lichen planus–like changes such as hyperkeratosis, irregular acanthosis, and lichenoid interface dermatitis. Accordingly, idiopathic lichen planus is an important differential diagnosis for lichenoid drug eruptions; however, compared to idiopathic lichen planus, lichenoid drug eruptions are more likely to be associated with eosinophils and parakeratosis.^1,3 In some cases, the histopathologic distinction between the 2 conditions is impossible, and clinical history needs to be considered to make a diagnosis.¹ Drugs known to cause lichenoid drug reactions more commonly include angiotensin-converting enzyme inhibitors, beta blockers, thiazides, gold, penicillamine, and antimalarials.² Lichenoid drug eruptions also have been documented in patients taking the second-generation nonsteroidal androgen receptor antagonist enzalutamide, which is used for the treatment of prostate cancer.⁴ More recently, the newer second-generation nonsteroidal androgen receptor antagonist apalutamide has been implicated in several cases of lichenoid drug eruptions.^5,6

We present a case of an apalutamide-induced lichenoid drug eruption that was resistant to dose reduction and required discontinuation of treatment due to the negative impact on the patient’s quality of life. Once the rash resolved, the patient transitioned to enzalutamide without any adverse events (AEs).

A 72-year-old man with a history of metastatic prostate cancer (stage IVB) presented to the dermatology clinic with a 4-month history of a dry itchy rash on the face, chest, back, and legs that had developed 2 to 3 months after oncology started him on apalutamide. The patient initially received apalutamide 240 mg/d, which was reduced by his oncologist 3 months later to 180 mg/d following the appearance of the rash. Then apalutamide was held as he awaited improvement of the rash.

One week after the apalutamide was held, the patient presented to dermatology. He reported that he had tried over-the-counter ammonium lactate 12% lotion twice daily when the rash first developed without improvement. When the apalutamide was held, oncology prescribed mupirocin ointment 2% 3 times daily which yielded minimal relief. On physical examination, widespread lichenified papules and plaques were noted on the face, chest, back, and legs (Figure 1). Dermatology initially prescribed triamcinolone ointment 0.1% twice daily. A 4-mm punch biopsy specimen of the upper back revealed a lichenoid interface dermatitis with numerous eosinophils compatible with a lichenoid hypersensitivity reaction (Figure 2). Considering the clinical and histologic findings, a diagnosis of lichenoid drug eruption secondary to apalutamide treatment was made.

To the Editor:

Lichenoid drug eruptions are lichen planus–like hypersensitivity reactions induced by medications. These reactions are rare but cause irritation to the skin, as extreme pruritus is common. One review of 300 consecutive cases of drug eruptions submitted to dermatopathology revealed that 12% of cases were classified as lichenoid drug reactions.¹ Lichenoid dermatitis is characterized by extremely pruritic, scaly, eczematous or psoriasiform papules, often along the extensor surfaces and trunk.² The pruritic nature of the rash can negatively impact quality of life. Treatment typically involves discontinuation of the offending medication, although complete resolution can take months, even after the drug is stopped. Although there have been some data suggesting that topical and/or oral corticosteroids can help with resolution, the rash can persist even with steroid treatment.²

The histopathologic findings of lichenoid drug eruptions show lichen planus–like changes such as hyperkeratosis, irregular acanthosis, and lichenoid interface dermatitis. Accordingly, idiopathic lichen planus is an important differential diagnosis for lichenoid drug eruptions; however, compared to idiopathic lichen planus, lichenoid drug eruptions are more likely to be associated with eosinophils and parakeratosis.^1,3 In some cases, the histopathologic distinction between the 2 conditions is impossible, and clinical history needs to be considered to make a diagnosis.¹ Drugs known to cause lichenoid drug reactions more commonly include angiotensin-converting enzyme inhibitors, beta blockers, thiazides, gold, penicillamine, and antimalarials.² Lichenoid drug eruptions also have been documented in patients taking the second-generation nonsteroidal androgen receptor antagonist enzalutamide, which is used for the treatment of prostate cancer.⁴ More recently, the newer second-generation nonsteroidal androgen receptor antagonist apalutamide has been implicated in several cases of lichenoid drug eruptions.^5,6

We present a case of an apalutamide-induced lichenoid drug eruption that was resistant to dose reduction and required discontinuation of treatment due to the negative impact on the patient’s quality of life. Once the rash resolved, the patient transitioned to enzalutamide without any adverse events (AEs).

A 72-year-old man with a history of metastatic prostate cancer (stage IVB) presented to the dermatology clinic with a 4-month history of a dry itchy rash on the face, chest, back, and legs that had developed 2 to 3 months after oncology started him on apalutamide. The patient initially received apalutamide 240 mg/d, which was reduced by his oncologist 3 months later to 180 mg/d following the appearance of the rash. Then apalutamide was held as he awaited improvement of the rash.

One week after the apalutamide was held, the patient presented to dermatology. He reported that he had tried over-the-counter ammonium lactate 12% lotion twice daily when the rash first developed without improvement. When the apalutamide was held, oncology prescribed mupirocin ointment 2% 3 times daily which yielded minimal relief. On physical examination, widespread lichenified papules and plaques were noted on the face, chest, back, and legs (Figure 1). Dermatology initially prescribed triamcinolone ointment 0.1% twice daily. A 4-mm punch biopsy specimen of the upper back revealed a lichenoid interface dermatitis with numerous eosinophils compatible with a lichenoid hypersensitivity reaction (Figure 2). Considering the clinical and histologic findings, a diagnosis of lichenoid drug eruption secondary to apalutamide treatment was made.

BOSTON — Social adversity is associated with worse survival among patients with pulmonary hypertension (PH), according to a new retrospective study of a New York City population. Among HIV+ patients with heart failure, PH was associated with about a threefold increase in all-cause mortality, but that risk increased to about sevenfold when social adversity, identified by a licensed social worker, was also present.

A sub-analysis of both HIV+ and HIV– patients showed worse mortality outcomes with social adversity in both groups.

“Almost the majority of patients that we treat have either some social adversity or no insurance or are undocumented, so as a group of residents, we decided to study the impact of these factors on their health and the care that can be provided. We started using the two cohorts and now we keep it going with every new resident,” said Luca Biavati, MD, who presented the study at the CHEST Annual Meeting.

“The presence of any form of socioeconomic disadvantage is negatively impacting care and for a large part of the population, there are some factors that could probably be addressed by either an institutional or hospital policy,” said Dr. Biavati, who is an internal medicine resident at Jacobi Medical Center, New York.

Other factors are more difficult to address, such as lack of education. “[Some patients] don’t understand the gravity of their issue and medical condition until it’s too late, and then they’re not fit enough for the treatment, or just because of the social situation, they cannot qualify for advanced therapies,” said Dr. Biavati.

The researchers established two cohorts: One consisting of patients with HIV and heart failure who may or may not have had PH and one comprising patients with PH with or without HIV and heart failure. In the HIV/heart failure group, PH without social adversity was associated with a nearly threefold increase in all-cause mortality (hazard ratio [HR], 2.83; P = .004), whereas PH with social adversity was linked to a more than sevenfold increase in all-cause mortality (HR, 7.14; P < .001). Social adversity without PA was associated with a more than fourfold increase (HR, 4.47; P < .001).

Within the PH cohort, social adversity was associated with lower survival (P < .001). When the researchers broke down the results by types of social adversity, they found statistically significant relationships between greater mortality risk and economic instability within the HIV+ population (HR, 2.59; P = .040), transportation issues within the HIV– population (HR, 12.8; P < .001), and lack of social or family support within both the HIV– (HR, 5.49; P < .001) and the HIV+ population (HR, 2.03; P = .028). 

The research has prompted interventions, which are now being studied at the institution, according to Dr. Biavati. “We have a policy of giving medications in bags when we discharge a patient with a social adversity. We literally go to the pharmacy, bring up the bag of medication, and we [put it] in their hands before they leave the hospital. They get a 1- or 3-month supply, depending on the medication, and then we usually discharge them with a clinical appointment already scheduled with either a pulmonary or primary care provider, and we usually call them before every appointment to confirm that they’re coming. That increases the chances of some success, but there’s still a very long way to go,” said Dr. Biavati.

Dr. Biavati was blinded to the results of the intervention, so he could not report on whether it was working. “But I can tell you that I’ve had busier clinics, so hopefully that means that they’re showing up more,” he said.

The problem is complex, according to Sandeep Jain, MD, who moderated the session. “Social adversity means lack of education. Lack of education means lack of compliance. Lack of compliance means what can you do if people are not taking medications? So it’s all matched together. It’s all lack of education and lack of money, lack of family support. And these drugs they have to take every single day. It’s not that easy. It’s very easy for us to say I had antiretroviral treatment for 6 months. It is almost impossible to continue regular treatment for that long [for a patient with social adversity]. You can’t blame them if they aren’t taking treatments. It’s very difficult for them,” said Dr. Jain.

That underscores the need for interventions that can address the needs of patients with social adversity. “We have to [practice] medicine considering the social situation of the patient and not just the medicine that we study in books. That’s kind of what we are faced with every day. We have therapies, and then life happens. It’s much harder to care for those patients,” said Dr. Biavati.

Dr. Biavati and Dr. Jain reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

BOSTON — Social adversity is associated with worse survival among patients with pulmonary hypertension (PH), according to a new retrospective study of a New York City population. Among HIV+ patients with heart failure, PH was associated with about a threefold increase in all-cause mortality, but that risk increased to about sevenfold when social adversity, identified by a licensed social worker, was also present.

A sub-analysis of both HIV+ and HIV– patients showed worse mortality outcomes with social adversity in both groups.

“Almost the majority of patients that we treat have either some social adversity or no insurance or are undocumented, so as a group of residents, we decided to study the impact of these factors on their health and the care that can be provided. We started using the two cohorts and now we keep it going with every new resident,” said Luca Biavati, MD, who presented the study at the CHEST Annual Meeting.

“The presence of any form of socioeconomic disadvantage is negatively impacting care and for a large part of the population, there are some factors that could probably be addressed by either an institutional or hospital policy,” said Dr. Biavati, who is an internal medicine resident at Jacobi Medical Center, New York.

Other factors are more difficult to address, such as lack of education. “[Some patients] don’t understand the gravity of their issue and medical condition until it’s too late, and then they’re not fit enough for the treatment, or just because of the social situation, they cannot qualify for advanced therapies,” said Dr. Biavati.

The researchers established two cohorts: One consisting of patients with HIV and heart failure who may or may not have had PH and one comprising patients with PH with or without HIV and heart failure. In the HIV/heart failure group, PH without social adversity was associated with a nearly threefold increase in all-cause mortality (hazard ratio [HR], 2.83; P = .004), whereas PH with social adversity was linked to a more than sevenfold increase in all-cause mortality (HR, 7.14; P < .001). Social adversity without PA was associated with a more than fourfold increase (HR, 4.47; P < .001).

Within the PH cohort, social adversity was associated with lower survival (P < .001). When the researchers broke down the results by types of social adversity, they found statistically significant relationships between greater mortality risk and economic instability within the HIV+ population (HR, 2.59; P = .040), transportation issues within the HIV– population (HR, 12.8; P < .001), and lack of social or family support within both the HIV– (HR, 5.49; P < .001) and the HIV+ population (HR, 2.03; P = .028). 

The research has prompted interventions, which are now being studied at the institution, according to Dr. Biavati. “We have a policy of giving medications in bags when we discharge a patient with a social adversity. We literally go to the pharmacy, bring up the bag of medication, and we [put it] in their hands before they leave the hospital. They get a 1- or 3-month supply, depending on the medication, and then we usually discharge them with a clinical appointment already scheduled with either a pulmonary or primary care provider, and we usually call them before every appointment to confirm that they’re coming. That increases the chances of some success, but there’s still a very long way to go,” said Dr. Biavati.

Dr. Biavati was blinded to the results of the intervention, so he could not report on whether it was working. “But I can tell you that I’ve had busier clinics, so hopefully that means that they’re showing up more,” he said.

The problem is complex, according to Sandeep Jain, MD, who moderated the session. “Social adversity means lack of education. Lack of education means lack of compliance. Lack of compliance means what can you do if people are not taking medications? So it’s all matched together. It’s all lack of education and lack of money, lack of family support. And these drugs they have to take every single day. It’s not that easy. It’s very easy for us to say I had antiretroviral treatment for 6 months. It is almost impossible to continue regular treatment for that long [for a patient with social adversity]. You can’t blame them if they aren’t taking treatments. It’s very difficult for them,” said Dr. Jain.

That underscores the need for interventions that can address the needs of patients with social adversity. “We have to [practice] medicine considering the social situation of the patient and not just the medicine that we study in books. That’s kind of what we are faced with every day. We have therapies, and then life happens. It’s much harder to care for those patients,” said Dr. Biavati.

Dr. Biavati and Dr. Jain reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

BOSTON — Social adversity is associated with worse survival among patients with pulmonary hypertension (PH), according to a new retrospective study of a New York City population. Among HIV+ patients with heart failure, PH was associated with about a threefold increase in all-cause mortality, but that risk increased to about sevenfold when social adversity, identified by a licensed social worker, was also present.

A sub-analysis of both HIV+ and HIV– patients showed worse mortality outcomes with social adversity in both groups.

“Almost the majority of patients that we treat have either some social adversity or no insurance or are undocumented, so as a group of residents, we decided to study the impact of these factors on their health and the care that can be provided. We started using the two cohorts and now we keep it going with every new resident,” said Luca Biavati, MD, who presented the study at the CHEST Annual Meeting.

“The presence of any form of socioeconomic disadvantage is negatively impacting care and for a large part of the population, there are some factors that could probably be addressed by either an institutional or hospital policy,” said Dr. Biavati, who is an internal medicine resident at Jacobi Medical Center, New York.

Other factors are more difficult to address, such as lack of education. “[Some patients] don’t understand the gravity of their issue and medical condition until it’s too late, and then they’re not fit enough for the treatment, or just because of the social situation, they cannot qualify for advanced therapies,” said Dr. Biavati.

The researchers established two cohorts: One consisting of patients with HIV and heart failure who may or may not have had PH and one comprising patients with PH with or without HIV and heart failure. In the HIV/heart failure group, PH without social adversity was associated with a nearly threefold increase in all-cause mortality (hazard ratio [HR], 2.83; P = .004), whereas PH with social adversity was linked to a more than sevenfold increase in all-cause mortality (HR, 7.14; P < .001). Social adversity without PA was associated with a more than fourfold increase (HR, 4.47; P < .001).

Within the PH cohort, social adversity was associated with lower survival (P < .001). When the researchers broke down the results by types of social adversity, they found statistically significant relationships between greater mortality risk and economic instability within the HIV+ population (HR, 2.59; P = .040), transportation issues within the HIV– population (HR, 12.8; P < .001), and lack of social or family support within both the HIV– (HR, 5.49; P < .001) and the HIV+ population (HR, 2.03; P = .028). 

The research has prompted interventions, which are now being studied at the institution, according to Dr. Biavati. “We have a policy of giving medications in bags when we discharge a patient with a social adversity. We literally go to the pharmacy, bring up the bag of medication, and we [put it] in their hands before they leave the hospital. They get a 1- or 3-month supply, depending on the medication, and then we usually discharge them with a clinical appointment already scheduled with either a pulmonary or primary care provider, and we usually call them before every appointment to confirm that they’re coming. That increases the chances of some success, but there’s still a very long way to go,” said Dr. Biavati.

Dr. Biavati was blinded to the results of the intervention, so he could not report on whether it was working. “But I can tell you that I’ve had busier clinics, so hopefully that means that they’re showing up more,” he said.

The problem is complex, according to Sandeep Jain, MD, who moderated the session. “Social adversity means lack of education. Lack of education means lack of compliance. Lack of compliance means what can you do if people are not taking medications? So it’s all matched together. It’s all lack of education and lack of money, lack of family support. And these drugs they have to take every single day. It’s not that easy. It’s very easy for us to say I had antiretroviral treatment for 6 months. It is almost impossible to continue regular treatment for that long [for a patient with social adversity]. You can’t blame them if they aren’t taking treatments. It’s very difficult for them,” said Dr. Jain.

That underscores the need for interventions that can address the needs of patients with social adversity. “We have to [practice] medicine considering the social situation of the patient and not just the medicine that we study in books. That’s kind of what we are faced with every day. We have therapies, and then life happens. It’s much harder to care for those patients,” said Dr. Biavati.

Dr. Biavati and Dr. Jain reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

A “digital twin” model successfully predicted adverse outcomes in intensive care unit (ICU) patients treated for sepsis. The research used an adaptive approach, updating time-sensitive values such as blood pressure and vitals every 15 minutes. The approach also took into account treatment decisions and has potential as a decision-making and educational tool.

The digital twin could reduce the risk for some interventions, according to Amos Lal, MD, who presented the study at the CHEST Annual Meeting. That’s because the model can predict the outcome. “You don’t actually have to make an intervention to the patient, which might be risky. By doing that, you can actually prevent a lot of harm,” said Dr. Lal, assistant professor of medicine at Mayo Clinic in Rochester, Minnesota.

The researchers used a one-dimensional convolutional neural network (CNN), similar to two-dimensional CNNs that are used to classify images, substituting the color channels used in imaging with 38 time-dependent variables. They applied it to predicting outcomes in the ICU, focusing on data generated within the first 24 hours of admission. The team made the model dynamic by adding time-sensitive data like vitals, laboratory values, and interventions every 15 minutes. That contrasts with existing models that are usually static, relying on values at admission or at 24 hours, for example. It also takes into account time-insensitive data like age, gender, and comorbidities. “Combining these two and coming up with the prediction model in real time can give you a more informed decision about how these patients are going to perform over a period of 2 weeks or 4 weeks of their stay within the ICU. And of course, as we get more and more data within the first 24 hours, the performance of the model improves as well,” said Dr. Lal.

The researchers tested the model by creating a virtual model of the patient and then performing an intervention on the patient and a simulated intervention on the virtual patient. “Then we advance the clock and the patient either improved or deteriorated, and we compared how the digital twin performed, whether the changes were concordant or discordant [between the virtual and real-world patients],” said Dr. Lal.

The model was designed to predict which patients with sepsis would be at greater risk for death or ICU stays longer than 14 days. It was created using data from 28,617 patients with critical care sepsis at a single hospital who were treated between 2011 and 2018, with 70% used as a training set, 20% as a test set, and 10% as a validation set. The researchers conducted an external validation using MIMIC-IV data on 30,903 patients from the Beth Israel Deaconess Medical Center in Boston. The model included 31 time-independent variables and 38 time-dependent variables that were collected every 15 minutes at the Mayo Clinic and every 60 minutes at Beth Israel Deaconess. Surgical patients represented 24% of the Mayo dataset and 58% of the MIMIC-IV dataset, but otherwise the two groups were demographically similar.

At 24 hours, the area under the receiver operating characteristic curve for predicting 14-day mortality was −0.82 in the Mayo validation cohort and −0.78 in the MIMIC validation cohort. The model improved in accuracy over time as more data were accumulated.

The session’s co-moderators, Sandeep Jain, MD, and Casey Cable, MD, praised the work. Dr. Cable, associate professor of pulmonary care medicine at VCU Health, Richmond, Virginia, noted that the model used both surgical patients and medical patients with sepsis, and the two groups can present quite differently. Another variable was the COVID pandemic, where some patients presented at the hospital when they were quite sick. “I’m curious how different starting points would play into it,” she said.

She called for institutions to develop such models on their own rather than relying on companies that might develop software solutions. “I think that this needs to be clinician-led, from the ground up,” said Dr. Cable.

Dr. Jain, an associate professor of pulmonary care medicine at Broward Health, suggested that such models might need to be individualized for each institution, but “my fear is it could become too expensive, so I think a group like CHEST could come together and [create] an open source system to have their researchers jumpstart the research on this,” he said.

Dr. Lal, Dr. Jain, and Dr. Cable reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A “digital twin” model successfully predicted adverse outcomes in intensive care unit (ICU) patients treated for sepsis. The research used an adaptive approach, updating time-sensitive values such as blood pressure and vitals every 15 minutes. The approach also took into account treatment decisions and has potential as a decision-making and educational tool.

The digital twin could reduce the risk for some interventions, according to Amos Lal, MD, who presented the study at the CHEST Annual Meeting. That’s because the model can predict the outcome. “You don’t actually have to make an intervention to the patient, which might be risky. By doing that, you can actually prevent a lot of harm,” said Dr. Lal, assistant professor of medicine at Mayo Clinic in Rochester, Minnesota.

The researchers used a one-dimensional convolutional neural network (CNN), similar to two-dimensional CNNs that are used to classify images, substituting the color channels used in imaging with 38 time-dependent variables. They applied it to predicting outcomes in the ICU, focusing on data generated within the first 24 hours of admission. The team made the model dynamic by adding time-sensitive data like vitals, laboratory values, and interventions every 15 minutes. That contrasts with existing models that are usually static, relying on values at admission or at 24 hours, for example. It also takes into account time-insensitive data like age, gender, and comorbidities. “Combining these two and coming up with the prediction model in real time can give you a more informed decision about how these patients are going to perform over a period of 2 weeks or 4 weeks of their stay within the ICU. And of course, as we get more and more data within the first 24 hours, the performance of the model improves as well,” said Dr. Lal.

The researchers tested the model by creating a virtual model of the patient and then performing an intervention on the patient and a simulated intervention on the virtual patient. “Then we advance the clock and the patient either improved or deteriorated, and we compared how the digital twin performed, whether the changes were concordant or discordant [between the virtual and real-world patients],” said Dr. Lal.

The model was designed to predict which patients with sepsis would be at greater risk for death or ICU stays longer than 14 days. It was created using data from 28,617 patients with critical care sepsis at a single hospital who were treated between 2011 and 2018, with 70% used as a training set, 20% as a test set, and 10% as a validation set. The researchers conducted an external validation using MIMIC-IV data on 30,903 patients from the Beth Israel Deaconess Medical Center in Boston. The model included 31 time-independent variables and 38 time-dependent variables that were collected every 15 minutes at the Mayo Clinic and every 60 minutes at Beth Israel Deaconess. Surgical patients represented 24% of the Mayo dataset and 58% of the MIMIC-IV dataset, but otherwise the two groups were demographically similar.

At 24 hours, the area under the receiver operating characteristic curve for predicting 14-day mortality was −0.82 in the Mayo validation cohort and −0.78 in the MIMIC validation cohort. The model improved in accuracy over time as more data were accumulated.

The session’s co-moderators, Sandeep Jain, MD, and Casey Cable, MD, praised the work. Dr. Cable, associate professor of pulmonary care medicine at VCU Health, Richmond, Virginia, noted that the model used both surgical patients and medical patients with sepsis, and the two groups can present quite differently. Another variable was the COVID pandemic, where some patients presented at the hospital when they were quite sick. “I’m curious how different starting points would play into it,” she said.

She called for institutions to develop such models on their own rather than relying on companies that might develop software solutions. “I think that this needs to be clinician-led, from the ground up,” said Dr. Cable.

Dr. Jain, an associate professor of pulmonary care medicine at Broward Health, suggested that such models might need to be individualized for each institution, but “my fear is it could become too expensive, so I think a group like CHEST could come together and [create] an open source system to have their researchers jumpstart the research on this,” he said.

Dr. Lal, Dr. Jain, and Dr. Cable reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A “digital twin” model successfully predicted adverse outcomes in intensive care unit (ICU) patients treated for sepsis. The research used an adaptive approach, updating time-sensitive values such as blood pressure and vitals every 15 minutes. The approach also took into account treatment decisions and has potential as a decision-making and educational tool.

The digital twin could reduce the risk for some interventions, according to Amos Lal, MD, who presented the study at the CHEST Annual Meeting. That’s because the model can predict the outcome. “You don’t actually have to make an intervention to the patient, which might be risky. By doing that, you can actually prevent a lot of harm,” said Dr. Lal, assistant professor of medicine at Mayo Clinic in Rochester, Minnesota.

The researchers used a one-dimensional convolutional neural network (CNN), similar to two-dimensional CNNs that are used to classify images, substituting the color channels used in imaging with 38 time-dependent variables. They applied it to predicting outcomes in the ICU, focusing on data generated within the first 24 hours of admission. The team made the model dynamic by adding time-sensitive data like vitals, laboratory values, and interventions every 15 minutes. That contrasts with existing models that are usually static, relying on values at admission or at 24 hours, for example. It also takes into account time-insensitive data like age, gender, and comorbidities. “Combining these two and coming up with the prediction model in real time can give you a more informed decision about how these patients are going to perform over a period of 2 weeks or 4 weeks of their stay within the ICU. And of course, as we get more and more data within the first 24 hours, the performance of the model improves as well,” said Dr. Lal.

The researchers tested the model by creating a virtual model of the patient and then performing an intervention on the patient and a simulated intervention on the virtual patient. “Then we advance the clock and the patient either improved or deteriorated, and we compared how the digital twin performed, whether the changes were concordant or discordant [between the virtual and real-world patients],” said Dr. Lal.

The model was designed to predict which patients with sepsis would be at greater risk for death or ICU stays longer than 14 days. It was created using data from 28,617 patients with critical care sepsis at a single hospital who were treated between 2011 and 2018, with 70% used as a training set, 20% as a test set, and 10% as a validation set. The researchers conducted an external validation using MIMIC-IV data on 30,903 patients from the Beth Israel Deaconess Medical Center in Boston. The model included 31 time-independent variables and 38 time-dependent variables that were collected every 15 minutes at the Mayo Clinic and every 60 minutes at Beth Israel Deaconess. Surgical patients represented 24% of the Mayo dataset and 58% of the MIMIC-IV dataset, but otherwise the two groups were demographically similar.

At 24 hours, the area under the receiver operating characteristic curve for predicting 14-day mortality was −0.82 in the Mayo validation cohort and −0.78 in the MIMIC validation cohort. The model improved in accuracy over time as more data were accumulated.

The session’s co-moderators, Sandeep Jain, MD, and Casey Cable, MD, praised the work. Dr. Cable, associate professor of pulmonary care medicine at VCU Health, Richmond, Virginia, noted that the model used both surgical patients and medical patients with sepsis, and the two groups can present quite differently. Another variable was the COVID pandemic, where some patients presented at the hospital when they were quite sick. “I’m curious how different starting points would play into it,” she said.

She called for institutions to develop such models on their own rather than relying on companies that might develop software solutions. “I think that this needs to be clinician-led, from the ground up,” said Dr. Cable.

Dr. Jain, an associate professor of pulmonary care medicine at Broward Health, suggested that such models might need to be individualized for each institution, but “my fear is it could become too expensive, so I think a group like CHEST could come together and [create] an open source system to have their researchers jumpstart the research on this,” he said.

Dr. Lal, Dr. Jain, and Dr. Cable reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

The viral burden of SARS-CoV-2 on floors, even in healthcare worker–only areas, was strongly associated with COVID-19 outbreaks in two acute-care hospitals, according to a new study from Ontario, Canada.

With every 10-fold increase in viral copies, the chance of an impending outbreak of COVID-19 rose 22-fold. The results suggest that frequent floor sampling could play an important role in a more localized surveillance of the virus, the authors wrote.

“These data add to the mounting evidence that built environment detection for SARS-CoV-2 may provide an additional layer of monitoring and could help inform local infection prevention and control measures,” they wrote.

The study was published online in Infection Control & Hospital Epidemiology. 
 

Preventing Future Suffering 

The current study builds on the researchers’ previous work, which found the same correlation between viral load on floors and COVID outbreaks in long-term care homes. 

Currently, the best-known method of environmental surveillance for COVID is wastewater detection. “Swabbing the floors would be another approach to surveillance,” senior author Caroline Nott, MD, infectious disease physician at the Ottawa Hospital, said in an interview. 

“We do have environmental surveillance with wastewater, but while this may tell you what’s going on in the city, it doesn’t tell you what is going on in a particular ward of a hospital, for instance,” she added. 

Nott and her colleagues believe that swabbing, which is easy and relatively inexpensive, will become another tool to examine the built environment. “Instead of having to close a whole hospital, for example, we could just close one room instead of an entire ward if swabbing showed a high concentration of COVID,” Nott said. 

The current study was conducted at two hospitals in Ontario between July 2022 and March 2023. The floors of healthcare worker–only areas on four inpatient adult wards were swabbed. These areas included changing rooms, meeting rooms, staff washrooms, nursing stations, and interdisciplinary team rooms.

SARS-CoV-2 RNA was detected on 537 of 760 floor swabs (71%). The overall positivity rate in the first hospital was 90% (n = 280). In the second hospital, the rate was 60% (n = 480).

Four COVID-19 outbreaks occurred in the first acute care hospital, and seven outbreaks occurred at the second hospital. Outbreaks occurred mostly among hospitalized patients (140 cases), but also in four hospital workers.

COVID-19 still requires vigilance, said Nott. “We weren’t prepared for COVID, and so as a result, many people died or have suffered long-term effects, especially vulnerable people like those being treated in hospital or in long-term care facilities. We want to develop methods to prevent similar suffering in the future, whether it’s a new COVID variant or a different pathogen altogether.” 
 

Changing Surveillance Practice?

“This is a good study,” Steven Rogak, PhD, professor of mechanical engineering at the University of British Columbia (UBC) in Vancouver, Canada, said in an interivew. “The fundamental idea is that respiratory droplets and aerosols will deposit on the floor, and polymerase chain reaction [PCR] tests of swabs will provide a surrogate measurement of what might have been inhaled. There are solid statistics that it worked for the hospitals studied,” said Rogak, who studies aerosols at UBC’s Energy and Aerosols Laboratory. Rogak did not participate in the study. 

“The authors note several limitations, including that increased healthcare worker testing may have been triggered by the higher values of PCR counts from the floor swabs. But this doesn’t seem to be a problem to me, because if the floor swabs motivate the hospital to test workers more, and that results in identifying outbreaks sooner, then great,” he said.

“Another limitation is that if the hospital has better HVAC or uses air purifiers, it could remove the most infectious aerosols, but the large droplets that fall quickly to the ground would remain, and this would still result in high PCR counts from floor swabs. In this case, perhaps the floor swabs would be a poorer indication of impending outbreaks,” said Rogak.

Determining the best timing and location for floor swabbing might be challenging and specific to the particular hospital, he added. ”For example, you would not want to take swabs from floors right after they are cleaned. Overall, I think this method deserves further development, and it could become a standard technique, but the details might require refinement for widespread application.”

Adrian Popp, MD, chair of the Infectious Disease Service at Huntington Hospital–Northwell Health in New York, said that, although interesting, the study would not change his current practice.

“I’m going to start testing the environment in different rooms in the hospital, and yes, I might find different amounts of COVID, but what does that mean? If pieces of RNA from COVID are on the floor, the likelihood is that they’re not infectious,” Popp said in an interview.

“Hospital workers do get sick with COVID, and sometimes they are asymptomatic and come to work. Patients may come into the hospital for another reason and be sick with COVID. There are many ways people who work in the hospital, as well as the patients, can get COVID. To me, it means that in that hospital and community there is a lot of COVID, but I can’t tell if there is causation here. Who is giving COVID to whom? What am I supposed to do with the information?” 

The study was supported by the Northern Ontario Academic Medicine Association Clinical Innovation Opportunities Fund, the Ottawa Hospital Academic Medical Organization Innovation Fund, and a Canadian Institutes of Health Research Operating Grant. One author was a consultant for ProofDx, a startup company creating a point-of-care diagnostic test for COVID-19, and is an advisor for SIGNAL1, a startup company deploying machine-learning models to improve inpatient care. Nott, Rogak, and Popp reported having no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The viral burden of SARS-CoV-2 on floors, even in healthcare worker–only areas, was strongly associated with COVID-19 outbreaks in two acute-care hospitals, according to a new study from Ontario, Canada.

With every 10-fold increase in viral copies, the chance of an impending outbreak of COVID-19 rose 22-fold. The results suggest that frequent floor sampling could play an important role in a more localized surveillance of the virus, the authors wrote.

“These data add to the mounting evidence that built environment detection for SARS-CoV-2 may provide an additional layer of monitoring and could help inform local infection prevention and control measures,” they wrote.

The study was published online in Infection Control & Hospital Epidemiology. 
 

Preventing Future Suffering 

The current study builds on the researchers’ previous work, which found the same correlation between viral load on floors and COVID outbreaks in long-term care homes. 

Currently, the best-known method of environmental surveillance for COVID is wastewater detection. “Swabbing the floors would be another approach to surveillance,” senior author Caroline Nott, MD, infectious disease physician at the Ottawa Hospital, said in an interview. 

“We do have environmental surveillance with wastewater, but while this may tell you what’s going on in the city, it doesn’t tell you what is going on in a particular ward of a hospital, for instance,” she added. 

Nott and her colleagues believe that swabbing, which is easy and relatively inexpensive, will become another tool to examine the built environment. “Instead of having to close a whole hospital, for example, we could just close one room instead of an entire ward if swabbing showed a high concentration of COVID,” Nott said. 

The current study was conducted at two hospitals in Ontario between July 2022 and March 2023. The floors of healthcare worker–only areas on four inpatient adult wards were swabbed. These areas included changing rooms, meeting rooms, staff washrooms, nursing stations, and interdisciplinary team rooms.

SARS-CoV-2 RNA was detected on 537 of 760 floor swabs (71%). The overall positivity rate in the first hospital was 90% (n = 280). In the second hospital, the rate was 60% (n = 480).

Four COVID-19 outbreaks occurred in the first acute care hospital, and seven outbreaks occurred at the second hospital. Outbreaks occurred mostly among hospitalized patients (140 cases), but also in four hospital workers.

COVID-19 still requires vigilance, said Nott. “We weren’t prepared for COVID, and so as a result, many people died or have suffered long-term effects, especially vulnerable people like those being treated in hospital or in long-term care facilities. We want to develop methods to prevent similar suffering in the future, whether it’s a new COVID variant or a different pathogen altogether.” 
 

Changing Surveillance Practice?

“This is a good study,” Steven Rogak, PhD, professor of mechanical engineering at the University of British Columbia (UBC) in Vancouver, Canada, said in an interivew. “The fundamental idea is that respiratory droplets and aerosols will deposit on the floor, and polymerase chain reaction [PCR] tests of swabs will provide a surrogate measurement of what might have been inhaled. There are solid statistics that it worked for the hospitals studied,” said Rogak, who studies aerosols at UBC’s Energy and Aerosols Laboratory. Rogak did not participate in the study. 

“The authors note several limitations, including that increased healthcare worker testing may have been triggered by the higher values of PCR counts from the floor swabs. But this doesn’t seem to be a problem to me, because if the floor swabs motivate the hospital to test workers more, and that results in identifying outbreaks sooner, then great,” he said.

“Another limitation is that if the hospital has better HVAC or uses air purifiers, it could remove the most infectious aerosols, but the large droplets that fall quickly to the ground would remain, and this would still result in high PCR counts from floor swabs. In this case, perhaps the floor swabs would be a poorer indication of impending outbreaks,” said Rogak.

Determining the best timing and location for floor swabbing might be challenging and specific to the particular hospital, he added. ”For example, you would not want to take swabs from floors right after they are cleaned. Overall, I think this method deserves further development, and it could become a standard technique, but the details might require refinement for widespread application.”

Adrian Popp, MD, chair of the Infectious Disease Service at Huntington Hospital–Northwell Health in New York, said that, although interesting, the study would not change his current practice.

“I’m going to start testing the environment in different rooms in the hospital, and yes, I might find different amounts of COVID, but what does that mean? If pieces of RNA from COVID are on the floor, the likelihood is that they’re not infectious,” Popp said in an interview.

“Hospital workers do get sick with COVID, and sometimes they are asymptomatic and come to work. Patients may come into the hospital for another reason and be sick with COVID. There are many ways people who work in the hospital, as well as the patients, can get COVID. To me, it means that in that hospital and community there is a lot of COVID, but I can’t tell if there is causation here. Who is giving COVID to whom? What am I supposed to do with the information?” 

The study was supported by the Northern Ontario Academic Medicine Association Clinical Innovation Opportunities Fund, the Ottawa Hospital Academic Medical Organization Innovation Fund, and a Canadian Institutes of Health Research Operating Grant. One author was a consultant for ProofDx, a startup company creating a point-of-care diagnostic test for COVID-19, and is an advisor for SIGNAL1, a startup company deploying machine-learning models to improve inpatient care. Nott, Rogak, and Popp reported having no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The viral burden of SARS-CoV-2 on floors, even in healthcare worker–only areas, was strongly associated with COVID-19 outbreaks in two acute-care hospitals, according to a new study from Ontario, Canada.

With every 10-fold increase in viral copies, the chance of an impending outbreak of COVID-19 rose 22-fold. The results suggest that frequent floor sampling could play an important role in a more localized surveillance of the virus, the authors wrote.

“These data add to the mounting evidence that built environment detection for SARS-CoV-2 may provide an additional layer of monitoring and could help inform local infection prevention and control measures,” they wrote.

The study was published online in Infection Control & Hospital Epidemiology. 
 

Preventing Future Suffering 

The current study builds on the researchers’ previous work, which found the same correlation between viral load on floors and COVID outbreaks in long-term care homes. 

Currently, the best-known method of environmental surveillance for COVID is wastewater detection. “Swabbing the floors would be another approach to surveillance,” senior author Caroline Nott, MD, infectious disease physician at the Ottawa Hospital, said in an interview. 

“We do have environmental surveillance with wastewater, but while this may tell you what’s going on in the city, it doesn’t tell you what is going on in a particular ward of a hospital, for instance,” she added. 

Nott and her colleagues believe that swabbing, which is easy and relatively inexpensive, will become another tool to examine the built environment. “Instead of having to close a whole hospital, for example, we could just close one room instead of an entire ward if swabbing showed a high concentration of COVID,” Nott said. 

The current study was conducted at two hospitals in Ontario between July 2022 and March 2023. The floors of healthcare worker–only areas on four inpatient adult wards were swabbed. These areas included changing rooms, meeting rooms, staff washrooms, nursing stations, and interdisciplinary team rooms.

SARS-CoV-2 RNA was detected on 537 of 760 floor swabs (71%). The overall positivity rate in the first hospital was 90% (n = 280). In the second hospital, the rate was 60% (n = 480).

Four COVID-19 outbreaks occurred in the first acute care hospital, and seven outbreaks occurred at the second hospital. Outbreaks occurred mostly among hospitalized patients (140 cases), but also in four hospital workers.

COVID-19 still requires vigilance, said Nott. “We weren’t prepared for COVID, and so as a result, many people died or have suffered long-term effects, especially vulnerable people like those being treated in hospital or in long-term care facilities. We want to develop methods to prevent similar suffering in the future, whether it’s a new COVID variant or a different pathogen altogether.” 
 

Changing Surveillance Practice?

“This is a good study,” Steven Rogak, PhD, professor of mechanical engineering at the University of British Columbia (UBC) in Vancouver, Canada, said in an interivew. “The fundamental idea is that respiratory droplets and aerosols will deposit on the floor, and polymerase chain reaction [PCR] tests of swabs will provide a surrogate measurement of what might have been inhaled. There are solid statistics that it worked for the hospitals studied,” said Rogak, who studies aerosols at UBC’s Energy and Aerosols Laboratory. Rogak did not participate in the study. 

“The authors note several limitations, including that increased healthcare worker testing may have been triggered by the higher values of PCR counts from the floor swabs. But this doesn’t seem to be a problem to me, because if the floor swabs motivate the hospital to test workers more, and that results in identifying outbreaks sooner, then great,” he said.

“Another limitation is that if the hospital has better HVAC or uses air purifiers, it could remove the most infectious aerosols, but the large droplets that fall quickly to the ground would remain, and this would still result in high PCR counts from floor swabs. In this case, perhaps the floor swabs would be a poorer indication of impending outbreaks,” said Rogak.

Determining the best timing and location for floor swabbing might be challenging and specific to the particular hospital, he added. ”For example, you would not want to take swabs from floors right after they are cleaned. Overall, I think this method deserves further development, and it could become a standard technique, but the details might require refinement for widespread application.”

Adrian Popp, MD, chair of the Infectious Disease Service at Huntington Hospital–Northwell Health in New York, said that, although interesting, the study would not change his current practice.

“I’m going to start testing the environment in different rooms in the hospital, and yes, I might find different amounts of COVID, but what does that mean? If pieces of RNA from COVID are on the floor, the likelihood is that they’re not infectious,” Popp said in an interview.

“Hospital workers do get sick with COVID, and sometimes they are asymptomatic and come to work. Patients may come into the hospital for another reason and be sick with COVID. There are many ways people who work in the hospital, as well as the patients, can get COVID. To me, it means that in that hospital and community there is a lot of COVID, but I can’t tell if there is causation here. Who is giving COVID to whom? What am I supposed to do with the information?” 

The study was supported by the Northern Ontario Academic Medicine Association Clinical Innovation Opportunities Fund, the Ottawa Hospital Academic Medical Organization Innovation Fund, and a Canadian Institutes of Health Research Operating Grant. One author was a consultant for ProofDx, a startup company creating a point-of-care diagnostic test for COVID-19, and is an advisor for SIGNAL1, a startup company deploying machine-learning models to improve inpatient care. Nott, Rogak, and Popp reported having no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved Orlynvah, a new oral treatment for uncomplicated urinary tract infections (UTIs) in women who have limited options for effective antibiotic therapy.

Uncomplicated UTIs are bladder infections that typically affect women who don’t have other issues like kidney disease or urinary tract abnormalities. These infections are common, affecting around half of all women at least once in their lives.

Treating UTIs can be difficult when standard antibiotics don’t work well, often because of antibiotic resistance or certain health conditions. Orlynvah offers a promising new option by combining two drugs, sulopenem etzadroxil and probenecid, in one oral tablet. This combination helps keep the antibiotic in the body longer, making it work better, especially against bacteria that resist traditional treatments. Orlynvah is specifically approved to target infections from bacteria like Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, which can be harder to treat.

Marjorie Golden, MD, an infectious disease specialist at Yale New Haven Hospital in Connecticut, described Orlynvah as a much-needed alternative for women struggling with difficult-to-treat UTIs. 

“Orlynvah has the potential to be an important treatment option for those who need it,” she said in a news release from Iterum Therapeutics, the drug’s maker.

The FDA approved Orlynvah based on two large clinical trials involving over 3,800 women. In these studies, Orlynvah worked as well as or better than antibiotics like ciprofloxacin and Augmentin. It was generally well-tolerated, though common side effects included diarrhea, nausea, yeast infections, and headaches.

The FDA advises people to discuss their medical history with their doctor before taking Orlynvah, especially if they have conditions like gout, kidney stones, or allergies to other antibiotics.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved Orlynvah, a new oral treatment for uncomplicated urinary tract infections (UTIs) in women who have limited options for effective antibiotic therapy.

Uncomplicated UTIs are bladder infections that typically affect women who don’t have other issues like kidney disease or urinary tract abnormalities. These infections are common, affecting around half of all women at least once in their lives.

Treating UTIs can be difficult when standard antibiotics don’t work well, often because of antibiotic resistance or certain health conditions. Orlynvah offers a promising new option by combining two drugs, sulopenem etzadroxil and probenecid, in one oral tablet. This combination helps keep the antibiotic in the body longer, making it work better, especially against bacteria that resist traditional treatments. Orlynvah is specifically approved to target infections from bacteria like Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, which can be harder to treat.

Marjorie Golden, MD, an infectious disease specialist at Yale New Haven Hospital in Connecticut, described Orlynvah as a much-needed alternative for women struggling with difficult-to-treat UTIs. 

“Orlynvah has the potential to be an important treatment option for those who need it,” she said in a news release from Iterum Therapeutics, the drug’s maker.

The FDA approved Orlynvah based on two large clinical trials involving over 3,800 women. In these studies, Orlynvah worked as well as or better than antibiotics like ciprofloxacin and Augmentin. It was generally well-tolerated, though common side effects included diarrhea, nausea, yeast infections, and headaches.

The FDA advises people to discuss their medical history with their doctor before taking Orlynvah, especially if they have conditions like gout, kidney stones, or allergies to other antibiotics.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved Orlynvah, a new oral treatment for uncomplicated urinary tract infections (UTIs) in women who have limited options for effective antibiotic therapy.

Uncomplicated UTIs are bladder infections that typically affect women who don’t have other issues like kidney disease or urinary tract abnormalities. These infections are common, affecting around half of all women at least once in their lives.

Treating UTIs can be difficult when standard antibiotics don’t work well, often because of antibiotic resistance or certain health conditions. Orlynvah offers a promising new option by combining two drugs, sulopenem etzadroxil and probenecid, in one oral tablet. This combination helps keep the antibiotic in the body longer, making it work better, especially against bacteria that resist traditional treatments. Orlynvah is specifically approved to target infections from bacteria like Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, which can be harder to treat.

Marjorie Golden, MD, an infectious disease specialist at Yale New Haven Hospital in Connecticut, described Orlynvah as a much-needed alternative for women struggling with difficult-to-treat UTIs. 

“Orlynvah has the potential to be an important treatment option for those who need it,” she said in a news release from Iterum Therapeutics, the drug’s maker.

The FDA approved Orlynvah based on two large clinical trials involving over 3,800 women. In these studies, Orlynvah worked as well as or better than antibiotics like ciprofloxacin and Augmentin. It was generally well-tolerated, though common side effects included diarrhea, nausea, yeast infections, and headaches.

The FDA advises people to discuss their medical history with their doctor before taking Orlynvah, especially if they have conditions like gout, kidney stones, or allergies to other antibiotics.

A version of this article first appeared on Medscape.com.

As the number of drug-resistant and other troublesome tinea infections grows, perhaps the only certainty is that these are not the tinea subtypes that most providers studied in medical school. As dermatologists, public health officials, and infectious disease specialists scramble to raise awareness about prevention and treatment, challenges ranging from a dearth of testing facilities and data to payer pushback over longer therapeutic courses remain.

Dermatophyte Discourse Changing

“Trichophyton indotineae is changing the way we talk about dermatophyte infections,” Avrom S. Caplan, MD, assistant professor in the Department of Dermatology at New York University, New York City, said in an interview. Called T mentagrophytes VIII (TMVIII) before a 2020 report in the journal Mycopathologia proposed the name T indotineae, this species requires clinicians to expand their conception of how tinea looks, acts, and responds to treatment.

Dr. Lu Yin, New York University

University of Alabama, Birmingham

Tracking Cases

Because T indotineae does not require reporting to public health agencies, said Jeremy Gold, MD, MS, a medical officer with the US Centers for Disease Control and Prevention (CDC) Mycotic Diseases Branch in Atlanta, “there is no official public health surveillance keeping track of exactly how many cases have occurred.”

Dr. Gold

The same is true for TMVII and terbinafine-resistant T rubrum, which are also on the rise. Regarding T indotineae, authors from the University of Texas Health Science Center at San Antonio retrospectively reported 21 terbinafine-resistant isolates from North America in the July 2023 Journal of Clinical Microbiology .

Dr. Vignesh Ramachandran, New York University

Caplan has seen approximately 12 T indotineae cases to date, including the first two confirmed US cases, which he and co-authors, including Gold, reported in the CDC’s Morbidity and Mortality Weekly Report in May 2023. T indotineae is likely underreported, he said, because it eludes standard culture-based techniques, and identifying it requires molecular testing, which is available at only a handful of labs nationally.

To help educate providers, in July, the American Academy of Dermatology (AAD) and the International League of Dermatological Societies unveiled an Emerging Diseases Resource Center, which includes resources for providers and a registry for reporting confirmed and suspected resistant dermatophytes.

Dr. Lu Yin, New York University

Dr. Lu Yin, New York University

The new registry resides within the AAD’s existing COVID-19, Mpox, and Emerging Infections Registry. “Our registry efforts have already captured 2500 COVID-19 and mpox cases from 72 different countries,” Freeman said. For all these infections, she added, “we hope that real-time data analysis of cases worldwide will provide information that helps physicians recognize and treat cases.”

Consistent with the registry’s approach, said Caplan and Gold, there is no silver bullet for battling dermatophyte resistance. What is needed, said Gold, is a coordinated approach involving public health officials, dermatologists, primary care providers, infectious disease specialists, pharmacists, and patients. “It’s going to be a team effort to address the challenge of emerging complex dermatophytosis,” he said.
 

Resistant T rubrum

“The biggest difference with T rubrum resistance is you may not see that widespread infection that we see with T indotineae,” said Caplan. T rubrum is probably the most common dermatophyte that dermatologists see, added Elewski, who encounters a resistant case at least monthly. One such patient, featured in a January 2021 British Journal of Dermatology research letter, cleared on itraconazole and ciclopirox cream but subsequently returned with itraconazole-resistant T rubrum because he had been doctor-shopping for the drug intermittently for years, she said. He cleared on posaconazole 300 mg daily, then was lost to follow-up.

TMVII

A 2023 Emerging Infectious Diseases report highlighted the potential for this dermatophyte to spread among men who have sex with men (MSM), presenting as an itchy, scaly rash affecting the pubic, genital, and buttocks skin. “People don’t generally think of a fungal infection as something that could behave like a sexually transmitted infection (STI),” said Gold.

Caplan and coauthors recently reported the first confirmed US TMVII case in JAMA Dermatology. Many experts suspect that unreported US cases existed previously, he said. “When it circulates in Europe and there’s so much travel, it’s probably here too.”

The fact that T indotineae was formerly called TMVIII has created confusion, added Caplan. “I’ve had patients say, ‘I’m worried I have that resistant ringworm that’s spreading among MSM.’ Whenever we talk about STIs and introduce the word ‘resistant,’ that comes with the potential for stigma, anxiety, and concern.” Fortunately, he said, TMVII has shown no resistance to first-line antifungals.

NYU Langone

Why the Rise

Gold said, “We don’t know for sure why we’re seeing these different drug-resistant species popping up.” One possibility, he said, is the common misuse and overuse of topical antifungals — especially those available overseas in combination with high-potency steroids, such as clobetasol. Consumers use these products for a few weeks until symptoms resolve, then reapply them off and on over years, fueling resistance, said Gold.

“We are worried that with warming temperatures, there’s potential to see expansion of the geographic range of epidemic fungi,” he added. “That could be part of what has fueled recent increases in resistant dermatophytes. But it’s hard to prove.”

Climate change may be behind the emergence of Candida auris, according to a 2022 article in The Lancet Regional Health – Americas. This potentially fatal multidrug-resistant infection spreads easily among sick patients in healthcare facilities, according to a CDC information page on C auris.
 

Confirming Dermatophyte Infection

“A biopsy will only confirm the presence of fungus,” said Elewski. “Here you will need a lab that knows how to do a fungal culture.” Most state laboratories can do this, she said, as can some hospitals and special labs such as CMM in Cleveland.

It takes a Clinical Laboratory Improvement Amendments–certified lab to perform KOH prep in-house, added Caplan, plus up-to-date gear and knowledge of where and how to scrape and what to look for microscopically. Moreover, identifying T indotineae requires molecular testing available at only a handful of laboratories — listed on the AAD Emerging Dermatophytes webpage — nationwide.

Nevertheless, said Caplan, nailing down a diagnosis can guide treatment, often supplanting empirically prescribed antifungal steroid creams. “Those are probably not going to help. And people may be using those on areas of the body they shouldn’t. Both the clinical clues and the steps to make the diagnosis need to come together. But that’s often easier said than done, especially in a busy practice.”

Identifying resistance requires antifungal sensitivity testing, he added, which few labs perform. “Practically speaking,” said Elewski, “if the patient failed terbinafine, I would try itraconazole. You don’t necessarily need proof” of resistance. But if a patient does not respond to itraconazole and terbinafine clinically, she said that she might consider fungal susceptibility testing.
 

Treatment Tips

To address any resistant dermatophyte, Elewski recommended getting comfortable with itraconazole. For decades, she said, dermatologists have avoided itraconazole because terbinafine typically costs patients $10 for 3 months. “Itraconazole could be $200 per month,” said Elewski. Because of potential drug-drug interactions and absorption issues — and a boxed warning regarding congestive heart failure — physicians historically reserved itraconazole for severe fungal infections.

Itraconazole labeled dosing for onychomycosis is 200 mg daily for 12 weeks. Elewski favors a two-pronged attack, often combining an -azole antifungal with topical ciclopirox.

Another element that emerging tinea pathogens share is slower response to treatment. For T indotineae, reports appearing in the Journal of the American Academy of Dermatology in 2022 and 2024 suggest duration from 6-8 weeks up to 20 weeks.

To avoid recurrences of resistant T rubrum, Elewski treats for a year. However, she has problems getting itraconazole approved, when often it is the only agent that works. “I’ve written more letters than I like to insurance companies” to document terbinafine failure, she said.

Rarely, said Gold, dermatophyte infections resist both terbinafine and itraconazole. Next-line agents such as voriconazole, which some dermatologists have used for resistant T indotineae, can be much harder to tolerate, with more drug interactions, he said.

And because itraconazole, voriconazole, and posaconazole are all triazoles, added Elewski, the latter two might not work better than the former. But because these drugs might outperform itraconazole in selected cases, she said, “that’s when you want to do fungal susceptibility testing.”

TMVII is so new, said Caplan, that optimal therapy duration remains unclear. “One of the challenges with TMVII is when it gets into the genital skin, it’s a hair-bearing area. And based on various grooming practices, there’s an opportunity for the tinea to get deeper into the hair follicle and dermis. That may also be true of T indotineae.”
 

Anemic Arsenal

Unfortunately, said Gold, the arsenal of antifungals available in the United States remains limited. “Depending on how you count, there are only three to four classes of antifungal drugs designed to treat severe or invasive infections. So whenever we hear about a new fungal pathogen that’s causing resistant infections, it causes public health concern.”

Promising drugs in development include olorofim (F2G) and fosmanogepix (Basilea), according to Gold. However, he said, the development of these drugs to date has targeted invasive fungal infections such as aspergillosis. In June 2023, the Food and Drug Administration rejected the new drug application for olorofim, requesting additional data and analyses. Regarding fosmanogepix, a double-blinded noninferiority phase 3 trial in invasive yeast infections was recently launched, according to a September 24 press release.

Gold, Caplan, and Elewski reported no relevant financial disclosures. Freeman is a COVID-19 co-author for UpToDate and chair of the AAD Emerging Diseases Task Force.
 

A version of this article appeared on Medscape.com.

As the number of drug-resistant and other troublesome tinea infections grows, perhaps the only certainty is that these are not the tinea subtypes that most providers studied in medical school. As dermatologists, public health officials, and infectious disease specialists scramble to raise awareness about prevention and treatment, challenges ranging from a dearth of testing facilities and data to payer pushback over longer therapeutic courses remain.

Dermatophyte Discourse Changing

“Trichophyton indotineae is changing the way we talk about dermatophyte infections,” Avrom S. Caplan, MD, assistant professor in the Department of Dermatology at New York University, New York City, said in an interview. Called T mentagrophytes VIII (TMVIII) before a 2020 report in the journal Mycopathologia proposed the name T indotineae, this species requires clinicians to expand their conception of how tinea looks, acts, and responds to treatment.

Dr. Lu Yin, New York University

University of Alabama, Birmingham

Tracking Cases

Because T indotineae does not require reporting to public health agencies, said Jeremy Gold, MD, MS, a medical officer with the US Centers for Disease Control and Prevention (CDC) Mycotic Diseases Branch in Atlanta, “there is no official public health surveillance keeping track of exactly how many cases have occurred.”

Dr. Gold

The same is true for TMVII and terbinafine-resistant T rubrum, which are also on the rise. Regarding T indotineae, authors from the University of Texas Health Science Center at San Antonio retrospectively reported 21 terbinafine-resistant isolates from North America in the July 2023 Journal of Clinical Microbiology .

Dr. Vignesh Ramachandran, New York University

Caplan has seen approximately 12 T indotineae cases to date, including the first two confirmed US cases, which he and co-authors, including Gold, reported in the CDC’s Morbidity and Mortality Weekly Report in May 2023. T indotineae is likely underreported, he said, because it eludes standard culture-based techniques, and identifying it requires molecular testing, which is available at only a handful of labs nationally.

To help educate providers, in July, the American Academy of Dermatology (AAD) and the International League of Dermatological Societies unveiled an Emerging Diseases Resource Center, which includes resources for providers and a registry for reporting confirmed and suspected resistant dermatophytes.

Dr. Lu Yin, New York University

Dr. Lu Yin, New York University

The new registry resides within the AAD’s existing COVID-19, Mpox, and Emerging Infections Registry. “Our registry efforts have already captured 2500 COVID-19 and mpox cases from 72 different countries,” Freeman said. For all these infections, she added, “we hope that real-time data analysis of cases worldwide will provide information that helps physicians recognize and treat cases.”

Consistent with the registry’s approach, said Caplan and Gold, there is no silver bullet for battling dermatophyte resistance. What is needed, said Gold, is a coordinated approach involving public health officials, dermatologists, primary care providers, infectious disease specialists, pharmacists, and patients. “It’s going to be a team effort to address the challenge of emerging complex dermatophytosis,” he said.
 

Resistant T rubrum

“The biggest difference with T rubrum resistance is you may not see that widespread infection that we see with T indotineae,” said Caplan. T rubrum is probably the most common dermatophyte that dermatologists see, added Elewski, who encounters a resistant case at least monthly. One such patient, featured in a January 2021 British Journal of Dermatology research letter, cleared on itraconazole and ciclopirox cream but subsequently returned with itraconazole-resistant T rubrum because he had been doctor-shopping for the drug intermittently for years, she said. He cleared on posaconazole 300 mg daily, then was lost to follow-up.

TMVII

A 2023 Emerging Infectious Diseases report highlighted the potential for this dermatophyte to spread among men who have sex with men (MSM), presenting as an itchy, scaly rash affecting the pubic, genital, and buttocks skin. “People don’t generally think of a fungal infection as something that could behave like a sexually transmitted infection (STI),” said Gold.

Caplan and coauthors recently reported the first confirmed US TMVII case in JAMA Dermatology. Many experts suspect that unreported US cases existed previously, he said. “When it circulates in Europe and there’s so much travel, it’s probably here too.”

The fact that T indotineae was formerly called TMVIII has created confusion, added Caplan. “I’ve had patients say, ‘I’m worried I have that resistant ringworm that’s spreading among MSM.’ Whenever we talk about STIs and introduce the word ‘resistant,’ that comes with the potential for stigma, anxiety, and concern.” Fortunately, he said, TMVII has shown no resistance to first-line antifungals.

NYU Langone

Why the Rise

Gold said, “We don’t know for sure why we’re seeing these different drug-resistant species popping up.” One possibility, he said, is the common misuse and overuse of topical antifungals — especially those available overseas in combination with high-potency steroids, such as clobetasol. Consumers use these products for a few weeks until symptoms resolve, then reapply them off and on over years, fueling resistance, said Gold.

“We are worried that with warming temperatures, there’s potential to see expansion of the geographic range of epidemic fungi,” he added. “That could be part of what has fueled recent increases in resistant dermatophytes. But it’s hard to prove.”

Climate change may be behind the emergence of Candida auris, according to a 2022 article in The Lancet Regional Health – Americas. This potentially fatal multidrug-resistant infection spreads easily among sick patients in healthcare facilities, according to a CDC information page on C auris.
 

Confirming Dermatophyte Infection

“A biopsy will only confirm the presence of fungus,” said Elewski. “Here you will need a lab that knows how to do a fungal culture.” Most state laboratories can do this, she said, as can some hospitals and special labs such as CMM in Cleveland.

It takes a Clinical Laboratory Improvement Amendments–certified lab to perform KOH prep in-house, added Caplan, plus up-to-date gear and knowledge of where and how to scrape and what to look for microscopically. Moreover, identifying T indotineae requires molecular testing available at only a handful of laboratories — listed on the AAD Emerging Dermatophytes webpage — nationwide.

Nevertheless, said Caplan, nailing down a diagnosis can guide treatment, often supplanting empirically prescribed antifungal steroid creams. “Those are probably not going to help. And people may be using those on areas of the body they shouldn’t. Both the clinical clues and the steps to make the diagnosis need to come together. But that’s often easier said than done, especially in a busy practice.”

Identifying resistance requires antifungal sensitivity testing, he added, which few labs perform. “Practically speaking,” said Elewski, “if the patient failed terbinafine, I would try itraconazole. You don’t necessarily need proof” of resistance. But if a patient does not respond to itraconazole and terbinafine clinically, she said that she might consider fungal susceptibility testing.
 

Treatment Tips

To address any resistant dermatophyte, Elewski recommended getting comfortable with itraconazole. For decades, she said, dermatologists have avoided itraconazole because terbinafine typically costs patients $10 for 3 months. “Itraconazole could be $200 per month,” said Elewski. Because of potential drug-drug interactions and absorption issues — and a boxed warning regarding congestive heart failure — physicians historically reserved itraconazole for severe fungal infections.

Itraconazole labeled dosing for onychomycosis is 200 mg daily for 12 weeks. Elewski favors a two-pronged attack, often combining an -azole antifungal with topical ciclopirox.

Another element that emerging tinea pathogens share is slower response to treatment. For T indotineae, reports appearing in the Journal of the American Academy of Dermatology in 2022 and 2024 suggest duration from 6-8 weeks up to 20 weeks.

To avoid recurrences of resistant T rubrum, Elewski treats for a year. However, she has problems getting itraconazole approved, when often it is the only agent that works. “I’ve written more letters than I like to insurance companies” to document terbinafine failure, she said.

Rarely, said Gold, dermatophyte infections resist both terbinafine and itraconazole. Next-line agents such as voriconazole, which some dermatologists have used for resistant T indotineae, can be much harder to tolerate, with more drug interactions, he said.

And because itraconazole, voriconazole, and posaconazole are all triazoles, added Elewski, the latter two might not work better than the former. But because these drugs might outperform itraconazole in selected cases, she said, “that’s when you want to do fungal susceptibility testing.”

TMVII is so new, said Caplan, that optimal therapy duration remains unclear. “One of the challenges with TMVII is when it gets into the genital skin, it’s a hair-bearing area. And based on various grooming practices, there’s an opportunity for the tinea to get deeper into the hair follicle and dermis. That may also be true of T indotineae.”
 

Anemic Arsenal

Unfortunately, said Gold, the arsenal of antifungals available in the United States remains limited. “Depending on how you count, there are only three to four classes of antifungal drugs designed to treat severe or invasive infections. So whenever we hear about a new fungal pathogen that’s causing resistant infections, it causes public health concern.”

Promising drugs in development include olorofim (F2G) and fosmanogepix (Basilea), according to Gold. However, he said, the development of these drugs to date has targeted invasive fungal infections such as aspergillosis. In June 2023, the Food and Drug Administration rejected the new drug application for olorofim, requesting additional data and analyses. Regarding fosmanogepix, a double-blinded noninferiority phase 3 trial in invasive yeast infections was recently launched, according to a September 24 press release.

Gold, Caplan, and Elewski reported no relevant financial disclosures. Freeman is a COVID-19 co-author for UpToDate and chair of the AAD Emerging Diseases Task Force.
 

A version of this article appeared on Medscape.com.

As the number of drug-resistant and other troublesome tinea infections grows, perhaps the only certainty is that these are not the tinea subtypes that most providers studied in medical school. As dermatologists, public health officials, and infectious disease specialists scramble to raise awareness about prevention and treatment, challenges ranging from a dearth of testing facilities and data to payer pushback over longer therapeutic courses remain.

Dermatophyte Discourse Changing

“Trichophyton indotineae is changing the way we talk about dermatophyte infections,” Avrom S. Caplan, MD, assistant professor in the Department of Dermatology at New York University, New York City, said in an interview. Called T mentagrophytes VIII (TMVIII) before a 2020 report in the journal Mycopathologia proposed the name T indotineae, this species requires clinicians to expand their conception of how tinea looks, acts, and responds to treatment.

Dr. Lu Yin, New York University

University of Alabama, Birmingham

Tracking Cases

Because T indotineae does not require reporting to public health agencies, said Jeremy Gold, MD, MS, a medical officer with the US Centers for Disease Control and Prevention (CDC) Mycotic Diseases Branch in Atlanta, “there is no official public health surveillance keeping track of exactly how many cases have occurred.”

Dr. Gold

The same is true for TMVII and terbinafine-resistant T rubrum, which are also on the rise. Regarding T indotineae, authors from the University of Texas Health Science Center at San Antonio retrospectively reported 21 terbinafine-resistant isolates from North America in the July 2023 Journal of Clinical Microbiology .

Dr. Vignesh Ramachandran, New York University

Caplan has seen approximately 12 T indotineae cases to date, including the first two confirmed US cases, which he and co-authors, including Gold, reported in the CDC’s Morbidity and Mortality Weekly Report in May 2023. T indotineae is likely underreported, he said, because it eludes standard culture-based techniques, and identifying it requires molecular testing, which is available at only a handful of labs nationally.

To help educate providers, in July, the American Academy of Dermatology (AAD) and the International League of Dermatological Societies unveiled an Emerging Diseases Resource Center, which includes resources for providers and a registry for reporting confirmed and suspected resistant dermatophytes.

Dr. Lu Yin, New York University

Dr. Lu Yin, New York University

The new registry resides within the AAD’s existing COVID-19, Mpox, and Emerging Infections Registry. “Our registry efforts have already captured 2500 COVID-19 and mpox cases from 72 different countries,” Freeman said. For all these infections, she added, “we hope that real-time data analysis of cases worldwide will provide information that helps physicians recognize and treat cases.”

Consistent with the registry’s approach, said Caplan and Gold, there is no silver bullet for battling dermatophyte resistance. What is needed, said Gold, is a coordinated approach involving public health officials, dermatologists, primary care providers, infectious disease specialists, pharmacists, and patients. “It’s going to be a team effort to address the challenge of emerging complex dermatophytosis,” he said.
 

Resistant T rubrum

“The biggest difference with T rubrum resistance is you may not see that widespread infection that we see with T indotineae,” said Caplan. T rubrum is probably the most common dermatophyte that dermatologists see, added Elewski, who encounters a resistant case at least monthly. One such patient, featured in a January 2021 British Journal of Dermatology research letter, cleared on itraconazole and ciclopirox cream but subsequently returned with itraconazole-resistant T rubrum because he had been doctor-shopping for the drug intermittently for years, she said. He cleared on posaconazole 300 mg daily, then was lost to follow-up.

TMVII

A 2023 Emerging Infectious Diseases report highlighted the potential for this dermatophyte to spread among men who have sex with men (MSM), presenting as an itchy, scaly rash affecting the pubic, genital, and buttocks skin. “People don’t generally think of a fungal infection as something that could behave like a sexually transmitted infection (STI),” said Gold.

Caplan and coauthors recently reported the first confirmed US TMVII case in JAMA Dermatology. Many experts suspect that unreported US cases existed previously, he said. “When it circulates in Europe and there’s so much travel, it’s probably here too.”

The fact that T indotineae was formerly called TMVIII has created confusion, added Caplan. “I’ve had patients say, ‘I’m worried I have that resistant ringworm that’s spreading among MSM.’ Whenever we talk about STIs and introduce the word ‘resistant,’ that comes with the potential for stigma, anxiety, and concern.” Fortunately, he said, TMVII has shown no resistance to first-line antifungals.

NYU Langone

Why the Rise

Gold said, “We don’t know for sure why we’re seeing these different drug-resistant species popping up.” One possibility, he said, is the common misuse and overuse of topical antifungals — especially those available overseas in combination with high-potency steroids, such as clobetasol. Consumers use these products for a few weeks until symptoms resolve, then reapply them off and on over years, fueling resistance, said Gold.

“We are worried that with warming temperatures, there’s potential to see expansion of the geographic range of epidemic fungi,” he added. “That could be part of what has fueled recent increases in resistant dermatophytes. But it’s hard to prove.”

Climate change may be behind the emergence of Candida auris, according to a 2022 article in The Lancet Regional Health – Americas. This potentially fatal multidrug-resistant infection spreads easily among sick patients in healthcare facilities, according to a CDC information page on C auris.
 

Confirming Dermatophyte Infection

“A biopsy will only confirm the presence of fungus,” said Elewski. “Here you will need a lab that knows how to do a fungal culture.” Most state laboratories can do this, she said, as can some hospitals and special labs such as CMM in Cleveland.

It takes a Clinical Laboratory Improvement Amendments–certified lab to perform KOH prep in-house, added Caplan, plus up-to-date gear and knowledge of where and how to scrape and what to look for microscopically. Moreover, identifying T indotineae requires molecular testing available at only a handful of laboratories — listed on the AAD Emerging Dermatophytes webpage — nationwide.

Nevertheless, said Caplan, nailing down a diagnosis can guide treatment, often supplanting empirically prescribed antifungal steroid creams. “Those are probably not going to help. And people may be using those on areas of the body they shouldn’t. Both the clinical clues and the steps to make the diagnosis need to come together. But that’s often easier said than done, especially in a busy practice.”

Identifying resistance requires antifungal sensitivity testing, he added, which few labs perform. “Practically speaking,” said Elewski, “if the patient failed terbinafine, I would try itraconazole. You don’t necessarily need proof” of resistance. But if a patient does not respond to itraconazole and terbinafine clinically, she said that she might consider fungal susceptibility testing.
 

Treatment Tips

To address any resistant dermatophyte, Elewski recommended getting comfortable with itraconazole. For decades, she said, dermatologists have avoided itraconazole because terbinafine typically costs patients $10 for 3 months. “Itraconazole could be $200 per month,” said Elewski. Because of potential drug-drug interactions and absorption issues — and a boxed warning regarding congestive heart failure — physicians historically reserved itraconazole for severe fungal infections.

Itraconazole labeled dosing for onychomycosis is 200 mg daily for 12 weeks. Elewski favors a two-pronged attack, often combining an -azole antifungal with topical ciclopirox.

Another element that emerging tinea pathogens share is slower response to treatment. For T indotineae, reports appearing in the Journal of the American Academy of Dermatology in 2022 and 2024 suggest duration from 6-8 weeks up to 20 weeks.

To avoid recurrences of resistant T rubrum, Elewski treats for a year. However, she has problems getting itraconazole approved, when often it is the only agent that works. “I’ve written more letters than I like to insurance companies” to document terbinafine failure, she said.

Rarely, said Gold, dermatophyte infections resist both terbinafine and itraconazole. Next-line agents such as voriconazole, which some dermatologists have used for resistant T indotineae, can be much harder to tolerate, with more drug interactions, he said.

And because itraconazole, voriconazole, and posaconazole are all triazoles, added Elewski, the latter two might not work better than the former. But because these drugs might outperform itraconazole in selected cases, she said, “that’s when you want to do fungal susceptibility testing.”

TMVII is so new, said Caplan, that optimal therapy duration remains unclear. “One of the challenges with TMVII is when it gets into the genital skin, it’s a hair-bearing area. And based on various grooming practices, there’s an opportunity for the tinea to get deeper into the hair follicle and dermis. That may also be true of T indotineae.”
 

Anemic Arsenal

Unfortunately, said Gold, the arsenal of antifungals available in the United States remains limited. “Depending on how you count, there are only three to four classes of antifungal drugs designed to treat severe or invasive infections. So whenever we hear about a new fungal pathogen that’s causing resistant infections, it causes public health concern.”

Promising drugs in development include olorofim (F2G) and fosmanogepix (Basilea), according to Gold. However, he said, the development of these drugs to date has targeted invasive fungal infections such as aspergillosis. In June 2023, the Food and Drug Administration rejected the new drug application for olorofim, requesting additional data and analyses. Regarding fosmanogepix, a double-blinded noninferiority phase 3 trial in invasive yeast infections was recently launched, according to a September 24 press release.

Gold, Caplan, and Elewski reported no relevant financial disclosures. Freeman is a COVID-19 co-author for UpToDate and chair of the AAD Emerging Diseases Task Force.
 

A version of this article appeared on Medscape.com.

Helicobacter pylori is one of the most common human bacterial chronic infections globally. Its prevalence has actually decreased in North America in recent years, although its current range of approximately 30%-40% remains substantial given the potential clinical implications of infection. 

Standards have changed considerably regarding the testing, treatment, and follow-up of H pylori. This is made clear by the just-published clinical practice guideline from the American College of Gastroenterology (ACG), which provides several new recommendations based on recent scientific evidence that should change your clinical approach to managing this common infection. 

This discussion aims to synthesize and highlight key concepts from the ACG’s comprehensive publication. 
 

Who Should Be Tested and Treated? 

The cardinal diseases caused by H pylori have traditionally included peptic ulcer disease, marginal zone B-cell lymphoma, gastric adenocarcinoma, and dyspepsia. 

Additional associations have been made with idiopathic thrombocytopenic purpura and otherwise unexplained iron deficiency. 

New evidence suggests that patients taking long-term nonsteroidal anti-inflammatory drugs, including low-dose aspirin, are relatively more susceptible to infection. 

The ACG’s guideline also recommends testing persons at an increased risk for gastric adenocarcinoma (eg, those with autoimmune gastritis, current or history of premalignant conditions, or first-degree relative with gastric cancer), as well as household members of patients with a positive nonserologic test for H pylori.

The authors note that those with an indication for testing should be offered treatment if determined to have an infection. These patients should also undergo a posttreatment test-of-cure, which should occur at least 4 weeks afterwards using a urea breath test, fecal antigen test, or gastric biopsy. 
 

Caveats to Treatment 

Patients with H pylori infections are advised to undergo treatment for a duration of 14 days. Some of the commercial prepackaged H pylori treatment options (eg, Pylera, which contains bismuth subcitrate/metronidazole/tetracycline) are dispensed in regimens lasting only 10 days and currently are viewed as inadequate.

In the United States, the patterns of antibiotic resistance for the previously used standard drugs in the treatment of H pylori have increased considerably. They range from 32% for clarithromycin, 38% for levofloxacin, and 42% for metronidazole, in contrast to 3% for amoxicillin, 1% for tetracycline, and 0% for rifabutin. 

Clarithromycin- and levofloxacin-containing treatments should be avoided in treatment-naive patients unless specifically directed following the results of susceptibility tests with either a phenotypic method (culture-based) or a molecular method (polymerase chain reaction or next-generation sequencing). Notably, the mutations responsible for both clarithromycin and levofloxacin resistance may be detectable by stool-based testing.

Maintenance of intragastric acid suppression is key to H pylori eradication, as elevated intragastric pH promotes active replication of H pylori and makes it more susceptible to bactericidal antibiotics. 

Therefore, the use of histamine-2 receptors is not recommended, as they are inadequate for achieving acid suppression. Instead, a dual-based therapy of either the potassium-competitive acid blocker (PCAB) vonoprazan (20 mg) or a high-dose proton pump inhibitor (PPI) and amoxicillin, administered twice daily, is effective, although this finding is based on limited evidence. 
 

Treatment-Naive Patients

In treatment-naive patients without penicillin allergy and for whom antibiotic susceptibility testing has not been obtained, the guideline offers its strongest recommendation for bismuth quadruple therapy. This therapy typically consists of a PPI, bismuth subcitrate or subsalicylate, tetracycline, and metronidazole. 

Among those with a penicillin allergy, bismuth quadruple therapy is also the primary treatment choice. The authors suggest that patients with a suspected allergy are referred to an allergist for possible penicillin desensitization, given that less than 1% of the population is thought to present with a “true” allergy.

The guideline also presented conditional recommendations, based on low- to moderate-quality evidence, for using a rifabutin-based triple regimen of omeprazole, amoxicillin, and rifabutin (Talicia); a PCAB-based dual regimen of vonoprazan and amoxicillin (Voquezna Dual Pak); and a PCAB-based triple regimen of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak). In patients with unknown clarithromycin susceptibility, the PCAB-based triple therapy is preferred over PPI-clarithromycin triple therapy.

Although probiotics have been suggested to possibly lead to increased effectiveness or tolerability for H pylori eradication, this was based on studies with significant heterogeneity in their designs. At present, no high-quality data support probiotic therapy.

Clinicians may substitute doxycycline for tetracycline due to availability or cost, and also may prescribe metronidazole at a lower dose than recommended (1.5-2 g/d) to limit side effects. Both modifications have been associated with lower rates of H pylori eradication and are not recommended.
 

Treatment-Experienced Patients

Quadruple bismuth therapy is the optimal approach among treatment-experienced patients with persistent H pylori infection who have not previously received this therapy. However, this recommendation was rated as conditional, given that it was based on a low quality of evidence. 

The guideline offered other recommendations for treatment-experienced patients with persistent infection who had received bismuth quadruple therapy — also conditionally based on a low quality of evidence. 

In such patients, it is recommended to consider the use of a rifabutin-based triple therapy (ie, a PPI standard to double dose, amoxicillin, and rifabutin) and a levofloxacin-based triple therapy (ie, a PPI standard dose, levofloxacin, and amoxicillin or metronidazole). 

Although significant evidence gaps prevented the authors from providing formal recommendations, they included a PCAB-based triple therapy of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak) and a high-dose dual therapy of either vonoprazan (20 mg) or PPI (double dose) and amoxicillin among their suggested salvage regimens for these patients.
 

A New Standard 

The ACG’s excellent clinical guideline offers new standards for clinicians involved in the diagnosis and treatment of H pylori. 

We must recognize, however, that there are still substantial evidence gaps, particularly around the use of a PCAB-based regimen and its relative advantages over a standard or high-dose PPI-based regimen. This may be of particular importance based on the variable prevalence of cytochrome P450 2C19 (CYP2C19) polymorphisms in the specific patient populations, as PCABs are not metabolized by CYP2C19. 

Reviewing the entirety of the ACG’s clinical guideline is encouraged for additional details about the management of H pylori beyond what is highlighted herein.

Dr. Johnson, Professor of Medicine, Chief of Gastroenterology, Eastern Virginia Medical School, Norfolk, Virginia, disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

Helicobacter pylori is one of the most common human bacterial chronic infections globally. Its prevalence has actually decreased in North America in recent years, although its current range of approximately 30%-40% remains substantial given the potential clinical implications of infection. 

Standards have changed considerably regarding the testing, treatment, and follow-up of H pylori. This is made clear by the just-published clinical practice guideline from the American College of Gastroenterology (ACG), which provides several new recommendations based on recent scientific evidence that should change your clinical approach to managing this common infection. 

This discussion aims to synthesize and highlight key concepts from the ACG’s comprehensive publication. 
 

Who Should Be Tested and Treated? 

The cardinal diseases caused by H pylori have traditionally included peptic ulcer disease, marginal zone B-cell lymphoma, gastric adenocarcinoma, and dyspepsia. 

Additional associations have been made with idiopathic thrombocytopenic purpura and otherwise unexplained iron deficiency. 

New evidence suggests that patients taking long-term nonsteroidal anti-inflammatory drugs, including low-dose aspirin, are relatively more susceptible to infection. 

The ACG’s guideline also recommends testing persons at an increased risk for gastric adenocarcinoma (eg, those with autoimmune gastritis, current or history of premalignant conditions, or first-degree relative with gastric cancer), as well as household members of patients with a positive nonserologic test for H pylori.

The authors note that those with an indication for testing should be offered treatment if determined to have an infection. These patients should also undergo a posttreatment test-of-cure, which should occur at least 4 weeks afterwards using a urea breath test, fecal antigen test, or gastric biopsy. 
 

Caveats to Treatment 

Patients with H pylori infections are advised to undergo treatment for a duration of 14 days. Some of the commercial prepackaged H pylori treatment options (eg, Pylera, which contains bismuth subcitrate/metronidazole/tetracycline) are dispensed in regimens lasting only 10 days and currently are viewed as inadequate.

In the United States, the patterns of antibiotic resistance for the previously used standard drugs in the treatment of H pylori have increased considerably. They range from 32% for clarithromycin, 38% for levofloxacin, and 42% for metronidazole, in contrast to 3% for amoxicillin, 1% for tetracycline, and 0% for rifabutin. 

Clarithromycin- and levofloxacin-containing treatments should be avoided in treatment-naive patients unless specifically directed following the results of susceptibility tests with either a phenotypic method (culture-based) or a molecular method (polymerase chain reaction or next-generation sequencing). Notably, the mutations responsible for both clarithromycin and levofloxacin resistance may be detectable by stool-based testing.

Maintenance of intragastric acid suppression is key to H pylori eradication, as elevated intragastric pH promotes active replication of H pylori and makes it more susceptible to bactericidal antibiotics. 

Therefore, the use of histamine-2 receptors is not recommended, as they are inadequate for achieving acid suppression. Instead, a dual-based therapy of either the potassium-competitive acid blocker (PCAB) vonoprazan (20 mg) or a high-dose proton pump inhibitor (PPI) and amoxicillin, administered twice daily, is effective, although this finding is based on limited evidence. 
 

Treatment-Naive Patients

In treatment-naive patients without penicillin allergy and for whom antibiotic susceptibility testing has not been obtained, the guideline offers its strongest recommendation for bismuth quadruple therapy. This therapy typically consists of a PPI, bismuth subcitrate or subsalicylate, tetracycline, and metronidazole. 

Among those with a penicillin allergy, bismuth quadruple therapy is also the primary treatment choice. The authors suggest that patients with a suspected allergy are referred to an allergist for possible penicillin desensitization, given that less than 1% of the population is thought to present with a “true” allergy.

The guideline also presented conditional recommendations, based on low- to moderate-quality evidence, for using a rifabutin-based triple regimen of omeprazole, amoxicillin, and rifabutin (Talicia); a PCAB-based dual regimen of vonoprazan and amoxicillin (Voquezna Dual Pak); and a PCAB-based triple regimen of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak). In patients with unknown clarithromycin susceptibility, the PCAB-based triple therapy is preferred over PPI-clarithromycin triple therapy.

Although probiotics have been suggested to possibly lead to increased effectiveness or tolerability for H pylori eradication, this was based on studies with significant heterogeneity in their designs. At present, no high-quality data support probiotic therapy.

Clinicians may substitute doxycycline for tetracycline due to availability or cost, and also may prescribe metronidazole at a lower dose than recommended (1.5-2 g/d) to limit side effects. Both modifications have been associated with lower rates of H pylori eradication and are not recommended.
 

Treatment-Experienced Patients

Quadruple bismuth therapy is the optimal approach among treatment-experienced patients with persistent H pylori infection who have not previously received this therapy. However, this recommendation was rated as conditional, given that it was based on a low quality of evidence. 

The guideline offered other recommendations for treatment-experienced patients with persistent infection who had received bismuth quadruple therapy — also conditionally based on a low quality of evidence. 

In such patients, it is recommended to consider the use of a rifabutin-based triple therapy (ie, a PPI standard to double dose, amoxicillin, and rifabutin) and a levofloxacin-based triple therapy (ie, a PPI standard dose, levofloxacin, and amoxicillin or metronidazole). 

Although significant evidence gaps prevented the authors from providing formal recommendations, they included a PCAB-based triple therapy of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak) and a high-dose dual therapy of either vonoprazan (20 mg) or PPI (double dose) and amoxicillin among their suggested salvage regimens for these patients.
 

A New Standard 

The ACG’s excellent clinical guideline offers new standards for clinicians involved in the diagnosis and treatment of H pylori. 

We must recognize, however, that there are still substantial evidence gaps, particularly around the use of a PCAB-based regimen and its relative advantages over a standard or high-dose PPI-based regimen. This may be of particular importance based on the variable prevalence of cytochrome P450 2C19 (CYP2C19) polymorphisms in the specific patient populations, as PCABs are not metabolized by CYP2C19. 

Reviewing the entirety of the ACG’s clinical guideline is encouraged for additional details about the management of H pylori beyond what is highlighted herein.

Dr. Johnson, Professor of Medicine, Chief of Gastroenterology, Eastern Virginia Medical School, Norfolk, Virginia, disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

Helicobacter pylori is one of the most common human bacterial chronic infections globally. Its prevalence has actually decreased in North America in recent years, although its current range of approximately 30%-40% remains substantial given the potential clinical implications of infection. 

Standards have changed considerably regarding the testing, treatment, and follow-up of H pylori. This is made clear by the just-published clinical practice guideline from the American College of Gastroenterology (ACG), which provides several new recommendations based on recent scientific evidence that should change your clinical approach to managing this common infection. 

This discussion aims to synthesize and highlight key concepts from the ACG’s comprehensive publication. 
 

Who Should Be Tested and Treated? 

The cardinal diseases caused by H pylori have traditionally included peptic ulcer disease, marginal zone B-cell lymphoma, gastric adenocarcinoma, and dyspepsia. 

Additional associations have been made with idiopathic thrombocytopenic purpura and otherwise unexplained iron deficiency. 

New evidence suggests that patients taking long-term nonsteroidal anti-inflammatory drugs, including low-dose aspirin, are relatively more susceptible to infection. 

The ACG’s guideline also recommends testing persons at an increased risk for gastric adenocarcinoma (eg, those with autoimmune gastritis, current or history of premalignant conditions, or first-degree relative with gastric cancer), as well as household members of patients with a positive nonserologic test for H pylori.

The authors note that those with an indication for testing should be offered treatment if determined to have an infection. These patients should also undergo a posttreatment test-of-cure, which should occur at least 4 weeks afterwards using a urea breath test, fecal antigen test, or gastric biopsy. 
 

Caveats to Treatment 

Patients with H pylori infections are advised to undergo treatment for a duration of 14 days. Some of the commercial prepackaged H pylori treatment options (eg, Pylera, which contains bismuth subcitrate/metronidazole/tetracycline) are dispensed in regimens lasting only 10 days and currently are viewed as inadequate.

In the United States, the patterns of antibiotic resistance for the previously used standard drugs in the treatment of H pylori have increased considerably. They range from 32% for clarithromycin, 38% for levofloxacin, and 42% for metronidazole, in contrast to 3% for amoxicillin, 1% for tetracycline, and 0% for rifabutin. 

Clarithromycin- and levofloxacin-containing treatments should be avoided in treatment-naive patients unless specifically directed following the results of susceptibility tests with either a phenotypic method (culture-based) or a molecular method (polymerase chain reaction or next-generation sequencing). Notably, the mutations responsible for both clarithromycin and levofloxacin resistance may be detectable by stool-based testing.

Maintenance of intragastric acid suppression is key to H pylori eradication, as elevated intragastric pH promotes active replication of H pylori and makes it more susceptible to bactericidal antibiotics. 

Therefore, the use of histamine-2 receptors is not recommended, as they are inadequate for achieving acid suppression. Instead, a dual-based therapy of either the potassium-competitive acid blocker (PCAB) vonoprazan (20 mg) or a high-dose proton pump inhibitor (PPI) and amoxicillin, administered twice daily, is effective, although this finding is based on limited evidence. 
 

Treatment-Naive Patients

In treatment-naive patients without penicillin allergy and for whom antibiotic susceptibility testing has not been obtained, the guideline offers its strongest recommendation for bismuth quadruple therapy. This therapy typically consists of a PPI, bismuth subcitrate or subsalicylate, tetracycline, and metronidazole. 

Among those with a penicillin allergy, bismuth quadruple therapy is also the primary treatment choice. The authors suggest that patients with a suspected allergy are referred to an allergist for possible penicillin desensitization, given that less than 1% of the population is thought to present with a “true” allergy.

The guideline also presented conditional recommendations, based on low- to moderate-quality evidence, for using a rifabutin-based triple regimen of omeprazole, amoxicillin, and rifabutin (Talicia); a PCAB-based dual regimen of vonoprazan and amoxicillin (Voquezna Dual Pak); and a PCAB-based triple regimen of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak). In patients with unknown clarithromycin susceptibility, the PCAB-based triple therapy is preferred over PPI-clarithromycin triple therapy.

Although probiotics have been suggested to possibly lead to increased effectiveness or tolerability for H pylori eradication, this was based on studies with significant heterogeneity in their designs. At present, no high-quality data support probiotic therapy.

Clinicians may substitute doxycycline for tetracycline due to availability or cost, and also may prescribe metronidazole at a lower dose than recommended (1.5-2 g/d) to limit side effects. Both modifications have been associated with lower rates of H pylori eradication and are not recommended.
 

Treatment-Experienced Patients

Quadruple bismuth therapy is the optimal approach among treatment-experienced patients with persistent H pylori infection who have not previously received this therapy. However, this recommendation was rated as conditional, given that it was based on a low quality of evidence. 

The guideline offered other recommendations for treatment-experienced patients with persistent infection who had received bismuth quadruple therapy — also conditionally based on a low quality of evidence. 

In such patients, it is recommended to consider the use of a rifabutin-based triple therapy (ie, a PPI standard to double dose, amoxicillin, and rifabutin) and a levofloxacin-based triple therapy (ie, a PPI standard dose, levofloxacin, and amoxicillin or metronidazole). 

Although significant evidence gaps prevented the authors from providing formal recommendations, they included a PCAB-based triple therapy of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak) and a high-dose dual therapy of either vonoprazan (20 mg) or PPI (double dose) and amoxicillin among their suggested salvage regimens for these patients.
 

A New Standard 

The ACG’s excellent clinical guideline offers new standards for clinicians involved in the diagnosis and treatment of H pylori. 

We must recognize, however, that there are still substantial evidence gaps, particularly around the use of a PCAB-based regimen and its relative advantages over a standard or high-dose PPI-based regimen. This may be of particular importance based on the variable prevalence of cytochrome P450 2C19 (CYP2C19) polymorphisms in the specific patient populations, as PCABs are not metabolized by CYP2C19. 

Reviewing the entirety of the ACG’s clinical guideline is encouraged for additional details about the management of H pylori beyond what is highlighted herein.

Dr. Johnson, Professor of Medicine, Chief of Gastroenterology, Eastern Virginia Medical School, Norfolk, Virginia, disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

The US Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices (ACIP) now recommends a pneumococcal conjugate vaccine (PCV) for all PCV-naive adults aged 50 years or older. The new recommendation, which passed with an ACIP member vote of 14 for and one against, expands the current age-based recommendations, which include children younger than 5 years and adults older than 65 years, as well as adults aged 19-64 years with underlying conditions or risk factors who have not received a PCV and certain adults who have received PCV13 but not PCV20.

The recommendation would leave the choice of PCV up to the clinician. The updated language calls for a single dose of PCV (which could be PCV15, PCV20, or PCV21) for all adults aged 50 years or older; adults aged 19-64 years with underlying conditions (for whom PCV is already recommended) could receive the newly approved PCV21 as an option.

The decision was based in part on economic analyses of the use of PCV in adults aged 50-64 years in the United States. Miwako Kobayashi, MD, presented the summary of the Pneumococcal Vaccines Work Group’s interpretation of the evidence and the proposed recommendation in a meeting of the ACIP on October 23, 2024, when the ACIP voting occurred.

Data from the CDC show an increase in the relative burden of pneumococcal disease in adults aged 50-64 years based in part on the success of the pediatric PCV program, she said.

Health equity was another main factor in the Work Group’s decision to recommend vaccination for adults aged 50 years or older. “Disparities in pneumococcal vaccine coverage by race and ethnicity exist for both age-based and risk-based indications,” Kobayashi noted in her presentation. The Work Group acknowledged that the overall effect of a vaccine recommendation on health equity is complex, but the majority agreed that the update would improve health equity by increasing vaccine coverage for those with known or unknown risk factors and providing protection at an earlier age when some populations already experience elevated disease rates, she said.

As for safety, the Work Group concluded that the undesirable anticipated effects of PCVs are minimal, despite the potential signal for Guillain-Barré Syndrome, and the CDC and US Food and Drug Administration will continue to monitor post-licensure safety of PCVs.

Support Not Universal

A majority of the ACIP Pneumococcal Vaccines Work Group supported the approved option, but agreed that a future booster dose may be needed, Work Group Chair James Loehr, MD, said in his introductory presentation.

Overall, key uncertainties remain, including indirect effects of new pediatric pneumococcal vaccines on adults, data on the duration of protection with adult vaccinations, and the impact new higher-valency vaccines have on adults, several of which are in development, Loehr said.

A new 21-valent PCV, known as PCV 21, was approved by the FDA for adults aged 18 years or older in June 2024, said Loehr. “PCV21 is not PCV20 with one additional serotype” and provides additional protection, he emphasized. The Work Group examined models involving PCV21 and the existing PCV20. However, a majority of the Work Group agreed that having age-based recommendations based on vaccine product would be more challenging to implement and that insurance coverage may be a factor given the recent approval of PCV21. Therefore, the proposal submitted to the full ACIP was not for a specific PCV.

Notably, Loehr said that, although as Work Group Chair he was tasked with making the motion in favor of the recommendation, he voted against it as a voting member because of his strong opinion that only the PCV21 vaccine is needed for vaccine-naive adults aged 50 or older. “I think that PCV21 is a better vaccine that targets more serotypes,” he said during the discussion. Data presented at the February 2024 ACIP meeting showed more than 80% coverage vs less than 60% coverage for invasive pneumococcal disease with PCV21 vs PCV20 among adults aged 65 years or older and those aged 19-64 years with a risk-based indication, Loehr said.

A version of this article appeared on Medscape.com.

The US Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices (ACIP) now recommends a pneumococcal conjugate vaccine (PCV) for all PCV-naive adults aged 50 years or older. The new recommendation, which passed with an ACIP member vote of 14 for and one against, expands the current age-based recommendations, which include children younger than 5 years and adults older than 65 years, as well as adults aged 19-64 years with underlying conditions or risk factors who have not received a PCV and certain adults who have received PCV13 but not PCV20.

The recommendation would leave the choice of PCV up to the clinician. The updated language calls for a single dose of PCV (which could be PCV15, PCV20, or PCV21) for all adults aged 50 years or older; adults aged 19-64 years with underlying conditions (for whom PCV is already recommended) could receive the newly approved PCV21 as an option.

The decision was based in part on economic analyses of the use of PCV in adults aged 50-64 years in the United States. Miwako Kobayashi, MD, presented the summary of the Pneumococcal Vaccines Work Group’s interpretation of the evidence and the proposed recommendation in a meeting of the ACIP on October 23, 2024, when the ACIP voting occurred.

Data from the CDC show an increase in the relative burden of pneumococcal disease in adults aged 50-64 years based in part on the success of the pediatric PCV program, she said.

Health equity was another main factor in the Work Group’s decision to recommend vaccination for adults aged 50 years or older. “Disparities in pneumococcal vaccine coverage by race and ethnicity exist for both age-based and risk-based indications,” Kobayashi noted in her presentation. The Work Group acknowledged that the overall effect of a vaccine recommendation on health equity is complex, but the majority agreed that the update would improve health equity by increasing vaccine coverage for those with known or unknown risk factors and providing protection at an earlier age when some populations already experience elevated disease rates, she said.

As for safety, the Work Group concluded that the undesirable anticipated effects of PCVs are minimal, despite the potential signal for Guillain-Barré Syndrome, and the CDC and US Food and Drug Administration will continue to monitor post-licensure safety of PCVs.

Support Not Universal

A majority of the ACIP Pneumococcal Vaccines Work Group supported the approved option, but agreed that a future booster dose may be needed, Work Group Chair James Loehr, MD, said in his introductory presentation.

Overall, key uncertainties remain, including indirect effects of new pediatric pneumococcal vaccines on adults, data on the duration of protection with adult vaccinations, and the impact new higher-valency vaccines have on adults, several of which are in development, Loehr said.

A new 21-valent PCV, known as PCV 21, was approved by the FDA for adults aged 18 years or older in June 2024, said Loehr. “PCV21 is not PCV20 with one additional serotype” and provides additional protection, he emphasized. The Work Group examined models involving PCV21 and the existing PCV20. However, a majority of the Work Group agreed that having age-based recommendations based on vaccine product would be more challenging to implement and that insurance coverage may be a factor given the recent approval of PCV21. Therefore, the proposal submitted to the full ACIP was not for a specific PCV.

Notably, Loehr said that, although as Work Group Chair he was tasked with making the motion in favor of the recommendation, he voted against it as a voting member because of his strong opinion that only the PCV21 vaccine is needed for vaccine-naive adults aged 50 or older. “I think that PCV21 is a better vaccine that targets more serotypes,” he said during the discussion. Data presented at the February 2024 ACIP meeting showed more than 80% coverage vs less than 60% coverage for invasive pneumococcal disease with PCV21 vs PCV20 among adults aged 65 years or older and those aged 19-64 years with a risk-based indication, Loehr said.

A version of this article appeared on Medscape.com.

The US Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices (ACIP) now recommends a pneumococcal conjugate vaccine (PCV) for all PCV-naive adults aged 50 years or older. The new recommendation, which passed with an ACIP member vote of 14 for and one against, expands the current age-based recommendations, which include children younger than 5 years and adults older than 65 years, as well as adults aged 19-64 years with underlying conditions or risk factors who have not received a PCV and certain adults who have received PCV13 but not PCV20.

The recommendation would leave the choice of PCV up to the clinician. The updated language calls for a single dose of PCV (which could be PCV15, PCV20, or PCV21) for all adults aged 50 years or older; adults aged 19-64 years with underlying conditions (for whom PCV is already recommended) could receive the newly approved PCV21 as an option.

The decision was based in part on economic analyses of the use of PCV in adults aged 50-64 years in the United States. Miwako Kobayashi, MD, presented the summary of the Pneumococcal Vaccines Work Group’s interpretation of the evidence and the proposed recommendation in a meeting of the ACIP on October 23, 2024, when the ACIP voting occurred.

Data from the CDC show an increase in the relative burden of pneumococcal disease in adults aged 50-64 years based in part on the success of the pediatric PCV program, she said.

Health equity was another main factor in the Work Group’s decision to recommend vaccination for adults aged 50 years or older. “Disparities in pneumococcal vaccine coverage by race and ethnicity exist for both age-based and risk-based indications,” Kobayashi noted in her presentation. The Work Group acknowledged that the overall effect of a vaccine recommendation on health equity is complex, but the majority agreed that the update would improve health equity by increasing vaccine coverage for those with known or unknown risk factors and providing protection at an earlier age when some populations already experience elevated disease rates, she said.

As for safety, the Work Group concluded that the undesirable anticipated effects of PCVs are minimal, despite the potential signal for Guillain-Barré Syndrome, and the CDC and US Food and Drug Administration will continue to monitor post-licensure safety of PCVs.

Support Not Universal

A majority of the ACIP Pneumococcal Vaccines Work Group supported the approved option, but agreed that a future booster dose may be needed, Work Group Chair James Loehr, MD, said in his introductory presentation.

Overall, key uncertainties remain, including indirect effects of new pediatric pneumococcal vaccines on adults, data on the duration of protection with adult vaccinations, and the impact new higher-valency vaccines have on adults, several of which are in development, Loehr said.

A new 21-valent PCV, known as PCV 21, was approved by the FDA for adults aged 18 years or older in June 2024, said Loehr. “PCV21 is not PCV20 with one additional serotype” and provides additional protection, he emphasized. The Work Group examined models involving PCV21 and the existing PCV20. However, a majority of the Work Group agreed that having age-based recommendations based on vaccine product would be more challenging to implement and that insurance coverage may be a factor given the recent approval of PCV21. Therefore, the proposal submitted to the full ACIP was not for a specific PCV.

Notably, Loehr said that, although as Work Group Chair he was tasked with making the motion in favor of the recommendation, he voted against it as a voting member because of his strong opinion that only the PCV21 vaccine is needed for vaccine-naive adults aged 50 or older. “I think that PCV21 is a better vaccine that targets more serotypes,” he said during the discussion. Data presented at the February 2024 ACIP meeting showed more than 80% coverage vs less than 60% coverage for invasive pneumococcal disease with PCV21 vs PCV20 among adults aged 65 years or older and those aged 19-64 years with a risk-based indication, Loehr said.

A version of this article appeared on Medscape.com.

LOS ANGELES — Use of preexposure prophylaxis (PrEP) to prevent HIV is increasing overall, but both the rate of increase for starting PrEP and the rate of unmet need differ widely by demographic group, according to new data from a large study.

An analysis by Li Tao, MD, MS, PhD, director of real-world evidence at Gilead Sciences, and colleagues looked at statistical trends from 2019 to 2023 and found that Black, Hispanic, and Medicaid-insured populations continue to lack equitable access to PrEP.

Among the findings were that most new PrEP users were men with HIV risk factors who are commercially insured and live in predominantly non-Hispanic White areas (53% in 2019 and 43% in 2023). For comparison, men living in predominantly Black or Hispanic neighborhoods, or who are insured by Medicaid, saw lower proportions of PrEP use (16% in 2019 and 17% in 2023) despite higher annual increases in PrEP use (11% per year) and higher unmet needs.
 

Half a Million Real-World Participants

Tao presented her team’s findings at the Infectious Disease Week (IDWeek) 2024 Annual Meeting. The study included “more than half a million real-world PrEP users over the past 5 years,” she said.

The group with the lowest growth in initiation of PrEP in the study period (an annual percentage increase of 2%) and the lowest unmet need included men with HIV risk factors, who were using commercial insurance and living in White-dominant neighborhoods.

HIV risk factors included diagnosis of any sexually transmitted disease, contact with and exposure to communicable diseases, high-risk sexual behavior, contact with a hypodermic needle, long-term prophylaxis, HIV prevention counseling, and HIV screening.

Other men with HIV risk factors (those who were commercially insured, living in Black/Hispanic neighborhoods, or those on Medicaid across all neighborhoods) had a moderate increase in PrEP initiation (an annual percentage increase of 11%-16%) and higher unmet needs.

Researchers gathered data on PrEP prescriptions and new HIV diagnoses (from 2019 to 2023) through the IQVIA pharmacy claims database. PrEP-to-need ratio (PNR) is the number of individuals using PrEP in a year divided by new HIV diagnoses in the previous year. It was calculated for subgroups defined by five PNR-associated factors: Sex, insurance, recorded HIV risk factors (identified by diagnosis or procedure codes), “Ending the HIV Epidemic” jurisdictions, and neighborhood race/ethnicity mix.
 

Disparities Persist

While PrEP use improved across all the groups studied in the 5 years, “disparities still persist and the need remains very significant,” Tao said. “It’s very crucial for guiding the future HIV prevention options.”

“Long-acting PrEP options may help to address some social determinants structural factors in HIV acquisition,” she added.
 

What Programs Are Helping?

Some guidelines and programs are helping increase uptake, Tao said.

The United States Preventive Services Task Force (USPSTF) guidelines “reinforce more accessible PrEP programs to individuals like zero-cost sharing or same-day dispensing,” Tao said in a press briefing. “Those kinds of policies are really effective. We can see that after the implementation of the USPSTF guidelines, the copay sharing is really decreasing and is coinciding with the HIV rates declining.”

The Medicaid coverage expansion in 40 states “has been really effective” in PrEP uptake, she added.

Colleen Kelley, MD, MPH, with the Division of Infectious Diseases at the Rollins School of Public Health, Emory University, in Atlanta, who was not part of the research, said there has been a slow but improving uptake of PrEP across the board in the United States, “but the issue is that the uptake has been inequitable.”
 

Large Study With Recent Data

“This is an extremely large study with very recent data,” Kelley said. “Additionally, they were able to couple (the uptake) with unmet need. People who are at higher risk of acquiring HIV or who live in high-risk areas for HIV should have greater access to PrEP. They have a greater need for PrEP. What we really need to do from an equity perspective is match the PrEP use with the PrEP need and we have not been successful in doing that.”

Kelley added that the finding that the group that had the highest unmet need for PrEP in the study also had no recorded HIV risk factors. “It’s an interesting time to start thinking about beyond risk factor coverage for PrEP,” she said.

Another issue, Kelley said, is that “people are using (PrEP) but they’re also stopping it. People will need to take PrEP many years for protection, but about half discontinue in the first 6-12 months.

“We need to look at how people will persist on PrEP over the long term. That’s the next frontier,” she said. “We hope the long-acting injectables will help overcome some of the PrEP fatigue. But some may just tire of taking medication repeatedly for an infection they don’t have,” she said.

The study was funded by Gilead Sciences. Tao is employed by and is a shareholder of Gilead Sciences. All relevant financial disclosures have been mitigated, according to the paper. Kelley has research grants to her institution from Gilead, Moderna, Novavax, ViiV, and Humanigen.
 

A version of this article first appeared on Medscape.com.

LOS ANGELES — Use of preexposure prophylaxis (PrEP) to prevent HIV is increasing overall, but both the rate of increase for starting PrEP and the rate of unmet need differ widely by demographic group, according to new data from a large study.

An analysis by Li Tao, MD, MS, PhD, director of real-world evidence at Gilead Sciences, and colleagues looked at statistical trends from 2019 to 2023 and found that Black, Hispanic, and Medicaid-insured populations continue to lack equitable access to PrEP.

Among the findings were that most new PrEP users were men with HIV risk factors who are commercially insured and live in predominantly non-Hispanic White areas (53% in 2019 and 43% in 2023). For comparison, men living in predominantly Black or Hispanic neighborhoods, or who are insured by Medicaid, saw lower proportions of PrEP use (16% in 2019 and 17% in 2023) despite higher annual increases in PrEP use (11% per year) and higher unmet needs.
 

Half a Million Real-World Participants

Tao presented her team’s findings at the Infectious Disease Week (IDWeek) 2024 Annual Meeting. The study included “more than half a million real-world PrEP users over the past 5 years,” she said.

The group with the lowest growth in initiation of PrEP in the study period (an annual percentage increase of 2%) and the lowest unmet need included men with HIV risk factors, who were using commercial insurance and living in White-dominant neighborhoods.

HIV risk factors included diagnosis of any sexually transmitted disease, contact with and exposure to communicable diseases, high-risk sexual behavior, contact with a hypodermic needle, long-term prophylaxis, HIV prevention counseling, and HIV screening.

Other men with HIV risk factors (those who were commercially insured, living in Black/Hispanic neighborhoods, or those on Medicaid across all neighborhoods) had a moderate increase in PrEP initiation (an annual percentage increase of 11%-16%) and higher unmet needs.

Researchers gathered data on PrEP prescriptions and new HIV diagnoses (from 2019 to 2023) through the IQVIA pharmacy claims database. PrEP-to-need ratio (PNR) is the number of individuals using PrEP in a year divided by new HIV diagnoses in the previous year. It was calculated for subgroups defined by five PNR-associated factors: Sex, insurance, recorded HIV risk factors (identified by diagnosis or procedure codes), “Ending the HIV Epidemic” jurisdictions, and neighborhood race/ethnicity mix.
 

Disparities Persist

While PrEP use improved across all the groups studied in the 5 years, “disparities still persist and the need remains very significant,” Tao said. “It’s very crucial for guiding the future HIV prevention options.”

“Long-acting PrEP options may help to address some social determinants structural factors in HIV acquisition,” she added.
 

What Programs Are Helping?

Some guidelines and programs are helping increase uptake, Tao said.

The United States Preventive Services Task Force (USPSTF) guidelines “reinforce more accessible PrEP programs to individuals like zero-cost sharing or same-day dispensing,” Tao said in a press briefing. “Those kinds of policies are really effective. We can see that after the implementation of the USPSTF guidelines, the copay sharing is really decreasing and is coinciding with the HIV rates declining.”

The Medicaid coverage expansion in 40 states “has been really effective” in PrEP uptake, she added.

Colleen Kelley, MD, MPH, with the Division of Infectious Diseases at the Rollins School of Public Health, Emory University, in Atlanta, who was not part of the research, said there has been a slow but improving uptake of PrEP across the board in the United States, “but the issue is that the uptake has been inequitable.”
 

Large Study With Recent Data

“This is an extremely large study with very recent data,” Kelley said. “Additionally, they were able to couple (the uptake) with unmet need. People who are at higher risk of acquiring HIV or who live in high-risk areas for HIV should have greater access to PrEP. They have a greater need for PrEP. What we really need to do from an equity perspective is match the PrEP use with the PrEP need and we have not been successful in doing that.”

Kelley added that the finding that the group that had the highest unmet need for PrEP in the study also had no recorded HIV risk factors. “It’s an interesting time to start thinking about beyond risk factor coverage for PrEP,” she said.

Another issue, Kelley said, is that “people are using (PrEP) but they’re also stopping it. People will need to take PrEP many years for protection, but about half discontinue in the first 6-12 months.

“We need to look at how people will persist on PrEP over the long term. That’s the next frontier,” she said. “We hope the long-acting injectables will help overcome some of the PrEP fatigue. But some may just tire of taking medication repeatedly for an infection they don’t have,” she said.

The study was funded by Gilead Sciences. Tao is employed by and is a shareholder of Gilead Sciences. All relevant financial disclosures have been mitigated, according to the paper. Kelley has research grants to her institution from Gilead, Moderna, Novavax, ViiV, and Humanigen.
 

A version of this article first appeared on Medscape.com.

LOS ANGELES — Use of preexposure prophylaxis (PrEP) to prevent HIV is increasing overall, but both the rate of increase for starting PrEP and the rate of unmet need differ widely by demographic group, according to new data from a large study.

An analysis by Li Tao, MD, MS, PhD, director of real-world evidence at Gilead Sciences, and colleagues looked at statistical trends from 2019 to 2023 and found that Black, Hispanic, and Medicaid-insured populations continue to lack equitable access to PrEP.

Among the findings were that most new PrEP users were men with HIV risk factors who are commercially insured and live in predominantly non-Hispanic White areas (53% in 2019 and 43% in 2023). For comparison, men living in predominantly Black or Hispanic neighborhoods, or who are insured by Medicaid, saw lower proportions of PrEP use (16% in 2019 and 17% in 2023) despite higher annual increases in PrEP use (11% per year) and higher unmet needs.
 

Half a Million Real-World Participants

Tao presented her team’s findings at the Infectious Disease Week (IDWeek) 2024 Annual Meeting. The study included “more than half a million real-world PrEP users over the past 5 years,” she said.

The group with the lowest growth in initiation of PrEP in the study period (an annual percentage increase of 2%) and the lowest unmet need included men with HIV risk factors, who were using commercial insurance and living in White-dominant neighborhoods.

HIV risk factors included diagnosis of any sexually transmitted disease, contact with and exposure to communicable diseases, high-risk sexual behavior, contact with a hypodermic needle, long-term prophylaxis, HIV prevention counseling, and HIV screening.

Other men with HIV risk factors (those who were commercially insured, living in Black/Hispanic neighborhoods, or those on Medicaid across all neighborhoods) had a moderate increase in PrEP initiation (an annual percentage increase of 11%-16%) and higher unmet needs.

Researchers gathered data on PrEP prescriptions and new HIV diagnoses (from 2019 to 2023) through the IQVIA pharmacy claims database. PrEP-to-need ratio (PNR) is the number of individuals using PrEP in a year divided by new HIV diagnoses in the previous year. It was calculated for subgroups defined by five PNR-associated factors: Sex, insurance, recorded HIV risk factors (identified by diagnosis or procedure codes), “Ending the HIV Epidemic” jurisdictions, and neighborhood race/ethnicity mix.
 

Disparities Persist

While PrEP use improved across all the groups studied in the 5 years, “disparities still persist and the need remains very significant,” Tao said. “It’s very crucial for guiding the future HIV prevention options.”

“Long-acting PrEP options may help to address some social determinants structural factors in HIV acquisition,” she added.
 

What Programs Are Helping?

Some guidelines and programs are helping increase uptake, Tao said.

The United States Preventive Services Task Force (USPSTF) guidelines “reinforce more accessible PrEP programs to individuals like zero-cost sharing or same-day dispensing,” Tao said in a press briefing. “Those kinds of policies are really effective. We can see that after the implementation of the USPSTF guidelines, the copay sharing is really decreasing and is coinciding with the HIV rates declining.”

The Medicaid coverage expansion in 40 states “has been really effective” in PrEP uptake, she added.

Colleen Kelley, MD, MPH, with the Division of Infectious Diseases at the Rollins School of Public Health, Emory University, in Atlanta, who was not part of the research, said there has been a slow but improving uptake of PrEP across the board in the United States, “but the issue is that the uptake has been inequitable.”
 

Large Study With Recent Data

“This is an extremely large study with very recent data,” Kelley said. “Additionally, they were able to couple (the uptake) with unmet need. People who are at higher risk of acquiring HIV or who live in high-risk areas for HIV should have greater access to PrEP. They have a greater need for PrEP. What we really need to do from an equity perspective is match the PrEP use with the PrEP need and we have not been successful in doing that.”

Kelley added that the finding that the group that had the highest unmet need for PrEP in the study also had no recorded HIV risk factors. “It’s an interesting time to start thinking about beyond risk factor coverage for PrEP,” she said.

Another issue, Kelley said, is that “people are using (PrEP) but they’re also stopping it. People will need to take PrEP many years for protection, but about half discontinue in the first 6-12 months.

“We need to look at how people will persist on PrEP over the long term. That’s the next frontier,” she said. “We hope the long-acting injectables will help overcome some of the PrEP fatigue. But some may just tire of taking medication repeatedly for an infection they don’t have,” she said.

The study was funded by Gilead Sciences. Tao is employed by and is a shareholder of Gilead Sciences. All relevant financial disclosures have been mitigated, according to the paper. Kelley has research grants to her institution from Gilead, Moderna, Novavax, ViiV, and Humanigen.
 

A version of this article first appeared on Medscape.com.

How can the immunogenicity and effectiveness of flu vaccines be improved in older adults? Several strategies are available, one being the addition of an adjuvant. For example, the MF59-adjuvanted vaccine has shown superior immunogenicity. However, “we do not have data from controlled and randomized clinical trials showing superior clinical effectiveness versus the standard dose,” Professor Odile Launay, an infectious disease specialist at Cochin Hospital in Paris, France, noted during a press conference. Another option is to increase the antigen dose in the vaccine, creating a high-dose (HD) flu vaccine.

Why is there a need for an HD vaccine? “The elderly population bears the greatest burden from the flu,” explained Launay. “This is due to three factors: An aging immune system, a higher number of comorbidities, and increased frailty.” Standard-dose flu vaccines are seen as offering suboptimal protection for those older than 65 years, which led to the development of a quadrivalent vaccine with four times the antigen dose of standard flu vaccines. This HD vaccine was introduced in France during the 2021/2022 flu season. A real-world cohort study has since been conducted to evaluate its effectiveness in the target population — those aged 65 years or older. The results were recently published in Clinical Microbiology and Infection.

Cohort Study

The study included 405,385 noninstitutionalized people aged 65 years or older matched with 1,621,540 individuals in a 1:4 ratio. The first group received the HD vaccine, while the second group received the standard-dose vaccine. Both the groups had an average age of 77 years, with 56% women, and 51% vaccinated in pharmacies. The majority had been previously vaccinated against flu (91%), and 97% had completed a full COVID-19 vaccination schedule. More than half had at least one chronic illness.

Hospitalization rates for flu — the study’s primary outcome — were 69.5 vs 90.5 per 100,000 person-years in the HD vs standard-dose group. This represented a 23.3% reduction (95% CI, 8.4-35.8; P = .003).
 

Strengths and Limitations

Among the strengths of the study, Launay highlighted the large number of vaccinated participants older than 65 years — more than 7 million — and the widespread use of polymerase chain reaction flu tests in cases of hospitalization for respiratory infections, which improved flu coding in the database used. Additionally, the results were consistent with those of previous studies.

However, limitations included the retrospective design, which did not randomize participants and introduced potential bias. For example, the HD vaccine may have been prioritized for the oldest people or those with multiple comorbidities. Additionally, the 2021/2022 flu season was atypical, with the simultaneous circulation of the flu virus and SARS-CoV-2, as noted by Launay.
 

Conclusion

In conclusion, this first evaluation of the HD flu vaccine’s effectiveness in France showed a 25% reduction in hospitalizations, consistent with existing data covering 12 flu seasons. The vaccine has been available for a longer period in the United States and Northern Europe.

“The latest unpublished data from the 2022/23 season show a 27% reduction in hospitalizations with the HD vaccine in people over 65,” added Launay.

Note: Due to a pricing disagreement with the French government, Sanofi’s HD flu vaccine Efluelda, intended for people older than 65 years, will not be available this year. (See: Withdrawal of the Efluelda Influenza Vaccine: The Academy of Medicine Reacts). However, the company has submitted a dossier for a trivalent form for a return in the 2025/2026 season and is working on developing mRNA vaccines. Additionally, a combined flu/COVID-19 vaccine is currently in development.

The study was funded by Sanofi. Several authors are Sanofi employees. Odile Launay reported conflicts of interest with Sanofi, MSD, Pfizer, GSK, and Moderna.
 

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

How can the immunogenicity and effectiveness of flu vaccines be improved in older adults? Several strategies are available, one being the addition of an adjuvant. For example, the MF59-adjuvanted vaccine has shown superior immunogenicity. However, “we do not have data from controlled and randomized clinical trials showing superior clinical effectiveness versus the standard dose,” Professor Odile Launay, an infectious disease specialist at Cochin Hospital in Paris, France, noted during a press conference. Another option is to increase the antigen dose in the vaccine, creating a high-dose (HD) flu vaccine.

Why is there a need for an HD vaccine? “The elderly population bears the greatest burden from the flu,” explained Launay. “This is due to three factors: An aging immune system, a higher number of comorbidities, and increased frailty.” Standard-dose flu vaccines are seen as offering suboptimal protection for those older than 65 years, which led to the development of a quadrivalent vaccine with four times the antigen dose of standard flu vaccines. This HD vaccine was introduced in France during the 2021/2022 flu season. A real-world cohort study has since been conducted to evaluate its effectiveness in the target population — those aged 65 years or older. The results were recently published in Clinical Microbiology and Infection.

Cohort Study

The study included 405,385 noninstitutionalized people aged 65 years or older matched with 1,621,540 individuals in a 1:4 ratio. The first group received the HD vaccine, while the second group received the standard-dose vaccine. Both the groups had an average age of 77 years, with 56% women, and 51% vaccinated in pharmacies. The majority had been previously vaccinated against flu (91%), and 97% had completed a full COVID-19 vaccination schedule. More than half had at least one chronic illness.

Hospitalization rates for flu — the study’s primary outcome — were 69.5 vs 90.5 per 100,000 person-years in the HD vs standard-dose group. This represented a 23.3% reduction (95% CI, 8.4-35.8; P = .003).
 

Strengths and Limitations

Among the strengths of the study, Launay highlighted the large number of vaccinated participants older than 65 years — more than 7 million — and the widespread use of polymerase chain reaction flu tests in cases of hospitalization for respiratory infections, which improved flu coding in the database used. Additionally, the results were consistent with those of previous studies.

However, limitations included the retrospective design, which did not randomize participants and introduced potential bias. For example, the HD vaccine may have been prioritized for the oldest people or those with multiple comorbidities. Additionally, the 2021/2022 flu season was atypical, with the simultaneous circulation of the flu virus and SARS-CoV-2, as noted by Launay.
 

Conclusion

In conclusion, this first evaluation of the HD flu vaccine’s effectiveness in France showed a 25% reduction in hospitalizations, consistent with existing data covering 12 flu seasons. The vaccine has been available for a longer period in the United States and Northern Europe.

“The latest unpublished data from the 2022/23 season show a 27% reduction in hospitalizations with the HD vaccine in people over 65,” added Launay.

Note: Due to a pricing disagreement with the French government, Sanofi’s HD flu vaccine Efluelda, intended for people older than 65 years, will not be available this year. (See: Withdrawal of the Efluelda Influenza Vaccine: The Academy of Medicine Reacts). However, the company has submitted a dossier for a trivalent form for a return in the 2025/2026 season and is working on developing mRNA vaccines. Additionally, a combined flu/COVID-19 vaccine is currently in development.

The study was funded by Sanofi. Several authors are Sanofi employees. Odile Launay reported conflicts of interest with Sanofi, MSD, Pfizer, GSK, and Moderna.
 

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

How can the immunogenicity and effectiveness of flu vaccines be improved in older adults? Several strategies are available, one being the addition of an adjuvant. For example, the MF59-adjuvanted vaccine has shown superior immunogenicity. However, “we do not have data from controlled and randomized clinical trials showing superior clinical effectiveness versus the standard dose,” Professor Odile Launay, an infectious disease specialist at Cochin Hospital in Paris, France, noted during a press conference. Another option is to increase the antigen dose in the vaccine, creating a high-dose (HD) flu vaccine.

Why is there a need for an HD vaccine? “The elderly population bears the greatest burden from the flu,” explained Launay. “This is due to three factors: An aging immune system, a higher number of comorbidities, and increased frailty.” Standard-dose flu vaccines are seen as offering suboptimal protection for those older than 65 years, which led to the development of a quadrivalent vaccine with four times the antigen dose of standard flu vaccines. This HD vaccine was introduced in France during the 2021/2022 flu season. A real-world cohort study has since been conducted to evaluate its effectiveness in the target population — those aged 65 years or older. The results were recently published in Clinical Microbiology and Infection.

Cohort Study

The study included 405,385 noninstitutionalized people aged 65 years or older matched with 1,621,540 individuals in a 1:4 ratio. The first group received the HD vaccine, while the second group received the standard-dose vaccine. Both the groups had an average age of 77 years, with 56% women, and 51% vaccinated in pharmacies. The majority had been previously vaccinated against flu (91%), and 97% had completed a full COVID-19 vaccination schedule. More than half had at least one chronic illness.

Hospitalization rates for flu — the study’s primary outcome — were 69.5 vs 90.5 per 100,000 person-years in the HD vs standard-dose group. This represented a 23.3% reduction (95% CI, 8.4-35.8; P = .003).
 

Strengths and Limitations

Among the strengths of the study, Launay highlighted the large number of vaccinated participants older than 65 years — more than 7 million — and the widespread use of polymerase chain reaction flu tests in cases of hospitalization for respiratory infections, which improved flu coding in the database used. Additionally, the results were consistent with those of previous studies.

However, limitations included the retrospective design, which did not randomize participants and introduced potential bias. For example, the HD vaccine may have been prioritized for the oldest people or those with multiple comorbidities. Additionally, the 2021/2022 flu season was atypical, with the simultaneous circulation of the flu virus and SARS-CoV-2, as noted by Launay.
 

Conclusion

In conclusion, this first evaluation of the HD flu vaccine’s effectiveness in France showed a 25% reduction in hospitalizations, consistent with existing data covering 12 flu seasons. The vaccine has been available for a longer period in the United States and Northern Europe.

“The latest unpublished data from the 2022/23 season show a 27% reduction in hospitalizations with the HD vaccine in people over 65,” added Launay.

Note: Due to a pricing disagreement with the French government, Sanofi’s HD flu vaccine Efluelda, intended for people older than 65 years, will not be available this year. (See: Withdrawal of the Efluelda Influenza Vaccine: The Academy of Medicine Reacts). However, the company has submitted a dossier for a trivalent form for a return in the 2025/2026 season and is working on developing mRNA vaccines. Additionally, a combined flu/COVID-19 vaccine is currently in development.

The study was funded by Sanofi. Several authors are Sanofi employees. Odile Launay reported conflicts of interest with Sanofi, MSD, Pfizer, GSK, and Moderna.
 

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.