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Delaying antibiotics in elderly with UTI linked to higher sepsis, death rates

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Older patients need prompt treatment

This study linking primary care prescribing to serious infections in elderly patients with urinary tract infections is timely, as rates of bloodstream infection and mortality are increasing in this age group, according to Alastair D. Hay, MB.ChB, a professor at University of Bristol, England.

“Prompt treatment should be offered to older patients, men (who are at higher risk than women), and those living in areas of greater socioeconomic deprivation who are at the highest risk of bloodstream infections,” Dr. Hay said in an editorial accompanying the report by Gharbi et al.

That said, the link between prescribing and infection in this particular study may not be causal: “The implications are likely to be more nuanced than primary care doctors risking the health of older adults to meet targets for antimicrobial stewardship,” Dr. Hay noted.

Doctors are cautious when managing infections in vulnerable groups, evidence shows, and the deferred prescribing reported in this study is likely not the same as the delayed prescribing seen in primary care, he explained.

“Most clinicians issue a prescription on the day of presentation, with verbal advice to delay treatment, rather than waiting for a patient to return or issuing a postdated prescription,” he said. “The group given immediate antibiotics in the study by Gharbi and colleagues likely contained some patients managed in this way.”

Patients who apparently had no prescription in this retrospective analysis may have had a same-day admission with a bloodstream infection; moreover, a number of bloodstream infections in older people are due to urinary tract bacteria, and so would not be prevented by treatment for urinary tract infection, Dr. Hay said.

“Further research is needed to establish whether treatment should be initiated with a broad or a narrow spectrum antibiotic and to identify those in whom delaying treatment (while awaiting investigation) is safe,” he concluded.

Dr. Hay is a professor in the Centre for Academic Primary Care, University of Bristol, England. His editorial appears in The BMJ (2019 Feb 27. doi: 10.1136/bmj.l780). Dr. Hay declared that he is a member of the managing common infections guideline committee for the National Institute for Health and Care Excellence (NICE).



Delaying or withholding antibiotics in elderly patients with a urinary tract infection (UTI) increases the risk of sepsis and death, results of a large, population-based study suggest.

An elderly man in a hospital bed andresr/Getty Images

The risk of bloodstream infection was more than seven times greater in patients who did not receive antibiotics immediately after seeing a general practitioner for a UTI versus those who did, according to results of the study based on primary care records and other data for nearly 160,000 U.K. patients aged 65 years or older. Death rates and hospital admissions were significantly higher for these patients, according to the study published in The BMJ by Myriam Gharbi, PharmD, Phd, Imperial College London, and her colleagues.

The publication of these findings coincides with an increase in Escherichia coli bloodstream infections in England.

“Our study suggests the early initiation of antibiotics for UTI in older high risk adult populations (especially men aged [older than] 85 years) should be recommended to prevent serious complications,” Dr. Gharbi and her coauthors said in their report.

The population-based cohort study comprised 157,264 adult primary care patients at least 65 years of age who had one or more suspected or confirmed lower UTIs from November 2007 to May 2015. The researchers found that health care providers had diagnosed a total of 312,896 UTI episodes in these patients during the period they studied. In 7.2% (22,534) of the UTI episodes, the researchers were unable to find records of the patients having been prescribed antibiotics by a general practitioner within 7 days of the UTI diagnosis. These 22,534 episodes included those that occurred in patients who had a complication before an antibiotic was prescribed. An additional 6.2% (19,292) of the episodes occurred in patients who were prescribed antibiotics, but not during their first UTI-related visit to a general practitioner or on the same day of such a visit. The researchers classified this group of patients as having been prescribed antibiotics on a deferred or delayed basis, as they were not prescribed such drugs within 7 days of their visit.

Overall, there were 1,539 cases (0.5% of the total number of UTIs) of bloodstream infection within 60 days of the initial urinary tract infection diagnosis, the researchers reported.

The bloodstream infection rate was 2.9% for patients who were not prescribed antibiotics ever or prior to an infection occurring, 2.2% in those who were prescribed antibiotics on a deferred basis, and 0.2% in those who were prescribed antibiotics immediately, meaning during their first visit to a general practitioner for a UTI or on the same day of such a visit (P less than .001). After adjustment for potential confounding variables such as age, sex, and region, the patients classified as having not been prescribed antibiotics or having been prescribed antibiotics on a deferred basis were significantly more likely to have a bloodstream infection within 60 days of their visit to a health care provider, compared with those who received antibiotics immediately, with odds ratios of 8.08 (95% confidence interval, 7.12-9.16) and 7.12 (95% CI, 6.22-8.14), respectively.

Hospital admissions after a UTI episode were nearly twice as high in the no- or deferred-antibiotics groups (27.0% and 26.8%, respectively), compared with the group that received antibiotics right away (14.8%), the investigators reported. The lengths of hospital stays were 12.1 days for the group classified as having not been prescribed antibiotics, 7.7 days for the group subject to delayed antibiotic prescribing, and 6.3 days for the group who received antibiotics immediately.

Deaths within 60 days of experiencing a urinary tract infection occurred in 5.4% of patients in the no-antibiotics group, 2.8% of the deferred-antibiotics group, and 1.6% of the immediate-antibiotics group. After adjustment for covariates, a regression analysis showed the risks for all-cause mortality were 1.16 and 2.18 times higher in the deferred-antibiotics group and the no-antibiotics group, respectively, according to the paper.

In the immediate-antibiotics group, those patients who received nitrofurantoin had a “small but significant increase” in 60-day survival versus those who received trimethoprim, the investigators noted in the discussion section of their report.

“This increase could reflect either higher levels of resistance to trimethoprim or a healthier population treated with nitrofurantoin, the latest being not recommended for patients with poor kidney function,” the researchers wrote.

This study was supported by the National Institute for Health Research and other U.K. sources. One study coauthor reported working as an epidemiologist with GSK in areas not related to the study.

SOURCE: Gharbi M et al. BMJ. 2019 Feb 27. doi: 10.1136/bmj.l525.

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