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Piperacillin-tazobactam tripled risk of death for patients with cephalosporin-resistant septicemia



Some observational studies do suggest a use for it in this setting but the combination had never been formally investigated. MERINO was designed to do so; investigators hoped to show that PTZ would be noninferior to meropenem in patients with septicemias caused by ESBL E. coli and K. pneumoniae.

The enrollment target for MERINO was 454 patients. Between 2014 and 2017, the study enrolled 391, of whom 379 were included in the final analysis. Patients had to start treatment with the study drugs within 72 hours of confirmatory blood culture. Both arms underwent 4 days of treatment with either PTZ 4.5 g every 6 hours or meropenem 1 g every 8 hours.

The study’s primary outcome was 30-day all-cause mortality. Secondary outcomes were days to clinical and microbiological resolution, clinical and microbiological success at day 4, relapsing septicemia or secondary infection with a PTZ- or meropenem-resistant organism, or Clostridium difficile infection.

The mean age of the patients was 66 years. Most (86%) were infected with resistant strains of E. coli; the rest had K. pneumoniae. About 60% of the infections were acquired in a health care or hospital setting, and about 50% originated in the urinary tract. APACHE II scores were different between the meropenem and PTZ groups (21 vs. 17.9). More patients in PTZ arm had immune compromise (27% vs. 21%).

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