Antibiotics Commonly used antibiotic brings more complications, death in the sickest patients (May 2024, n=7569) Mortality of Patients With Sepsis Administered Piperacillin-Tazobactam vs Cefepime

Michael Harrop

Active member
Jul 6, 2023

to compare rates of death in hospitalized patients with sepsis who were administered two different types of antibiotics—one that spares the gut microbiome and one that profoundly alters it.

“These are powerful antibiotics that are administered to patients every day in every hospital nationwide,” said Chanderraj. “Clinicians use them because they are trying to treat every possible pathogen that might be causing their patients’ illness. But our results suggest that their effects on the microbiome might also have important effects on patient outcomes.”

The study builds on previous work by the study team that suggested critically ill patients may do worse when given antibiotics that deplete the gut of anaerobes. They have also seen similar effects when studying animal models.

Physicians should give more thought about whether anti-anerobic antibiotics are warranted before prescribing them, added Chanderraj. “We need to think about antibiotics like chemotherapy. In the right context, treatment can be lifesaving, but in the wrong context, it can be quite harmful.”

Key Points​

Question In patients with sepsis without a specific indication for antianaerobic antibiotics, is use of a combination of vancomycin and piperacillin-tazobactam associated with increased mortality risk compared with a combination of vancomycin and cefepime?

Findings In this cohort study of 7569 patients with sepsis, an instrumental variable analysis using a 15-month piperacillin-tazobactam shortage as a natural experiment was conducted. The results found that treatment with vancomycin and piperacillin-tazobactam was associated with higher mortality than vancomycin combined with cefepime.

Meaning The findings of this study suggest that, for patients with sepsis not requiring antianaerobic antibiotics, a combination of vancomycin and piperacillin-tazobactam may pose a greater mortality risk than vancomycin and cefepime.


Importance Experimental and observational studies have suggested that empirical treatment for bacterial sepsis with antianaerobic antibiotics (eg, piperacillin-tazobactam) is associated with adverse outcomes compared with anaerobe-sparing antibiotics (eg, cefepime). However, a recent pragmatic clinical trial of piperacillin-tazobactam and cefepime showed no difference in short-term outcomes at 14 days. Further studies are needed to help clarify the empirical use of these agents.

Objective To examine the use of piperacillin-tazobactam compared with cefepime in 90-day mortality in patients treated empirically for sepsis, using instrumental variable analysis of a 15-month piperacillin-tazobactam shortage.

Design, Setting, and Participants In a retrospective cohort study, hospital admissions at the University of Michigan from July 1, 2014, to December 31, 2018, including a piperacillin-tazobactam shortage period from June 12, 2015, to September 18, 2016, were examined. Adult patients with suspected sepsis treated with vancomycin and either piperacillin-tazobactam or cefepime for conditions with presumed equipoise between piperacillin-tazobactam and cefepime were included in the study. Data analysis was conducted from December 17, 2022, to April 11, 2023.

Main Outcomes and Measures The primary outcome was 90-day mortality. Secondary outcomes included organ failure–free, ventilator-free, and vasopressor-free days. The 15-month piperacillin-tazobactam shortage period was used as an instrumental variable for unmeasured confounding in antibiotic selection.

Results Among 7569 patients (4174 men [55%]; median age, 63 [IQR 52-73] years) with sepsis meeting study eligibility, 4523 were treated with vancomycin and piperacillin-tazobactam and 3046 were treated with vancomycin and cefepime. Of patients who received piperacillin-tazobactam, only 152 (3%) received it during the shortage. Treatment groups did not differ significantly in age, Charlson Comorbidity Index score, Sequential Organ Failure Assessment score, or time to antibiotic administration. In an instrumental variable analysis, piperacillin-tazobactam was associated with an absolute mortality increase of 5.0% at 90 days (95% CI, 1.9%-8.1%) and 2.1 (95% CI, 1.4-2.7) fewer organ failure–free days, 1.1 (95% CI, 0.57-1.62) fewer ventilator-free days, and 1.5 (95% CI, 1.01-2.01) fewer vasopressor-free days.

Conclusions and Relevance Among patients with suspected sepsis and no clear indication for antianaerobic coverage, administration of piperacillin-tazobactam was associated with higher mortality and increased duration of organ dysfunction compared with cefepime. These findings suggest that the widespread use of empirical antianaerobic antibiotics in sepsis may be harmful.
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That's interesting. Have had many septic patients who are just given more antibiotics or a different class of antibiotics to treat their sepsis. Many times those with a history of sepsis just get worse. It's interesting to see if they were given a fecal transplant how they would do.
Ive taken anti-aerobic antibiotics a few times but it wasn't until I took a two week course of flagyl for minor tooth pain almost a decade ago is when my health began to deteriorate.