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Published on: August 30, 2018
Mortality of Patients With Sepsis Administered Piperacillin-Tazobactam vs Cefepime
Rishi Chanderraj1,2,3, Andrew J Admon3,4,5, Ying He4
1Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor.
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.
Insights
Piperacillin-tazobactam use in sepsis patients without anaerobic infection risk was linked to higher 90-day mortality and organ dysfunction compared to cefepime. This suggests empirical antianaerobic antibiotics may be harmful.
Area of Science:
- Infectious Diseases
- Clinical Pharmacology
- Critical Care Medicine
Background:
- Empirical antianaerobic antibiotics like piperacillin-tazobactam are commonly used for sepsis.
- Previous studies suggested potential harm from piperacillin-tazobactam compared to anaerobe-sparing agents like cefepime.
- A recent trial found no short-term outcome difference, necessitating further investigation.
Purpose of the Study:
- To evaluate the association between piperacillin-tazobactam and cefepime use and 90-day mortality in sepsis patients.
- To assess secondary outcomes including organ failure, ventilator use, and vasopressor dependence.
- To utilize instrumental variable analysis, leveraging a piperacillin-tazobactam shortage, to mitigate confounding.
Main Methods:
- Retrospective cohort study of adult sepsis patients at the University of Michigan (2014-2018).
- Inclusion criteria: suspected sepsis, vancomycin plus either piperacillin-tazobactam or cefepime, and presumed equipoise in antibiotic choice.
- Instrumental variable analysis using a 15-month piperacillin-tazobactam shortage period to address unmeasured confounding.
Main Results:
- The study included 7569 patients; 4523 received piperacillin-tazobactam and 3046 received cefepime.
- Instrumental variable analysis revealed piperacillin-tazobactam was associated with a 5.0% absolute increase in 90-day mortality.
- Piperacillin-tazobactam use was also linked to significantly fewer organ failure-free, ventilator-free, and vasopressor-free days.
Conclusions:
- In sepsis patients without a clear need for anaerobic coverage, piperacillin-tazobactam was associated with increased 90-day mortality and prolonged organ dysfunction compared to cefepime.
- These findings indicate that the broad empirical use of antianaerobic antibiotics for sepsis may lead to adverse outcomes.
- Further research is warranted to optimize antibiotic selection for sepsis management.
