Study Finds Higher Mortality Risk with Piperacillin-Tazobactam in Sepsis Patients

A recent study found that the antibiotic combination of piperacillin-tazobactam is associated with a higher 90-day mortality rate and increased organ dysfunction compared to cefepime in adults hospitalized with suspected sepsis. The study analyzed data from 7,569 patients at the University of Michigan and found a 5% absolute increase in 90-day mortality with piperacillin-tazobactam treatment.

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Nitish Verma
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Study Finds Higher Mortality Risk with Piperacillin-Tazobactam in Sepsis Patients

Study Finds Higher Mortality Risk with Piperacillin-Tazobactam in Sepsis Patients

A recent retrospective cohort study published in JAMA Internal Medicine has found that the antibiotic combination of piperacillin-tazobactam is associated with a higher 90-day mortality rate and increased organ dysfunction compared to cefepime in adults hospitalized with suspected sepsis at the University of Michigan. The findings suggest that for sepsis patients who do not require anti-anaerobic antibiotics, the widely used empirical regimen of vancomycin and piperacillin-tazobactam may pose a greater risk than the alternative combination of vancomycin and cefepime.

Why this matters: The study's findings have significant implications for the treatment of sepsis, a life-threatening condition that affects millions of people worldwide. The widespread use of piperacillin-tazobactam could be contributing to thousands of preventable deaths each year, highlighting the need for healthcare providers to reassess their antibiotic selection and treatment strategies.

The study, led by Rishi Chanderraj, MD, MSc, analyzed data from 7,569 adult patients who presented to the emergency department at the University of Michigan from July 2014 through December 2018 and received empirical treatment for sepsis. The researchers found that treatment with vancomycin and piperacillin-tazobactam resulted in a 5% absolute increase in 90-day mortality compared with vancomycin and cefepime (22.5% vs 17.5%, P=0.002). Piperacillin-tazobactam was also associated with 2.1 fewer organ failure-free days, 1.1 fewer ventilator-free days, and 1.5 fewer vasopressor-free days compared to cefepime.

"When it comes to early treatment in sepsis, all broad-spectrum antibiotics are not created equal," said Chanderraj, the study's lead author. "Unless the patient has a specific indication for anti-anaerobic antibiotics, physicians should think carefully before using them and exposing their patients to unnecessary harm." The researchers estimate that the combination of vancomycin and piperacillin-tazobactam, the most frequently prescribed empirical regimen for sepsis, may contribute to one additional death per every 20 patients with sepsis.

The study leveraged a 15-month piperacillin-tazobactam shortage that occurred during the study period as an instrumental variable to account for unmeasured confounding in antibiotic selection. This allowed the researchers to conduct the retrospective analysis in a way that mimicked a randomized trial. The median age of the patients was 63, and 55% were men.

The study relied on data from electronic medical records at a single center, which may limit the generalizability of the findings to other clinical settings or populations. However, the results highlight the potential harm of the widespread use of empirical anti-anaerobic antibiotics in sepsis treatment. "A 2% to 5% mortality difference may not initially sound like much, but given how common and deadly sepsis is, the routine use of anti-anaerobic antibiotics in sepsis may lead to thousands of deaths per year," Chanderraj noted.

The study was funded by grants from the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Agency for Healthcare Research and Quality. The findings underscore the importance of carefully considering the choice of empirical antibiotics in the treatment of sepsis and the need for further research to optimize antibiotic selection and improve patient outcomes in this critical illness.

Key Takeaways

  • A recent study found piperacillin-tazobactam associated with higher 90-day mortality and organ dysfunction in sepsis patients.
  • Vancomycin and cefepime combo may be safer than vancomycin and piperacillin-tazobactam for sepsis treatment.
  • Piperacillin-tazobactam linked to 5% absolute increase in 90-day mortality compared to cefepime.
  • Study suggests piperacillin-tazobactam may contribute to thousands of preventable deaths each year.
  • Researchers recommend reassessing antibiotic selection and treatment strategies for sepsis patients.