Commonly used antibiotics associated with increased complications- JAMA study

According to a study published in the journal JAMA Internal Medicine, in patients with sepsis, the use of a combination of vancomycin and piperacillin-tazobactam is associated with increased mortality risk compared with a combination of vancomycin and cefepime.

Piperacillin/tazobactam is a broad-spectrum antibiotic that is commonly administered for sepsis, a life-threatening complication from infection. In its absence, clinicians commonly use another antibiotic, cefepime, which has similar activity against common sepsis pathogens but, unlike piperacillin/tazobactam, has minimal effects on anaerobic gut bacteria.

In health, the gut microbiome is largely populated by anaerobic bacteria that rarely cause disease. Prior research has revealed that even a single dose of piperacillin/tazobactam kills most of these anaerobic gut bacteria, which play important roles in the body’s metabolism, immunity, and prevention of infections.

In their study, Dr. Rishi Chanderraj and his multidisciplinary team from the University of Michigan's Division of Infectious Disease analysed patient records from a cohort of 7,569 individuals. They compared outcomes between 4,523 patients treated with piperacillin/tazobactam and 3,046 patients who received cefepime.

Their findings revealed significant disparities: patients treated with piperacillin-tazobactam experienced a 5 percent rise in 90-day mortality, longer durations on ventilators, and increased instances of organ failure. Moreover, opting for piperacillin/tazobactam over cefepime could potentially result in one additional fatality for every 20 septic patients treated.

“These are powerful antibiotics that are administered to patients every day in every hospital nationwide. Clinicians use them because they are trying to treat every possible pathogen that might be causing their patients’ illnesses. But our results suggest that their effects on the microbiome might also have important effects on patient outcomes,” said Chanderraj. “Our previous research hinted at potential harm associated with piperacillin/tazobactam, but it was based on observational data with limitations. The drug shortage presented a unique opportunity, acting as a nearly perfect natural experiment to rigorously compare the outcomes of patients treated with these two drugs. Physicians should carefully consider the necessity of prescribing anti-anaerobic antibiotics.”

Reference: Chanderraj R, Admon AJ, He Y, et al. Mortality of Patients With Sepsis Administered Piperacillin-Tazobactam vs Cefepime. JAMA Intern Med. Published online May 13, 2024. doi:10.1001/jamainternmed.2024.0581