People believed to have sepsis who take piperacillin-tazobactam (Zosyn) and vancomycin have a 5% absolute mortality increase at 90 days compared with those who take cefepime and vancomycin, a new study shows.
The study, published Monday in JAMA Internal Medicine, shows that the mortality rate is equivalent to one additional death for every 20 people who have sepsis. Many older adults develop sepsis, a condition in which the body responds improperly to an infection.
Piperacillin-tazobactam is a combination of penicillin with a beta-lactamase inhibitor, and has potent activity against anaerobic gut bacteria. Clinicians mix piperacillin-tazobactam with vancomycin to treat sepsis patients when they want to cover as many potential pathogens as possible. Some research has shown that piperacillin-tazobactam is associated with adverse outcomes in people who are critically ill, as well as higher death rates.
In 2015, a nationwide shortage of piperacillin-tazobactam forced clinicians to use vancomycin and cefepime, which doesn’t work against anaerobic bacteria. The authors of the study had conducted a previous trial that found early treatment with antianaerobic antibiotics may harm patients. They used the shortage to test if using piperacillin-tazobactam was linked to higher death compared with cefepime.
“We saw this Zosyn shortage as a one-of-a-kind opportunity to ask whether this antibiotic, which we know depletes the gut of anaerobic bacteria, makes a difference in terms of patient outcomes,” Robert Dickson, MD, a co-author and researcher at the University of Michigan Medical School’s division of pulmonary and critical care medicine, said in a university press release.
The team assessed records of adults with suspected sepsis who were treated with either regimen in the emergency department of the University of Michigan from July 2014 through December 2018. Of 7,569 participants with a median age of 63 years old, 4,523 were treated with vancomycin and piperacillin-tazobactam and 3,046 got vancomycin and cefepime.
The 90-day mortality in people who took piperacillin-tazobactam was 22.5%. That compares with 17.5% in those who took cefepime, which results in an absolute increase in 90-day mortality of 5%. Piperacillin-tazobactam was linked with 2.1 fewer organ failure-free days, 1.1 fewer ventilator-free days and 1.5 fewer vasopressor-free days.
An additional evaluation found that metronidazole, another potent anti-anaerobic antibiotic that was used in sepsis patients during the piperacillin-tazobactam shortage, was also linked with higher 90-day mortality.
“These findings suggest that broad-spectrum antibiotics with anti-anaerobic activity, such as piperacillin-tazobactam, may cause harm in patients without a clear indication,” the authors wrote.
