The use of the commonly prescribed antibiotic piperacillin/tazobactam was linked to a 5 percent rise in 90-day mortality, increased time on a ventilator, and longer periods of organ failure for sepsis patients, according to a recent study.
Healthcare providers in emergency rooms and intensive care units across the nation must make rapid decisions regarding which antibiotics to administer to patients suspected of having life-threatening infections. A new study from U-M shows that these decisions could have unforeseen impacts on patient outcomes.
Starting in 2015, a 15-month shortage occurred nationally for a par rnrnThe commonly prescribed antibiotic, piperacillin/tazobactam, also known as Zosyn, was used to compare death rates in hospitalized sepsis patients who received different types of antibiotics. One antibiotic spares the gut microbiome while the other profoundly alters it.
Piperacillin/tazobactam is a broad-spectrum antibiotic often given for sepsis, a life-threatening complication of infection. When not using piperacillin/tazobactam, clinicians frequently use cefepime, another antibiotic with similar activity against sepsis pathogens but minimal impact on the gut microbiome.The Zosyn shortage presented a unique opportunity for researchers to investigate the impact of the antibiotic on patient outcomes, specifically its effect on anaerobic gut bacteria. Dr. Robert Dickson, from the Department of Medicine’s Division of Pulmonary & Critical Care Medicine and Deputy Director of the Weil Institute for Critical Care Research & Innovation, commented, “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.” In healthy individuals, the gut microbiome is primarily made up of anaerobic bacteria that seldom result in disease. Previous studies by the research team have shown that even a single dose of piperacillin/tazobactam can eliminate most of these anaerobic bacteria.Gut bacteria play important roles in the body’s metabolism, immunity, and prevention of infections. Dr. Dickson and Dr. Sjoding, along with their team at U-M and the VA Ann Arbor, conducted a study using patient record data to compare outcomes in 7,569 patients. They compared 4,523 patients treated with piperacillin/tazobactam with 3,046 patients who received cefepime. The study found that treatment with piperacillin/tazobactam was associated with a 5 percent increase in 90-day mortality.The use of powerful antibiotics in hospitals nationwide is a common practice to treat a wide range of pathogens that cause illness in patients, according to Chanderraj, a researcher. However, a recent study suggests that these antibiotics may have significant effects on patient outcomes due to their impact on the microbiome. The study team’s previous work also indicated that critically ill patients may experience worse outcomes when given antibiotics that deplete the gut of anaerobes.The researchers observed similar effects in animal models. Sjoding, the senior author of the study, explained, “Our previous research indicated potential harm with piperacillin/tazobactam, but it was based on an observational study with limitations. The drug shortage provided a unique opportunity for a natural experiment to rigorously test the difference between these two drugs on patient outcomes.”
A recent clinical trial compared the side effects and mortality of these two antibiotics after two weeks, but did not find any differences in the short term.– a discovery that the U-M team also noticed in their analysis.
“In our research, we didn’t find any differences in the two-week outcomes,” Chanderraj stated. “However, the discrepancies at three months were significant.”
On the whole, the recent findings indicate that using piperacillin/tazobactam instead of cefepime as treatment may lead to one additional fatality for every 20 septic patients treated.
“A 5% difference in mortality has significant consequences because sepsis is so prevalent,” Dickson remarked. “Every day, numerous clinicians have to make decisions about which of these medications to use for septic patients.”
Physicians should pay more attention to th
Rishi Chanderraj emphasized the importance of considering whether anti-anaerobic antibiotics are necessary before prescribing them. He compared the use of antibiotics to chemotherapy, stating that while they can be life-saving in the right context, they can also be harmful if used inappropriately.
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