A University of Michigan study links the use of the antibiotic piperacillin/tazobactam in sepsis treatment with a 5% increase in 90-day mortality, demonstrating the impact of antibiotics on the gut microbiome when treating life-threatening infections. The importance of considering this is emphasized.
In emergency rooms and intensive care units across the country, medical professionals must quickly make antibiotic decisions for patients with suspected severe infections. A recent study from the University of Michigan shows that these quick decisions can have unexpected effects on patient outcomes.
Since 2015, there has been a 15-month national shortage of the commonly prescribed antibiotic piperacillin/tazobactam (known by the trade name Zosyn), so hospitalized patients with sepsis were given two different antibiotics. This provided a unique opportunity to compare mortality rates. One is to preserve the gut microbiome, and the other is to significantly change the gut microbiome.
Piperacillin/tazobactam is a broad-spectrum antibiotic commonly given for sepsis, a life-threatening complication of infection. If this antibiotic is not available, clinicians usually use another antibiotic, cefepime. Cefepime has similar activity against common sepsis pathogens, but unlike piperacillin/tazobactam, it has minimal effects on anaerobic enterobacteria.
“We saw this Zosyn deficiency as a unique opportunity to ask whether this antibiotic, which is known to deplete anaerobic bacteria in the gut, could make a difference in patient outcomes.” said Dr. Robert Dixon. in the Department of Pulmonary and Critical Care Medicine at the School of Medicine and Deputy Director of the Weill Institute for Critical Care Research and Innovation.
In health, the gut microbiome is largely populated by anaerobic bacteria that rarely cause disease. Previous studies by the research team have shown 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 infection prevention. There is.
Research results and implications
Dixon, Rishi Chanderaj, MD, of the Division of Infectious Diseases, Michael Schoeding, MD, of the Division of Pulmonary and Critical Care Medicine, and a multidisciplinary team from UM and VA Ann Arbor used patient record data to determine outcomes for 7,569 patients. investigated. The research team compared 4,523 patients treated with piperacillin/tazobactam to 3,046 patients who received cefepime.
They found a noticeable difference. Treatment with piperacillin-tazobactam was associated with a 5 percent increase in 90-day mortality, increased days on mechanical ventilation, and increased time in organ failure.
“These are powerful antibiotics that are administered to patients every day in all hospitals across the country,” Chanderaj said. “Clinicians use these because they are trying to treat any pathogens that may be causing a patient’s illness. However, our results show that their impact on the microbiome may affect patient outcomes. This suggests that it may also have an important impact.
This research is based on Previous studies by the research team It suggests that giving critically ill patients antibiotics that deplete anaerobes in the intestines may worsen their symptoms. They observed similar effects when studying animal models.
“Our previous research suggested that piperacillin/tazobactam may be harmful, but it was an observational study and had some limitations,” said the study’s senior author. said author Schoding. “That’s why the drug shortage was a great opportunity. It created a near-perfect natural experiment in which we could test the differences between these two drugs on patient outcomes in a very rigorous way.”
a Recent clinical trials They compared these two antibiotics against each other and compared side effects and mortality after two weeks. This trial did not find any differences in the short term. This was also observed in the UM team’s analysis.
“When the study looked at the two-week results, they found no difference,” Chanderaj said. “But after three months, the difference was dramatic.”
Overall, the new findings suggest that treatment with piperacillin/tazobactam instead of cefepime may contribute to 1 additional death for every 20 treated sepsis patients.
“Sepsis is so common that a 5% difference in mortality is very significant,” Dixon said. “Every day, thousands of clinicians decide which of these drugs to use on patients with sepsis.”
Doctors need to give more consideration to whether anti-anaerobic antibiotics are warranted before prescribing them, Chanderaj added. “We need to think of antibiotics like chemotherapy. In the right circumstances, the treatment can be lifesaving, but in the wrong circumstances, it can be extremely harmful.” ”
Reference: “Mortality in patients with sepsis treated with piperacillin-tazobactam and cefepime” Rishi Chanderraj, Andrew J. Admon, Ying He, Mark Nuppnau, Owen R. Albin, Hallie C. Prescott, Robert P. Dickson, Michael W. Written by Sjoding, May 13, 2024 JAMA Internal Medicine.
DOI: 10.1001/jamainternmed.2024.0581
