Piperacillin-Tazobactam Very Disruptive to Gut Flora

Piperacillin-tazobactam is especially harmful to microbiota in the human gut, according to the results of a new study published online November 1, 2018, in the journal Clinical Infectious Diseases. Additionally, its use is associated with colonization of the gastrointestinal tract by lower relative quantities of some potentially protective bacterial organisms.

“Antibiotics are major contributors to dysbiosis in the gastrointestinal microbiota,” wrote Melinda M. Pettigrew, PhD, from Yale School of Public Health, New Haven, Connecticut, and colleagues. “However, data to guide clinicians in the selection of antibiotics that minimize microbiota disruption remain limited.”

According to the authors, many hospitalized patients experience the collapse of their gastrointestinal microbiota, which increases their risk of colonization and infection by antibiotic-resistant pathogens. Nevertheless, in contrast, most studies investigating the effect of antibiotics on the gut microbiota tend to focus on healthy individuals, they say.

In particular, Dr. Pettigrew and colleagues note that Pseudomonas aeruginosa readily colonizes hospitalized patients, and carbapenem-resistant Pseudomonas aeruginosa (CRPA) has been reported to cause infections in 28% of colonized patients in intensive care units (ICUs).

As a consequence, “prevention of CRPA colonization-acquisition represents an important target for interventions to reduce infection and spread of CRPA in the hospital,” the authors stressed.

With this in mind, Dr. Pettigrew and colleagues conducted a study in 109 ICU patients. They collected peri-rectal swabs from patients at the time of admission to ICU, and at subsequent times thereafter, as part of an ongoing surveillance program to culture for vancomycin-resistant Enterococcus (VRE). Swabs were also cultured for imipenem-resistant P aeruginosa to identify CRPA colonization-acquisition.

The investigators also performed rRNA sequencing analysis on the swabs to examine the links between factors such as patient characteristics, medications, gastrointestinal microbiota, and CRPA colonization-acquisition.

In particular, the study showed that ICU patients have a gastrointestinal microbiota composed of large quantities of pathogenic bacterial species such as Enterococcus, Escherichia, Staphylococcus, Enterobacteriaceae, and Pseudomonas.

Additionally, patients with CRPA colonization-acquisition had more commonly received piperacillin-tazobactam than patients without colonization. And piperacillin-tazobactam use was associated with the presence of lower quantities of potentially protective bacterial species. These included Lactobacillus, which tends to be more abundant in patients without multidrug-resistant infections, and Blautia, which is thought to protect against Clostridium difficile infection.

Patients who had received piperacillin-tazobactam also had a greater risk of colonization by high levels of Enterococcus species.

“Our data suggest that piperacillin-tazobactam contributes to microbiota disruption, and indicate that low relative abundances of specific taxa may be related to the risk of CRPA colonization-acquisition,” Dr. Pettigrew and colleagues wrote.

They stressed the need for further studies to determine which commensal organisms are causally related to colonization resistance. Increased understanding of these relationships will assist the development of microbiota disruption indices for monitoring patients at risk of CRPA colonization and infection, they concluded, as well as the development of strategies to minimize infection and spread of CRPA in the hospital.

Dr. Parry, a board-certified veterinary pathologist, graduated from the University of Liverpool in 1997. After 13 years in academia, she founded Midwest Veterinary Pathology, LLC, where she now works as a private consultant. Dr. Parry writes regularly for veterinary organizations and publications.