Infectious Diseases

A Kinder, Gentler Antibiotic?

By Adam Marcus

The antibiotic cephalothin appears to be kinder to the gut microbiome than other first-line antimicrobial agents, researchers in Japan have found, suggesting it may be a good choice to avoid inducing diarrhea.

“Cephalothin sodium is an antibiotic that we have used for many years in Japan, especially at our facilities,” said Yuta Kinoshita, DVM, PhD, of the Equine Research Institute at the Japan Racing Association, in Tochigi. “From our clinical experience, we’ve long known that it causes few gastrointestinal issues. Our study provides scientific data to support this observation.”

In a recent study, Dr. Kinoshita and his colleagues compared the effects of IV cephalothin and other antibiotics on the gut microbiome in 62 horses. Of those horses, 39 were clinically normal; 16 had received antibiotics—cephalothin (n=5), minocycline (n=5) and metronidazole (n=6)—for 5 days each; and 7 had had at least 1 bout of colitis.

The horses that received minocycline and metronidazole experienced significant changes in the diversity of their gut bacteria, including the number of organisms and the variety of species; however, those given cephalothin did not appear to experience such a disruption. While horses that experienced colitis exhibited “severe” disruptions in a panel of 52 gut bacteria, giving cephalothin did not appear to exacerbate these changes. This suggests “its gut-microbiota–friendly characteristics,” the researchers reported.

“Notably, Verrucomicrobia subdivision 3, associated with mucosal integrity, remained stable in the cephalothin group, whereas its relative abundance significantly decreased in the minocycline, metronidazole and colitis groups (P <0.05),” they added.

“Verrucomicrobia is known to be an important bacterial group for maintaining a healthy gut barrier and balance,” Dr. Kinoshita explained. “The fact that this group was maintained in horses treated with cephalothin suggested that the drug is less likely to weaken the gut’s natural defenses.”

However, he noted, determining the direct effect of a single bacterial group is complicated. “To use other species as reliable markers for gut health, we need more research that combines data on what these bacteria do and their population sizes and relative abundance in a wide range of horses,” he said.

The findings “provide a strong scientific reason for veterinarians to choose cephalothin” as a first-line agent, “especially for horses at high risk for gut problems,” such as those under stress or after surgery. “Our own choice of antibiotics hasn’t changed much, as we have a long history of using this drug. However, we have heard that other veterinary clinics in Japan have started using cephalothin as a first-choice treatment in appropriate cases,” Dr. Kinoshita added.

He stressed that cephalosporins are used mainly for gram-positive infections, such as those caused by Staphylococcus and Streptococcus.

“We use minocycline, which has a broader spectrum, for suspected mixed infections that might include gram-negative bacteria. Metronidazole is used for infections caused by anaerobic bacteria like Bacteroides or Clostridioides difficile,” he said.

Preventing dysbiosis does not begin and end with the antimicrobial agent, he said. “We think it’s important to remember that many things can cause dysbiosis—not just antibiotics, but also surgery, pain and diet changes. Our approach is to minimize and separate the factors that can cause dysbiosis,” he added. “The risk increases when multiple factors happen at the same time. So, we try to reduce the impact of each factor and avoid having them overlap—by managing pain well before surgery, not making sudden diet changes and avoiding unnecessary antibiotic use.” MeV

For more information:
Kinoshita Y, Niwa H, Ueno T. Minimal disruption of equine gut microbiota by intravenous cephalothin treatment. J Vet Med Sci. 2025;87(6):690-696. doi: 10.1292/jvms.25-0105
https://www.jstage.jst.go.jp/article/jvms/87/6/87_25-0105/_article