Oral Regimen Temporarily Suppresses Resistant Gut Bacteria.


 

An oral regimen of colistin and neomycin suppresses extended-spectrum beta-lactamase in patients, but the effect of treatment disappeared within 7 days, according to a new study.

There have been attempts to eradicate these resistant bacteria, but most previous research has been uncontrolled or used case studies. “This is the first really methodologically sound and well-controlled study in this area. We tried to improve the evidence base,” Stephan Harbarth, MD, associate professor of infectious diseases and infection control at Geneva University Hospitals in Switzerland, told Medscape Medical News.

This regimen could be used to combat outbreaks and prepare patients for surgery, said Dr. Harbarth, who presented findings here at the 23rd European Congress of Clinical Microbiology and Infectious Diseases.

In the single-center, double-blind, placebo-controlled trial, adults with a rectal swab that tested positive for extended-spectrum beta-lactamase were randomized to 1 of 2 groups. A total 27 patients received colistin (50 mg 4 times daily) and neomycin (250 mg 4 times daily) for 10 days, plus nitrofurantoin (100 mg 3 times daily) for 5 days if they had a positive urine culture at baseline; and 27 patients received placebo.

The researchers conducted cultures (rectal, inguinal, urine) on day 6 of treatment, day 1 after the end of treatment, and day 7 after the end of treatment. The primary outcome was the detection of Enterobacteriaceae by rectal swab at 28 ± 7 days after the end of treatment. When primary outcome data were missing, they were imputed on the basis of the last observation.

There was no significant difference between the 2 groups at 28 ± 7 days after the end of treatment. However, there were differences during and soon after treatment.

Patients in the treatment group were more likely to experience liquid stool than those in the placebo group (25.9% vs 6.9%; = .05). Inguinal Enterobacteriaceae colonization was present in 29 of 58 patients at baseline, whereas urinary colonization was present in 12 patients in the treatment group and 7 in the placebo group. There was no difference between the 2 groups for inguinal or urinary colonization at any point during the study.

In the treatment group, there was no significant change in minimum inhibitory concentration of colistin from baseline to 28 ± 7 days after the end of treatment.

Although the primary end point was not met and the regimen can’t be used for broad-scale control of infection, “it’s an infection-control measure that could be useful for suppression of this multiresistant carriage in the gut flora. In certain situations, like epidemics or prior to high-risk surgery, this could be a valuable intervention,” said Dr. Harbarth.

He pointed out that modifications to the regimen might be more successful. Different agents that are more active in the colon might improve outcome, probiotics could be used, and drug dosages could be refined. It could also be that one of the drugs used — neomycin — was underdosed in the study, Dr. Harbarth added.

“The results were interesting, but sadly disappointing,” session moderator Hilary Humphreys, MD, professor of clinical microbiology at the Royal College of Surgeons in Dublin, Ireland, told Medscape Medical News. This study confirms that “it’s very difficult with a temporary suppression regimen to see permanent eradication in the gastrointestinal tract, because there are huge numbers of bacteria and the physiology and the environment where those bacteria exist is very complex.”

Dr. Humphreys said he agrees that the regimen could be applied to outbreaks and during preparation for major surgery. “I think those are probably its major uses.”

Source: medscape.com