Gram-Negative Hospital Infections Now Showing Resistance to Polymixin B

Alice Goodman

November 06, 2009

November 6, 2009 (Philadelphia, Pennsylvania) — Over the past 2 years, clinicians have come to rely on polymixin B, an older drug that had fallen out of favor, to treat the increasing numbers of hospital infections caused by gram-negative organisms resistant to conventional therapy. Now, however, a study reported here at the Infectious Diseases Society of America 47th Annual Meeting shows a growing trend toward resistance to polymixin B as well. The older drug was one of the few treatment options left in this setting.

"There is a growing concern about gram-negative organisms becoming multiply resistant in hospitalized patients. The percentage of resistant organisms is still low, but it is slowly increasing, which may hamper clinicians' ability to treat the increasing proportion [of] these infections, especially in the [intensive care unit] setting," stated Jason Kessler, MD, from the Columbia University–New York Presbyterian Hospital in New York City. He also noted that increased use of clinical microbiologic testing for these isolates has both cost and resource implications.

Polymixin B is an injectable drug developed in the 1960s and then shelved because of concerns about kidney toxicity. The drug is now back in favor because of the emergence of resistance to newer drugs, Dr. Kessler said. "In our hands, polymixin B has been fairly well-tolerated, but we have little information on how best to use it," he noted.

The study was based on samples of isolates submitted to the microbiology lab at Columbia University Medical Center between 2005 and 2008. The most common source sites were respiratory infections (46%) and urinary tract infections (26%). Nearly 40% of specimens came from the intensive care unit. Specimens growing Klebsiella pneumonia, Acinetobacter baumannii, or Pseudomonas aeruginosa spp. were evaluated for in vitro susceptibility to polymixin B.

A dramatic increase was seen in the number of isolates tested for susceptibility to polymixin B over the 3-year study, "a relatively short time," Dr. Kessler said. In 2005, 239 isolates from 99 patients were tested and 223 were sensitive to the drug. In 2008, 1248 isolates from 416 patients were tested at his hospital, and about 30% of patients (n = 122) harbored resistance to the drug. Over the course of the study period, 74% of isolates tested for susceptibility to polymixin were resistant to at least three other classes of drug, and 32% were resistant to five classes, he said.

"Polymixin B may be the only...drug that can be used to treat these organisms," he added.

In 2008, 6% of the isolates tested were resistant to polymixin B, representing a 50% increase from 2006.

Threat Perceived

"We may be in danger of losing even the limited antibiotics we have to treat some of our most resistant gram-negative organisms," said Neil Fishman, MD, from the Hospital of the University of Pennsylvania, Philadelphia.

Even with organisms that are susceptible to polymixin B, there is little information about how to use the drug, he continued. "When I was in medical school, all I was taught about polymixin B was that you'd never have to use it. Then 2 years ago, I had to use it with little guidance. Some centers have a short supply of this drug, and with increasing use, it may be more difficult to obtain," he said, raising another concern about sufficient supply.

Dr. Kessler and Dr. Fishman have disclosed no relevant financial relationships.

Infectious Diseases Society of America 47th Annual Meeting: Abstract 903. Presented October 31, 2009.