PHILADELPHIA — An old antibiotic — one of the last drugs still active against many bacteria — is facing rapidly developing resistance, a researcher said here.
Polymyxin B, which fell out of favor because of toxicity after it was developed in the 1960s, is becoming the treatment of last resort for some drug-resistant Gram-negative bacteria, according to Jason Kessler, MD, of Columbia University in New York.
But a retrospective analysis of clinical isolates tested at his institution showed that resistance to polymyxin B, while still low, increased 50% between 2006 and 2008, he said at the annual meeting of the Infectious Diseases Society of America.
The drug is an injectable agent and member of a class called polymyxins that also includes colistin, Kessler told reporters. They were left on the shelf because of kidney toxicity.
“Our clinical experience has been that the drug is relatively well-tolerated,” Kessler said, perhaps because several decades of progress have made it easier to manage the kidney issues.
Precisely because it has not been widely used, polymixin B is often still potent against bacteria, such as Klebsiella pneumoniae and Pseudomonas aeruginosa — that are resistant to many other classes of antibiotics. This has led to wider use of the old antibiotic, Kessler said.
In an attempt to measure that use, Kessler and colleagues checked to see how often clinical isolates were tested for resistance to polymyxin B at Columbia University Medical Center from 2005 through 2008.
Such testing, he said, could be considered a proxy for actual use, which is harder to measure. But it also offers information about the change in resistance over time, he said.
In 2005, Kessler said, the hospital tested 239 isolates from 99 patients and found that the vast majority of samples — 223 — were sensitive to the drug.
But in the following years, while the number of patients grew steadily, the proportion of resistant strains also grew sharply: In 2006, 937 isolates from 319 patients were tested, and 66 were resistant. In 2007, 1,210 isolates were tested from 382 patients and 138 were resistant. In 2008, 1,248 were tested, from 416 patients, and 122 were resistant.
Over the study period, Kessler and colleagues reported, 74% of the isolates tested for polymyxin susceptibility were resistant to at least three other classes of drugs and 32% to five classes.
The increasing use of polymyxin is not an isolated phenomenon, according to Neil Fishman, MD, of the University of Pennsylvania, who was not part of the study but who moderated a news conference at which it was discussed.
Fishman said his medical training in the 1980s included almost no mention of the drugs, except for the warning: “they’re toxic and you’ll never have to use them.”
“Starting two years ago, I did have to use them,” he said, adding that he and colleagues are still trying to learn how to use the drugs and to manage the toxicity.
An additional issue, he said, is that some of the drugs are in short supply. “Because they are old antibiotics, there aren’t a lot of companies making them and their use in increasing,” he said, “and it has become increasingly difficult to obtain some of the polymyxins for clinical use.”
The researchers did not report any external support or any conflicts.