Antibiotic-resistant bacteria strike drug of last resort

Effective 1960s-era medicine shows first signs of failing in some infections

PHILADELPHIA — Little-known drugs dating from the 1960s that have proved useful against stubborn bacterial infections are showing the first signs of falling prey to bacterial resistance, a study presented October 30 at a meeting of the Infectious Diseases Society of America shows.

Polymyxins are antibiotics that were developed and approved more than 40 years ago, but which fell out of favor because they showed some kidney toxicity. But with the ability to monitor kidneys closely, the drugs have made a quiet return to use in the past five years as one of the few medications that doctors can rely on to knock out certain hospital-acquired infections that are impervious to front line antibiotics, says Jason Kessler,an infectious disease physician at Columbia University Medical Center. Polymyxins fend off a broad category of gram-negative microbes that opportunistically infect the lungs, surgery sites, the urinary tract and catheter sites, often hitting patients who are in the intensive care units of hospitals.

Kessler and his colleagues analyzed bacterial samples from more than 1,000 patients between 2005 and 2008 at New York Presbyterian Hospital who had been treated for these kinds of infections. The review found that 6 percent of infections were resistant to polymyxin B, which along with polymyxin E (Colistin), is one of two polymyxins approved for use.

What’s more, incidence of bacterial resistance to polymyxin B doubled from 2006 to 2008, says Kessler, who presented the findings. The resistant bacteria were Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. These microbes show up in most large hospitals, Kessler says.

Neil Fishman, an infectious disease physician at the University of Pennsylvania hospital in Philadelphia, describes the recent history of polymyxins as an example of how ever-changing microbes can send medical care lurching to and fro.

“These are old antibiotics,” he says. Polymyxins work like detergents, degrading the bacterial cell wall. This harshness also accounts for their kidney toxicity in people. That makes them drugs of last resort. “I was told I would never have to use them, back in med school. But starting two years ago, I did have to use them,” Fishman says. “And now we’re seeing increased resistance to them.”

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