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Hospitals Report Linezolid Resistance

Kate Traynor

Researchers in Chicago urge that clinicians test the susceptibility of vancomycin-resistant enterococci to linezolid before prescribing this new antimicrobial to patients.

The researchers made their recommendation after studying the medical course of five patients infected with vancomycin-resistant Enterococcus faecium (VREF) who received linezolid but then showed signs of emergent resistance to treatment. Four of the five patients who harbored linezolid-resistant VREF were transplant recipients, and the fifth had been hospitalized for repair of an aortic aneurysm. Resistance arose after about three to six weeks of therapy with linezolid, which is used to treat VREF infections.

The five patients had been treated at three Chicago area hospitals in the last three months of 2000. Since then, those hospitals test all isolates of VREF for susceptibility to linezolid, the researchers reported in the April 14 issue of Lancet (PDF). At the time the researchers submitted their report for publication, one of the 45 hospital patients infected with VREF had been found to harbor a linezolid-resistant isolate—a frequency about twice as high as that cited by linezolid's manufacturer during a compassionate-use program for the antimicrobial.

Two of the five original patients responded well to linezolid therapy despite the development of bacterial resistance to the drug, the researchers said. The other three patients, two of whom later died, were switched to quinupristin–dalfopristin after their infection sites were found to harbor linezolid-resistant bacteria. None of the linezolid-resistant bacteria cultured from the patients became resistant to quinupristin–dalfopristin.

Linezolid, manufactured by Pharmacia Corp. under the brand name Zyvox, was approved by the Food and Drug Administration (FDA) a year ago and is the first oxazolidinone available for use in this country. In response to the Lancet article, Pharmacia issued a press release stating that the recent findings were in line with those encountered during clinical trials of Zyvox. The company described the patients in the Lancet article as having unusually complicated infections and other illnesses that led to the emergence of linezolid resistance.

Pharmacia also noted that VREF is the only bacterial strain in which linezolid resistance has ever been confirmed and stressed that the antimicrobial is an important product for treating VREF infections.