FDA Warns About Risk of Linezolid (Zyvox) for Septicemia

ROCKVILLE, Md., March 20 -- The FDA has issued a safety alert for linezolid (Zyvox) after clinical trial data the suggested excess mortality when the drug was used to treat Gram-negative septicemia.

In an open-label study that compared linezolid to vancomycin, oxacillin, or dicloxacillin for treatment of intravascular catheter-related bloodstream infections, the agency said, "patients treated with linezolid had a higher chance of death than did patients treated with any comparator antibiotic, and the chance of death was related to the type of organism causing the infection."

There was no increased risk associated with Gram-positive infections, but there was higher mortality when linezolid was used to treat Gram-negative infections, both Gram-positive and -negative organisms, or those who had no infection when entering the study.

One hundred and fifty-one of the 363 patients randomized to linezolid had bacteremia as did 136 of the 363 patients treated with comparator antibiotics. With 84 days of follow-up, there were 78 deaths in the linezolid arm versus 58 in the comparator arm.

In each arm 37 patients with Gram-positive infections died.

At baseline 34 patients in the linezolid arm and 32 patients in the comparator arm had Gram-negative bacteremia. An additional 28 patients in the linezolid arm and 17 patients in the comparator arm developed Gram-negative bacteremia during treatment. The greatest imbalance occurred during treatment and within seven days following discontinuation of study drug with 43 of 363 (12%) deaths in the linezolid arm versus 22 of 363 (6%) in the comparator arm.

Linezolid is approved for the treatment of vancomycin-resistant Enterococcus faecium infections, nosocomial pneumonia, community-acquired pneumonia, uncomplicated skin and skin structure infections, and complicated skin and skin structure infections, including diabetic foot infections, without concomitant osteomyelitis.

Linezolid is not approved for the treatment of catheter-related bloodstream infections, catheter-site infections, or for the treatment of infections caused by Gram-negative bacteria. If infection with Gram-negative bacteria is known or suspected, appropriate therapy should be started immediately. The FDA is evaluating the new study along with other information about linezolid.

The FDA said the alert was based on the agency's preliminary analysis of data concerning the drug, and the agency has not reached a final conclusion.