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Linezolid has benefits in MRSA nosocomial pneumonia: study

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – For nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA), linezolid is more effective and better tolerated than the gold standard vancomycin, according to a randomized controlled trial.

MRSA accounts for 10% to 40% of cases of healthcare-associated (HCAP), hospital-acquired (HAP) and ventilator-acquired (VAP) pneumonia and exacts a high toll in terms of health care dollars, illness and death.

Dr. Richard G. Wunderink from Northwestern University Feinberg School of Medicine in Chicago, Illinois and colleagues enrolled 1,184 patients with HAP or HCAP MRSA pneumonia in their study.  They assessed the efficacy, safety and tolerability of fixed-dose linezolid (600 mg every 12 hours) compared with vancomycin (15 mg/kg every 12 hours).

According to a report online January 12 in Clinical Infectious Diseases, treatment was given for 7 to 14 days, continuing to 21 days if bacteremia was documented. Unlike prior studies, vancomycin doses were adjusted based on trough levels.

In the per-protocol population, significantly more linezolid-treated than vancomycin-treated patients were clinically cured (95 of 165 [58%] vs 81 of 174 [47%]) at the end of the study, defined as 7 to 30 days after the end of treatment).  Microbiologic responses paralleled clinical outcomes and MRSA clearance at the end of treatment was 30% greater with linezolid than with vancomycin.

The fact that the vancomycin dose was optimized suggests “true differences in efficacy, rather than potentially inadequate vancomycin dosing,” the investigators say.

Despite better clinical and microbiologic responses with linezolid, there were no statistically significant differences in mortality rates at 60 days (16% with linezolid and 17% with vancomycin).

There were also no significant differences in the incidence of adverse events, except for nephrotoxicity, which was more than twice as common with vancomycin.

In a commentary published with the study, Dr. Antoni Torres from the Pneumology Department, Hospital Clinic of Barcelona in Spain notes that the risk of renal failure with vancomycin is a “strong argument in favor” of linezolid given its better demonstrated efficacy.

“In addition, many HAP and VAP patients may receive aminoglycosides for empirical or definitive treatment, and this may increase the risk of developing renal failure.”

Dr. Torres notes that current recommendations from the Infectious Diseases Society of America and American Thoracic Society on linezolid and vancomycin placed these two antibiotics at similar a level; however, linezolid is preferred in case of baseline renal failure or in nonresponding patients.

“Now, with all of the information that we have in our possession, the recommendations regarding linezolid must be reconsidered and probably expanded,” Dr. Torres writes.

Still, the researcher says the higher cost of linezolid and potential appearance of outbreaks of MRSA resistant to the antibiotic as recently described cannot be disregarded.

The study was funded by Pfizer Inc, which manufactures linezolid. The authors of the study and editorial have disclosed financial relationships with Pfizer. A complete list of individual author disclosures can be found with the original articles.


Linezolid in Methicillin-Resistant Staphylococcus aureus Nosocomial Pneumonia: A Randomized, Controlled Study

Clin Infect Dis 2012. Published online January 12, 2012.