MRSA Article

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http://www.medscape.com/viewarticle/455936

Linezolid May Provide Survival Advantage Over Vancomycin in MRSA

Pneumonia

Peggy Peck

Medscape Medical News 2003. © 2003 Medscape May 20, 2003 (Seattle) —

In phase III studies, linezolid demonstrated comparability with

vancomycin for treatment of gram-positive nosocomial pneumonia, but a

post-hoc subset analysis suggests that linezolid is superior to

vancomycin for treatment of methicillin-resistant Staphylococcus aureus

(MRSA) pneumonia, according to results released Monday.

Lead author Wunderick, MD, director of research at Methodist

University Hospital and clinical associate professor of medicine at the

University of Tennessee, both in Memphis, said that linezolid treatment

significantly improves survival in patients with MRSA. " Compared to

vancomycin, patients treated with linezolid were twice as likely to

survive, " he said at a press conference here sponsored by the American

Thoracic Society (ATS). The paper was presented during a poster session

at the ATS 99th International Conference. Dr. Wunderick went so far as

to say that for some patients — notably those with renal complications

— linezolid should be considered as first-line therapy.

That is " a major statement to make for such a new drug, " said Syed

Rizvi, MD, a pulmonologist and critical care fellow at North Shore

University Hospital in Manhasset, New York. Dr. Rizvi was not involved

in the study. " This is a new drug, and it is an expensive drug. We would

not consider using it as first-line therapy without evidence from a

large prospective study, " he said.

Linezolid, marketed as Zyvox, received U.S. Food and Drug Administration

(FDA) approval in April 2000. Dr. Wuderick told Medscape that linezolid

costs " about $100 or so a day compared to vancomycin, which costs only a

few dollars a day. "

Still, " it is hard to argue with mortality figures, " said Dr. Wuderick.

Linezolid is the first FDA-approved member of a new class of antibiotics

known as oxazolidinones. It is a bacteriostatic agent indicated for the

treatment of nosocomial infections involving gram-positive organisms

including MRSA, multidrug-resistant strains of Streptococcus pneumoniae,

and vancomycin-resistant Enterococcus faecium (VRE). Dr. Wuderick and

colleagues analyzed data from 160 MRSA patients with nosocomial

pneumonia (NP). Patients were enrolled in one of two phase III studies

that compared linezolid with vancomycin for treatment of gram-positive

NP.

Patients received either linezolid 600 mg twice daily or vancomycin 1 g

adjusted for renal status intravenously every 12 hours for 7 to 21 days.

" In treatment regimens, the length of therapy is probably too long.

Typically, linezolid treatment should be for 7 to 10 days and with

vancomycin if there is no response by 14 days, that is probably a

treatment failure, " Dr. Wuderick said.

Patients received aztreonam as needed for gram-negative coverage. After

adjusting for age, single or multilobe NP, pleural effusion, bacteremia,

mechanical ventilation, baseline bilirubin and creatine levels, baseline

cardiac, diabetic, hepatic, oncologic, renal, respiratory, and vascular

comorbidities as well as APACHE-II scores, linezolid treatment was a

significant independent predictor of survival in patients with MRSA NP,

with an odds ratio of 2.2 (P = .05), said Wunderick.

" There are a couple of possible explanations for this finding, " said Dr.

Wunderick. " First, vancomycin is associated with renal toxicity, so in

patients at risk for renal problems it may be underdosed. Linezolid has

no association with renal toxicity. "

But he said the more important mechanism may be the greater lung

penetration seen with linezolid. " Only about one sixth of the vancomycin

in the blood makes it into the lungs, while the concentration of

linezolid in the lungs is twice the level found in the blood. " While

both theories are plausible, Dr. Rizvi reiterated his concern that the

survival benefit is based on a " retrospective, post-hoc analysis, " which

is not a solid basis for clinical decisions, he said.

ATS 99th International Conference: Abstract P-801. Presented May 20,

2003.

Becki

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