Combined analysis of two studies comparing the drugs appears online in the journal Intensive Care Medicine and is expected to be published in print March 8. The paper represents the largest group of patients ever studied with this form of pneumonia, called ventilator-associated pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). Once primarily associated with intensive care units, the strain has become increasingly common in the general population, particularly in children.
"The reality is medicine is falling behind infectious organisms," says principal investigator Marin H. Kollef, M.D., associate professor of medicine. "Our results are encouraging, though, because they suggest linezolid succeeds in penetrating the lungs and eradicating a particularly resilient form of bacterial infection."
Pharmacia Corp., now part of Pfizer Inc., funded the research. Both studies included in the analysis were "double-blind," meaning neither the treating physicians nor the patients knew which medication was being administered.
Hospitalized patients often develop bacterial infections such as pneumonia. Individuals using ventilators for breathing support are particularly vulnerable, because bacteria can enter the lungs through the breathing tube. Ventilator-associated pneumonia is estimated to result in about 1.75 million additional hospital days each year.
Further complicating the issue, many bacteria have become resistant to medicine's standard arsenal of antibiotic treatments. MRSA is one of the more common and lethal forms of drug-resistant pneumonia.
One antibiotic still effective in killing bacteria is vancomycin, which has been used for the past decade to treat pneumonia. But evidence suggests the drug does not properly infiltrate the lungs and therefore may not be the most effective treatment.
"Vancomycin is a difficult drug to use for the treatment of pneumonia," Kollef explains. "You obviously want a drug to be able to reach the site of infection. Because vancomycin does not fully penetrate the lungs, it is necessary to constantly monitor blood levels of the drug, and even then the correlation between those levels and the amount of drug that reaches the lungs is unclear."
In contrast, linezolid is smaller, enabling it to penetrate farther and more effectively target bacterial infections deep within the lungs. According to Kollef, there is no need to monitor blood levels with linezolid therapy, and there are fewer known side effects than with vancomycin.
Kollef's team previously published the first two controlled studies comparing the two drugs in hospital-associated pneumonia. They randomly assigned patients to receive either linezolid or vancomycin. In their current paper, the team combined data from those two studies and analyzed results from the 544 patients who had ventilator-associated pneumonia.
Linezolid was about 15 percent more effective in eradicating the infection than vancomycin (49 percent versus 34 percent), and overall survival rates in this population were marginally better with linezolid compared with vancomycin.
The most striking difference appeared when the team separately analyzed results from the subset of patients with MRSA. In this group, linezolid was more than 40 percent more effective in curing the infection (60 percent were cured with linezolid compared to 22 percent with vancomycin). Patients treated with linezolid were more than 22 percent more likely to survive than those given vancomycin (84 percent survived with linezolid versus 62 percent with vancomycin).
"The main downside about linezolid is that it's more expensive than vancomycin, so one has to balance the cost against the potential improved efficacy," Kollef says. "Based on our findings so far, I believe the cost is outweighed by the benefits when treating patients with MRSA pneumonia."
Kollef's team plans to confirm these results in a larger group of MRSA patients. They also will examine whether higher doses of vancomycin improve the drug's efficacy in this population.
Kollef MH, Rello J, Cammarata SK, Croos-Dabrera RV, Wunderink RG. Clinical cure and survival in Gram-positive ventilator-associated pneumonia: retrospective analysis of two double-blind studies comparing linezolid with vancomycin. Intensive Care Medicine, March 8, 2004.
Funding from Pharmacia Corp., now part of Pfizer Inc, supported this research.
The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Journal
Intensive Care Medicine