SAN FRANCISCO — Linezolid is being used too often for staphylococcal infections when other options are available, William E. Dismukes, M.D., said at the annual meeting of the American College of Physicians.
For example, linezolid is being used increasingly often for treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia.
The drug is approved for the treatment of hospital-acquired MRSA pneumonia, and its use may be increasing largely in response to an article published in 2003 in the journal Chest, said Dr. Dismukes, director of the division of infectious diseases at the University of Alabama, Birmingham.
In the paper, the authors combined data from two separate studies in which vancomycin and linezolid were used. They concluded that survival and clinical cure rates were both better with linezolid.
The survival rate was reported to be 80% with linezolid versus 63% with vancomycin. The clinical cure rate, defined as resolution of signs and symptoms at the end of treatment with improvement or no change in x-rays, was 59% for linezolid and 35% for vancomycin (Chest 2003;124:1789–97).
But not everyone is convinced, including Dr. Dismukes. “This paper has generated all kinds of controversy,” he said.
In his opinion, the analysis is less than definitive because it included groups from two different trials, and there were only 160 MRSA patients. “You do get higher lung-tissue levels with linezolid,” Dr. Dismukes said. “But I am skeptical.”
Another use for linezolid that is becoming increasingly common is staphylococcal endocarditis. There are anecdotal reports of successful treatments, but no clinical trial data. In contrast, much experience and data are available on use of nafcillin and gentamicin, or vancomycin with or without gentamicin, Dr. Dismukes said.
“I think we use too much of this drug for indications such as this for which there [are] no data,” he said.
Linezolid is approved for complicated and uncomplicated soft tissue infections, both methicillin resistant and methicillin susceptible. But community-acquired MRSA infections are different from hospital-acquired MRSA, and so, for uncomplicated infections, cost is an issue.
Hospital-acquired Staphylococcus aureus that is methicillin resistant most often has a resistance pattern that includes resistance to other non-β-lactam antibiotics, because the gene that confers methicillin resistance most commonly comes as part of a cassette chromosome that contains other resistance determinants. But that is not generally true of community-acquired MRSA, which is usually susceptible to doxycycline, trimethoprim/sulfamethoxazole, and quinolones, Dr. Dismukes said.
A single course of linezolid can cost over $1,000, whereas in some of these cases trimethoprim/sulfamethoxazole would do, he said.
Moreover, adverse events do occur. Linezolid can cause bone marrow suppression, neuropathies with long-term use, and serotonin syndrome in patients on drugs such as selective serotonin reuptake inhibitors.