Linezolid Superior to Vancomycin?
Abstract & Commentary
Synopsis: Randomized trial data suggest that linezolid is superior to vancomycin in the treatment of nosocomial MRSA pneumonia.
Source: Wunderink RG, et al. Linezolid vs vancomycin: Predictors of survival in patients with MRSA nosocomial pneumonia. Poster 801, 99th International Conference, American Thoracic Society, Seattle, WA. May 2003.
In this poster presentation, data from 2 global, phase III, randomized, double-blind linezolid (LZD) trials in patients with Gram-positive nosocomial pneumonia (NP) were analyzed retrospectively to identify significant (P < .05) independent predictors of survival. In this study, 1019 patients with Gram-positive ventilator-associated nosocomial pneumonia were randomized to receive either intravenous LZD (600 mg every 24 hours) or vancomycin (1 gram every 24 hours adjusted for renal status). Therapy was for 7-21 days with aztreonam added if Gram-negative coverage was necessary. A total of 160 patients with MRSA NP were treated, and these patients were analyzed in depth. The data demonstrated that the overall survival in MRSA patients was 80% (60/75) for linezolid, compared with 63.5% (54/85) for vancomycin (P = .022). Linezolid was a significant independent predictor of survival identified by logistic regression, with an odds ration of 2.2 (P = .05).
At the conference, Dr. M.H. Kollef was quoted as saying that "clinicians should consider [linezolid] as an appropriate component of initial therapy." He also stated that although the cost of linezolid therapy is approximately $80 more per day than vancomycin therapy, the fact that linezolid does not require renal monitoring and is available in oral form greatly reduces any cost disadvantage.
|
Table |
|
| Some Potential Interacting Drugs | |
|
* identifies a significant reaction |
|
| Atomoxetine | * Heterocyclic antidepressants |
| * Beta-blockers | Levodopa |
| Brimonidine | * Local anesthetics |
| Bupropion | Meperidine |
| Buspirone | Methylphenidate |
| Caffeine | Modafinil |
| Cocaine | * Monoamine Oxidase Inhibitors |
| Cocaine | (MAOIs) |
| Cyclobenzaprine | Nefazodone |
| Dexmethyphenidate | procarbazine |
| Dextromethorphan | Reserpine |
| Duloxetine | * Selective Serotonin Reuptake |
| Duloxetine | Inhibitors (SSRIs) |
| Entacapone | * Serotonin-receptor agonists |
| Ethanol | St. John’s Wort, |
| Ethanol | Hypericum perforatum |
| Foods (containing tyramine | Hypericum perforatum |
| or caffeine) | * Sympathomimetics |
| Furazolidone | Tolcapone |
| * General anesthetics | Tramadol |
| Guanadrel | * Tricyclic antidepressants |
| Guanethidine | Tryptophan, 5-Hydroxytryptophan |
| Guarana | Venlafaxine |
Comment by Thomas G. Schleis, MS, RPh
While the data are compelling and may indicate a niche for linezolid in this patient population, we should be concerned with replacing vancomycin with linezolid as a first-line therapy in other patient populations. While significant side effects to vancomycin are fairly rare, the potential hematological side effects of linezolid are more worrisome. Bone marrow suppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported in patients receiving linezolid, especially when administered for longer than 14 days.1 Linezolid is also a nonselective inhibitor of monoamine oxidase (MAO). This creates the potential for hypertensive crisis if linezolid is combined with alcohol, excessive caffeine, or certain foods or beverages. A recent case that resulted in death was reported in a previous edition of Infectious Disease Alert.2 A list of some food and drugs that may cause a drug interaction with linezolid is shown in the Table.
The potential for antimicrobial resistance is another reason to be concerned over indiscriminate use of linezolin. Given that it is one of the few options in treating some vancomycin-resistant organisms, if resistance were to develop against linezolid, the treatment options would diminish.
On a final note, while the potential side effects of vancomycin are well known, the extent of potential side effects to linezolid is not yet well established. A recent report of possible teeth discoloration from linezolid therapy in an 11-year-old,3 while certainly not a serious side effect, reminds us that this drug is relatively new and that other unknown side effects may be discovered. We should continue with a strategy of cautious use of linezolid and reserve it for those instances where it truly is the most appropriate antibiotic.
Dr. Schleis is Director of Pharmacy Services Infections Limited Tacoma, WA Section Editor, Pharmacology.
References
1. Linezolid Package Insert. Pharmacia and Upjohn Company, Kalamazoo, Mich.
2. Bernard L, et al. Serotonin syndrome after concomitant treatment with linezolid and citalopram. Clin Infect Dis. 2003;36:1197.
3. ISMP Adverse Drug Reactions. Tooth discoloration with linezolid. Hospital Pharmacy. 2003;38:633.
Randomized trial data suggest that linezolid is superior to vancomycin in the treatment of nosocomial MRSA pneumonia.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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