COMMENTARY

Community-Acquired Pneumonia: March 2006

John G. Bartlett, MD

Disclosures

March 08, 2006

In This Article

Methicillin-Resistant Staphylococcus aureus

Micek ST, Dunne M, Kolleff MH. Pleuropulmonary complications of Panton-Valentine leukocidin-positive community-acquired methicillin-resistant Staphylococcus aureus: importance of treatment with antimicrobials inhibiting exotoxin production. Chest. 2005;128:2732-2738. Four patients were seen at Barnes-Jewish Hospital, St. Louis, Missouri, with severe necrotizing pneumonia, empyema, and/or adult respiratory distress syndrome (ARDS) complicating pneumonia. Patients had positive cultures of blood (3), respiratory secretions (3), or empyema fluid (1) for methicillin-resistant Staphylococcus aureus (MRSA) that were positive for Panton-Valentine leukocidin (PVL). Details of the cases are provided in Table 6 .

With regard to treatment, all patients received vancomycin treatment initially, but 3 failed to respond, including 2 who had persistent bacteremia despite at least 48 hours of vancomycin. Substitution with linezolid or clindamycin yielded good results in these cases.

Conclusion: Pulmonary infections involving PVL-positive MRSA should be treated with antibiotics that inhibit exotoxin production.

Comment: The study authors point out that the PVL-producing strains of MRSA (primarily USA 300 and 400 strains, according to the US Centers for Disease Control and Prevention [CDC] classification) should be treated with antimicrobial agents that inhibit protein synthesis, including PVL. They also point out that alpha toxin, which is encoded by the human leukocyte antigen (HLA) gene, is a major virulence factor of S. aureus.[12] Prior studies show that vancomycin has no effect on this gene in subinhibitory doses, but low concentrations of clindamycin reduced HLA expression by 98%.[13] Other studies showed that clindamycin inhibits the production of toxic shock syndrome toxin 1 (TSST-1).[14] There is justifiable concern about the "disassociated cross-resistance" of clindamycin when S aureus strains are resistant to macrolides, but this can easily be determined by the disk-diffusion test ("D-test") in the laboratory. Thus, the recommendation for serious infections involving PVL-positive S aureus is clindamycin or linezolid; linezolid would be preferred in cases in which there is resistance in vitro to clindamycin or inducible resistance according to the D-test. The potential of linezolid to inhibit the toxin production of S aureus in subinhibitory concentrations has been well demonstrated in vitro.[15]

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