MRSA & PVL: A Nasty Package

Abstract & Commentary

Synopsis: A clonally related strain of S aureus that produces the Panton-Valentine leukocidin associated with severe cutaneous and pulmonary infections has been detected in a number of regions of France.

Source: Dufour P, et al. Community-acquired methicillin-resistant Staphylococcus aureus infections in France: Emergence of a single clone that produces panton-valentine leukocidin. Clin Infect Dis. 2002;35:819-824.

Dufour and colleagues in Lyon and Nantes examined 593 isolates of S aureus that had been sent to their reference laboratory from throughout France for detection of toxin production. Eighty three (14%) of these were Panton-Valentin leukocidin (PVL)-positive and 14 of these were also methicillin-resistant. The median age of the patients was 13.5 years (range, 2.5 months to 69 years). Half the patients had cutaneous infections and 2 had bacteremic necrotizing pneumonia. Except for the presence of genes encoding LukF-LukD leukocidin, which were also present in all 14, genes for a wide range of additional toxins, including toxic shock and exfoliative toxins, were not detected. Genetic analysis indicated that the 14 isolates were related.

Comment by Stan Deresinski, MD, FACP

PVL is a bicomponent toxin produced by some strains of S aureus that has been associated with community-acquired primary skin infections and severe necrotizing pneumonia. It is not, in contrast, associated with skin infections occurring secondary to cutaneous trauma, nosocomial pneumonia, or endocarditis.1,2 The severity of illness associated with PVL-producing strains of S aureus can be assessed from a study of community-acquired pneumonia due to this organism. In that study, a comparison of 16 cases of PVL-positive S aureus pneumonia with 36 PVL-negative cases demonstrated an association of the former with prior influenza-like illness, younger median age (14.8 vs 70.1 years), greater severity, and higher mortality at 48 hours (63% vs 94%).2

Thus, it appears to be a virulence factor, allowing enhanced infectivity and the severity of S aureus infection in the absence of other promoters of invasion. In contrast, the LukF-LukD leukocidin, also detected in this study, is not highly associated with similar infections.

Exposure of leukocytes to PVL leads to formation of transmembrane octameric pores and release of a variety of inflammatory mediators, and intradermal injection of PVL in rabbits is associated with severe inflammatory lesions and skin necrosis.3-5 Neutrophils are killed as the result of lysis by the toxin. Thus, these important effector cells, while contributing to the inflammatory response at the site of infection, are eliminated from participation in eradicating the infection.

Dufour et al report that their 14 related strains of PVL-producing MRSA were isolated from throughout France and were epidemiologically unrelated. This raises the fear that this "superadapted" strain containing an ominous confluence of an antibiotic resistance gene and a toxin gene may already be widespread there and, perhaps, elsewhere.

Dr. Deresinski, Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor of Infectious Disease Alert.

References

1. Dinges MM, et al. Exotoxins of Staphylococcus aureus. Clin Microbiol Rev. 2000;12:16-34; Lancet. 2002;359(9308):753-759.

2. Gillet Y, et al. Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet. 2002;359: 753-759.

3. Miles G, et al. Subunit composition of a bicomponent toxin: Staphylococcal leukocidin forms an octameric transmembrane pore. Protein Sci. 2002;11:894-902.

4. Konig B, et al. Effects of Staphylococcus aureus leukocidins on inflammatory mediator release from human granulocytes. J Infect Dis. 1995;171:607-613.

5. Ward PD, Turner WH. Identification of Panton-Valentine leukocidin as a potent dermonecrotic toxin. Infect Immun. 198;28:393-397.