Correspondence

Methicillin-Resistant Staphylococcus aureus Infections

N Engl J Med 2007; 357:2090November 15, 2007

Article

To the Editor:

In his review of skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA), Daum (July 26 issue)1 cites a study2 indicating that intravenous trimethoprim–sulfamethoxazole (TMP-SMX) is significantly less effective than vancomycin for the treatment of serious S. aureus infections. However, in this randomized, double-blind, comparative trial of TMP-SMX and vancomycin, therapeutic failures occurred only in patients with methicillin-susceptible S. aureus (MSSA) infections. TMP-SMX was successful in treating all MRSA infections, including tricuspid-valve endocarditis. Clinical failures commonly occurred with MSSA tricuspid-valve endocarditis; otherwise, the cure rates with TMP-SMX and with vancomycin were similar. On the basis of the results of this study, vancomycin may be superior for MSSA infections; however, the same cannot be concluded for MRSA infections. Although the currently available clinical data for community-associated MRSA skin infections are sparse, in this era of an increasing incidence of MRSA infection and concern about the variable efficacy of vancomycin, TMP-SMX may be a useful alternative in selected cases.

Fredrick M. Abrahamian, D.O.
Gregory J. Moran, M.D.
Olive View–UCLA Medical Center, Sylmar, CA 91342
fmasjc@ucla.edu

2 References

1. 1

   Daum RS. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. N Engl J Med 2007;357:380-390[Erratum, N Engl J Med 2007;357:1357.]
   Full Text | Web of Science | Medline

2. 2

   Markowitz N, Quinn EL, Saravolatz LD. Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection. Ann Intern Med 1992;117:390-398
   Web of Science | Medline

Author/Editor Response

The suggestion by Abrahamian and Moran that TMP-SMX may be an alternative parenteral therapy for invasive MRSA infections may, in selected cases, turn out to be correct after additional study. At the present time, I continue to urge caution. Markowitz et al.1 showed that parenteral TMP-SMX was inferior to vancomycin for invasive S. aureus infections, but a subanalysis showed that it was equally efficacious for invasive MRSA infections. They acknowledged that the power to detect differences between methicillin-susceptible and methicillin-resistant infections was not large. The biologic plausibility of better efficacy for MRSA infections is unclear. The resistance mechanisms for methicillin and TMP-SMX have nothing in common; one would not anticipate cross-resistance. The MRSA and MSSA isolates that Markowitz et al. studied did not vary in their TMP-SMX susceptibility. Although MRSA infections have sometimes proved more difficult to treat with a given antibiotic than MSSA infections — a difference without an obvious explanation — the converse has not been documented. In addition, the MRSA infections that Markowitz et al. studied occurred before the epidemic of community-acquired MRSA infections; the genetic backgrounds of the isolates may have been different from those one would encounter now. Alternatives to vancomycin, such as linezolid, tigecycline, and daptomycin, have become available since 1992, although as I mentioned in my article, they also have their limitations.

Robert S. Daum, M.D.
University of Chicago, Chicago, IL 60637

1 References

1. 1

   Markowitz N, Quinn EL, Saravolatz LD. Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection. Ann Intern Med 1992;117:390-398
   Web of Science | Medline