JAC Advance Access originally published online on October 24, 2006
Journal of Antimicrobial Chemotherapy 2006 58(6):1307-1308; doi:10.1093/jac/dkl439
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Correspondence |
Bactericidal activity of orally available agents against methicillin-resistant Staphylococcus aureus: authors' response
1 Section of Infectious Diseases, Michael E. Debakey Veterans Affairs Medical Center 2002 Holcombe Boulevard, Houston, TX 77030, USA 2 Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine Houston, TX 77030, USA
*Correspondence address. Section of Infectious Diseases (111G), Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard, Houston, TX 77030, USA. Tel: +1-713-794-7384; Fax: +1-713-794-7045; E-mail: daniel.musher{at}med.va.gov
Keywords: S. aureus , MRSA , trimethoprim/sulfamethoxazole , rifampicin , osteomyelitis , antagonism , antimicrobial activity
Sir,
We thank Hmouda et al.1 for their comments and are pleased that their clinical experience with treating methicillin-resistant Staphylococcus aureus (MRSA) infections correlates nicely with our in vitro study and our own clinical experience. We would however like to comment on the use of trimethoprim/sulfamethoxazole and rifampicin in combination for the treatment of MRSA infections. Our in vitro time–kill studies of trimethoprim/sulfamethoxazole with rifampicin in combination against multiple strains of community- and hospital-acquired MRSA showed the combination to trend towards antagonism in all isolates tested.2 The only evidence that we could find in the literature of possible synergism of trimethoprim/sulfamethoxazole and rifampicin against S. aureus in vivo was for the treatment of S. aureus osteomyelitis. A rabbit model of chronic S. aureus osteomyelitis showed that trimethoprim and rifampicin in combination was more effective in sterilizing bone than either agent alone.3 However, of note, the combination did not prevent development of rifampicin resistance in S. aureus. The authors proposed that this synergy in vivo despite antagonism in vitro was probably a pharmacodynamic effect, with the rifampicin concentrations in bone tissue being much higher relative to the low rifampicin MIC for the infecting strain as compared with trimethoprim.3 Few uncontrolled, non-randomized human studies of S. aureus osteomyelitis associated with foreign bodies showed good cure rates when treated with trimethoprim/sulfamethoxazole and rifampicin in combination.4,5 There have been to-date no randomized, clinical studies for S. aureus infections demonstrating a clinical benefit of the combination as compared with trimethoprim/sulfamethoxazole alone. Despite that, treating the increasing numbers of MRSA skin and soft tissue infections with trimethoprim/sulfamethoxazole and rifampicin in combination seems to be common clinical practice at our and other institutions. We have reviewed the successful experience of Jemni et al.6 with eight patients with MRSA infection treated with the combination of trimethoprim/sulfamethoxazole and rifampicin; of note three had bone infections. However, the overall difference in cure rates between the patients treated with trimethoprim/sulfamethoxazole versus the combination was not statistically significant. We agree with Hmouda et al. that in vitro antagonism does not imply clinical failure of therapy. However, when in vitro data have consistently demonstrated antagonism of trimethoprim/sulfamethoxazole and rifampicin in combination against MRSA, and there is a paucity of clinical data to suggest otherwise (possible exception of foreign-body-associated orthopaedic infections), we feel that it is prudent to avoid the use of the combination until further randomized clinical studies are available.
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References
1 Hmouda H, Ben Salem C, Bouraoui K, et al. (2006) Comment on: Bactericidal activity of orally available agents against methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother 58:203.
2
Kaka AS, Rueda AM, Shelburne SA III, et al. (2006) Bactericidal activity of orally available agents against methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother 58:680–3.
3
Norden CW and Keleti E. (1980) Treatment of experimental staphylococcal osteomyelitis with rifampin and trimethoprim, alone and in combination. Antimicrob Agents Chemother 17:591–4.
4 Sanchez C, Matamala A, Salavert M, et al. (1997) Cotrimoxazole plus rifampicin in the treatment of staphylococcal osteoarticular infection. Enferm Infecc Microbiol Clin 15:10–3.[Medline]
5 Javaloyas de Morlius M and Monreal Portella M. (1999) Oral antibiotic therapy in the adult bacterial osteomyelitis: results after two years of follow-up. Med Clin (Barc) 113:488–9.[Medline]
6 Jemni L, Hmouda H, Letaief A. (1994) Efficacy of trimethoprim-sulfamethoxazole against clinical isolates of methicillin-resistant Staphylococcus aureus: a report from Tunisia. Clin Infect Dis 19:202–3.[Web of Science][Medline]
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