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Oral Trimethoprim-Sulfamethoxazole for S. aureus and MRSA Osteomyelitis
Brad Spellberg Harbor-UCLA Medical Center Torrance, CA Trimethoprim (TMP) penetrates bone at approximately 50% of serum levels, while sulfamethoxazole penetration is somewhat lower (15%) (1). Serum concentrations of TMP-SMX are high (especially the sulfamethoxazole component). At a dose of 1 double strength (DS) BID of TMP-SMX, the concentration will exceed the MICs of most S. aureus isolates. In general, TMP-SMX should be dosed at about 7.5-10 mg/kg/d of TMP, or about the equivalent of 2 DS BID for a 70 kg adult. At these doses, bone concentrations are manyfold above the MIC of most S. aureus isolates. From a PK-PD perspective, TMP-SMX is a rational choice for treating S. aureus bone infections. A number of retrospective studies report the use of TMP-SMX for Staphylococcus osteomyelitis in adults (2-6). High cure rates were reported including MRSA osteomyelitis, especially when surgical debridement was used and rifampin was added to the TMP-SMX. Anecdotally, we have successfully treated chronic osteomyelitis in adults with TMP-SMX at 7.5 to 10 mg/kg/d. Rifampin is often added although drug interactions may limit its use for adults with chronic osteomyelitis, who are often on drugs that are hepatically-metabolized. Duration of oral therapy is individualized. In general, for adults with chronic osteomyelitis we treat for 6-12 weeks. Serial MRIs and C-reactive protein (or ESRs) are used to assess response to therapy and decision for terminating antibiotics. References 1. Saux MC, et al. Bone diffusion of trimethoprim and sulfamethoxazole high pressure liquid chromatography (HPLC) (author's transl). Pathol Biol (Paris) 1982;30:385-8. [PubMed] 2. Javaloyas de Morlius M, Monreal Portella M. Oral antibiotic therapy in the adult bacterial osteomyelitis: results after two years of follow-up. Med Clin (Barc) 1999;113:488-9. [PubMed] 3. Stein A, Bataille JF, Drancourt M, Curvale G, Argenson JN, Groulier P, Raoult D. Ambulatory treatment of multidrug-resistant Staphylococcus-infected orthopedic implants with high-dose oral co-trimoxazole (trimethoprim-sulfamethoxazole). Antimicrob Agents Chemother. 1998;42:3086-91. [PubMed] 4. de Barros JW, Calapodopulos CJ, Oliveira DJ, Miki Junior P. The treatment of chronic osteomyelitis. Rev Soc Bras Med Trop 1992;25:235-9. [PubMed] 5. Sanchez C, Matamala A, Salavert M, et al. Cotrimoxazole plus rifampicin in the treatment of staphylococcal osteoarticular infection. Enferm Infecc Microbiol Clin 1997;15:10-3. [PubMed] 6. Saengnipanthkul S, Pongvivat T, Mahaisavariya B, Laupattarakasem W. Co-trimoxazole in the treatment of chronic osteomyelitis. J Med Assoc Thai 1988;71:186-91.[PubMed] |
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