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82 Trimethoprim/Sulfamethoxazole Compared to Daptomycin or Linezolid for the Treatment of Infections due to Methicillin-Resistant Staphylococcus aureus

Saturday, April 2, 2011
Trinity Ballroom (Hilton Anatole)
Michelle Campbell, BA , Detroit Medical Center, Wayne State University, Detroit, MI
Bharath Sunkara, MD , Detroit Medical Center, Wayne State University, Detroit, MI
Neelu Chugh, MD , Detroit Medical Center, Wayne State University, Detroit, MI
Aparna Poona, PharmB , Detroit Medical Center, Wayne State University, Detroit, MI
Melanie N. Wilson, BS , Detroit Medical Center, Wayne State University, Detroit, MI
Judy Moshos, MT , Detroit Medical Center, Wayne State University, Detroit, MI
Suchitha Bheemreddy, MD , Detroit Medical Center, Wayne State University, Detroit, MI
Kimberley Ku, BS , Detroit Medical Center, Wayne State University, Detroit, MI
Karambir Singh, MD , Detroit Medical Center, Wayne State University, Detroit, MI
Teena Chopra, MD , Detroit Medical Center, Wayne State University, Detroit, MI
Kayoko Hayakawa, MD, PhD , Detroit Medical Center, Wayne State University, Detroit, MI
Odaliz Abreu-Lanfranco, MD , Detroit Medical Center, Wayne State University, Detroit, MI
Paul R. Lephart, PhD , Detroit Medical Center, Wayne State University, Detroit, MI
Jason M. Pogue, PharmD , Detroit Medical Center, Wayne State University, Detroit, MI
Sorabh Dhar, MD , Detroit Medical Center, Wayne State University, Detroit, MI
Keith S. Kaye, MD, MPH , Detroit Medical Center, Wayne State University, Detroit, MI
Dror Marchaim, MD , Detroit Medical Center, Wayne State University, Detroit, MI
Background: Clinical data suggests that vancomycin should be avoided for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) when the MIC to vancomycin is 2 µg/mL. Main therapeutic options include daptomycin and linezolid, 2 newer and relatively expensive drugs; and Trimethoprim/Sulfamethoxazole (TMP/SMX), an older and inexpensive agent.

Objective: Compare the efficacy of daptomycin and linezolid to TMP/SMX for the treatment of infections caused by MRSA with an MIC to vancomycin of 2 µg/mL.

Methods: A retrospective study was conducted at Detroit Medical Center. For calendar year 2009, unique adult patients (>18 years) with infections due to MRSA with MIC to vancomycin of 2 µg/mL were included if they received ≥2 doses of TMP/SMX and/or daptomycin and/or linezolid during the period of 3 days prior to 14 days after their culture date. Various parameters and outcomes were abstracted from patient charts. Isolates were processed through the use of MicroScan® automated panels.

Results: There were 328 patients who were included in the study, 62 with bloodstream infections, 85 with pneumonia, and 134 with skin and soft tissue infections. 143 received TMP/SMX alone, 89 received daptomycin alone, 75 received linezolid alone, and 21 patients received a combination of TMP/SMX and either daptomycin or linezolid.  5 (1.5%) isolates were non-susceptible to TMP/SMX, and all were susceptible to daptomycin (mean MIC=0.5 ±0.4 μg/mL), and linezolid (mean MIC=2.5 ±0.9 μg/mL). In bivariate analysis, patients on TMP/SMX had significantly better outcomes, in terms of in-hospital mortality (p=0.003), 3-months mortality (p<0.001), length of stay (p<0.001), functional status deterioration (p<0.001), discharge to an institution after being admitted from home (p<0.001), additional hospitalizations in the next 6 months (p=0.005), and bacteriologic failures (p<0.001). Patients on TMP/SMX were also significantly younger (48±18 vs. 56±16 years, p<0.001), with less co-morbidities (p<0.001), less blood isolations (p<0.001), and lower intervals to initiation of effective therapy (61±72 vs. 97±68 hours, p=0.001). In multivariate models for in-hospital and 3-months mortality, after controlling for various confounders (age, functional status, Charlson’s score, bacteremia vs. other sites, and time to effective therapy), the association between TMP/SMX treatment and mortality was no longer significant (OR=1.4, p=0.5 and OR=1.14, p=0.8, respectively).

Conclusions: TMP/SMX compared favorably with linezolid and daptomycin in terms of treatment success and mortality.  The comparisons were complicated by differences in case-mix and types of MRSA infection. Controlled trials comparing TMP/SMX to daptomycin and linezolid might provide definitive data regarding comparative efficacy.