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Avoid Trimethoprim-Sulfamethoxazole for Severe MRSA Infections


Clinical question: Is trimethoprim-sulfamethoxazole equivalent to vancomycin for the treatment of severe infections caused by methicillin-resistant Staphyloccus aureus?

Bottom line: Trimethoprim-sulfamethoxazole (TMP-SMX) did not achieve noninferiority as compared with vancomycin for the treatment of severe methicillin-resistant Staphyloccus aureus (MRSA) infections in hospitalized patients, and it may lead to increased mortality in the subset of patients with bacteremia. (LOE = 1b)

Reference: Paul M, Bishara J, Yahav D, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin-resistant Staphylococcus aureus. BMJ 2015;350:h2219.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (any location)


Although TMP-SMX can be used to treat uncomplicated skin and soft-tissue infections caused by MRSA, it is not currently recommended for more serious MRSA infections such as bacteremia or pneumonia. In this study, investigators tested whether TMP-SMX is noninferior to vancomycin for the treatment of hospitalized patients with severe MRSA infections. Patients included in the study (N = 252) had microbiologically documented MRSA infections, including complicated skin and soft-tissue infections, bone or joint infections, pneumonia, or primary bacteremia. Patients with MRSA isolates resistant to TMP-SMX or vancomycin were excluded.

Using concealed allocation, the investigators randomized the patients to receive either high-dose TMP-SMX (320 mg trimethoprim/1600 mg sulfamethoxazole intravenously twice daily) or vancomycin (1 mg intravenously twice daily) for at least 7 days. In the TMP-SMX group, treatment could be transitioned to an oral regimen of an equivalent dose at the clinician's discretion. The 2 groups had similar baseline characteristics with a mean age of 66 years and similar comorbidities, though the vancomycin group had a higher percentage of patients with bacteremia than the TMP-SMX group (30% vs 43%; P = .042). The primary outcome was treatment failure at 7 days, defined as a composite of death, persistent fever or hypotension, stable or worsening Sequential Organ Failure Assessment score, or persistent bacteremia. There was no statistically significant difference detected between the 2 groups for this outcome (38% treatment failure with TMP-SMX vs 27% with vancomycin; absolute difference 10.4%, 95% CI -1.2% to 21.5%).

However, since the 95% confidence interval for the absolute difference fell outside the predefined lower limit of noninferiority of 15%, the authors concluded that TMP-SMX failed to achieve noninferiority as compared with vancomycin. Additionally, in the subgroup of patients with bacteremia, patients were more likely to die in the TMP-SMX group as compared with the vancomycin group, although this difference again was not statistically significant (34% with TMP-SMX vs 18% with vancomycin; relative risk 1.90, 0.92-3.93).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

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