Trimethoprim-sulfamethoxazole vs vancomycin for severe infections caused by meticillin resistant Staphylococcus aureus: randomised controlled trial.
BMJ. MAY.14, 2015 V.350 .
Paul M1, Bishara J2, Yahav D3, Goldberg E4, Neuberger A5, Ghanem-Zoubi N6, Dickstein Y7, Nseir W8, Dan M9, Leibovici L3.
1Unit of Infectious Diseases, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel firstname.lastname@example.org.
2Unit of Infectious Diseases, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel.
3Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel Unit of Infectious Diseases, Medicine E, Rabin Medical Center, Beilinson Hospital, Petah-Tikva.
4Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel Unit of Infectious Diseases, Medicine F, Rabin Medical Center, Beilinson Hospital, Petah-Tikva.
5Division of Infectious Diseases, Medicine B, Rambam Health Care Campus, Haifa, Israel Technion-Israel Institute of Technology and the Ruth & Bruce Rappaport Faculty of Medicine, Haifa.
6Division of Infectious Diseases, Rambam Health Care Campus, Haifa.
7Technion-Israel Institute of Technology and the Ruth & Bruce Rappaport Faculty of Medicine, Haifa Division of Infectious Diseases, Medicine A, Rambam Health Care Campus, Haifa.
8Internal Medicine Department, Holy Family Hospital, Nazareth, Faculty of Medicine in the Galilee, Bar-Ilan Univesity, Safed, Israel.
9Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel Infectious Diseases Unit, E Wolfson Hospital, Holon, Israel.
To show non-inferiority of trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of severe infections due to meticillin resistant Staphylococcus aureus (MRSA).
Parallel, open label, randomised controlled trial.
Four acute care hospitals in Israel.
Adults with severe infections caused by MRSA susceptible to trimethoprim-sulfamethoxazole and vancomycin. Patients with left sided endocarditis, meningitis, chronic haemodialysis, and prolonged neutropenia were excluded.
Trimethoprim-sulfamethoxazole 320 mg/1600 mg twice daily versus vancomycin 1 g twice daily for a minimum of seven days and then by indication.
MAIN OUTCOME MEASURES:
The primary efficacy outcome was treatment failure assessed at day 7, consisting of death, persistence of haemodynamic instability or fever, stable or worsening Sequential Organ Failure Assessment score, and persistence of bacteraemia. The primary safety outcome was all cause mortality at day 30. Non-inferiority was defined by a difference of less than 15% for treatment failure.
252 patients were included in the trial, of whom 91 (36%) had bacteraemia. No significant difference in treatment failure was seen for trimethoprim-sulfamethoxazole (51/135, 38%) versus vancomycin (32/117, 27%)-risk ratio 1.38 (95% confidence interval 0.96 to 1.99). However, trimethoprim-sulfamethoxazole did not meet the non-inferiority criterion-absolute difference 10.4% (95% confidence interval -1.2% to 21.5%). For patients with bacteraemia, the risk ratio was 1.40 (0.91 to 2.16). In a multivariable logistic regression analysis, trimethoprim-sulfamethoxazole was significantly associated with treatment failure (adjusted odds ratio 2.00, 1.09 to 3.65). The 30 day mortality rate was 32/252 (13%), with no significant difference between arms. Among patients with bacteraemia, 14/41 (34%) treated with trimethoprim-sulfamethoxazole and 9/50 (18%) with vancomycin died (risk ratio 1.90, 0.92 to 3.93).
High dose trimethoprim-sulfamethoxazole did not achieve non-inferiority to vancomycin in the treatment of severe MRSA infections. The difference was particularly marked for patients with bacteraemia. Trial registration Clinical trials NCT00427076.