Randomized non-inferiority trial to compare trimethoprim/sulfamethoxazole plus rifampicin versus linezolid for the treatment of MRSA infection

Abstract

Objectives: The therapeutic arsenal for MRSA infections is limited. The aim of this study was to assess the noninferiority of a combination of trimethoprim/sulfamethoxazole plus rifampicin versus linezolid alone for the treatment of MRSA infection. Methods:We conducted a randomized, open-label, single-centre, non-inferiority trial comparing trimethoprim/ sulfamethoxazole (160 mg/800 mg three times daily) plus rifampicin (600 mg once a day) versus linezolid (600 mg twice a day) alone in adult patients with various types of MRSA infection. Patients were allocated 1: 1 to either regimen. The primary outcome was clinical cure at 6 weeks after the end of treatment (non-inferiority margin 20%) assessed by both ITT and PP analyses. Secondary outcomes included the microbiologically documented persistence of MRSA in clinical cultures, mortality and adverse events. The study protocol has been registered with ClinicalTrials.gov (NCT00711854).Results: Overall, 150 patients were randomized to one of the two treatment arms between January 2009 and December 2013 and were included in the ITT analysis. Of these 56/75 (74.7%) in the linezolid group and 59/75 (78.7%) in the trimethoprim/sulfamethoxazole and rifampicin group experienced clinical success (risk difference 4%, 95% CI 29.7% to 17.6%). The results were confirmed by the PP analysis, with 54/66 (81.8%) cured patients in the linezolid group versus 52/59 (88.1%) in the trimethoprim/sulfamethoxazole and rifampicin group (risk difference 6.3%, 95% CI 26.8% to 19.2%). There were no statistically significant differences between the two groups in any of the secondary outcomes, including microbiologically documented failure. Four adverse drug reactions attributed to the study medication occurred in the linezolid group versus nine in the trimethoprim/ sulfamethoxazole and rifampicin group.Conclusions: Compared with linezolid, trimethoprim/sulfamethoxazole and rifampicin seems to be non-inferior in the treatment of MRSA infection.

IWGDF guidance on the diagnosis and management of foot infections in persons with diabetes

“…Based on data from available studies, for mild to moderate skin and soft tissue infections, 1-2 weeks is usually effective [8,130,172], while for more serious skin and soft tissue infections, 3 weeks is usually sufficient [8,172,196,197,214,215]. Antibiotic therapy can generally be discontinued when [270] (for now, we think that rifamp(ic)in should only be used for osteomyelitis).…”

A Highly Potent Class of Halogenated Phenazine Antibacterial and Biofilm-Eradicating Agents Accessed Through a Modular Wohl-Aue Synthesis

“…Despite the historical significance of natural products and phenotype screening in antibiotic discovery, the paradigm shift in drug discovery to high throughput screening of synthetic libraries in target-based screens has generated no new chemical entities that have entered the market to date 16 . To make matters worse, few pharmaceutical companies continue antibiotic discovery programs 17 .…”

Antimicrobial activity of ceftaroline against methicillin-resistant Staphylococcus aureus (MRSA) isolates collected in 2013–2014 at the Geneva University Hospitals

“…MRSA, initially identified as a nosocomial pathogen, is now responsible for both hospital- and community-acquired infections [1]. MRSA treatment options include glycopeptides and combination regimens [2], as well as new agents like daptomycin and last-generation cephalosporins (ceftobiprole and ceftaroline). Despite the availability of several antimicrobials, resistance to a particular antibiotic has repeatedly brought complications for the successful treatment of MRSA infections.…”