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Combination fosfomycin/imipenem shows promise as rescue therapy for MRSA
A combination regimen of fosfomycin and imipenem appears to be safe and effective as rescue therapy for invasive bloodstream infections caused by MRSA and infective endocarditis, according to recent findings.
“There is an urgent need for alternative rescue therapies in invasive infections caused by MRSA,” researchers wrote.
In a multicenter clinical trial, the researchers evaluated MRSA patients seen at three Spanish teaching facilities. Eligible patients were undergoing appropriate antibiotic treatment for MRSA bacteremia or infective endocarditis, but needed salvage therapy due to persistent bacteremia, intolerable antibiotic side effects, or relapse. Patients underwent a regimen of 2 g every 6 hours IV fosfomycin tromethamine (Monurol, Zambon SPA) and imipenem (1 g every 6 hours IV). This regimen was administered for a median of 28 days. Of the patients undergoing the combination intervention, 12 had infective endocarditis, two had vascular graft infection and two had complicated bacteremia. Unsuccessful treatment with vancomycin had been attempted in nine patients, daptomycin (Cubicin, Cubist Pharmaceuticals) was unsuccessful in two, and five patients failed to respond to sequential antibiotics.
The researchers defined the study’s primary efficacy endpoints as the proportion of sterile blood cultures seen at 72 hours and the clinical success rate evaluated at 45 days post-therapy (the “test-of-cure” visit).
At 72 hours after administration of the first dose of the combination treatment, blood cultures were negative in all patients. The regimen achieved a success rate of 69%; only one of the five reported deaths was MRSA-related. Although the regimen was found to be safe in 94% of patients, one patient with liver cirrhosis died of multi-organ failure related to sodium overload. No relapses or breakthrough bacteremia episodes were chronicled.
According to the researchers, previous antibiotic therapy may have influenced the study’s final outcome and factored into possible treatment selection bias.
“However, our findings do provide evidence of the efficacy and safety profile of fosfomycin plus imipenem as rescue therapy for MRSA bloodstream infections, which is also being assessed in an ongoing randomized clinical trial,” they wrote.
Disclosure: One of the researchers has received consulting honoraria and/or research grants from Abbott, Boehringer-Ingelheim, Bristol-Myers Squibb, Cubist, Gilead Sciences, GlaxoSmithKline, Novartis, Pfizer, Roche and Theravance. Another researcher received consulting honoraria from Novartis and Janssen-Cilag.