Efficacy and Safety of Fosfomycin Plus Imipenem as Rescue Therapy for Complicated Bacteremia and Endocarditis due to Methicillin-Resistant Staphylococcus aureus: A Multi-center Clinical Trial.
Clin Infect Dis. 2014 Jul 21;
Authors: Del Río A, Gasch O, Moreno A, Peña C, Cuquet J, Soy D, Mestres CA, Suarez C, Pare JC, Tubau F, de la Maria CG, Marco F, Carratalà J, Gatell JM, Gudiol F, Miró JM, the FOSIMI investigators
Abstract
BACKGROUND: There is an urgent need for alternative rescue therapies in invasive infections caused by methicillin-resistant Staphylococcus aureus(MRSA). We assessed the clinical efficacy and safety of the combination of fosfomycin and imipenem as rescue therapy for MRSA infective endocarditis and complicated bacteremia.
METHODS: The trial was conducted between 2001 and 2010 in three Spanish hospitals. Adult patients with complicated MRSA bacteremia or endocarditis requiring rescue therapy were eligible for the study. Treatment with fosfomycin (2 g/6 h iv) plus imipenem (1 g/6 h iv) was started and monitored. The primary efficacy endpoints were the percentage of sterile blood cultures at 72 hours and the clinical success rate assessed at the test-of-cure visit (45 days after the end of therapy).
RESULTS: The combination was administered in 12 patients with endocarditis, two with vascular graft infection, and two with complicated bacteremia. Therapy had previously failed with vancomycin in nine patients, daptomycin in two, and sequential antibiotics in five. Blood cultures were negative 72 hours after the first dose of the combination in all cases. The success rate was 69%, and only one out of five deaths was related to the MRSA infection. Although the combination was safe in most patients (94%), a patient with liver cirrhosis died of multi-organ failure secondary to sodium overload. There were no episodes of breakthrough bacteremia or relapse.
CONCLUSIONS: Fosfomycin plus imipenem was an effective and safe combination when used as rescue therapy for complicated MRSA bloodstream infections and deserves further clinical evaluation as initial therapy in these infections.
PMID: 25048851 [PubMed - as supplied by publisher]