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Clin Infect Dis. 2014 Oct 15;59(8):1105-12. doi: 10.1093/cid/ciu580. Epub 2014 Jul 21.

Efficacy and safety of fosfomycin plus imipenem as rescue therapy for complicated bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: a multicenter clinical trial.

Author information

1
Hospital Clínic-Institut d' Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona.
2
Hospital de Bellvitge-Institut d'Investigació Biomèdica de Bellvitge, University of Barcelona, L'Hospitalet de Llobregat Corporació Sanitària Parc Taulí, Universitat Autònoma de Barcelona, Sabadell.
3
Hospital de Bellvitge-Institut d'Investigació Biomèdica de Bellvitge, University of Barcelona, L'Hospitalet de Llobregat.
4
Hospital General de Granollers, Universitat Internacional de Catalunya, Barcelona.
5
Hospital de Bellvitge-Institut d'Investigació Biomèdica de Bellvitge, University of Barcelona, L'Hospitalet de Llobregat CIBERES (CIBER de Enfermedades Respiratorias), ISCIII, Madrid.
6
Hospital Clínic-Institut d' Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Spain.

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 3 Spanish hospitals. Adult patients with complicated MRSA bacteremia or endocarditis requiring rescue therapy were eligible for the study. Treatment with fosfomycin (2 g/6 hours IV) plus imipenem (1 g/6 hours IV) was started and monitored. The primary efficacy endpoints were percentage of sterile blood cultures at 72 hours and 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, 2 with vascular graft infection, and 2 with complicated bacteremia. Therapy had previously failed with vancomycin in 9 patients, daptomycin in 2, and sequential antibiotics in 5. Blood cultures were negative 72 hours after the first dose of the combination in all cases. The success rate was 69%, and only 1 of 5 deaths was related to the MRSA infection. Although the combination was safe in most patients (94%), a patient with liver cirrhosis died of multiorgan 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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00871104.

KEYWORDS:

MRSA; bacteremia; fosfomycin; imipenem; infective endocarditis

PMID:
25048851
DOI:
10.1093/cid/ciu580
[Indexed for MEDLINE]

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