title: 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.
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.
authors.affiliation: Hospital Clínic-Institut d' Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona.
authors.forename: Ana
authors.initials: A
authors.lastname: del Río
authors.affiliation: 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.
authors.forename: Oriol
authors.initials: O
authors.lastname: Gasch
authors.affiliation: Hospital Clínic-Institut d' Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona.
authors.forename: Asunción
authors.initials: A
authors.lastname: Moreno
authors.affiliation: Hospital de Bellvitge-Institut d'Investigació Biomèdica de Bellvitge, University of Barcelona, L'Hospitalet de Llobregat.
authors.forename: Carmen
authors.initials: C
authors.lastname: Peña
authors.affiliation: Hospital General de Granollers, Universitat Internacional de Catalunya, Barcelona.
authors.forename: Jordi
authors.initials: J
authors.lastname: Cuquet
authors.affiliation: Hospital Clínic-Institut d' Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona.
authors.forename: Dolors
authors.initials: D
authors.lastname: Soy
authors.affiliation: Hospital Clínic-Institut d' Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Mestres
authors.affiliation: Hospital de Bellvitge-Institut d'Investigació Biomèdica de Bellvitge, University of Barcelona, L'Hospitalet de Llobregat.
authors.forename: Cristina
authors.initials: C
authors.lastname: Suárez
authors.affiliation: Hospital Clínic-Institut d' Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Pare
authors.affiliation: Hospital de Bellvitge-Institut d'Investigació Biomèdica de Bellvitge, University of Barcelona, L'Hospitalet de Llobregat CIBERES (CIBER de Enfermedades Respiratorias), ISCIII, Madrid.
authors.forename: Fe
authors.initials: F
authors.lastname: Tubau
authors.affiliation: Hospital Clínic-Institut d' Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona.
authors.forename: Cristina
authors.initials: C
authors.lastname: Garcia de la Mària
authors.affiliation: 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.
authors.forename: Francesc
authors.initials: F
authors.lastname: Marco
authors.affiliation: Hospital de Bellvitge-Institut d'Investigació Biomèdica de Bellvitge, University of Barcelona, L'Hospitalet de Llobregat.
authors.forename: Jordi
authors.initials: J
authors.lastname: Carratalà
authors.affiliation: Hospital Clínic-Institut d' Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona.
authors.forename: José M
authors.initials: JM
authors.lastname: Gatell
authors.affiliation: Hospital de Bellvitge-Institut d'Investigació Biomèdica de Bellvitge, University of Barcelona, L'Hospitalet de Llobregat.
authors.forename: Francisco
authors.initials: F
authors.lastname: Gudiol
authors.affiliation: Hospital Clínic-Institut d' Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona.
authors.forename: José M
authors.initials: JM
authors.lastname: Miró
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy*; D001769:Blood / Q000382:microbiology; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D004697:Endocarditis, Bacterial / Q000188:drug therapy*; D005260:Female; D005578:Fosfomycin / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D015378:Imipenem / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000302:isolation & purification; D008875:Middle Aged; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D013030:Spain; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin; D015378:Imipenem
keywords: MRSA; bacteremia; fosfomycin; imipenem; infective endocarditis