title: Should daptomycin-rifampin combinations for MSSA/MRSA isolates be avoided because of antagonism?
abstract: OBJECTIVE
  There is increasing clinical evidence from observational studies, that combination therapy of daptomycin with rifampin is a valuable treatment option for biofilm-associated difficult to treat Staphylococcus aureus infections such as osteomyelitis, prosthetic joint infection and endocarditis. However, two studies analyzing a limited number of S. aureus isolates reported an antagonism of those two drugs questioning the benefit of this combination.
  
  
  METHODS
  To estimate the frequency of this possible antagonism, we performed in vitro checkerboard assays on 58 consecutive clinical isolates of S. aureus (MSSA n = 9, MRSA n = 49). We determined the fractional inhibitory concentration index (FICI) and the susceptible breakpoint index (SBPI). All isolates were characterized by a microprobe array detecting 336 different genes/alleles to ensure their non-clonal origin.
  
  
  RESULTS
  For all isolates, the FICI was between 1.00 and 1.25 indicating additive effects for the daptomycin/rifampin combination. Neither antagonism nor synergism as defined by the FICI was found for any of the isolates.
  
  
  CONCLUSIONS
  Based on these data, there is no evidence to advise against the daptomycin/rifampin combination therapy.
authors.affiliation: Center for Infectious Diseases and Infection's Control, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Stein
authors.affiliation: Center for Infectious Diseases and Infection's Control, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Makarewicz
authors.affiliation: Center for Infectious Diseases and Infection's Control, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany.|Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Forstner
authors.affiliation: Center for Infectious Diseases and Infection's Control, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Weis
authors.affiliation: Center for Infectious Diseases and Infection's Control, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hagel
authors.affiliation: Institute of Medical Microbiology, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Löffler
authors.affiliation: Center for Infectious Diseases and Infection's Control, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany. mathias.pletz@med.uni-jena.de.
authors.forename: M W
authors.identifier: http://orcid.org/0000-0001-8157-2753
authors.initials: MW
authors.lastname: Pletz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002675:Child, Preschool; D017576:Daptomycin / Q000494:pharmacology*; D004336:Drug Antagonism; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012293:Rifampin / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin; D012293:Rifampin
keywords: Checkerboard; Fractional inhibitory concentration index; Staphylococcus aureus; Synergism