Review Article

Antibiotic Combinations with Daptomycin for Treatment of Staphylococcus aureus Infections

Table 3

In vitro synergy of antibiotic combinations.

MethodStrainCombinationObservationRef.

Etest and time-kill studyhGISA/MSSADaptomycin with vancomycin, gentamicin, rifampin, linezolid, quinupristin/ dalfopristin, ampicilin-sulbactamEtest: additive effect with daptomycin + vancomycin and daptomycin + gentamycin, other combinations with daptomycin indifferent Time-kill study: additive effect with daptomycin + gentamycin, other combinations with daptomycin indifferent[40]

Etest and time-kill studyGISA/MRSADaptomycin with vancomycin, gentamicin, rifampin, linezolid, quinopristine/ dalfopristine, ampicilin-sulbactamEtest: additive effect only with daptomycin + gentamycin, other combinations with daptomycin indifferent Time-kill study: indifference[40]

Time-kill studyMRSADaptomycin + gentamicinSynergy in all three strains[41]

Time-kill studyMRSADaptomycin + rifampinAntagonism in one strain and indifference in two other strains[41]

Time-kill studyMRSADaptomycin at 0.0625 MIC to 2 MIC + oxacillin or ampicillin- sulbactamSynergy of daptomycin at 0.5 MIC + oxacillin 32 mg/L or ampicillin-sulbactam 2–8 mg/L (ampicillin)[57]

In vitro model of biofilmMSSADaptomycin 10 mg/kg/d + clarithromycin 250 mg q12 hSustained bactericidal activity against planctonic and biofilm bacteria[54]

In vitro model of biofilmMRSADaptomycin 10 mg/kg/d + rifampin at 600 mg q24 hSustained bactericidal activity against planctonic and biofilm bacteria[54]

In vitro selection for resistanceMRSA and GISADaptomycin + 0.25 MIC ampicillin, amoxicillin-clavulanic acid, gentamicin, rifampinCombination with ampicillin, amoxicillin-clavulanic acid delayed/prevented occurrence of non-susceptibility; rifampin delayed non-susceptibility[58]

Checkerboard methodMRSA, MSSADaptomycin + rifampicin, moxifloxacin or fusidic acidDaptomycin + fusidic acid: antagonism in one MSSA strain reported[68]

MRSA: meticillin-resistant S. aureus; MSSA: meticillin-susceptible S. aureus; GISA: glycopeptide-intermediate S. aureus; hGISA: heteroresistant glycopeptide-intermediate S. aureus; MIC: minimal inhibitory concentration (mg/L).