Addition of Daptomycin to Levofloxacin Increased the Efficacy of Levofloxacin Monotherapy against a Methicillin-Susceptible Staphylococcus aureus Strain in Experimental Meningitis and Prevented Development of Resistance

Daptomycin and levofloxacin were tested as monotherapies and in combination against the antibiotic-susceptible S. aureus strain MSSA 1112 in a rabbit meningitis model and the effect of the combination on induction of resistance was determined in vitro. Changes of the susceptibility to fluoroquinolones and daptomycin was determined by the measurement of the MIC and mutations were detected by whole genome sequence comparison of the mutants with the parent strain MSSA 1112. Meningitis was induced by intracisternal inoculation of 105 CFU of MSSA 1112 and treatment was started 10 h later by injection of daptomycin (15 mg/kg) and levofloxacin (10 mg/kg) standard doses. Cerebrospinal fluid (CSF) samples were repeatedly collected during therapy in order to determine killing rates and results of bactericidal activity were expressed in Dlog10 CFU/ml over 8 h. The combination of daptomycin with levofloxacin was significantly (p