Killing Activities of Trovafloxacin Alone and in Combination with β-Lactam Agents, Rifampin, or Vancomycin against Streptococcus pneumoniae Isolates with Various Susceptibilities to Extended-Spectrum Cephalosporins at Concentrations Clinically Achievable in Cerebrospinal Fluid

The killing activities of trovafloxacin alone and in combination with β-lactam agents (extended-spectrum cephalosporins, meropenem), rifampin, or vancomycin were evaluated against 20 genotypically characterized Streptococcus pneumoniae isolates for which amoxicillin MICs were ≥4 μg/ml (cefotaxime MICs, ≥4 μg/ml for six strains) at concentrations clinically achievable in cerebrospinal fluid. At 6 h the mean killing activity of trovafloxacin alone (range, 2.6 to 2.9 log(10) CFU/ml) did not vary significantly according to the susceptibility of the strains to β-lactam agents. The activities of trovafloxacin or vancomycin added to the β-lactam agents and the combination trovafloxacin-vancomycin were additive or indifferent. Against the ceftriaxone-resistant isolates, the killing activity of the combination of a β-lactam agent and trovafloxacin did not differ significantly from that of a β-lactam agent and vancomycin.