Article: article from journal or magazin.
Cefotaxime acts synergistically with levofloxacin in experimental meningitis due to penicillin-resistant pneumococci and prevents selection of levofloxacin-resistant mutants in vitro.
Antimicrobial Agents and Chemotherapy
Cefotaxime, given in two doses (each 100 mg/kg of body weight), produced a good bactericidal activity (-0.47 Deltalog(10) CFU/ml. h) which was comparable to that of levofloxacin (-0.49 Deltalog(10) CFU/ml. h) against a penicillin-resistant pneumococcal strain WB4 in experimental meningitis. Cefotaxime combined with levofloxacin acted synergistically (-1.04 Deltalog(10) CFU/ml. h). Synergy between cefotaxime and levofloxacin was also demonstrated in vitro in time killing assays and with the checkerboard method for two penicillin-resistant strains (WB4 and KR4). Using in vitro cycling experiments, the addition of cefotaxime in sub-MIC concentrations (one-eighth of the MIC) drastically reduced levofloxacin-induced resistance in the same two strains (64-fold increase of the MIC of levofloxacin after 12 cycles versus 2-fold increase of the MIC of levofloxacin combined with cefotaxime). Mutations detected in the genes encoding topoisomerase IV (parC and parE) and gyrase (gyrA and gyrB) confirmed the levofloxacin-induced resistance in both strains. Addition of cefotaxime in low doses was able to suppress levofloxacin-induced resistance.
Animals, Anti-Infective Agents/cerebrospinal fluid, Anti-Infective Agents/pharmacology, Cefotaxime/cerebrospinal fluid, Cefotaxime/pharmacology, Cephalosporins/cerebrospinal fluid, Cephalosporins/pharmacology, DNA, Bacterial/genetics, Drug Resistance, Bacterial, Drug Synergism, Meningitis, Pneumococcal/drug therapy, Meningitis, Pneumococcal/microbiology, Microbial Sensitivity Tests, Mutation/genetics, Ofloxacin/cerebrospinal fluid, Ofloxacin/pharmacology, Penicillin Resistance, Rabbits, Reverse Transcriptase Polymerase Chain Reaction, Streptococcus pneumoniae/drug effects, Streptococcus pneumoniae/genetics
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