Time-kill studies of antibiotic combinations against penicillin-resistant and -susceptible Streptococcus pneumoniae

Time-kill studies were conducted to evaluate antibiotic combinations against four strains of Streptococcus pneumoniae for which the MICs of penicillin were 0.03, 0.25, 1 and 4 mg/L, respectively. After 8 h of antibiotic exposure the combination of ceftriaxone and vancomycin showed enhanced activity against all four strains. Penicillin plus vancomycin and ceftriaxone plus gentamicin showed enhanced activity against the three penicillin-resistant strains. Combinations of vancomycin and rifampicin were indifferent. These results are similar to those found previously in the rabbit meningitis model suggesting that time-kill studies over 8 h may be useful in predicting in-vivo antibiotic interactions in resistant pneumococcal infections.