Efficacy of beta-lactam antibiotics combined with gentamicin against penicillin-resistant pneumococcal pneumonia in CBA/J mice.
We examined the efficacy of gentamicin combined with beta-lactam antibiotics against penicillin-resistant Streptococcus pneumoniae (PRSP) in a noncompromised mouse model of pneumonia. In the presence of 8 mg/L (0.25 x MIC) and 16 mg/L (0.5 x MIC) of gentamicin, MICs of penicillin G against 23 strains of PRSP decreased from 1-4 mg/L to 0.03 mg/L in 14 (61%) and 23 strains (100%), respectively. A short-time killing study using strain 741 showed that 8 mg/L of gentamicin (0.25 x MIC) increased the killing activity of penicillin G, cefotaxime and imipenem (at 0.25, 1 and 4 x MIC) during a 6 h incubation period. Survival studies showed that the combined treatment of penicillin-G (160 mg/kg) and gentamicin (10 mg/kg), which commenced 2 days after infection (twice a day for 5 days), provided complete protection, while no animal survived when either antibiotic was used alone. A significant improvement in mortality was observed when a small dose of imipenem (2.5 and 10 mg/kg) was used with gentamicin. Our results suggest that gentamicin, when combined with beta-lactam antibiotics, especially imipenem, may be potentially useful against PRSP pneumonia in noncompromised individuals.
Tateda
K
K
Department of Microbiology, Toho University School of Medicine, Tokyo, Japan. kazu@med.toho-u.ac.jp
Matsumoto
T
T
Miyazaki
S
S
Yamaguchi
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D005839:Gentamicins / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008826:Microbial Sensitivity Tests; D010400:Penicillin G / Q000494:pharmacology; D010403:Penicillin Resistance; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy*; D013296:Streptococcus pneumoniae / Q000187:drug effects
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D010400:Penicillin G