Correlation of in-vitro activity and pharmacokinetic parameters with in-vivo effect of amoxycillin, co-amoxiclav and cefotaxime in a murine model of pneumococcal pneumonia.
In an attempt to determine the susceptibility breakpoints for amoxycillin, co-amoxiclav and cefotaxime in pneumococcal pneumonia, a neutropenic mouse model was established and tested with two strains having different susceptibility to penicillins and cefotaxime. With a penicillin-sensitive strain (MIC/MBC = 0.01/0.01 mg/L) the minimum dosage tested achieving significant cure was 2 mg/kg for amoxycillin, co-amoxiclav and cefotaxime. For the penicillin-insensitive strain (MIC/MBC = 1/2 mg/L), the minimum dosage tested giving significant cure was 50 mg/kg for amoxycillin and co-amoxiclav but 100 mg/kg for cefotaxime. Our results support the belief that MICs of amoxycillin, co-amoxiclav and cefotaxime for pneumococcal strains of < or = 0.5 or < or = 1 mg/L can be considered as clinically relevant susceptibility breakpoints.
Soriano
F
F
Department of Medical Microbiology, Fundación Jiménez Díaz, Madrid, Spain.
Ponte
C
C
Nieto
E
E
Parra
A
A
D000658:Amoxicillin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019980:Amoxicillin-Potassium Clavulanate Combination; D000818:Animals; D002439:Cefotaxime / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002969:Clavulanic Acids / Q000493:pharmacokinetics / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D051379:Mice; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy*; D013296:Streptococcus pneumoniae / Q000187:drug effects
D002511:Cephalosporins; D002969:Clavulanic Acids; D010406:Penicillins; D019980:Amoxicillin-Potassium Clavulanate Combination; D000658:Amoxicillin; D002439:Cefotaxime