Application of mathematical model to experimental chemotherapy of fatal murine pneumonia.
Two beta-lactam antibiotics, cefazolin and cefmenoxime, were administered in an experimental model of murine pneumonia caused by Klebsiella pneumoniae in a way which enabled us to approximate the serum antibiotic concentration time course in humans. Bacterial counts during the experiments were subjected to nonlinear least-squares analyses by using a mathematical model that explained the bacterial killing by the antibiotic concentration time course and other factors associated with antimicrobial potency and bacterial growth. Cefazolin gave a killing curve that changed synchronously with the drug levels in serum; in contrast, cefmenoxime gave a curve that was prolonged as compared with the change in the drug levels in serum. Multiple correlation coefficients were about 0.9, and the model worked well for bacterial count data. Parameters relating to antimicrobial potency of the drugs, bacterial growth rate, and drug distribution into the tissue were estimated numerically.
Hishikawa
T
T
New Product Planning and Development Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Kusunoki
T
T
Tsuchiya
K
K
Uzuka
Y
Y
Sakamoto
T
T
Nagatake
T
T
Matsumoto
K
K
D000818:Animals; D002437:Cefazolin / Q000008:administration & dosage / Q000627:therapeutic use; D015281:Cefmenoxime / Q000008:administration & dosage / Q000627:therapeutic use; D002511:Cephalosporins / Q000627:therapeutic use*; D007710:Klebsiella Infections / Q000188:drug therapy*; D007711:Klebsiella pneumoniae; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D011014:Pneumonia / Q000188:drug therapy* / Q000209:etiology
D002511:Cephalosporins; D002437:Cefazolin; D015281:Cefmenoxime