Effects of subminimal inhibitory concentrations of antibiotics in experimental infections.
The antibacterial effects of subminimal inhibitory concentrations (sub-MICs) of antibiotics were studied in two animal models. In mice, the oral cephalosporin CGP 9000 was effective in 11 of 20 different gram-negative infections and cephalexin was effective in one of these infections, both at 50% effective doses (ED(50)) that produced peak concentrations of drug in plasms equal to one-half to one-sixteenth the minimal inhibitory concentration (MIC) for the infecting organism. In gram-positive infections, both antibiotics were effective only at concentrations above the MIC. In rabbits, sub-MICs of cephaloridine, ampicillin, and gantamicin were maintained for 6-10 hr by intravenous infusion. At steady-state concentrations equal to one half to one-eighth the MIC, the beta-lactam antibiotics caused elongation and filamentation, and gentamicin caused enlargement, of Proteus mirabilis, Escherichia coli, and Salmonella typhimurium in peritoneal exudate; the number of viable cells of each of these bacteria was temporarily reduced. In infections with E. coli and P. mirabilis, sub-MIC's of beta-lactam antibiotics and of gentamicin prolonged the survival rates for infected animals beyond those for control animals. Rabbits infected with S. typhimurium and treated with ampicillin at a concentration of one-third the MIC Tended to die sooner than did control animals.
D000667:Ampicillin / Q000008:administration & dosage; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood; D001424:Bacterial Infections / Q000097:blood / Q000517:prevention & control*; D002506:Cephalexin / Q000008:administration & dosage; D002509:Cephaloridine / Q000008:administration & dosage; D002515:Cephradine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004927:Escherichia coli Infections / Q000382:microbiology / Q000517:prevention & control; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage; D008297:Male; D051379:Mice; D011512:Proteus Infections / Q000382:microbiology; D011513:Proteus mirabilis / Q000166:cytology; D011817:Rabbits; D012480:Salmonella Infections / Q000382:microbiology; D012486:Salmonella typhimurium / Q000166:cytology; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D000667:Ampicillin; C012671:cefroxadine; D002515:Cephradine; D002509:Cephaloridine; D002506:Cephalexin