Temocillin efficacy in experimental Klebsiella pneumoniae meningitis after infusion into rabbit plasma to simulate antibiotic concentrations in human serum.
An infusion system was developed to simulate in the plasma of rabbits the concentrations of temocillin in human serum measured after administration of a 2-g intravenous bolus dose. The efficacy of therapy with this infusion against experimental Klebsiella pneumoniae meningitis was compared with that of a conventional bolus dose to the animals. The marked difference between the elimination half-life (t1/2) of temocillin in rabbit plasma and human serum (0.3 and 5 h, respectively) was reflected in concentrations in cerebrospinal fluid (CSF). The mean peak concentration after infusion occurred 3.5 h later than after bolus dosing, and levels were more prolonged (t1/2 in CSF was 6.3 h compared with 0.83 h following the bolus dose). After infusion, the mean viable count in CSF decreased by 4 log10 CFU/ml, whereas the bolus dose was ineffective because of the rapid fall to subinhibitory concentrations. These results suggest that the infusion system used is valuable for experimental studies with antibacterial agents whose elimination kinetics differ markedly between animals and humans.
Woodnutt
G
G
Beecham Pharmaceuticals Research Division, Chemotherapeutic Research Centre, Betchworth, Surrey, England.
Catherall
E J
EJ
Kernutt
I
I
Mizen
L
L
D000818:Animals; D002555:Cerebrospinal Fluid / Q000382:microbiology; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous / Q000295:instrumentation; D007275:Injections, Intravenous; D007710:Klebsiella Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D008581:Meningitis / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D010406:Penicillins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D013997:Time Factors
D010406:Penicillins; C031367:temocillin