Document Detail

Simulation of human serum pharmacokinetics of ticarcillin-clavulanic acid and ceftazidime in rabbits, and efficacy against experimental Klebsiella pneumoniae meningitis.
MedLine Citation:
PMID:  2665641     Owner:  NLM     Status:  MEDLINE    
The penetration into cerebrospinal fluid (CSF) and efficacy of ticarcillin-clavulanic acid, ticarcillin alone, and ceftazidime were compared in rabbits with experimentally induced Klebsiella pneumoniae meningitis. The compounds were administered to simulate in rabbit plasma the concentration-versus-time curves observed in humans after 30-min infusions of Timentin (3 g of ticarcillin plus 100 mg of clavulanic acid), ticarcillin (3 g), and ceftazidime (2 g). Single- and multiple-dosing schedules were used. The penetrations of clavulanic acid into CSF (expressed as [area under the concentration-time curve for CSF/area under the curve for plasma] x 100) after the two dosing schedules were 28 and 24.5%, similar to that for ceftazidime (21%; multiple-dosing only) and greater than those for ticarcillin (8.4 and 9.3%). Ticarcillin was ineffective in reducing viable counts in CSF but, in the presence of clavulanic acid, reduced bacterial numbers by approximately 99% at 4 h after a single dose and by 99.99% at 12 h after three doses given at 4-h intervals. Two doses of ceftazidime given 8 h apart were more effective than the three doses of ticarcillin-clavulanic acid, in keeping with the in vitro activities of these compounds against the infecting organism. These results illustrate the ability of clavulanic acid to penetrate the blood-CSF barrier such that concentrations of the inhibitor in CSF potentiate the activity of ticarcillin against the ticarcillin-resistant, beta-lactamase-producing strain of K. pneumoniae.
L Mizen; G Woodnutt; I Kernutt; E J Catherall
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  33     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  1989 May 
Date Detail:
Created Date:  1989-08-25     Completed Date:  1989-08-25     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  693-9     Citation Subset:  IM    
Beecham Pharmaceuticals Research Division, Chemotherapeutic Research Centre, Betchworth, Surrey, England.
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MeSH Terms
Ceftazidime / administration & dosage,  pharmacokinetics*,  therapeutic use
Clavulanic Acids / administration & dosage,  pharmacokinetics*,  therapeutic use
Klebsiella pneumoniae
Meningitis / drug therapy*,  microbiology
Microbial Sensitivity Tests
Penicillins / pharmacokinetics*
Ticarcillin / administration & dosage,  pharmacokinetics*,  therapeutic use
Time Factors
Reg. No./Substance:
0/Clavulanic Acids; 0/Penicillins; 34787-01-4/Ticarcillin; 78439-06-2/Ceftazidime

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