Impact of the antibiotic dosage schedule on efficacy in experimental lung infections.
In agreement with results obtained in the thigh infection model for which there is no human equivalent, the impact of the dosage schedule on efficacy in various clinically relevant experimental lung infections is related to the class of antibiotic. The efficacy of beta-lactams increases with increasing frequency of administration. Sustained antibiotic concentrations in serum at a relatively low level are more effective than high peak concentrations at intervals. In contrast, the dosing interval has little impact on the activity of aminoglycosides, which is mainly dependent on the total amount of antibiotic in serum during treatment, either as short lasting high peaks or as long lasting relatively low concentrations. Limited data available on quinolones suggest a slight increase in efficacy with increasing dosing intervals. These differences in efficacy correlate with differences in the pharmacodynamics of antibiotics of different classes as seen in vitro as well as in the lungs of infected animals. Knowledge about both the pharmacokinetics and pharmacodynamics of antibiotics is required for the correct interpretation of comparative studies on antibiotic efficacy in experimental infections, and also for the evaluation of experimental data as support for the proper design of clinical trials.
Roosendaal
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Department of Clinical Microbiology and Antimicrobial Therapy, Erasmus University Rotterdam, The Netherlands.
Bakker-Woudenberg
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IA
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D007710:Klebsiella Infections / Q000188:drug therapy*; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D011014:Pneumonia / Q000188:drug therapy*; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy*; D011552:Pseudomonas Infections / Q000188:drug therapy
D000900:Anti-Bacterial Agents