Pharmacokinetic/pharmacodynamic evaluation of antimicrobial treatments of orofacial odontogenic infections

To evaluate the efficacy of antimicrobial therapy in oral odontogenic infections using estimated pharmacokinetic/pharmacodynamic parameters or efficacy indices, and to compare pharmacokinetic/pharmacodynamic breakpoints with National Committee for Clinical Laboratory Standards' (NCCLS) breakpoi...

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Bibliographic Details
Published in:Clinical pharmacokinetics 2005-01, Vol.44 (3), p.305-316
Main Authors: ISIA, Arantxa, CANUT, Andrés, GASCON, Alicia R, LABORA, Alicia, ARDANZA-TREVIJANO, Bruno, SOLINIS, Maria Angelés, PEDRAZ, Jose Luis
Format: Article
Language:English
Subjects:
Anti-Infective Agents - pharmacokinetics
Anti-Infective Agents - pharmacology
Anti-Infective Agents - therapeutic use
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Area Under Curve
Bacteria - drug effects
Biological and medical sciences
Humans
Infections - drug therapy
Infections - microbiology
Medical sciences
Microbial Sensitivity Tests
Mouth - microbiology
Mouth Diseases - drug therapy
Mouth Diseases - microbiology
Pharmacology. Drug treatments
Tooth Diseases - drug therapy
Tooth Diseases - microbiology
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Summary:To evaluate the efficacy of antimicrobial therapy in oral odontogenic infections using estimated pharmacokinetic/pharmacodynamic parameters or efficacy indices, and to compare pharmacokinetic/pharmacodynamic breakpoints with National Committee for Clinical Laboratory Standards' (NCCLS) breakpoints. Retrospective literature search to obtain minimum inhibitory concentration (MIC) values, pharmacokinetic parameters of antimicrobials and NCCLS breakpoints. Pharmacokinetic simulations were carried out using WinNonlin software (Pharsight Corporation, Mountain View, CA, USA). For antimicrobials with time-dependent activity, the time that the plasma drug concentration exceeds the MIC as the percentage of dose interval at steady state was calculated. For antimicrobials with concentration-dependent activity, the total area under the plasma concentration-time curve over 24 hours at steady state divided by the MIC was calculated. Pharmacokinetic/pharmacodynamic breakpoints were calculated according to these parameters. Only amoxicillin/clavulanic acid and clindamycin showed adequate efficacy indices against the most commonly isolated bacteria in odontogenic infections. Metronidazole reached good indices against anaerobes only. Pharmacokinetic/pharmacodynamic susceptibility breakpoints do not coincide exactly with NCCLS breakpoints. Owing to the scarcity of double-blind, clinical trials on the use of antimicrobials in endodontics, this study may be useful in determining the best antimicrobial treatment in these infections. However, as we have not used concentration data in infected tissue to determine pharmacokinetic/pharmacodynamic indices, it would be necessary to design clinical trials in order to confirm these results.
ISSN:0312-5963
1179-1926
DOI:10.2165/00003088-200544030-00006