Publication: Pharmacodynamic evaluation of tigecycline against Acinetobacter baumannii in a murine pneumonia model
Issued Date
2009-04-21
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14602091
03057453
03057453
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2-s2.0-64649095374
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Antimicrobial Chemotherapy. Vol.63, No.5 (2009), 982-987
Suggested Citation
Pornpan Koomanachai, Aryun Kim, David P. Nicolau Pharmacodynamic evaluation of tigecycline against Acinetobacter baumannii in a murine pneumonia model. Journal of Antimicrobial Chemotherapy. Vol.63, No.5 (2009), 982-987. doi:10.1093/jac/dkp056 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/28113
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Title
Pharmacodynamic evaluation of tigecycline against Acinetobacter baumannii in a murine pneumonia model
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Abstract
Objectives: Tigecycline is an extended-spectrum antibiotic with activity against Acinetobacter spp. (ACB), an increasingly common cause of nosocomial pneumonia. Although this compound is under investigation for this indication, supportive pharmacodynamic data are not yet available at this infection site. The objective of this study was to characterize the exposure-response relationship of tigecycline with ACB in an established murine pneumonia model. Methods: The pharmacokinetic profile of tigecycline was evaluated in infected neutropenic mice. Tigecycline 6.25, 12.5, 25, 50, 100, 200, 300 and 400 mg/kg, in single or two to six divided subcutaneous doses, were tested against all ACB isolates. Efficacy, defined as the log10change in bacterial cfu/mL, was assessed after a 24 h course of therapy. Tigecycline exposures in serum were corrected for dose-specific protein binding. The relationship between the area under the free concentration-time curve to MIC (f AUC/MIC) and change in bacterial density was determined using the sigmoid Emaxmodel. Results: Tigecycline displayed linear pharmacokinetics with a mean half-life of 11.3 ± 1.4 h. Efficacy correlated well with f AUC/MIC (R2= 0.96). The mean 80%, 50% effective and stasis exposures (f AUC/MIC) were 17, 8 and 6, respectively. Maximal efficacy for the five Acinetobacter baumannii studied was 3.4 log kill. Conclusions: Tigecycline efficacy in this murine ACB pneumonia model was well predicted by f AUC/MIC. Requisite tigecycline exposures for efficacy appear to be higher for ACB pneumonia than for other pathogens reported of non-respiratory infections. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.