Tam, Vincent H.2018-12-042018-12-04August 2012017-08August 201Portions of this document appear in: Bowers, Dana R., Henry Cao, Jian Zhou, Kimberly R. Ledesma, Dongxu Sun, Olga Lomovskaya, and Vincent H. Tam. "Assessment of minocycline and polymyxin B combination against Acinetobacter baumannii." Antimicrobial agents and chemotherapy (2015): AAC-04110. DOI: 10.1128/AAC.04110-14. And in: Zhou, Jian, Kimberly R. Ledesma, Kai-Tai Chang, Henrietta Abodakpi, Song Gao, and Vincent H. Tam. "Pharmacokinetics and pharmacodynamics of minocycline against Acinetobacter baumannii in a neutropenic murine pneumonia model." Antimicrobial agents and chemotherapy (2017): AAC-02371. And in: Zhou, Jian, Brian T. Tran, and Vincent H. Tam. "The complexity of minocycline serum protein binding." Journal of Antimicrobial Chemotherapy 72, no. 6 (2017): 1632-1634.http://hdl.handle.net/10657/3637Multi-drug resistant (MDR) Acinetobacter baumannii is increasingly more prevalent in nosocomial infections. Although in vitro susceptibility of A. baumannii to minocycline is promising, the in vivo efficacy of minocycline has not been well established. Moreover, the shortage of new effective antibiotics against MDR A. baumannii has created a need for maximizing the usage of currently available antibiotics. Therefore, we proposed to improve the therapeutic outcomes of minocycline for infections caused by A. baumannii. Our working hypothesis was that therapeutic outcomes could be improved by maximizing minocycline efficacy and suppressing the development of resistance in A. baumannii. We intended to achieve this proposed goal by: 1) deriving PK parameters for minocycline using a murine infection model; 2) determine the exposure-response relationship of minocycline; 3) suppressing the development of minocycline resistance. Our findings will fill the gaps in knowledge needed to optimize the use of minocycline and support its role as a first-line agent in the treatment of A. baumannii infections. Moreover, it is anticipated that our strategies for optimizing treatment with minocycline may be applicable to other tetracyclines, thereby expanding the viable options for MDR A. baumannii infections.application/pdfengThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. UH Libraries has secured permission to reproduce any and all previously published materials contained in the work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).MinocyclineAcinetobacter baumannii2018-12-04Thesisborn digital