Improving Outcomes of Minocycline Treatment in Severe Infections Caused by Acinetobacter Baumannii
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Abstract
Multi-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.