期刊
OPEN FORUM INFECTIOUS DISEASES
卷 7, 期 11, 页码 -出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/ofid/ofaa460
关键词
Acinetobacter; pharmacology; optimal dosing; rifabutin
资金
- National Institute of Allergy and Infectious Diseases (NIAID) [R01AI139052, R01AI130060, R01AI117211]
- Food and Drug Administration (BAA) [HHSF223201710199C]
Acinetobacter baumannii has among the highest rates of antibiotic resistance encountered in hospitals. New therapies are critically needed. We found that rifabutin has previously unrecognized hyperactivity against most strains of A. baumannii. Here we review the pharmacology and adverse effects of rifabutin to inform potential oral dosing strategies in patients with A. baumannii infections. Rifabutin demonstrates dose-dependent increases in blood levels up to 900 mg per day, but plateaus thereafter. Furthermore, rifabutin induces its own metabolism after prolonged dosing, lowering its blood levels. Pending future development of an intravenous formulation, a rifabutin oral dose of 900-1200 mg per day for 1 week is a rational choice for adjunctive therapy of A. baumannii infections. This dosage maximizes AUC(24) to drive efficacy while simultaneously minimizing toxicity. Randomized controlled trials will be needed to definitively establish the safety and efficacy of rifabutin to treat A. baumannii infections.
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