Article
Pharmacokinetic and Pharmacodynamic Profiling of Minocycline for Injection Following a Single Infusion in Critically Ill Adults in a Phase IV Open-Label Multi-Center Study (ACUMIN)
Antimicrobial Agents and Chemotherapy
(2020)
Abstract
Intravenous (IV) minocycline is increasingly used to treat infections caused by multi-drug resistant (MDR)-Acinetobacter baumannii. Despite being approved nearly 50 years ago, published information on its pharmacokinetic (PK) prolife is limited. This multi-center study examined the PK and probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment profile of IV minocycline in critically ill patients, with suspected or documented infection with Gram-negative bacteria. The PK study population included 55 patients who received a single 200 mg IV dose of minocycline. Plasma PK samples were collected pre-dose and 1, 4, 12, 24, 36, and 48 hours after initiation of minocycline. Total and unbound minocycline concentrations were determined at each timepoint. Probabilities of achieving the PK-PD targets associated with stasis and 1-log killing (fAUC:MIC of 12 and 18, respectively) were evaluated. A two-compartment population PK model with zero-order IV input and first-order elimination, which estimated a constant fraction unbound (fub) for minocycline, best characterized the total and unbound plasma minocycline concentration-time data. The only two covariates retained in the final PK model were body surface area [associated with central volume of distribution] and albumin (associated with fub). In the PK-PD target attainment analyses, minocycline 200 mg IV Q12H was predicted to result in a suboptimal PK-PD profile for patients with A. baumannii infections with MIC values ≥ 1 mg/L. These findings cast uncertainty on the appropriateness of the current minocycline FDA susceptibility breakpoints and suggest that clinicians should strongly consider only combination antibiotic therapy with IV minocycline for all patients with serious Acinetobacter sp. infections.
Disciplines
Publication Date
November 9, 2020
DOI
10.1128/AAC.01809-20
Citation Information
Lodise TP, Van Wart S, Sund ZM, Bressler AM, Khan A, Makley AT, Hamad Y, Salata RA, Silveira FP, Sims MD, Kabchi BA, Saad MA, Brown C, Oler RE Jr, Fowler V Jr, Wunderink RG. Pharmacokinetic and Pharmacodynamic Profiling of Minocycline for Injection following a Single Infusion in Critically Ill Adults in a Phase IV Open-Label Multicenter Study (ACUMIN). Antimicrob Agents Chemother. 2021 Feb 17;65(3):e01809-20. doi: 10.1128/AAC.01809-20. PMID: 33168615; PMCID: PMC8092545.