Manjunath P Pai1. 1. Pharmacokinetics Core, Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan. Electronic address: amitpai@med.umich.edu.
Abstract
PURPOSE: Obesity is recognized to be a risk factor for acute bacterial skin and skin structure infections (ABSSSIs) that are associated with methicillin-resistant Staphylococcus aureus (MRSA). Several new antimicrobial agents have been introduced to treat MRSA-related ABSSSI and are dosed with and without regard to weight. This review seeks to explain the pharmacokinetic and pharmacodynamic (PK-PD) rationale for initial and maintenance dosage selection of these newer agents in obese adults. METHODS: A PubMed search was performed using the key words obese or obesity, pharmacokinetics, and the name of each MRSA active drug evaluated in this review. Major themes were identified through a review of this literature. A synopsis of key findings from population PK studies (including reference sources) and independent studies of the PK properties of each new MRSA active agent used to treat ABSSIs were reviewed to derive practical dosing considerations. FINDINGS: Clinical trials of ABSSSIs have increasingly incorporated individuals across a wide body size spectrum. This inclusion of obese adults has been reflected in population PK analyses that have permitted the evaluation of weight and other body size descriptors. In general, the volume of distribution is higher in obese patients, suggesting the need for higher initial (loading) doses if PK bioequivalence is desired. Less certainty exists with selection of a higher maintenance dose, especially for antimicrobial agents with time-dependent PK-PD properties. Selection of higher maintenance doses through alternate scaling approaches in obese patients can be justified on an individual clinical basis. IMPLICATIONS: Maintenance dose modification of several MRSA-targeted anti-infective agents is unlikely to be necessary in obese patients and should be capped if dosed on total weight or this higher dose justified with therapeutic drug monitoring.
PURPOSE:Obesity is recognized to be a risk factor for acute bacterial skin and skin structure infections (ABSSSIs) that are associated with methicillin-resistant Staphylococcus aureus (MRSA). Several new antimicrobial agents have been introduced to treat MRSA-related ABSSSI and are dosed with and without regard to weight. This review seeks to explain the pharmacokinetic and pharmacodynamic (PK-PD) rationale for initial and maintenance dosage selection of these newer agents in obese adults. METHODS: A PubMed search was performed using the key words obese or obesity, pharmacokinetics, and the name of each MRSA active drug evaluated in this review. Major themes were identified through a review of this literature. A synopsis of key findings from population PK studies (including reference sources) and independent studies of the PK properties of each new MRSA active agent used to treat ABSSIs were reviewed to derive practical dosing considerations. FINDINGS: Clinical trials of ABSSSIs have increasingly incorporated individuals across a wide body size spectrum. This inclusion of obese adults has been reflected in population PK analyses that have permitted the evaluation of weight and other body size descriptors. In general, the volume of distribution is higher in obesepatients, suggesting the need for higher initial (loading) doses if PK bioequivalence is desired. Less certainty exists with selection of a higher maintenance dose, especially for antimicrobial agents with time-dependent PK-PD properties. Selection of higher maintenance doses through alternate scaling approaches in obesepatients can be justified on an individual clinical basis. IMPLICATIONS: Maintenance dose modification of several MRSA-targeted anti-infective agents is unlikely to be necessary in obesepatients and should be capped if dosed on total weight or this higher dose justified with therapeutic drug monitoring.
Authors: Kristen L Bunnell; Manjunath P Pai; Monica Sikka; Susan C Bleasdale; Eric Wenzler; Larry H Danziger; Keith A Rodvold Journal: Antimicrob Agents Chemother Date: 2018-03-27 Impact factor: 5.191
Authors: M L Rizk; S M Bhavnani; G Drusano; A Dane; A E Eakin; T Guina; S H Jang; J F Tomayko; J Wang; L Zhuang; T P Lodise Journal: Antimicrob Agents Chemother Date: 2019-04-25 Impact factor: 5.191