Comprehensive guidance for antibiotic dosing in obese adults: 2022 update

Abstract

Drug dosing in obese patients continues to be challenging due to a lack of high-quality evidence to guide dosing recommendations. We first published guidance for antibiotic dosing in obese adults in 2017, in which we critically reviewed articles identified from a broad search strategy to develop dosing recommendations for 35 antimicrobials. In this updated narrative review, we searched Pubmed, Web of Science, and the Cochrane Library using Medical Subject Headings including anti-infectives, specific generic antimicrobial names, obese, pharmacokinetics, and others. We reviewed 393 articles, cross-referenced select cited references, and when applicable, referenced drug databases, package inserts, and clinical trial data to update dosing recommendations for 41 antimicrobials. Most included articles were pharmacokinetic studies, other less frequently included articles were clinical studies (mostly small, retrospective), case reports, and very rarely, guidelines. Pharmacokinetic changes are frequently reported, can be variable, and sometimes conflicting in this population, and do not always translate to a documented difference in clinical outcomes, yet are used to inform dosing strategies. Extended infusions, high doses, and therapeutic drug monitoring remain important strategies to optimize dosing in this population. Additional studies are needed to clinically validate proposed dosing strategies, clarify optimal body size descriptors, dosing weight scalars, and estimation method of renal function in obese patients.

The Effect of Vancomycin and Piperacillin-Tazobactam on Incidence of Acute Kidney Injury in Patients With Obesity

“…7,8,25 Future research should evaluate AUC guided vancomycin dosing along with use of extended antibiotic infusions (vancomycin and piperacillin-tazobactam), as these strategies may prove to be pharmacokinetically superior for obese patients and in reducing AKI. 1,14 Our study has limitations, including that it was a small retrospective study with mostly male veteran patients, which may limit the external validity and application of our findings to other patient populations. Confounding was likely present due to administration of nephrotoxic agents and higher vancomycin doses affecting our primary outcome.…”

“…7,8,25 Future research should evaluate AUC guided vancomycin dosing along with use of extended antibiotic infusions (vancomycin and piperacillin-tazobactam), as these strategies may prove to be pharmacokinetically superior for obese patients and in reducing AKI. 1,14…”

“…6 Obesity affects nearly 40% of the United States population and can cause significant differences in the pharmacokinetic properties of antibiotics including a non-linear increase in volume of distribution (Vd), and an increase in renal clearance. 1,[13][14][15] Despite the well-known nephrotoxic effects of VPT, its effects on renal function have not been specifically evaluated in an obese patient population, whose prevalence is increasing. However, monotherapy with either vancomycin or piperacillin-tazobactam has been evaluated in patients with obesity.…”

Weighing the Odds: Novel β-Lactam/β-Lactamase Inhibitor Use in Hospital-Acquired and Ventilator-Associated Pseudomonas aeruginosa Pneumonia for Patients Who Are Morbidly Obese

“…Selecting appropriate antimicrobial dose regimens for patients who are critically ill and obese is challenging due to the various pathophysiologic alterations associated with obesity, including differences in cardiac output, lean fat masses, and renal blood flow [ 10 , 11 ]. Such alterations can affect drug pharmacokinetics (PK), resulting in altered drug exposure and therapeutic failure [ 11 ].…”

“…Clinicians frequently employ novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations to treat challenging cases of HABP/VABP caused by P aeruginosa [ 14 ]. Limited data exist to guide the dosing of novel BL/BLI in patients who are morbidly obese [ 10 , 15 , 16 ]. This study aimed to compare clinical and safety outcomes in patients with and without morbid obesity with P aeruginosa HABP/VABP who were receiving ceftazidime/avibactam, ceftolozane/tazobactam, or meropenem/vaborbactam as definitive therapy.…”