title: Impact of hospital guideline for weight-based antimicrobial dosing in morbidly obese adults and comprehensive literature review.
abstract: OBJECTIVE
  Obesity is a significant burden on the healthcare system in the United States, and determining the appropriate antimicrobial dosing regimen in morbidly obese patients is challenging. Morbidly obese patients have documented differences in pharmacokinetic and pharmacodynamic properties compared to normal-weight patients, which impact antibiotic efficacy and toxicity. The Food and Drug Administration does not recognize obesity as a special population and does not require pharmaceutical companies to perform studies specific to obese patients. However, there are an increasing number of post-approval studies in obese patients, and this manuscript reviews available clinical and pharmacokinetic literature regarding weight-based antimicrobial agents. Additionally, we describe a single-centre approach to optimize dosing in morbidly obese patients.
  
  
  METHODS
  A comprehensive literature search was performed on 15 weight-based antimicrobials in the setting of obesity: acyclovir, aminoglycosides, amphotericin B, cidofovir, colistimethate, daptomycin, flucytosine, foscarnet, ganciclovir, quinupristin/dalfopristin, trimethoprim/sulfamethoxazole, vancomycin and voriconazole. A weight-based antimicrobial dosing guideline for morbidly obese patients was developed. An analysis of guideline compliance and cost analysis were performed following guideline implementation.
  
  
  CONCLUSIONS
  This review describes the pharmacokinetic changes that occur in obese patients, including increased volume of distribution, altered hepatic metabolism, renal excretion and changes in protein binding. The majority of weight-based antimicrobials result in increased serum concentrations in morbidly obese patients compared to normal-weight patients when the calculated dose is based on actual body weight.
  
  
  CONCLUSIONS
  This review demonstrates different antibiotic pharmacokinetic properties are altered in obese patients that could impact efficacy and toxicity. A single-centre guideline for weight-based antimicrobial dosing in obesity was developed and provides recommendations for using ideal body weight, adjusted body weight or actual body weight when calculating antimicrobial doses. However, more research is needed to better elucidate optimal dosing of weight-based antimicrobials in obesity, with particular focus on efficacy and toxicity.
authors.affiliation: Department of Pharmacy, University of Michigan Hospitals and Health Centers, Ann Arbor, MI, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Polso
authors.forename: J L
authors.initials: JL
authors.lastname: Lassiter
authors.forename: J L
authors.initials: JL
authors.lastname: Nagel
mesh_terms: D000328:Adult; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001835:Body Weight / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006761:Hospitals; D006801:Humans; D009767:Obesity, Morbid / Q000503:physiopathology*; D017410:Practice Guidelines as Topic; D014018:Tissue Distribution
chemical_list: D000890:Anti-Infective Agents
keywords: antibiotics; antimicrobials; obesity; pharmacodynamic; pharmacokinetic