Dosing of antibacterial agents in obese adults: does one size fit all?

Abstract

Obesity is a global pandemic affecting 33% of adults in the United States. Obese persons receiving cefazolin or fluconazole have been shown to have worse outcomes with suboptimal dosing. Studies evaluating the safety of colistin, daptomycin, and vancomycin have shown increased weight or obesity may potentially increase toxicity. Many antimicrobials lack pharmacokinetic data to support dose individuation in obese persons, due in part to the lack of obese patients in drug development studies. A one size fits all approach to dose optimization for obese patients is not likely. Current expert opinion suggests some antimicrobials (i.e. vancomycin) be dosed according to total body weight, whereas others (i.e. aminoglycosides) require adjusted body weight for dose calculations. Yet other antimicrobials are reported to need no dose adjustment, largely based on studies using body mass index groups. Therefore, each drug should be individually evaluated to determine the proper dose for obese persons.

Keywords::

• antibacterial
• BMI
• body weight
• dose adjustment
• obesity
• pharmacokinetics

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Obesity is a global pandemic.

• Obesity alters pharmacokinetic parameters such as the volume of distribution, clearance, maximum and minimum drug concentrations (C_max, C_min), area under the curve and half-life.

• Few studies have been performed to assess what weight descriptors or overall method of creatinine clearance estimation is most accurate for obese patients.

• Few studies have been performed in the obese populations for most antibacterial agents.

• Existing data for dosing antibacterials in obese persons are limited by small sample sizes.

• Vancomycin initial doses should be calculated using total body weight with patient-specific dosing adjustments performed based on steady-state trough concentrations following the initial dose.

• Aminoglycosides (amikacin, gentamicin, tobramycin) initial dosing should utilize ideal body weight plus a 40% excess body weight (total body weight-ideal body weight) correction factor with patient-specific adjustments based on peak and trough concentrations for subsequent doses.

• Obese patients have a higher risk of failing antituberculosis therapy than normal weight patients due to alterations in pharmacokinetic parameters.

• Other antimicrobial classes have varying alterations of pharmacokinetic parameters, necessitating evaluation of each individual agent.

• When dosing antibiotic agents, considerations should be given for severity of infection, infection site, infecting pathogen, local susceptibilities and patient-specific factors that affect the pharmacokinetics and pharmacodynamics of the medications.