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Optimal antibiotic dosing for obese patients a challenge for clinicians
It is sometimes unclear whether total body weight should be used or if an adjusted body weight may be more appropriate.
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According to statistics from the National Institute of Diabetes and Digestive Kidney Disorders, more than 65% of Americans are overweight or obese. Much attention is paid to the negative consequences of excess body weight, including the risk for diabetes and cardiovascular disease. However, there is little guidance for clinicians treating infection in this patient population.
One particular challenge is determining optimal antibiotic dosing for obese patients. An obvious concern is how to approach agents that rely on weight-based dosing. Based on drug distribution properties, it is sometimes unclear whether total body weight should be used or if an adjusted body weight may be more appropriate (such as for drugs not distributed in adipose tissue). Further concerns arise from altered pharmacokinetics due to physiologic changes in the obese patient.
This article will summarize the limited data available for dosing anti-infective agents in the obese patient, as well as the effect of obesity on estimating renal function.
Agent-specific data
Elizabeth Dodds Ashley
Table 1 summarizes available data and recommendations regarding available anti-infective agents. When available, suggestions for dosing are included.
Effect of obesity
An estimate of glomerular filtration rate is necessary to appropriately dose any medication that relies on renal elimination. The Cockcroft-Gault equation, one of the most common methods for estimating creatinine clearance as a surrogate for GFR, relies on body weight as part of the calculation.
Source: Elizabeth Dodds Ashley, PharmD, MHS
Total body weight greatly overestimates renal function in obese patients. However, since obese patients have slightly increased renal function, ideal body weight does not sufficiently estimate this parameter in the obese patient, either. Use of an adjusted body weight (IBW + 0.4 [TBW-IBW]) may provide a more accurate estimate in obese patients but still has many limitations.
Two newer equations, the Salazar-Cororan and the Modification of Diet in Renal Disease (MDRD), both attempt to address the effect of body weight on estimates of GFR.
The Salazar-Corcoran equation to calculate creatinine clearance has been validated in obese patients. However, as it still includes body weight, it also may overestimate clearance when using total body weight.
The MDRD does not include body weight as a factor; however, this method of estimating GFR has not been validated in obese patients. In addition, studies of drug dosing in renal failure are generally performed using creatinine clearance estimates, and therefore, dosing guidelines may not be consistent when using GFR estimates as a tool for drug dosing.
Drug dosing in the obese patient population remains an inexact science. It is clear that we need more data in this patient population to effectively treat infections. Further clinical investigations into this issue are warranted and should be pursued.
Source: Elizabeth Dodds Ashley, PharmD, MHS
For more information:
- Pai MP, Bearden DT. Antimicrobial dosing considerations in obese adult patients. Society of Infectious Diseases Newsletter; Winter 2007.
- Siu D. “Weighing in” on antibiotic dosing in obese patients. Drug Therapy Topics. 2006;35:1-4.
- Wurtz R, Itokazu G, Rodvold K. Antimicrobial dosing in obese patients. Clin Infect Dis. 1997;25:112-118.