Antibiotic dosing in obesity: the search for optimum dosing strategies

Abstract

Global obesity has nearly doubled and is now a common occurrence in high-income and developing countries. The World Health Organization estimates that more than 1.4 billion adults are obese. Although the prevalence of obesity is increasing over the last decades, pharmacokinetic evaluations are still conducted in individuals with a body weight of approximately 70 kg. Morbid obesity is associated with several pathophysiological changes that can profoundly affect drug distribution and clearance. There are currently no specific dosing recommendations for antibiotics in obese patients, making dosing suggestions primarily based on pharmacokinetic characteristics of the medications and dosing recommendations in other disease states. Understanding of the pharmacokinetic alterations and maximum doses of antibiotics safely used is paramount to appropriate treatment in the obese population.

Population Pharmacokinetics of Cefazolin in Serum and Adipose Tissue From Overweight and Obese Women Undergoing Cesarean Delivery

“…Obesity has a complex influence on the pharmacokinetics of antimicrobials, including but not limited to an increase in the volume of distribution and changes in hepatic metabolism and renal excretion, affecting drug clearance. Combined with pharmacokinetic changes induced by pregnancy, there is a need to determine a correct dosage of cefazolin for overweight and obese pregnant women who are undergoing CD …”

“…Combined with pharmacokinetic changes induced by pregnancy, there is a need to determine a correct dosage of cefazolin for overweight and obese pregnant women who are undergoing CD. [10][11][12] Two recently published clinical studies in which the current study authors were involved (M.L.S., 13 L.M., 14 B.L.H., 14 D.N. 13,14 ) determined the concentrations of cefazolin in adipose tissue (AT) after 2-or 3-g prophylactic doses in obese patients undergoing CD.…”

Besonderheiten der Antibiotikatherapie bei Adipositas

“…Klare Empfehlungen zur Dosierung von Antibiotika bei adipösen Patienten sind leider selten: Dosisangaben in den Leitlinien und Fachinformationen beziehen sich in der Regel auf ein durchschnittliches Körpergewicht von 70 kg und fallen damit möglicherweise zu niedrig aus. Das immer noch vorherrschende Dogma "one size fits all" (5) (9,10). ▶ Tabelle 1 listet die Antibiotika auf, für die Empfehlungen anhand der genannten Gewichtseinheiten identifiziert werden konnten.…”

“…Da das Verteilungsvolumen und die Clearance dieser Antibiotika bei adipösen Patienten verändert sind, würde die Standarddosis für Bakterien mit erhöhter minimaler Hemmkonzentration nicht ausreichen. Für einige Betalaktam-Antibiotika wie beispielsweise Cefazolin, Cefepim, Piperacillin/Tazobactam und Er-Lipophilie von Antibiotika (modifiziert nach[9,10]). Dosisempfehlungen ausgewählter Standard-Antibiotika bei häufigen Erkrankungen (FI -jeweilige Fachinformation(18).…”

“…Körpergewichtsformeln und deren Anwendung bei der gewichtsadaptierten Antibiotika-Dosierung (modifiziert nach[9,10]). …”