Optimization of Antibiotic Therapy in the Obese, Critically Ill Patient

As the prevalence of obesity increases worldwide, clinicians will be more and more frequently confronted with obese, critically ill patients. Optimal administration of antibiotics is already a challenge in the critically ill patient because pharmacokinetics (PK) of antibiotics is often altered, and infections are more frequently caused by resistant pathogens than in the non-critically ill patient. Obesity per se may further alter the PK of antibiotics. This paper provides a narrative review of the potential PK changes of antibiotics in the obese, critically ill patient, and recommendations for optimal antibiotic therapy for the most frequently used antibiotics. However, these recommendations are essentially based on small sample-sized PK studies with no evaluation of outcome, and thus must be considered with caution. On one hand, critically ill patients may need higher than recommended regimens of beta-lactams, linezolid, moxifloxacin, levofloxacin, tigecycline, and colistin; however, no further dose adjustment is necessary in obese, septic patients. Increased dosage regimens of beta-lactams may be necessary only to treat obese, non-critically ill patients. On the opposite, dosage regimens should be based on total body weight for amikacin in patients with a body mass index (BMI) between 20 and 40 kg/m(2), vancomycin, and daptomycin, and on adjusted body weight for ciprofloxacin, gentamycin, tobramycin, and amikacin in patients with a BMI greater than 40 kg/m(2). Because of the lack of PK studies in this special patient population, and the large inter- and intra-individual PK drug variability in critically ill patients, we recommend therapeutic drug monitoring of all antibiotics administered, whenever possible, to optimize drug therapy.