Updated Guidelines on Optimal Antibiotic Dosing for Patients With Obesity

Updated recommendations for antibiotic dosing in patients with obesity were published in Pharmacotherapy.

Some patients with obesity have sufficiently altered muscle and fat composition to alter the pharmacokinetics (PK) dosing regimens of antimicrobials. In general, the higher total body weight increases the volume of distribution, but this relationship is not always linear and the nonlinearity can affect loading dose calculations. For medications with limited ability to enter adipose tissue, adjusted body weight may be a better way to calculate loading doses.

The previous recommendations on antibiotic dosing in obesity were published in 2017 and covered dosing recommendations for 34 antimicrobial agents.

For these updates, the review authors searched publication databases for studies published between 2017 and 2022. Data from 120 articles were used to update dosing recommendations for 41 antimicrobials. The review authors focused on patients with a BMI equal to or greater than 30 kg/m² and normal kidney function.

β-lactams

In β-lactams, there were insufficient data to formulate specific obesity-related guidelines for the use of ampicillin, cefazolin, cefpodoxime, ceftriaxone, cephalexin, imipenem, and nafcillin. There also were no updates on the use of avibactam, ceftazidime, ceftolozane, ertapenem, or tazobactam.

The β-lactams-specific updated dosing recommendations were for the use of 2-g intravenous (IV) infusion of cefepime or ceftazidime every 8 hours; a 2-g IV infusion of meropenem every 8 hours; and a 4.5-g IV infusion of piperacillin-tazobactam every 6 or 8 hours.

Monobactams

For monobactams such as aztreonam, there were insufficient data to update dosing recommendations for patients with obesity.

Fluoroquinolones

There were no changes to dosing recommendations for the use of moxifloxacin or delafloxacin. For ciprofloxacin and levofloxacin, updated recommendations included the administration of a 400-mg IV infusion every 8 hours and a 750-mg IV infusion or oral dose every 24 hours, respectively.

Aminoglycosides

In regard to amikacin, gentamicin, and tobramycin, the authors recommended for an area under the curve or minimum inhibitory concentration dosing approach, as well as the use of Cockcroft-Gault adjusted body weight for the calculation of initial the loading dose. No changes were recommended for trough-based dosing.

Polymyxins

There were no updates for colistin methanesulfonate dosing. In regard to polymyxin B, there were limited data to update dosing recommendations. However, the authors recommended that a maximum daily dose of 200 to 249 mg be considered to limit toxicity risk, though this recommendation was not based on clinically validated data.

Anti-Methicillin Resistant Staphylococcus aureus (MRSA) Agents

There were no changes to dosing recommendations for ceftaroline, dalbavancin, daptomycin, eravacycline, linezolid, omadacycline, or tedizolid. In addition, data were insufficient to update dosing recommendations for oritavancin.

Updated recommendations were provided for clindamycin, trimethoprim-sulfamethoxazole, telavancin tigecycline, and vancomycin. For clindamycin, The authors recommended a 600- or 900-mg IV infusion every 6 to 8 hours, respectively; recommendations for oral dosing included 450 to 600 mg every 6 hours or 600 to 900 mg every 8 hours.

For the use of trimethoprim-sulfamethoxazole in the settings of severe or complicated urinary tract infection and skin and soft tissue infection, a dose of up to 320 mg every 12 hours was recommended. For telavancin, a 750-mg dose every 24 hours was recommended. For tigecycline, updated recommendations included a 100-mg dose every 12 hours in the setting of resistant infection due to Gram-negative organisms. For vacomycin, the authors recommended a maximum loading dose of 3 g and an initial dose of 4.5 g.

There were either no or insufficient data to recommend changes for metronidazole, fosfomycin, or lefamulin dosing.

Of note, patients with obesity were either missing or underrepresented in most of the reviewed studies.

In regard to patients with obesity, “Extended infusions of time-dependent antibiotics may provide a safe way to overcome any potential PK variability,” the authors noted. “Areas for future studies include identification of optimal body size descriptors, dosing weight scalars, estimation method of renal function, and role for cystatin C in obese patients,” they concluded.