Standard Dosage Regimens of Broad-Spectrum β-Lactams are Inadequate to Treat “Difficult-to-Treat” Pathogens in Obese Noncritically Ill Patients

Phil Vinall

doi:10.1177/155989771214013

Summary

Results of a large case series of broad spectrum β-lactam agents in obese noncritically ill patients with infection treated using standard dose regimens showed insufficient measured serum concentrations to treat difficult-to-treat pathogens. This article presents a poster [Hites et al. ICAAC 2012 a-637] that suggested altered pharmacokinetics in obese patients may be responsible.

Emerging Therapies
Bacterial Infections
Obesity

Results of a large case series of broad spectrum β-lactam agents in obese noncritically ill patients with infection treated using standard dose regimens showed insufficient measured serum concentrations to treat difficult-to-treat pathogens. Maya Hites, MD, Hôpital Erasme, Brussels, Belgium, presented a poster [Hites et al. ICAAC 2012 a-637] that suggested altered pharmacokinetics (PKs) in obese patients may be responsible.

This prospective study was conducted between October 2011 and May 2012 at a single institution. All consecutive adult (>18 years of age) obese (body mass index [BMI] ≥30 kg/m²) patients with acute infection treated with standard doses of broad spectrum β-lactams (cefepime or ceftazidime [CEF], piperacillin-tazobactam [TZP], or meropenem [MEM]) were enrolled (Table 1).

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Table 1.

Standard Doses of β-lactams Adapted to Renal Function.

Two serum samples were taken during the elimination phase after 30 minutes of intravenous β-lactam infusion to estimate PK and calculate the percentage of time spent above minimum inhibitory concentration (MIC). Serum drug concentrations were measured with high-pressure liquid chromatography. Adequate therapy was defined as a serum concentration 4 to 8 times the MIC for difficult-to-treat Gram-negative bacteria (eg, for Pseudomonas aeruginosa, optimal time>MIC: >70% for CEF, >50% for TZP, or >40% for MEM).

Thirteen men and 16 women were enrolled in the study. Subjects were a mean age of 64 years. Mean BMI and creatinine clearance were 35 kg/m² and 91.5 mL/min, respectively. Comorbidities included chronic obstructive pulmonary disease (13.8%), diabetes (41%), cardiomyopathy (48%), renal insufficiency (21%), and neoplasia (41%); 28% of patients reported no comorbidities. The sites of infection included the abdomen (48%), skin (21%), urinary tract (17%), lung (10%), and other (4%).

Thirty-eight drug levels were obtained from the 29 patients treated with standard-dose regimens; 10 serum drug concentrations were obtained in 5 of these patients who were treated with an increased dose regimen (1 g every 6 hours of MEM as a 3-hour infusion and a median of 22 g/day TZP as a continuous infusion). Twenty-nine of 38 serum drug concentrations (3/5 CEF, 10/11 MEM, 16/22 TZP) were insufficient to treat difficult-to-treat pathogens. Four of 10 serum drug concentrations in 5 patients treated with increased drug regimens were adequate (1/2 MEM, 3/8 TZP).

Prof. Hites concluded that recommended dosage regimens of broad spectrum β-lactam agents for obese noncritically ill patients needs to be reconsidered.

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