Abstract
Background: Ceftriaxone has standard, set dosing regimens that may not achieve adequate serum concentrations in obese patients compared to non-obese patients. The purpose of this study was to evaluate the effect of obesity on ceftriaxone efficacy when used as definitive monotherapy to treat infections. Methods: This retrospective cohort included adult inpatients treated with ceftriaxone monotherapy for ≥72 h between July 01, 2015–July 31, 2017. Patients were excluded if their infection lacked source control within 72 h or if they had polymicrobial infections requiring more than one antibiotic for definitive therapy. The primary outcome was the rate of clinical failure between obese versus non-obese patients, defined as a composite of (1) change in definitive therapy > 72 h due to clinical worsening; (2) residual leukocytosis (white blood cell count (WBC) > 10 × 109/L) > 72 h after treatment initiation; (3) presence of a fever (single temperature > 100.9 °F) > 72 h after treatment initiation; or (4) readmission within 30 days due to re-infection with the same organism. Results: A total of 101 patients were included in the study: 39 obese and 62 non-obese. The most common indications for ceftriaxone were urinary tract (52.5%), respiratory tract (24.8%), and bloodstream (24.8%) infections. The most commonly isolated organisms were Escherichia coli (48.5%) and Klebsiella species (15.8%). Most patients received 1g every 24 h. Clinical failure was observed in 61.5% of obese patients versus 40.3% of non-obese patients (p = 0.038). Conclusion: Obese patients treated with ceftriaxone were more likely to experience clinical failure when compared to non-obese patients. Further analyses are warranted to determine if weight-based dosing is required in obese patients treated with ceftriaxone.
Highlights
Ceftriaxone has standard, set dosing regimens that may not achieve adequate serum concentrations in obese patients compared to non-obese patients
Irrespective of the source of infection or organism isolated, obese patients treated with ceftriaxone were more likely to experience clinical failure when compared to non-obese patients
A study by Herishanu et al noted that obese patients were more likely to have a low-grade reactive leukocytosis [7], which could explain the findings of persistent leukocytosis and possibly the addition of a second antibiotic in our cohort
Summary
Ceftriaxone has standard, set dosing regimens that may not achieve adequate serum concentrations in obese patients compared to non-obese patients. The primary outcome was the rate of clinical failure between obese versus non-obese patients, defined as a composite of (1) change in definitive therapy > 72 h due to clinical worsening; (2) residual leukocytosis (white blood cell count (WBC) > 10 × 109 /L) > 72 h after treatment initiation; (3) presence of a fever (single temperature > 100.9 ◦ F) > 72 h after treatment initiation; or (4) readmission within 30 days due to re-infection with the same organism. Conclusion: Obese patients treated with ceftriaxone were more likely to experience clinical failure when compared to non-obese patients. Are morbidly obese (≥40 kg/m2 ) [1,2] These patients are at an increased risk of infection and poor therapeutic outcomes when compared to average weight patients [3]. Clinicians are increasingly faced with the challenge of dosing medications in obese patients
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