Impact of Obesity on Ceftriaxone Efficacy

Abstract

<jats:p>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 &gt; 72 h due to clinical worsening; (2) residual leukocytosis (white blood cell count (WBC) &gt; 10 × 109/L) &gt; 72 h after treatment initiation; (3) presence of a fever (single temperature &gt; 100.9 °F) &gt; 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.</jats:p>

Ceftriaxone 1 g Versus 2 g Daily for the Treatment of Enterobacterales Bacteremia: A Retrospective Cohort Study

“…30,31 Another variable cited in the literature that may influence outcomes is the BMI of patients, notably a BMI of ≥30 kg/m 2 . 32,33 Prior literature has displayed an association of increased rates of clinical failure in this patient population, although we found no statistically significant difference in clinical failure with this subgroup. These inconsistent finding could have likely been due to the limited population we had available within that group.…”

“…These inconsistent finding could have likely been due to the limited population we had available within that group. 32,33 Along with EUCAST currently recommending breakpoints based on 2-g CRO daily dosing, certain global guidelines make recommendations for 2 g of CRO daily in contrast to certain Infectious Diseases Society of America guidelines that give 1 to 2 g ranges for other types of infections. 18,34,35 Clinical data are limited, but current extrapolated PK and clinical data along with our findings further argue that CRO 2 g standard dosing for most infections may be needed for optimal CRO target attainment in the general population, especially with limited access to beta-lactam therapeutic drug monitoring for many institutions.…”

Antimicrobial Dosing in Specific Populations and Novel Clinical Methodologies: Obesity

“…These findings confirm results of a larger Canadian survey demonstrating an adjusted odds ratio of 1.26 (95% confidence interval 1.03–1.52) associated with obesity and antibiotic treatment failure based on a review of the most frequently prescribed antibiotics: amoxicillin, ciprofloxacin, phenoxymethylpencillin, trimethoprim/sulfamethoxazole, and clarithromycin 21 . A higher failure rate was recently reported with the use of ceftriaxone in obese compared with nonobese patients 22 . Although it is uncertain if drug dosing contributes directly to these difference in clinical outcomes, it serves as the most actionable intervention because, in most instances, standard fixed doses are used irrespective of body size.…”

“…21 A higher failure rate was recently reported with the use of ceftriaxone in obese compared with nonobese patients. 22 Although it is uncertain if drug dosing contributes directly to these difference in clinical outcomes, it serves as the most actionable intervention because, in most instances, standard fixed doses are used irrespective of body size. Bridging the "real-world" and regulatory drug dosing gap for patients with severe obesity begins with inclusion of more details about the underlying study population body size in the drug dosing label.…”

Septic shock from multiple intra-abdominal Streptococcus constellatus abscesses unamenable to percutaneous drainage

“…Guidelines recommend Ceftriaxone as the preferred antimicrobial agent [ 12 ]. However, Ceftriaxone has been associated with treatment failure in obese patients and this may be the reason for continued sepsis in our patient despite higher dosing of 2g IV daily [ 13 ]. Other commonly available antimicrobial options include Penicillin and Amoxicillin.…”