Ceftriaxone (CRO), while highly protein bound, retains a small volume of distribution. Obese patients have larger volumes of distributions and higher clearance than non-obese patients. The effect of these differences on the pharmacokinetics and efficacy of CRO remain unclear.
This retrospective cohort study included adult inpatients who received CRO for ≥72 hours (h) as definitive monotherapy from July 2015 to July 2017. Patients were excluded if there was a lack of adequate source control at 72h or if there was a polymicrobial infection requiring multiple antibiotics. Obesity was defined as BMI ≥30 kg/m2. The primary outcome was clinical treatment failure, defined as changing therapy at >72h due to clinical worsening, leukocytosis (WBC>10x109/L), fever (single temperature >100.9°F)for >72h, or readmission to the hospital within 30 days for re-infection. Secondary outcomes included discharge disposition and 30-day readmission.
One hundred one patients were included: 39 obese patients and 62 non-obese patients. Median [IQR] age was 62 [51-70] years; 55% males. Median weight was 103 [95-120] kg in obese patients versus 66 [58-77] kg in non-obese patients (p<0.001). There were no differences in comorbidities (Charlson 3[1-5] obese vs 2[1-4] non-obese; p=0.293). Infection sources were similar: urinary tract (54% obese vs 52% non-obese; p=0.827), respiratory (28% obese vs 23% non-obese; p=0.524), bloodstream (20% obese vs 23% non-obese; p=0.806). The most common causative organism was E. coli(48%). There were no differences in CRO regimen between groups (1g q24h: obese 54% vs non-obese 69%; p=0.115). Treatment failure occurred in 24 (61%) obese patients compared to 25(40%) non-obese patients (p=0.038). Obese patients had delayed resolution of leukocytosis (54% vs 29%, p=0.013). Eight patients died (13% obese vs 5% non-obese; p=0.255); 82% of patients were not readmitted within 30 days.
Obese patients treated with ceftriaxone had higher rates of treatment failure compared with non-obese patients. While not statistically significant, there was numerically higher mortality in obese patients compared with non-obese patients. Obese patients may be slow to recover from infection when treated with CRO.
J. L. Wagner,
A. R. Morrison, None
K. R. Stover, None
K. E. Barber, None