Clinical Outcomes of Failing to Dose-Reduce Cephalosporin Antibiotics in Older Adults with CKD

Background and objectives Current dosing recommendations for cephalosporin antibiotics are on the basis of pharmacokinetic studies and are frequently ignored in practice. This study was undertaken to investigate the clinical outcomes of failing to dose-reduce cephalosporin antibiotics in CKD. Design, setting, participants, & measurements Retrospective cohort study conducted in Ontario, Canada using linkedpopulation-basedhealthcaredatabases. Nine thousandthreehundred forty-sevenoutpatients (median age 83; interquartile range, 77-88 years; 57% women) with an eGFR, 30 ml/min per 1.73 m2 and no prior history of dialysis were dispensed oral cephalexin, cefuroxime, or cefprozil between April of 2007 andMarch of 2016. Two thirds of the patients (6253 of 9347) received a higher than recommended daily dose of cephalexin (>1000 mg), cefuroxime (>500mg), or cefprozil (>500mg). The primary outcome was a hospital encounter (emergency room visit or hospital admission) with a condition listed as a possible side-effect of cephalosporins. Secondary outcomes were antibiotic treatment failure and all-cause mortality. All measures were assessed in the 30 days after cephalosporin initiation. Results Patients who received a higher than recommended dose of a cephalosporin antibiotic were similar in multiple indicators of baseline health to patientswho received a reduced dose. Overall, 6% of patients presented to hospitalwith a possible cephalosporin side-effect, 13% failed antibiotic treatment, and 3% died. Comparedwith a reduced dose, receiving a higher dose of antibiotic was not associatedwith a different rate of side-effects (adjusted odds ratio, 1.00; 95% confidence interval, 0.84 to 1.20), treatment failure (1.01; 0.88 to 1.15), or death (0.99; 0.76 to 1.29). Conclusions In this study we failed to demonstrate any association between the dose of cephalosporin antibiotic administered to elderly patientswithCKDand the risk of side-effects leading to hospitalization, treatment failure, or mortality.