By Stan Deresinski, MD, FIDSA, FACP
Cefdinir was inferior to cephalexin in the treatment of uncomplicated urinary tract infections in women due to a high rate of early recurrence.
Mitzner TM, Eid KM, Hughson DM, et al. Cefdinir versus cephalexin for the treatment of uncomplicated urinary tract infections. Open Forum Infect Dis. 2025;12(10):ofaf501.
Mitzner and colleagues retrospectively examined the relative efficacies of cefdinir and cephalexin in the treatment of uncomplicated urinary tract infections (UTIs) in non-pregnant adult females. All patients were symptomatic, but urine culture was not required for inclusion. Of the 367 patients in this multicenter study, 167 had been prescribed cefdinir 300 mg twice daily and 200 were prescribed cephalexin 500 mg twice daily, each for five to seven days. Treatment failure was defined as recurrent or continued urinary symptoms necessitating re-treatment within 30 days.
Those prescribed cefdinir were older, with a median age of 67 years, compared to 52 years in the cephalexin recipients (P < 0.001). They also had a lower median creatinine clearance (72 mL/min vs. 83 mL/min; P < 0.001) and a higher Charlson comorbidity index (3 vs. 2; P < 0.001). Those who received cefdinir also were more likely to have had a urine culture at baseline — 92% vs. 79% (P < 0.001). As expected, Escherichia coli was the most frequently isolated organism.
Treatment failure occurred in 1.8% of cefdinir recipients and 1% of those prescribed cephalexin during their initial treatment, but by the end of the study period at 30 days the rate of symptomatic recurrence was significantly greater in the cefdinir group, in whom it occurred in 21.6% compared to 11.5% (P = 0.009). Overall, 30-day treatment failure occurred in 23.4% and 12.5% (P = 0.006) of cefdinir and cephalexin recipients, respectively. Multivariate logistic regression determined that cefdinir treatment was the only variable independently associated with treatment failure (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1 to 3.4).
Positive urine culture at recurrence yielded a cefazolin-resistant pathogen in 37% who had been treated with cefdinir but in 0% of cephalexin-treated patients (P = 0.024); the comparison was similar with ceftriaxone. In each case of emergent resistance, their isolates had been susceptible to cephalosporins at baseline.
Commentary
While suffering from its non-randomized retrospective design, together with the lack of a baseline urine culture in a portion of the subjects, the results of this study are clear: Cefdinir is an inferior antibiotic for the treatment of urinary tract infection. The oral bioavailability of the drug is only 16% to 20%, and after a 300-mg dose only 18.4% is excreted unchanged in the urine. In contrast, the oral bioavailability of cephalexin is approximately 90%, which also is the proportion of excreted unchanged in urine.
The selection of cephalosporin-resistance with cefdinir use is remarkable, especially when compared to its absence with cephalexin. One possibility is differential effects on the intestinal microbiome, with recurrence caused by selection of resistant organisms whose proportion had increased with exposure to cefdinir.
Stan Deresinski, MD, FACP, FIDSA, is Clinical Professor of Medicine, Stanford University.
