Ceftibuten plus amoxicillin-clavulanic acid for oral treatment of urinary tract infections with ESBL producing E. coli and K. pneumoniae: a retrospective observational case-series

Abstract

This study aimed to evaluate the clinical and bacteriological effect of oral treatment with ceftibuten plus amoxicillin-clavulanic acid in patients with a urinary tract infection (UTI) caused by an extended-spectrum β-lactamase (ESBL)-producing micro-organism. In this retrospective observational case-series, oral treatment with ceftibuten 400 mg QD plus amoxicillin-clavulanic acid 625 mg TID for 14 days was evaluated in ten patients with pyelonephritis caused by an ESBL-positive micro-organism resistant to ciprofloxacin and co-trimoxazole. Presence of ESBL genes was confirmed using PCR and micro-array. EUCAST breakpoints were used for susceptibility testing. Ten patients (five women) were evaluated in 2016 and 2017. Six patients were from outpatient hospital care, and four from primary care. Urinary cultures yielded seven E. coli and three K. pneumoniae ESBL-positive isolates. Using Vitek-2, all isolates were resistant to cefotaxime, and resistant (n = 7) or intermediately susceptible (n = 3) to ceftazidime. With disc diffusion, all isolates were susceptible to ceftibuten (zones 25-32 mm), while with MIC test strips eight of ten isolates were resistant to ceftibuten (MICs 0.5-4 mg/L). An amoxicillin-clavulanic acid disc next to the ceftibuten disc extended the ceftibuten zone by 2-8 mm. All patients experienced clinical cure. Bacteriological cure (absence of pretreatment micro-organism in the first follow-up culture obtained within 3 months after treatment) was observed in all eight patients with follow-up cultures. This case-series shows that the synergistic combination of ceftibuten plus amoxicillin-clavulanic acid may be an option for oral treatment of UTIs caused by ESBL producing E. coli or K. pneumoniae.