7432-s and Klebsiella-Infections

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.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactamases; Ceftibuten; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Urinary Tract Infections; Uropathogenic Escherichia coli

Increasing resistance in Escherichia coli and Klebsiella pneumoniae to firstline antibiotics makes therapeutic options for urinary tract infections (UTIs) challenging. This study investigated the in vitro efficacies of 6 antibiotics against multidrug resistant (MDR) uropathogens.. Minimum inhibitory concentrations to ceftibuten, cefpodoxime, fosfomycin, mecillinam, temocillin, and trimethoprim were determined against 155 MDR-isolates of E. coli and K. pneumoniae. The presence of extended-spectrum beta-lactamases (ESBL) and plasmid-borne AmpC enzymes was determined by phenotypic testing with genotyping performed by multiplex polymerase chain reaction.. Temocillin demonstrated highest susceptibility rates for both E. coli (95%) and K. pneumoniae (95%) when breakpoints for uncomplicated UTIs were applied; however, temocillin susceptibility was substantially lower when "systemic infection" breakpoints were used. Fosfomycin demonstrated the best in vitro efficacy of the orally available agents, with 78% and 69% of E. coli and K. pneumoniae isolates susceptible, respectively. The next most effective antibiotics were ceftibuten (45%) and mecillinam (32%). ESBL and ampC genes were present in 47 (30%) and 59 (38%) isolates.. This study demonstrated few oral therapeutic options for MDR-uropathogens, with fosfomycin demonstrating the best in vitro activity.

Topics: Amdinocillin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cefpodoxime; Ceftibuten; Ceftizoxime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Genotype; Humans; In Vitro Techniques; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multiplex Polymerase Chain Reaction; Penicillins; Singapore; Trimethoprim; Urinary Tract Infections

Infections caused by Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) are a growing clinical problem. However, there is wide variation in the level of resistance to third generation beta-lactams conferred by these enzymes.. We studied 33 Klebsiella pneumoniae and 4 Escherichia coli isolates producing ESBLs obtained from outbreaks in 14 different hospitals and a nursing home in the United States. Microdilution testing with standard (10(4-5) colony-forming units/ml) and large (10(6-7) colony-forming units/ml) inocula, was used to compare the minimum inhibitory concentrations (MICs) of ceftibuten, a novel oral oxyimino beta-lactam, with those of other third generation beta-lactams (cefotaxime, ceftazidime, aztreonam, cefixime, cefpodoxime and cefoxitin).. Twenty-seven of the clinical isolates had well-characterized ESBLs of 10 different types, 7 of which produced TEM-1; 1 isolate also produced LXA-1. Two strains produced more than 1 ESBL. The remaining 10 strains produced 8 as yet uncharacterized types of ESBL. With large inocula 73% tested susceptible to ceftibuten, whereas 8 to 22% tested susceptible to the other third generation beta-lactam antibiotics. Ceftibuten MICs increased with higher inocula when tested against strains producing SHV-4 or SHV-5 and, to a lesser extent, strains producing multiple beta-lactamases. Only cefoxitin showed a smaller inoculum effect.. Ceftibuten merits clinical evaluation in infections caused by bacteria that produce ESBLs.

Topics: Anti-Bacterial Agents; beta-Lactamases; Ceftibuten; Cephalosporins; Disease Outbreaks; Escherichia coli; Escherichia coli Infections; Hospitals; Isoelectric Focusing; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Nursing Homes

Transferable resistance to cefotaxime was demonstrated in 21 nosocomial strains of Klebsiella pneumoniae and Escherichia coli subsequently isolated from patients in two large University clinics. Using the double-disk diffusion test, we could detect, in each such strain, as well as in E. coli 3110 K-12 transconjugants after the transfer, the production of an Extended Spectrum Beta-Lactamase (ESBL). Ceftibuten was demonstrated to be effective against the majority of strains studied.

Topics: beta-Lactamases; Cefotaxime; Ceftibuten; Cephalosporins; Conjugation, Genetic; Cross Infection; Drug Resistance, Microbial; Escherichia coli; Escherichia coli Infections; Humans; Hydrolysis; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Slovakia