7432-s and Escherichia-coli-Infections

This double-blind, multicentre study was performed at nine centres on a total of 171 patients who presented with fever (> 38.5 degrees C) and signs of acute pyelonephritis. All were initially treated with intravenous cefuroxime. After 2-3 d, when the fever had subsided and urinary culture had revealed growth of Gram-negative bacteria ( > 10(7) colony-forming units per litre), treatment was changed to oral administration of ceftibuten 200 mg b.i.d. or norfloxacin 400 mg b.i.d. for 10 d. The patients were followed for signs of bacterial or clinical relapse 7-14 d after the end of treatment. The initial clinical and bacteriological cure was excellent in both groups, but there were significantly fewer bacterial relapses after oral treatment with norfloxacin than with ceftibuten in acute febrile pyelonephritis initially treated with intravenous cefuroxime. The causal strain was eradicated in 75% of patients (73% of males, 76% of females) in the ceftibuten group and in 89% of patients (94% of males, 85% of females) in the norfloxacin group. The relative frequency of eradication was 0.84 (p < 0.05; 95%, confidence interval 0.74-0.97). Adverse events were reported by 47% of the patients in the ceftibuten group and by 38% in the norfloxacin group. This difference was not significant, but diarrhoea or loose stools occurred more frequently in the ceftibuten group.

Topics: Acute Disease; Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Ceftibuten; Cefuroxime; Cephalosporins; Double-Blind Method; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Female; Humans; Injections, Intravenous; Male; Middle Aged; Norfloxacin; Prospective Studies; Pyelonephritis; Recurrence; Treatment Outcome

In a prospective randomized study at two clinical sites, ceftibuten was compared with trimethoprim-sulfamethoxazole (TMP-SMX), both given orally for a period of 5 days, for the treatment of dysentery. Twenty-two children were found to have bacillary dysentery caused by Shigella and/or enteroinvasive Escherichia coli. All organisms isolated were susceptible to ceftibuten; 6 of 20 Shigella strains and 4 of 5 enteroinvasive E. coli were resistant to TMP-SMX. The diarrhea persisted for a mean (+/- SD) period of 2.4 +/- 1.4 days in the ceftibuten-treated patients vs. 3.4 +/- 1.7 days in the TMP-SMX-treated patients. The duration of fever was similar for both treatment groups. Patients treated with ceftibuten or TMP-SMX had equivalent clinical responses unless the pathogen was found to be TMP-SMX-resistant. Those who were randomized to receive TMP-SMX but who were eventually found to have TMP-SMX-resistant organisms had significantly more stools at days 3, 4 and 5 (P less than 0.02 to less than 0.00006) with more watery consistency for these days (P less than 0.02 to less than 0.005) compared to patients treated with ceftibuten. No clinical relapses were reported and no drug-related side effects were observed. We conclude that ceftibuten is at least as effective as TMP-SMX in the treatment of diarrhea caused by Shigella and enteroinvasive E. coli in children.

Topics: Adolescent; Ceftibuten; Cephalosporins; Child; Child, Preschool; Dysentery, Bacillary; Escherichia coli Infections; Humans; Infant; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

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

Inadequate and delayed antibiotic treatment of extended spectrum beta-lactamase (ESBL)-producing isolates have been associated with increased mortality of affected patients. The purpose of this study was to compare the host response of human renal epithelial cells and polymorphonuclear leucocyte (PMN) cells when infected by ESBL-producing uropathogenic Escherichia coli (UPEC) isolates in the presence or absence of ineffective antibiotics. The renal epithelial cell line A498 and PMN cells were stimulated with ESBL-producing UPEC isolates in the presence or absence of three different antibiotics (trimetoprim, ceftibuten and ciprofloxacin). Host cell responses were evaluated as release of cytokines (IL-6, IL-8), reactive oxygen species (ROS), ATP and endotoxins. Bacterial morphology and PMN phagocytosis were evaluated by microscopy. In the presence of ceftibuten, 2 out of 3 examined ESBL-isolates changed their morphology into a filamentous form. The presence of ceftibuten enhanced IL-6, IL-8 and ROS-production from host cells, but only from cells stimulated by the filamentous isolates. The bacterial supernatant and not the filamentous bacteria per se was responsible for the increased release of IL-6, IL-8 and ROS. Increased endotoxin and ATP levels were found in the bacterial supernatants from filamentous isolates. Apyrase decreased IL-6 secretion from A498 cells and polymyxin B abolished the increased ROS-production from PMN cells. PMN were able to inhibit the bacterial growth of some ESBL-isolates in the presence of ceftibuten. In conclusion, antibiotic-induced filamentation of ESBL-producing UPEC isolates and the associated release of ATP and endotoxins can alter the host cell response in the urinary tract.

Topics: Adenosine Triphosphate; Anti-Bacterial Agents; beta-Lactamases; Ceftibuten; Cell Line; Cephalosporins; Escherichia coli Infections; Escherichia coli Proteins; Humans; Interleukin-6; Interleukin-8; Reactive Oxygen Species; Uropathogenic Escherichia coli

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