Cefuroxime axetil in the treatment of uncomplicated UTI: a comparison with cefaclor and augmentin.

Cefuroxime axetil (CAE) is an acetoxyethyl ester prodrug of cefuroxime. The efficacy and safety of cefuroxime axetil was studied in a randomized general practice trial in urological infections where cefuroxime axetil 250 mg b.d. was compared with amoxycillin/clavulanate (Augmentin, AUG) 375 mg t.d.s. A randomized trial was then performed in hospital outpatients, who received cefuroxime axetil 250 mg b.d. or cefaclor (CCL) 250 mg t.d.s. Of 140 clinically assessable patients, 108 were cured and 28 improved on cefuroxime axetil (97% success) compared with 75 cured and 13 improved out of 89 on Augmentin (99% success) and 31 cured and 7 improved out of 38 patients treated with cefaclor (97% success). Bacteriology was assessable in 101 patients given cefuroxime axetil (72% cleared), 61 of those given Augmentin (70% cleared) and 27 out of 28 (96%) given cefaclor. As expected, the predominant pathogen was E. coli, accounting for 61% of isolates overall. Drug-related adverse events occurred in 10% of patients given cefuroxime axetil, including diarrhoea in 4%. Eleven percent of patients given Augmentin suffered adverse events (5% diarrhoea) and 5% of those given cefaclor. Superinfections occurred in 4 cefaclor patients (2 Pseudomonas aeruginosa, 1 Candida, 1 E. coli) compared with 2 on cefuroxime axetil (1 Candida, 1 E. coli). Uncomplicated UTI accounted for 92% of cases in the G.P. trial and 82% of cases in the hospital trial. Cefuroxime axetil may be used safely and effectively to treat uncomplicated UTI at a dose of 250 mg b.d.

Qualitative and quantitative aspects of beta-lactamase production as mechanisms of beta-lactam resistance in a survey of clinical isolates from faecal samples.

A study has been conducted to identify the beta-lactamases most likely to contribute to beta-lactam resistance in clinical populations and to investigate their interactions with cefuroxime and newer cephalosporins. A total of 217 ampicillin-resistant, Gram-negative isolates from faecal samples of healthy volunteers in Germany, South America and Amman were investigated. Such strains represent the 'gene pool' from which infections might arise. Escherichia coli was the prevalent species (59.9%) followed by Klebsiella spp. (20.3%) and Enterobacter cloacae (12.0%). At least 56.7% and possibly as high as 64.5% of strains owed their principal beta-lactamase activity to enzymes mediated by R-plasmids. The most prevalent R-plasmid mediated beta-lactamase was TEM-1 which was produced by 109 strains. The beta-lactamase activity of strains producing only a chromosomal enzyme was often markedly higher than that of strains also producing an R-plasmid mediated enzyme. The qualitative and quantitative aspects of beta-lactamase production were investigated in cell free and whole cell tests and this confirmed the superior broad spectrum beta-lactamase resistance of ceftazidime over other new cephalosporins.

The origin and properties of beta-lactamase satellite bands seen in isoelectric focusing.

Citrobacter diversus 2046E and Branhamella catarrhalis 2001E each produce a constitutive, chromosomally mediated broad-spectrum beta-lactamase. Isoelectric focusing of both enzymes revealed patterns of multiple 'satellite' bands. The principal satellite bands of each enzyme were isolated and characterized. Individual bands of each enzyme gave similar substrate profiles, molecular weights and responses to inhibitors to one another. The results support the theory that satellite bands are due to the loss and/or modification of specific amino acid residues resulting in biologically active molecules with altered nett charges.