Activities of amoxicillin and clavulanic acid combinations against urinary tract infections

Abstract

Urinary tract infections caused by P-lactamase-producing bacteria were treated with 500 mg of amoxicillin three times daily plus either 250 or 125 mg of clavulanic acid three times daily. The overall cure rate was 63.6%, 77.7% with the high dose of clavulanic acid and 53.8% with the low dose. Gastrointestinal intolerance was common in the high-dose clavulanic acid regimen.Formulations of amoxicillin with potassium clavulanate possess activity against many plasmid-mediated P-lactamase-producing bacteria (3, 4, 7-11, 13-15, 19) and have been used successfully in the therapy of urinary tract infections (1,8).Two formulations were assessed in this trial, which included 22 adult in-patients (17 women and 5 men, ranging in age from 50 to 90 years) suffering from 24 episodes of urinary tract infection caused by amoxicillin-resistant organisms. Ten episodes (9 patients, group 1) were treated for 10 days with the 2:1 combination (500 mg of amoxicillin plus 250 mg of clavulanic acid administered three times daily), and fourteen episodes (13 patients, group 2) were treated with the 4:1 combination (500 mg of amoxicillin plus 125 mg of clavulanic acid administered three times daily). Tablets were taken with food. Exclusion criteria were allergy to P-lactams, renal impairment (creatinine clearance, <30 ml/ min), hepatic failure, bleeding disorders, bladder catheterization, recent administration of an effective antibiotic, and infection with an organism resistant to combinations of amoxicillin and clavulanic acid. Complete physical examinations were obtained before, during, and after treatment. Complete blood counts with differential leukocyte counts, platelets counts, hemoglobin levels, and concentrations of creatinine, urea, alkaline phosphatase, transaminases, and bilirubin in serum were also made at these times. "Clean-catch" urine was considered infected if yielding i105 organisms per ml on at least two separate occasions, together with significant pyuria (8). Clinical pyelonephritis was confirmed by the presence of antibody-coated bacteria (18). Antibiotic susceptibility was determined by an agar diffusion method (2), using filter-paper disks impregnated with amoxicillin alone (20 ,ug) and in combination with clavulanic acid (20 ,ug of amoxicillin and 10 ,ug of clavulanic acid), both kindly provided by Beecham Laboratories. Bacteria were considered susceptible if the diameter of the growth inhibition zone was >'19 mm and resistant if the zone was -14 mm. Minimal inhibitory concentrations (MICs) were determined by an agar dilution method. A multiinoculator (16) was used to deliver 4 x 103 colonyforming units per spot on the surfaces of Mueller-Hinton agar plates containing twofold serial dilutions of the combination over a suitable concentration range. The stock solution (300 ,ug/ml), prepared from pellets (provided by Beecham Laboratories) containing 2 mg of amoxicillin and 1 mg of clavulanic acid, was diluted in distilled water. The breakpoints were identical for amoxicillin alone and for the drug combination; i.e.,...

Comparative study of amoxicillin-clavulanic acid and cephalexin in the treatment of bacteriuria during pregnancy

“…Although more relapses at 6 weeks were seen in the cephalexin group, this difference was not statistically significant. The bacteriological cure rates were similar to those previously reported (1,3,4,6). When the treatment failed, this was not due to emergence of resistance to either drug.…”

“…It has been shown in vitro that this agent will render an ampicillin-resistant organism susceptible to ampicillin if resistance is due to production of a P-lactamase which is inhibited by clavulanic acid (1,5,10,12). This in vitro effect has been confirmed in vivo in several trials of a combination of amoxicillin with clavulanic acid in the treatment of urinary tract infections (1,3,4,6 Growth from this specimen was regarded as significant if it yielded more than 105 CFU/ml of a single species. Significant pyuria was defined as -20 pus cells per ,ul.…”

Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: data from spontaneous reporting in Italy

“…Two clinical trials found that the frequency of gastrointestinal events is related to the dosage of clavulanic acid. 30,31 Moreover, the higher incidence of amoxicillin/clavulanic acid-induced diarrhoea could be explained by its greater resistance to b-lactamases, which may result in a higher concentration of amoxicillin in the intestine and a consequent stronger modification of the bacterial flora. In addition, a double-blind cross-over study demonstrated that amoxicillin/clavulanic acid is often associated with small intestinal motor disturbances.…”

Prospective comparison of amoxicillin-clavulanic acid and cefaclor in treatment of uncomplicated urinary tract infections

“…Several clinical trials have demonstrated that amoxicillin plus the beta-lactamase inhibitor clavulanic acid (A-C) is effective in urinary tract infections due largely to amoxicillin-resistant bacteria (1,3,5,8). The cure rate for infections due to amoxicillin-resistant bacteria is similar to that caused by amoxicillin-susceptible organisms, and the addition of low doses of clavulanic acid to amoxicillin did not appear to increase the incidence of adverse reactions (7).…”