Recently, the number of β-lactamase producing organisms isolated from urinary tract infections has increased. This phenomenon is almost certainly because of the extremely high usage of β-lactam antibiotics, and it has created a need for the development of antimicrobial agents which are stable to β-lactamases. BRL 28500, which is a new formulation of a β-lactam antibiotic, ticarcillin (TIPC), and a β-lactamase inhibitor, clavulanic acid (CVA) (ratio of TIPC to CVA is 15:1), is a promising new antimicrobial agent.
In vitro studies have already shown this preparation to have strong activity against β-lactamase producing organisms.
We carried out a well-controlled comparison of BRL 28500, ticarcillin (TIPC) and cefoperasone (CPZ) in the treatment of complicated urinary tract infections in the following manner. Patients who were over 16 years old and had an underlying urinary tract disease, bacteriuria of more than 104 CFU/ml and pyuria of more than 5 WBCs/HPF (×400) of urine were randomly assigned to receive 1.6 g of BRL 28500, 1.5 g of TIPC or 1.0 g of CPZ twice a day for 5 days by intravenous injection. The overall clinical efficacy of each regimen was evaluated according to the criteria proposed by the “UTI Committee in Japan” as excellent, moderate or poor (including failed cases) based on the improvement in both the bacteriuria and pyuria.
A total of 476 patients were treated, and 110, 124 and 119patients received BRL 28500, TIPC and CPZ, respectively, were found to be evaluable for the clinical efficacy. No significant differences in various background characteristics were observed among the treatment groups. The efficacy rates, which were calculated based on the excellent and moderate responses, were 64.5%, 47.6%, and 53.8%, in the BRL 28500, TIPC and CPZ patient groups.
The efficacy rate with BRL 28500 (64.5%) was significantly higher than that with TIPC (47.6%), but no significant difference was observed between the efficacies of BRL 28500 and CPZ, or TIPC and CPZ. Especially in the patients with polymicrobial infections and patients with monomicrobial infections due to indwelling catheters, the efficacy rate with BRL 28500 was found to be significantly higher than that with TIPC.
Bacteriologically, the eradication rates with BRL 28500, TIPC and CPZ were 84%, 75% and 76%, respectively. Although the eradication rate with BRL 28500 was the highest, no significant differences were observed among those eradication rates. However, against
E. coli, and gram-negative rode as a whole, BRL 28500 showed significantly higher eradication rates than did TIPC. Against β-lactamase producing organisms, the eradication rate with BRL 28500 (83.9%) was also higher than those with TIPC (72.3%) and CPZ (73.7%). This tendency was particularly clear in relation to β-lactamase producing gram-negative rods.
Especially against Klebsiello app. strains producing large amounts of β-lactamase, BRL 28500 and CPZ also exhibited higher eradication rates (100%, 91% respectively) than TIPC (33%). The eradication rate with BRL 28500 against β-lactamase highly-producing
E. coli (100%) was also revealed to be much higher than that with TIPC (40%).
Clinical adverse reactions, consisting mainly of gastrointestinal and allergic reactions, were observed in 1, 3 and 7 cases in the BRL 28500, TIPC and CPZ treatment groups, respectively. Laboratory adverse reactions, mainly hepatic function disorders, were recorded in 12, 5 and 6 cases in the BRL 28500, TIPC and CPZ groups. These adverse reactions were all mild and transient, and the treatment groups showed no significant differences in the appearance rates of those reactions. The patients' tolerance of each of BRL 28500, TIPC and CPZ was thus good.
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