brl-28500 and Escherichia-coli-Infections

We compared the efficacy and safety of two beta-lactam-beta-lactamase inhibitor combinations, namely, piperacillin-tazobactam and ticarcillin-clavulanate, in the treatment of complicated bacterial infections of skin that required hospitalization. The study was a randomized, double-blind, comparative trial involving 20 centers. The infections were classified as (i) cellulitis with drainage, (ii) cutaneous abscess, (iii) diabetic or ischemic foot infection, and (iv) infected wounds and ulcers with drainage. The clinical response rates were comparable for the two treatment regimens (61% of the patients were cured with piperacillin-tazobactam and ticarcillin-clavulanate and improvement was seen in 15 and 16% of patients treated with piperacillin-tazobactam and ticarcillin-clavulanate, respectively). Both regimens were found to be safe and well tolerated. These data support the use of piperacillin-tazobactam for initial empiric therapy of hospitalized patients with complicated skin and skin structure infections.

Topics: Bacteroides Infections; Clavulanic Acids; Double-Blind Method; Drug Therapy, Combination; Escherichia coli Infections; Female; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Staphylococcus aureus; Tazobactam; Ticarcillin

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; beta-Lactamases; Cephalosporins; Clavulanic Acids; Drug Resistance, Microbial; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Humans; Isoelectric Focusing; Ticarcillin

The pharmacokinetics and bacteriological efficacy of ticarcillin and clavulanic acid administered individually or in combination were assessed in rabbits with experimental Escherichia coli K-1 and Haemophilus influenzae type b meningitis. The mean penetrations into the cerebrospinal fluid (CSF) of infected animals after a single dose of ticarcillin-clavulanic acid were approximately 11 and 28% for ticarcillin and clavulanic acid, respectively. In continuous-infusion experiments, the mean penetrations into CSF were 14.6 and 35% for ticarcillin and clavulanic acid, respectively, in rabbits with E. coli meningitis and 6.1 and 24%, respectively, in rabbits with H. influenzae meningitis. In animals that received a continuous infusion of the two drugs alone or in combination, the median CSF bactericidal titers for E. coli were less than 1:2, less than 1:2, and 1:2 for ticarcillin, clavulanic acid, and ticarcillin-clavulanic acid, respectively, and for H. influenzae the titers were less than 1:2, less than 1:2, and 1:4, respectively. The addition of clavulanic acid potentiated significantly the bacteriological efficacy of ticarcillin in reducing the number of bacteria in CSF of infected rabbits. Additional studies in animals and humans are required before recommendations can be made regarding the use of ticarcillin-clavulanic acid for treatment of meningitis.

Topics: Animals; Clavulanic Acid; Clavulanic Acids; Drug Combinations; Escherichia coli Infections; Meningitis; Meningitis, Haemophilus; Microbial Sensitivity Tests; Penicillins; Rabbits; Ticarcillin