brl-28500 and Respiratory-Tract-Infections

Sulbactam (SB) and clavulanic acid (CA) are irreversible inhibitors of the beta-lactamases in the Richmond and Sykes classes II-VI. When combined with ampicillin and ticarcillin, SB and CA, respectively, extend the spectrum of activity of these penicillins to include some beta-lactamase-producing aerobes (Enterobacteriaceae, Hemophilus influenzae, staphylococci) and anaerobes (Bacteroides fragilis group) which would otherwise be resistant. Neither effectively inhibits the class I beta-lactamases frequently produced by Pseudomonas aeruginosa, Enterobacter, and Serratia, in part explaining the resistance observed with these organisms. Clinically, both agents were as effective as the comparative therapies in all but two of the trials reviewed. Given the current data, the decision to add these agents to the formulary should be based on hospital resistance patterns and on the cost of these antimicrobials in comparison to conventional therapies.

Topics: Ampicillin; Arthritis, Infectious; Bacterial Infections; Bacteroides fragilis; beta-Lactamase Inhibitors; Clavulanic Acids; Clinical Trials as Topic; Drug Resistance, Microbial; Drug Therapy, Combination; Enterobacteriaceae; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Microbial Sensitivity Tests; Osteomyelitis; Pelvic Inflammatory Disease; Respiratory Tract Infections; Sulbactam; Ticarcillin

Topics: Bacteria; Clavulanic Acids; Drug Evaluation; Drug Therapy, Combination; Humans; Penicillin Resistance; Penicillins; Respiratory Tract Infections; Ticarcillin; Urinary Tract Infections

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Clavulanic Acids; Drug Combinations; Humans; Respiratory Tract Infections; Ticarcillin

The efficacy and safety of a new combination parenteral antibiotic, piperacillin/tazobactam, was compared with that of parenteral ticarcillin/clavulanate in the treatment of adult patients with community-acquired lower respiratory tract infections. A total of 299 patients were enrolled in this multicentre, double-blind, comparative study; 177 received piperacillin/tazobactam and 122 received ticarcillin/clavulanate. Of these, 119 met the evaluability criteria (69, piperacillin/tazobactam and 50, ticarcillin/clavulanate). The study drugs (piperacillin/tazobactam 3 g/375 mg or ticarcillin/clavulanate 3 g/100 mg) were given every 6 h by slow iv infusion for a minimum of 5 days. The favourable clinical response (cured and improved) rates of evaluable patients were 84% and 64% at endpoint (P < 0.01) for piperacillin/tazobactam and ticarcillin/clavulanate, respectively. The favourable bacteriological response at the early follow-up (eradicated and presumed eradicated) were 91% and 67% for piperacillin/tazobactam and ticarcillin/clavulanate, respectively (P < 0.01). At endpoint, 84% and 64%, respectively (P = 0.02) had a favourable response. The most common adverse experiences involved the gastrointestinal tract and occurred in 31.6% of the piperacillin/tazobactam group compared with 20.5% in the ticarcillin/clavulanate group (P = 0.02). These events were mild and generally did not affect therapy. Piperacillin/tazobactam appears to be more effective than ticarcillin/clavulanate in this patient population and is generally well tolerated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteria; beta-Lactamase Inhibitors; Clavulanic Acids; Community-Acquired Infections; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Respiratory Tract Infections; Tazobactam; Ticarcillin

In four prospective randomized clinical trials between November 1983 and March 1988, we studied 270 patients with severe bacterial infections, mainly lower respiratory tract ones. We compared ciprofloxacin and imipenem/cilastatin in the first study, ciprofloxacin and ofloxacin in the second study, ciprofloxacin and ticarcillin/clavulanic acid in the third study, and ofloxacin and cefpirome in the fourth study. A total of 90 pneumonias, 139 LRTIs, 22 septicaemias and 19 other bacterial infections were treated; the dominant pathogens were Pseudomonas aeruginosa and enterobacteria. Clinical success rates were high; cure or improvement was registered in 89% of the patients on ciprofloxacin, 89% on ofloxacin and 85% on beta-lactams. Treatment failures occurred mainly in ICU patients with terminal underlying diseases. Bacteriologically, eradication rates were high for enterobacteria and Staphylococcus aureus, but a relatively high persistence rate was seen for P. aeruginosa due to increased resistance and/or specific type and location of the infections. The incidence of side-effects was relatively high (23%-29%) which was related to careful monitoring. Adverse effects were group-specific (CNS reactions with quinolones, diarrhoea with beta-lactam antibiotics).

Topics: Cilastatin; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Clavulanic Acids; Drug Combinations; Drug Therapy, Combination; Humans; Imipenem; Ofloxacin; Pneumonia; Prospective Studies; Remission Induction; Respiratory Tract Infections; Sepsis; Ticarcillin

Topics: Adult; Aged; Aged, 80 and over; beta-Lactamase Inhibitors; Clavulanic Acids; Clinical Trials as Topic; Drug Combinations; Female; Humans; Male; Middle Aged; Penicillins; Piperacillin; Respiratory Tract Infections; Ticarcillin

Topics: Adult; Aged; Aged, 80 and over; beta-Lactamase Inhibitors; Clavulanic Acids; Clinical Trials as Topic; Drug Combinations; Humans; Middle Aged; Penicillins; Respiratory Tract Infections; Ticarcillin

A total of 3903 pathogens from 48 Canadian medical centres were tested against 19 antimicrobial agents. Five agents showed activity against > or = 90% of all 1982 respiratory tract pathogens tested (ciprofloxacin, 90%; cefoperazone, 91%; ticarcillin/clavulanate, 92%; ceftazidime and imipenem, 93% each). Nine agents had > or = 90% activity against Enterobacteriaceae from respiratory tract infection (cefotaxime and ticarcillin/clavulanate, 90% each; aztreonam, ceftizoxime and ceftriaxone, 91% each; ceftazidime, 93%; ciprofloxacin, 97%; imipenem and netilmicin, 98% each). Similarly, five agents had activity against > or = 90% of all 1921 urinary tract pathogens tested (ciprofloxacin and ticarcillin/clavulanate, 90% each; cefoperazone and netilmicin, 91% each; imipenem, 99%). Nine agents had > or = 95% activity against Enterobacteriaceae from urinary tract infection (ciprofloxacin, 95%; cefotetan, 97%; aztreonam, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone and netilmicin, 98% each; imipenem, 99%). Seventeen agents had activity against > or = 95% of Staphylococcus aureus strains. Susceptibility of Pseudomonas aeruginosa isolates ranged from 2% to 91%.

Topics: Acinetobacter; Anti-Bacterial Agents; Cefoperazone; Ceftazidime; Ciprofloxacin; Clavulanic Acids; Enterobacteriaceae; Enterobacteriaceae Infections; Enterococcus; Haemophilus; Humans; Imipenem; Inhibitory Concentration 50; Microbial Sensitivity Tests; Moraxella; Pseudomonas; Respiratory Tract Infections; Staphylococcus; Streptococcus; Ticarcillin; Urinary Tract Infections

Topics: Amoxicillin-Potassium Clavulanate Combination; beta-Lactamase Inhibitors; Clavulanic Acids; Connective Tissue Diseases; Drug Therapy, Combination; Enzyme Inhibitors; Gram-Negative Bacteria; Gram-Positive Bacteria; Microbial Sensitivity Tests; Penicillins; Respiratory Tract Infections; Skin Diseases, Bacterial; Ticarcillin; Urinary Tract Infections

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Clavulanic Acids; Ear Diseases; Female; Humans; Infections; Male; Nose Diseases; Respiratory Tract Infections; Ticarcillin; Tonsillitis