brl-28500 and sultamicillin

Broad-spectrum beta-lactam antibiotics have several advantages in the treatment of intra-abdominal infections. These agents are effective against gram-negative rods and anaerobes, reach therapeutic levels rapidly after parenteral administration, and, in the absence of penicillin allergy, generally exhibit low toxicity. The second-generation cephalosporins (e.g., cefoxitin, cefotetan) are used widely in surgical prophylaxis, trauma, and treatment of mild-to-moderate community-acquired infections, but limitations in their spectra and microbial resistance restrict their utility in more serious infections. Extended-spectrum penicillin/beta-lactamase-inhibitor combinations are effective in the treatment of intra-abdominal infections and include enterococci in their spectrum. Gram-negative aerobe resistance has developed to ampicillin/sulbactam. Piperacillin/tazobactam, a ureidopenicillin with increased gram-negative coverage and enhanced antipseudomonal activity, has proved to be effective in clinical trial therapy for intra-abdominal infections. The very broad spectrum carbapenems--imipenem/cilastatin and meropenem--are effective for serious infections or resistant organisms and are often used in the intensive care unit or for nosocomial intra-abdominal infection. These classes of beta-lactams comprise a range of antimicrobials that can be targeted effectively as single agents to both prevention and treatment of intra-abdominal infection.

Topics: Abdomen; Abdominal Abscess; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; beta-Lactamase Inhibitors; Carbapenems; Cephalosporins; Clavulanic Acids; Drug Resistance, Bacterial; Drug Therapy, Combination; Enzyme Inhibitors; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Surgical Wound Infection; Ticarcillin

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: Aeromonas; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Animals; Anti-Bacterial Agents; Cattle; Clavulanic Acids; Lactoferrin; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Ticarcillin

To evaluate the efficacy and cost of treatment with two beta-lactam/beta-lactamase-inhibitor combinations.. Retrospective, open-label multicenter study.. Fifty-four hospitals across the United States.. Eight hundred ninety patients with skin and soft tissue, intraabdominal, gynecologic, respiratory, urinary tract, or other infections that required parenteral antibiotic therapy.. Patients were administered either ampicillin-sulbactam 1.5 or 3.0 g every 6 hours or ticarcillin-clavulanate 3.1 g every 6 hours.. The agents did not differ significantly in efficacy for most infections; although, ampicillin-sulbactam was bacteriologically superior to ticarcillin-clavulanate in the treatment of intraabdominal infections (p=0.0011). Costs of ampicillin-sulbactam, particularly the 1.5-g dose, were lower than those of ticarcillin-clavulanate for skin and soft tissue (p<0.001), intraabdominal (p=0.005), and respiratory tract (p<0.001) infections.. Ampicillin-sulbactam provides effective coverage for patients with the above infections and is as effective as the broader-spectrum agent.

Topics: Adult; Aged; Ampicillin; Analysis of Variance; Bacterial Infections; Clavulanic Acids; Drug Costs; Drug Therapy, Combination; Female; Hospitalization; Humans; Male; Middle Aged; Retrospective Studies; Sulbactam; Ticarcillin; Treatment Outcome; United States

A high incidence (39%) of positive direct antiglobulin tests (DATs) has been reported in patients taking Unasyn [ampicillin sodium plus sulbactam sodium (a beta-lactamase inhibitor)]. Three of four patients, with positive DATs, receiving Unasyn or Timentin [ticarcillin disodium plus clavulanate potassium (also a beta-lactamase inhibitor)] developed a haemolytic anaemia (HA) associated with a positive DAT, which resolved when drug therapy was stopped. The patients' sera did not react with red blood cells (RBCs) in the presence of Unasyn or Timentin, but when drug-treated RBCs were tested, patients' sera and normal sera reacted equally by indirect antiglobulin test. Following incubation in normal sera, RBCs treated with Unasyn, Timentin, Augmentin (amoxicillin + clavulanate), sulbactam and clavulanate reacted with anti-human globulin and anti-human albumin (an index of non-specific adsorption); RBCs treated with ampicillin and amoxicillin were nonreactive. The beta-lactamase inhibitors sulbactam and clavulanate seem to cause nonimmunologic adsorption of protein onto RBCs in vitro. This may explain the high incidence of positive DATs detected in patients taking Unasyn, which contains sulbactam. It was not possible to prove that there was a direct association between the nonspecific uptake of protein onto drug-treated RBCs in vitro with the positive DATs or the HA.

Topics: Adult; Aged; Aged, 80 and over; Ampicillin; Anemia, Hemolytic; Clavulanic Acids; Coombs Test; Drug Therapy, Combination; Enzyme Inhibitors; Erythrocytes; Female; Humans; Male; Middle Aged; Proteins; Sulbactam; Ticarcillin

MICs of eight beta-lactams (piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, ceftazidime, and ceftriaxone) were determined by agar dilution against 64 penicillin-susceptible, 70 intermediately penicillin-resistant, and 66 fully penicillin-resistant pneumococci. The MICs of piperacillin with and without tazobactam for 90% of the susceptible, intermediately resistant, and resistant strains tested (MIC90s) were < or = 0.064, 2.0, and 4.0 micrograms/ml, respectively. By comparison, those of ampicillin with and without sulbactam were 0.125, 2.0, and 4.0 micrograms/ml and those of ceftriaxone were < or = 0.064, 1.0, and 2.0 micrograms/ml, respectively. Strains were less susceptible to ticarcillin with and without clavulanate (MIC90s, 2.0, 64.0, and 128.0 micrograms/ml) and ceftazidime (MIC90s, 1.0, 8.0, and 32.0 micrograms/ml).

Topics: Ampicillin; Anti-Bacterial Agents; Ceftazidime; Ceftriaxone; Clavulanic Acids; Microbial Sensitivity Tests; Penicillanic Acid; Penicillin Resistance; Piperacillin; Streptococcus pneumoniae; Sulbactam; Tazobactam; Ticarcillin

Thirteen antimicrobial agents and beta-lactamase inhibitor combinations were tested simultaneously for their in-vitro activity against a range of anaerobic Gram-negative bacilli with a standard reference agar dilution method. Overall, metronidazole, imipenem, ampicillin/sulbactam, ticarcillin/clavulanic acid and cefoperazone/sulbactam, followed by clindamycin, cefoxitin, and piperacillin, had the greatest activity. Cefotetan, ceftizoxime, and cefoperazone were moderately active, while ampicillin and penicillin were least active. Metronidazole was the only drug active against all strains, but only one strain was resistant to imipenem. Resistance was highest among certain members of the Bacteroides fragilis group, but was observed also among numerous other Bacteroides species. beta-Lactamase was produced by 94% of strains in the B. fragilis group, and by 64% of strains overall. The activities of clindamycin and cefoxitin were compared with those in previous surveys since 1982 at our institution. No clear evidence of increasing resistance was demonstrated, but the data emphasized the significant effects resulting from variations in susceptibility testing.

Topics: Ampicillin; Anti-Bacterial Agents; Antiprotozoal Agents; beta-Lactamase Inhibitors; Cefoperazone; Clavulanic Acids; Drug Resistance, Microbial; Drug Therapy, Combination; Gram-Negative Anaerobic Bacteria; Microbial Sensitivity Tests; Sulbactam; Ticarcillin

The resistance of bacteria to beta-lactam antibiotics was first associated with the production of the enzyme beta-lactamase as long ago as 1940. Since then, increasing numbers of beta-lactamase-producing bacteria capable of inactivating penicillins and cephalosporins have been isolated clinically. One approach to the problem posed by beta-lactamase-producing bacteria has been to seek substances that function as inhibitors of beta-lactamase and that can be used to protect beta-lactam antibiotics from destruction by the bacterial enzymes. The first clinically available inhibitor was clavulanic acid, a metabolite of Streptomyces clavuligerus that was identified in a screening program for naturally occurring beta-lactamase inhibitors. Clavulanic acid is a potent inhibitor of many bacterial beta-lactamases and has been formulated with amoxicillin and ticarcillin to produce broad-spectrum antibiotic combinations active against beta-lactamase-producing bacteria. After the discovery of clavulanic acid, various compounds have been reported to function as inhibitors of bacterial beta-lactamases, but only sulbactam and its prodrug, sultamicillin, have become available commercially. The success of clavulanic acid has confirmed beta-lactamase inhibitors as one solution to the problem of antibiotic-resistant bacteria.

Topics: Ampicillin; Bacteria; beta-Lactamase Inhibitors; Clavulanic Acid; Clavulanic Acids; Drug Therapy, Combination; Drugs, Investigational; Humans; Penicillins; Sulbactam; Ticarcillin