scholarly journals Degradation of .BETA.-lactamase inhibitor, (2S,3R,5S)-3-methyl-7-oxo-3-(1H-1,2,3-triazol-1-yl-methyl)-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid 4,4-dioxide(YTR-830H), in aqueous solutions and alkaline methanol solution. Pathway and structural elucidation of products.

1988 ◽  
Vol 36 (11) ◽  
pp. 4478-4487 ◽  
Author(s):  
TERUYOSHI MARUNAKA ◽  
EIJI MATSUSHIMA ◽  
YOSHINORI MINAMI ◽  
KEN-ICHIRO YOSHIDA ◽  
RYOTARO AZUMA
Keyword(s):  
Carboxylic Acid ◽  
Aqueous Solutions ◽  
Structural Elucidation ◽  
Methanol Solution ◽  
Beta Lactamase ◽  
Lactamase Inhibitor

scholarly journals Importance of beta-lactamase inhibitor pharmacokinetics in the pharmacodynamics of inhibitor-drug combinations: studies with piperacillin-tazobactam and piperacillin-sulbactam.

1997 ◽  
Vol 41 (4) ◽  
pp. 721-727 ◽  
Author(s):  
P D Lister ◽  
A M Prevan ◽  
C C Sanders
Keyword(s):  
Antibacterial Activity ◽  
Critical Concentration ◽  
Specific Inhibitor ◽  
Logarithmic Phase ◽  
Critical Ratio ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Dosing Regimens ◽  
Lactamase Inhibitor

An in vitro pharmacokinetic model was used to study the pharmacodynamics of piperacillin-tazobactam and piperacillin-sulbactam against gram-negative bacilli producing plasmid-encoded beta-lactamases. Logarithmic-phase cultures were exposed to peak antibiotic concentrations observed in human serum after the administration of intravenous doses of 3 g of piperacillin and 0.375 g of tazobactam or 0.5 g of sulbactam. Piperacillin and inhibitor were either dosed simultaneously or piperacillin was dosed sequentially 0.5 h after dosing with the inhibitor. In studies with all four test strains, the pharmacodynamics observed after simultaneous dosing were similar to those observed with the sequential regimen. Since the ratio between piperacillin and tazobactam was in constant fluctuation after sequential dosing, these data suggest that the pharmacodynamics of the piperacillin-inhibitor combinations were not dependent upon maintenance of a critical ratio between the components. Furthermore, when regrowth was observed, the time at which bacterial counts began to increase was similar between the simultaneous and sequential dosing regimens. Since the pharmacokinetics of the inhibitors were the same for all regimens, these data suggest that the length of time that the antibacterial activity was maintained over the dosing interval with these combinations was dictated by the pharmacokinetics of the beta-lactamase inhibitor in the combination. The antibacterial activity of the combination appeared to be lost when the amount of inhibitor available fell below some critical concentration. This critical concentration varied depending upon the type and amount of enzyme produced, as well as the specific inhibitor used. These results indicate that the antibacterial activity of drug-inhibitor combinations, when dosed at their currently recommended ratios, is more dependent on the pharmacokinetics of the inhibitor than on those of the beta-lactam drug.

Orally effective acid prodrugs of the .beta.-lactamase inhibitor sulbactam

1990 ◽  
Vol 33 (1) ◽  
pp. 344-347 ◽  
Author(s):  
Arthur R. English ◽  
Dennis Girard ◽  
V. John Jasys ◽  
Robert J. Martingano ◽  
Michael S. Kellogg
Keyword(s):  
Beta Lactamase ◽  
Lactamase Inhibitor

Piperacillin/Tazobactam: A New Beta-Lactam/Beta-Lactamase Inhibitor Combination

1995 ◽  
Vol 29 (5) ◽  
pp. 501-514 ◽  
Author(s):  
Lori L Schoonover ◽  
Donna J Occhipinti ◽  
Keith A Rodvold ◽  
Larry H Danziger
Keyword(s):  
Antimicrobial Activity ◽  
Clinical Efficacy ◽  
Clinical Laboratory ◽  
National Committee ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
In Vitro Susceptibility ◽  
Tract Infections ◽  
Inhibitor Combination ◽  
Lactamase Inhibitor

Objective: To discuss the antimicrobial activity, pharmacokinetics, clinical efficacy, and adverse effect profile of piperacillin/tazobactam, a new beta-lactam/beta-lactamase inhibitor combination. Data Sources: Literature was identified by MEDLINE search of the medical literature, review of selected references, and data provided by the manufacturer. Study Selection: In vitro susceptibility data were surveyed from studies following the methods of the National Committee for Clinical Laboratory Standards. Data evaluating clinical efficacy were selected from all published trials and abstracts. Additional information concerning safety, chemistry, and pharmacokinetics was reviewed. Data Synthesis: The antimicrobial activity of piperacillin is enhanced by addition of tazobactam against gram-positive, gram-negative, and anaerobic bacteria. Tazobactam is active against a broad spectrum of plasmid and chromosomally mediated enzymes and has minimal ability to induce class I chromosomally mediated beta-lactamase enzymes. Piperacillin/tazobactam's expanded activity appears encouraging in the treatment of mixed aerobic and anaerobic infections. Direct comparisons of ticarcillin/clavulanate and piperacillin/tazobactam for the treatment of lower respiratory tract infections showed piperacillin/tazobactam to be clinically superior, and in the treatment of skin and soft tissue infections the 2 agents were comparable. For the treatment of intraabdominal infections, piperacillin/tazobactam was at least as effective as imipenem/cilastatin and clindamycin plus gentamicin. Conclusions: The combination of tazobactam with piperacillin results in an antimicrobial agent with enhanced activity against most beta-lactamase–producing organisms. Preliminary data indicate that piperacillin/tazobactam has proven clinical efficacy in the treatment of a variety of infections, especially polymicrobic infections.

Sign in / Sign up

Export Citation Format

Share Document