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.

scholarly journals Multicenter Clinical Evaluation of Etest Meropenem-Vaborbactam (bioMérieux) for Susceptibility Testing of Enterobacterales (Enterobacteriaceae) and Pseudomonas aeruginosa

2019 ◽  
Vol 58 (1) ◽  
Author(s):  
Sophonie Jean ◽  
Sheri Garrett ◽  
Claire Anglade ◽  
Laurence Bridon ◽  
Leanne Davies ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Susceptibility Testing ◽  
Reference Method ◽  
Individual Species ◽  
Beta Lactamase ◽  
Content Type ◽  
European Committee ◽  
Tract Infections ◽  
Inhibitor Combination ◽  
Lactamase Inhibitor

ABSTRACT Meropenem-vaborbactam (MEV) is a novel carbapenem–beta-lactamase inhibitor combination antibiotic approved by the U.S. Food and Drug Administration (FDA) for treatment of complicated urinary tract infections, including pyelonephritis, in adults. In this study, we evaluated the performance of Etest MEV (bioMérieux, Marcy l’Etoile, France) compared to that of broth microdilution for 629 Enterobacterales and 163 Pseudomonas aeruginosa isolates. According to CLSI/FDA breakpoints, 13 Enterobacterales isolates (12 clinical and 1 challenge) were resistant to MEV. Overall, Etest MEV demonstrated 92.4% essential agreement (EA), 99.2% category agreement (CA), 0% very major errors (VME), 0% major errors (ME), and 0.8% minor errors (mE) with clinical and challenge isolates of Enterobacterales. Individual species demonstrated EA rates of ≥80%, with the exception of Proteus mirabilis, for which clinical and challenge isolates demonstrated 34.3% EA, 97.1% CA, 0% ME, and 2.9% mE, precluding the use of Etest MEV with this species. Excluding P. mirabilis, MEV Etest MEV demonstrated 95.8% EA, 99.3% CA, 0% VME, 0% ME, and 0.7% mE with Enterobacterales isolates. When evaluated using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, Etest MEV performance with clinical (16 MEV resistant) and challenge (12 MEV resistant) isolates of Enterobacterales (excluding P. mirabilis) and P. aeruginosa demonstrated an unacceptably high VME rate of 7.1% despite 95.2% EA, 99.2% CA, and 0.5% ME compared to the reference method. In conclusion, we report that Etest MEV is accurate and reproducible for MEV susceptibility testing for P. aeruginosa and Enterobacterales, with the exception of P. mirabilis, using CLSI/FDA breakpoints. Etest MEV should not be used with P. mirabilis due to unacceptable analytical performance.

Sulbactam/Ampicillin, a New Beta-Lactamase Inhibitor/Beta-Lactam Antibiotic Combination

1988 ◽  
Vol 22 (7-8) ◽  
pp. 534-541 ◽  
Author(s):  
John M. Benson ◽  
Milap C. Nahata
Keyword(s):  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactamases ◽  
Cervical Adenitis ◽  
Elimination Half ◽  
Lactam Antibiotic ◽  
Acquisition Costs ◽  
Tract Infections ◽  
Gynecological Infections ◽  
Lactamase Inhibitor

Sulbactam/ampicillin is a combination of a beta-lactamase inhibitor with minimal intrinsic antibacterial activity (sulbactam sodium), and an aminopenicillin (ampicillin sodium). The addition of sulbactam to ampicillin has no effect on the chemical stability of ampicillin in aqueous solution, and the administration guidelines of the combination are the same as for ampicillin alone. Sulbactam acts primarily by irreversible inactivation of beta-lactamases from most beta-lactamase-producing organisms. The pharmacokinetics of sulbactam are similar to those of ampicillin with an elimination half-life of about one hour in most patients. One difference is that serum and tissue concentrations of sulbactam are usually twice those of ampicillin, at equivalent doses. The sulbactam/ampicillin combination has been approved for the treatment of adults with intraabdominal, skin and skin structure, and gynecological infections due to beta-lactamase-producing bacteria such as Staphylococcus aureus, Escherichia coli, and species of Klebsiella and Bacteroides. Clinical studies to date have also shown the combination to be effective for the treatment of meningitis, pneumonia, gonorrhea, epiglottitis, urinary tract infections, cervical adenitis, and as prophylaxis for abdominal and gynecological surgeries. Many of these studies, however, have included small numbers of patients and/or had design flaws. Adverse effects have been minor with most being attributed to the ampicillin component. Sulbactam/ampicillin compares favorably with other antibiotic regimens in terms of acquisition costs and ease of administration.

scholarly journals A Cross-Canada Surveillance of Antimicrobial Resistance in Respiratory Tract Pathogens

1999 ◽  
Vol 10 (2) ◽  
pp. 128-133 ◽  
Author(s):  
Ross J Davidson ◽  
Canadian Bacterial Surveillance Network ◽  
Donald E Low
Keyword(s):  
Antimicrobial Resistance ◽  
Clinical Laboratory ◽  
Clinical Isolates ◽  
National Committee ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Minimal Inhibitory Concentrations ◽  
Beta Lactam Antibiotics ◽  
Significant Difference ◽  
High Level

OBJECTIVE: To determine the prevalence of antimicrobial resistance in clinical isolates ofStreptococcus pneumoniae, Haemophilus influenzaeandMoraxella catarrhalisfrom medical centres across Canada.METHODS: Fifty laboratories from across Canada were asked to collect up to 25 consecutive clinical isolates ofS pneumoniae,H influenzaeandM catarrhalisat some time between September 1994 and May 1995, and then again between September and December of 1996. A total of 2364S pneumoniae, 575H influenzaeand 200M catarrhalissamples were collected.H influenzaeandM catarrhalisisolates were tested for the production of beta-lactamase.S pneumoniaeisolates were characterized as penicillin susceptible, intermediately resistant or high level penicillin-resistant. Minimal inhibitory concentrations (MICs) were determined using a microbroth dilution technique described by the National Committee of Clinical Laboratory Standards.RESULTS: Between the two collection periods, there was a significant increase in highly penicillin-resistantS pneumoniaefrom 2.1% to 4.4% (P<0.05) and an increase in intermediately penicillin-resistant strains from 6.4% to 8.9% (P<0.05). A significant increase in high level penicillin-resistantS pneumoniaewas noted among paediatric isolates. No significant difference in the susceptibilities of comparator agents was detected. A significant increase in the number of beta-lactamase producingH influenzae, 34% to 43% (P<0.05) was observed. Ninety-five per cent ofM catarrhalisisolates were beta-lactamase producers in both time periods.CONCLUSIONS: During the course of this study, the incidence of penicillin resistance inS pneumoniaedoubled. As a result of this increase, infections due to this organism in sites where poor penetration of beta-lactam antibiotics occur may become increasingly difficult to manage.

Ceftibuten: A New Expanded-Spectrum Oral Cephalosporin

1997 ◽  
Vol 31 (9) ◽  
pp. 1022-1033 ◽  
Author(s):  
David RP Guay
Keyword(s):  
Antimicrobial Activity ◽  
Respiratory Tract ◽  
Clinical Efficacy ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Acute Otitis Media ◽  
Lower Respiratory Tract Infections ◽  
Oral Cephalosporin ◽  
In Vitro Susceptibility ◽  
Tract Infections

Objective To review the antimicrobial activity, pharmacokinetics, clinical efficacy, and tolerability of ceftibuten, a new expanded-spectrum oral cephalosporin. Data Sources Literature was identified by a MEDLINE search (January 1983–June 1996) of the medical literature, review of English-language literature and bibliographies of these articles, and data on file. Study Selection Clinical efficacy data were selected from all published and unpublished trials and abstracts that mentioned ceftibuten. Additional information concerning in vitro susceptibility, safety, chemistry, and pharmacokinetic profile of ceftibuten also was reviewed. Data Synthesis Ceftibuten, an oral expanded-spectrum cephalosporin, has a broad spectrum of activity against many gram-negative and selected gram-positive organisms, including Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis, and Haemophilus influenzae. Ceftibuten is stable to hydrolysis by many common p-lactamases. Ceftibuten is rapidly and almost completely absorbed from the gastrointestinal tract and is primarily eliminated renally as unchanged drug. The elimination half-life of ceftibuten is slightly longer than 2 hours. Efficacy has been demonstrated in a number of clinical trials in adults and children with upper and lower respiratory tract infections (e.g., acute otitis media, pharyngitis, sinusitis, bronchitis) and urinary tract infections. The adverse effect profile is equal to that of comparator agents. Conclusions Ceftibuten is an alternative to other antimicrobial agents with convenient once-daily dosing in the treatment of upper and lower respiratory tract infections. Similar to other oral expanded-spectrum cephalosporins, ceftibuten has antimicrobial activity against common pathogens of the respiratory tract and is stable in the presence of many β-lactamases. The clinical choice of an oral expanded-spectrum cephalosporin will be based on patient acceptance, frequency of administration, and cost.

scholarly journals Allergic Reactions and Cross-Reactivity Potential with Beta-Lactamase Inhibitors

Pharmacy ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 77 ◽  
Author(s):  
Kayla R. Stover ◽  
Katie E. Barber ◽  
Jamie L. Wagner
Keyword(s):  
Antimicrobial Activity ◽  
Case Reports ◽  
Cross Reactivity ◽  
Allergic Reactions ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Beta Lactamases ◽  
Chemical Structures ◽  
Lactamase Inhibitor

Although beta-lactam allergies are an emerging focus of stewardship programs and interventions, less is publicly released regarding allergies to beta-lactamase inhibitors. This review presents and evaluates the data regarding allergic reactions with beta-lactamase inhibitors. Clavulanate, sulbactam, and tazobactam are beta-lactam-based beta-lactamase inhibitors that are combined with several penicillins or cephalosporins in order to preserve antimicrobial activity in the presence of beta-lactamases. Avibactam, relebactam, and vaborbactam are non-beta-lactam beta-lactamase inhibitors that are combined with cephalosporins or carbapenems in order to expand the antimicrobial activity against broader-spectrum beta-lactamases. Case reports document hypersensitivity reactions to clavulanate, sulbactam, and tazobactam, but not to avibactam, relebactam, or vaborbactam. Based on these reports and considering the chemical structures, cross-allergenicity with beta-lactams is likely with sulbactam and tazobactam. Considering the slightly altered beta-lactam structure, cross-allergenicity is less likely with clavulanate, but still possible. It appears that cross-allergenicity between beta-lactam antimicrobials and the newer, non-beta-lactam beta-lactamase inhibitors is unlikely. It is important for clinicians to perform allergy testing to both the beta-lactam and the beta-lactamase inhibitor in order to confirm the specific allergy and reaction type.

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.

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