Hospital outbreak of Klebsiella pneumoniae resistant to broad-spectrum cephalosporins and beta-lactam-beta-lactamase inhibitor combinations by hyperproduction of SHV-5 beta-lactamase.

1996 ◽  
Vol 34 (2) ◽  
pp. 358-363 ◽  
Author(s):  
G L French ◽  
K P Shannon ◽  
N Simmons
Keyword(s):  
Klebsiella Pneumoniae ◽  
Broad Spectrum ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Hospital Outbreak ◽  
Lactamase Inhibitor

scholarly journals In Vivo Activity of QPX7728, an Ultrabroad-Spectrum Beta-Lactamase Inhibitor, in Combination with Beta-Lactams against Carbapenem-Resistant Klebsiella pneumoniae

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Mojgan Sabet ◽  
Ziad Tarazi ◽  
David C. Griffith
Keyword(s):  
Klebsiella Pneumoniae ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Bacterial Killing ◽  
Clinical Issue ◽  
Content Type ◽  
Beta Lactam Antibiotics ◽  
Carbapenem Resistant ◽  
Lactamase Inhibitor

ABSTRACT Resistance to beta-lactams has created a major clinical issue. QPX7728 is a novel ultrabroad-spectrum cyclic boronic acid beta-lactamase inhibitor with activity against both serine and metallo-beta-lactamases developed to address this resistance for use in combination with beta-lactam antibiotics. The objective of these studies was to evaluate the activity of QPX7728 in combination with multiple beta-lactams against carbapenem-resistant Klebsiella pneumoniae isolates in a neutropenic mouse thigh infection model. Neutropenic mice were infected with strains with potentiated beta-lactam MICs of ≤2 mg/liter in the presence of 8 mg/liter QPX7728. Two strains of carbapenem-resistant K. pneumoniae were tested with aztreonam, biapenem, cefepime, ceftazidime, ceftolozane, and meropenem alone or in combination with 12.5, 25, or 50 mg/kg of body weight of QPX7728 every 2 hours for 24 hours. Treatment with all beta-lactams alone either was bacteriostatic or allowed for bacterial growth. The combination of QPX7728 plus each of these beta-lactams produced bacterial killing at all QPX7728 doses tested. Overall, these data suggest that QPX7728 administered in combination with different partner beta-lactam antibiotics may have utility in the treatment of bacterial infections due to carbapenem-resistant K. pneumoniae.

The Ultra-Broad-Spectrum Beta-lactamase Inhibitor QPX7728 Restores the Potency of Multiple Oral Beta-lactam Antibiotics against Beta-lactamase Producing Strains of Resistant Enterobacterales

2021 ◽  
Author(s):  
Olga Lomovskaya ◽  
Debora Rubio-Aparicio ◽  
Ruslan Tsivkovski ◽  
Jeff Loutit ◽  
Michael Dudley
Keyword(s):  
Broad Spectrum ◽  
Resistance Mechanisms ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Intrinsic Resistance ◽  
Beta Lactamases ◽  
Beta Lactam Antibiotics ◽  
The Impact ◽  
Lactamase Inhibitor

QPX7728 is a cyclic boronate ultra-broad-spectrum beta-lactamase inhibitor, with potent activity against both serine and metallo beta-lactamases. QPX7728 can be delivered systemically by the IV or oral route of administration. Oral β-lactam antibiotics alone or in combination with QPX7728 were evaluated for 1) sensitivity to hydrolysis by various common beta-lactamases and inhibition of hydrolysis by QPX7728; 2) the impact of non-beta-lactamase-mediated resistance mechanisms on potency of beta-lactams; and 3) in vitro activity against a panel of clinical strains producing diverse beta-lactamases. The carbapenem tebipenem had stability for many serine beta-lactamases from all molecular classes followed by cephalosporin ceftibuten. Addition of QPX7728 to tebipenem, ceftibuten and mecillinam completely reversed beta-lactamase-mediated resistance in cloned beta-lactamases from serine and metallo enzyme classes; the degree of potentiation of other beta-lactams varied according to the beta-lactamase produced. Tebipenem, ceftibuten and cefixime had the lowest MICs against laboratory strains with various combinations of beta-lactamases and the intrinsic drug-resistance mechanisms of porin and efflux mutations. There was a high degree of correlation between potency of various combinations against cloned beta-lactamases and efflux/porin mutants and the activity against clinical isolates, showing the importance of both inhibition of beta-lactamase along with minimal impact of general intrinsic resistance mechanisms affecting the beta-lactam. Tebipenem and ceftibuten appeared to be the best beta-lactam antibiotics when combined with QPX7728 for activity against Enterobacterales that produce serine or metallo beta-lactamases.

scholarly journals Extended Spectrum Beta-Lactamase ( ESBL )

2018 ◽  
Vol 1 (1) ◽  
pp. 1
Author(s):  
Verna Biutifasari
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Clinical Microbiology ◽  
Molecular Detection ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
Lactamase Inhibitor

<p>Antibiotika telah banyak digunakan sekarang ini. Pemakaian antibiotika yang berlebihan dan tidak sesuai dengan klinis dapat menyebabkan terjadinya resistensi terhadap antibiotika tersebut</p><p>Salah satu antibiotika yang dipakai adalah antibiotika golongan <em>beta-lactam</em> yang bekerja menghambat dinding sel. Pemakaian antibiotika <em>beta-lactam</em> yang tidak sesuai dapat menyebabkan terjadi resistensi terhadap antibiotika tersebut. Resistensi terhadap <em>beta-lactam</em> dapar terjadi di berbagai tingkatan. Salah satu resistensi dapat terjadi adalah  resistensi terhadap <em>extendedspectrum broad lactamase (ESBL)</em></p><p><em>Extended spectrum beta-lactamase</em> adalah enzim yang mempunyai kemampuan dalam menghidrolisis antibiotika golongan <em>penicillin, cephalosporin</em> generasi satu, dua, dan tiga serta golongan <em>monobactam </em>dan menyebabkan resistensi ke seluruh antibiotika tersebut.</p><p>ESBL banyak dihasilkan oleh <em>Enterobactericeae </em>(terutama <em>Escherichia coli</em>) dan <em>Klebsiella pneumoniae. </em><em>Enterobacteriacea</em><em>e</em> mempunyai 3 pola resistensi yang disebabkan b<em>road spectrum beta-lactamase,inhibitor </em>resistant beta-lactamase (derivat TEM) , <em>Cephalosporinase </em>yang berlebihan. ESBL dapat sulit terdeteksi karena ESBL mempunyai perbedaan tingkatan aktifitas terhadap bermacam-macam <em>cephalosporin</em></p><p>ESBL dapat dideteksi secara <em>clinical microbiology (phenotypic</em><em>)</em> dan <em>molecular detection (genotypic).</em></p><p><em> </em></p><p><strong>Keyword</strong><strong>s</strong><strong>:</strong> Antiobiotika, resistensi, ESBL</p>

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.

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.

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