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Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method
Published on: April 18, 2019
New β-lactam-β-lactamase inhibitor combinations in clinical development.
1Anti-Infectives Consulting, LLC, Stonington, Connecticut, USA. Shlaes.david@earthlink.net
Annals of the New York Academy of Sciences
|January 26, 2013
Summary
New beta-lactam and beta-lactamase inhibitor combinations are emerging to combat increasing Gram-negative bacterial resistance. These novel agents, including avibactam and MK-7655, show promise in late-stage clinical trials.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- The increasing complexity of beta-lactamase-mediated resistance in Gram-negative bacilli poses a significant challenge to existing antibiotic therapies.
- The approval of piperacillin-tazobactam highlighted the need for effective strategies against resistant bacteria.
- Over two decades since the first combination (amoxicillin-clavulanic acid), new therapeutic options are critically needed.
Purpose of the Study:
- To review the biochemistry, antimicrobial activity, pharmacodynamics, and clinical development of novel beta-lactam-beta-lactamase inhibitor combinations.
- To highlight the mechanisms of action and spectra of activity of new inhibitors like avibactam and MK-7655.
- To provide an overview of agents in late-stage clinical trials and preclinical development.
Main Methods:
- Review of scientific literature and clinical trial data.
- Analysis of the biochemical properties of novel beta-lactamase inhibitors.
- Evaluation of antimicrobial activity and pharmacodynamic profiles of new combination therapies.
Main Results:
- Several new beta-lactam-beta-lactamase inhibitor combinations have advanced to late-stage clinical trials, including ceftolozane-tazobactam, ceftazidime-avibactam, ceftaroline-avibactam, and imipenem-cilastatin-MK-7655.
- Avibactam and MK-7655, non-beta-lactam diazabicyclooctane (DABCO) inhibitors, exhibit activity against class A carbapenemases and class C enzymes.
- Ceftolozane-tazobactam combines an antipseudomonal cephalosporin with tazobactam to overcome extended-spectrum beta-lactamases.
Conclusions:
- Novel beta-lactam-beta-lactamase inhibitor combinations represent a promising frontier in combating antimicrobial resistance.
- Agents like avibactam and MK-7655 offer expanded spectra of activity, including against challenging Gram-negative pathogens.
- Continued research and clinical development are essential to bring these vital new therapies to patients facing resistant infections.
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