Overcoming Bacterial Resistance Using Antibiotic Combinations

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotics Use and Antimicrobial Stewardship".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 956

Special Issue Editors


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Guest Editor
Gause Institute of New Antibiotics, Moscow, Russia
Interests: in vitro model studies; antibiotic pharmacodynamics; antimicrobial resistance

E-Mail Website
Guest Editor
Gause Institute of New Antibiotics, Moscow, Russia
Interests: in vitro model studies; antibiotic pharmacodynamics; antimicrobial resistance

Special Issue Information

Dear Colleagues,

Resistance of bacteria to antibiotics is a growing problem. One of the existing ways to overcome the emergence of microbial resistance is combined use of antibiotics of different classes and/or antibiotics with beta-lactamase inhibitors. The search of such combinations or new active compounds characterized with potent efficacy against resistant organisms is one of the main areas of research. For these purposes, different approaches based on in vitro activity assay of combinations, including checkerboard techniques, time-kill experiments and investigation of pharmacodynamics in in vitro dynamic models, are used. In vitro dynamic models simulate the human pharmacokinetics of drugs and allow predicting the antibiotic combination effectiveness in clinic. Along with the search for novel antibiotic combinations, new approaches to evaluate their possible efficacy in clinic are valuable. In vivo experiments with infected animals hold a special place in the investigation of perspective drug combinations. Articles exploring the antimicrobial potential of drug combinations to overcome antibiotic resistance are welcome.

Dr. Maria V. Golikova
Dr. Elena N. Strukova
Guest Editors

Manuscript Submission Information

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Keywords

  • antibiotic resistance
  • antibiotic combinations
  • beta-lactamase inhibitors
  • novel approaches to predict efficacy of antibiotic combinations
  • checkerboard assay
  • in vitro time-kill assay
  • in vitro dynamic model studies
  • antibiotic pharmacodynamics

Published Papers (1 paper)

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Research

13 pages, 2263 KiB  
Article
Pharmacodynamics of Doripenem Alone and in Combination with Relebactam in an In Vitro Hollow-Fiber Dynamic Model: Emergence of Resistance of Carbapenemase-Producing Klebsiella pneumoniae and the Inoculum Effect
by Elena N. Strukova, Maria V. Golikova, Svetlana A. Dovzhenko, Mikhail B. Kobrin and Stephen H. Zinner
Antibiotics 2023, 12(12), 1705; https://doi.org/10.3390/antibiotics12121705 - 07 Dec 2023
Viewed by 742
Abstract
The emergence of bacteria resistant to beta-lactam/beta-lactamase inhibitor combinations is insufficiently studied, wherein the role of the inoculum effect (IE) in decreased efficacy is unclear. To address these issues, 5-day treatments with doripenem and doripenem/relebactam combination at different ratios of the agents were [...] Read more.
The emergence of bacteria resistant to beta-lactam/beta-lactamase inhibitor combinations is insufficiently studied, wherein the role of the inoculum effect (IE) in decreased efficacy is unclear. To address these issues, 5-day treatments with doripenem and doripenem/relebactam combination at different ratios of the agents were simulated in a hollow-fiber dynamic model against carbapenemase-producing K. pneumoniae at standard and high inocula. Minimal inhibitory concentrations (MICs) of doripenem alone and in the presence of relebactam at two inocula were determined. Combination MICs were tested using traditional (fixed relebactam concentration) and pharmacokinetic-based approach (fixed doripenem-to-relebactam concentration ratio equal to the therapeutic 24-h area under the concentration-time curve (AUC) ratio). In all experiments, resistant subpopulations were noted, but combined simulations reduced their numbers. With doripenem, the IE was apparent for both K. pneumoniae isolates in combined treatments for one strain. The pharmacokinetic-based approach to combination MIC estimation compared to traditional showed stronger correlation between DOSE/MIC and emergence of resistance. These results support (1) the constraint of relebactam combined with doripenem against the emergence of resistance and IE; (2) the applicability of a pharmacokinetic-based approach to estimate carbapenem MICs in the presence of an inhibitor to predict the IE and to describe the patterns of resistance occurrence. Full article
(This article belongs to the Special Issue Overcoming Bacterial Resistance Using Antibiotic Combinations)
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