Effect of Porins and blaKPC Expression on Activity of Imipenem with Relebactam in Klebsiella pneumoniae: Can Antibiotic Combinations Overcome Resistance?

Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease
Gregory BalabanianJohn Quale

Abstract

Imipenem with relebactam is a novel β-lactam-β-lactamase inhibitor that has activity against most KPC-producing Enterobacteriaceae. Using 10 isolates of KPC-possessing Klebsiella pneumoniae, we assessed the relationship between imipenem-relebactam minimum inhibitory concentrations (MICs) and mechanisms known to contribute to antimicrobial resistance. The effect of adding a second agent was assessed by time-kill experiments. Mutations affecting the genes encoding porins ompK35 and ompK36 and identification of β-lactamases were assessed by PCR. Expression of blaKPC and acrB was assessed by real-time reverse-transcriptase (RT)-PCR, and production of OmpK36 by SDS-PAGE. Time-kill studies were performed using combinations of imipenem-relebactam with polymyxin B, amikacin, or tigecycline. Seven isolates having a disruption in a single porin, or in neither porin, remained susceptible to imipenem-relebactam. The addition of a second agent did not improve the activity of imipenem-relebactam for these isolates, although the addition of tigecycline was antagonistic for three isolates. Three isolates had major disruptions in both ompK35 and ompK36 that correlated with reduced activity of imipenem-relebactam (MICs 2/4, 8/4, and 512/4 μg/mL)...Continue Reading

References

Aug 6, 2005·Journal of Clinical Microbiology·Laure DiancourtSylvain Brisse
Jun 27, 2009·Journal of Medical Microbiology·David LandmanJohn Quale
Mar 2, 2012·The Journal of Antimicrobial Chemotherapy·David LandmanJohn Quale
May 28, 2015·Antimicrobial Agents and Chemotherapy·Amabel LapueblaJohn Quale
Jul 22, 2015·Antimicrobial Agents and Chemotherapy·Romney M HumphriesAric Gregson
Sep 15, 2016·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Ryan K ShieldsM Hong Nguyen

❮ Previous
Next ❯

Citations

Apr 25, 2019·Antibiotics·Justin R LenhardKeith S Kaye
Dec 4, 2019·Nature Reviews. Microbiology·Julia VergalliJean-Marie Pagès
Mar 3, 2019·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Irene GalaniUNKNOWN Study Collaborators
Mar 11, 2020·Nature Reviews. Microbiology·Ursula TheuretzbacherGuy E Thwaites
Dec 4, 2020·Infection and Drug Resistance·Toni A Campanella, Jason C Gallagher
Feb 4, 2021·The Journal of Antimicrobial Chemotherapy·Ursula TheuretzbacherEvelina Tacconelli
Apr 16, 2021·International Journal of Antimicrobial Agents·Luigia ScudellerEvelina Tacconelli

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Beta-lactamase Inhibitors

Beta-lactamase inhibitors are a class of antibiotics that inhibit beta-lactamases, a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. Here is the latest research.

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Carbapenems (ASM)

Carbapenems are members of the beta lactam class of antibiotics and are used for the treatment of severe or high-risk bacterial infections. Discover the latest research on carbapenems here.

Beta-lactamase Inhibitors (ASM)

Beta-lactamase inhibitors are a class of antibiotics that inhibit beta-lactamases, a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. Here is the latest research.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Carbapenems

Carbapenems are members of the beta lactam class of antibiotics and are used for the treatment of severe or high-risk bacterial infections. Discover the latest research on carbapenems here.