Tags

Type your tag names separated by a space and hit enter

Effect of Porins and blaKPC Expression on Activity of Imipenem with Relebactam in Klebsiella pneumoniae: Can Antibiotic Combinations Overcome Resistance?
Microb Drug Resist. 2018 Sep; 24(7):877-881.MD

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). Two of these isolates also had overexpression of blaKPC, including the isolate with the highest MIC. These isolates were also resistant to polymyxin B and amikacin. The addition of amikacin provided both synergistic and bactericidal activity for the two more resistant isolates. The activity of imipenem-relebactam against K. pneumoniae is affected by major disruptions of both ompK35 and ompK36 and by expression of the KPC gene. Combining imipenem-relebactam with an aminoglycoside may be a promising approach for isolates with reduced susceptibility to imipenem-relebactam.

Authors+Show Affiliations

Department of Medicine and Division of Infectious Diseases, SUNY Downstate Medical Center , Brooklyn, New York.Department of Medicine and Division of Infectious Diseases, SUNY Downstate Medical Center , Brooklyn, New York.Department of Medicine and Division of Infectious Diseases, SUNY Downstate Medical Center , Brooklyn, New York.Department of Medicine and Division of Infectious Diseases, SUNY Downstate Medical Center , Brooklyn, New York.Department of Medicine and Division of Infectious Diseases, SUNY Downstate Medical Center , Brooklyn, New York.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29782237

Citation

Balabanian, Gregory, et al. "Effect of Porins and blaKPC Expression On Activity of Imipenem With Relebactam in Klebsiella Pneumoniae: Can Antibiotic Combinations Overcome Resistance?" Microbial Drug Resistance (Larchmont, N.Y.), vol. 24, no. 7, 2018, pp. 877-881.
Balabanian G, Rose M, Manning N, et al. Effect of Porins and blaKPC Expression on Activity of Imipenem with Relebactam in Klebsiella pneumoniae: Can Antibiotic Combinations Overcome Resistance? Microb Drug Resist. 2018;24(7):877-881.
Balabanian, G., Rose, M., Manning, N., Landman, D., & Quale, J. (2018). Effect of Porins and blaKPC Expression on Activity of Imipenem with Relebactam in Klebsiella pneumoniae: Can Antibiotic Combinations Overcome Resistance? Microbial Drug Resistance (Larchmont, N.Y.), 24(7), 877-881. https://doi.org/10.1089/mdr.2018.0065
Balabanian G, et al. Effect of Porins and blaKPC Expression On Activity of Imipenem With Relebactam in Klebsiella Pneumoniae: Can Antibiotic Combinations Overcome Resistance. Microb Drug Resist. 2018;24(7):877-881. PubMed PMID: 29782237.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Porins and blaKPC Expression on Activity of Imipenem with Relebactam in Klebsiella pneumoniae: Can Antibiotic Combinations Overcome Resistance? AU - Balabanian,Gregory, AU - Rose,Michael, AU - Manning,Nyla, AU - Landman,David, AU - Quale,John, Y1 - 2018/05/21/ PY - 2018/5/22/pubmed PY - 2018/12/15/medline PY - 2018/5/22/entrez KW - Klebsiella pneumoniae KW - carbapenemase KW - relebactam SP - 877 EP - 881 JF - Microbial drug resistance (Larchmont, N.Y.) JO - Microb Drug Resist VL - 24 IS - 7 N2 - 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). Two of these isolates also had overexpression of blaKPC, including the isolate with the highest MIC. These isolates were also resistant to polymyxin B and amikacin. The addition of amikacin provided both synergistic and bactericidal activity for the two more resistant isolates. The activity of imipenem-relebactam against K. pneumoniae is affected by major disruptions of both ompK35 and ompK36 and by expression of the KPC gene. Combining imipenem-relebactam with an aminoglycoside may be a promising approach for isolates with reduced susceptibility to imipenem-relebactam. SN - 1931-8448 UR - https://www.unboundmedicine.com/medline/citation/29782237/Effect_of_Porins_and_blaKPC_Expression_on_Activity_of_Imipenem_with_Relebactam_in_Klebsiella_pneumoniae:_Can_Antibiotic_Combinations_Overcome_Resistance L2 - https://www.liebertpub.com/doi/10.1089/mdr.2018.0065?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -