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Carbapenemase Producing Enterobacteriaceae

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Dear Colleagues,

Carbapanem-producing Enterobacteriaceae (CPE) represent a serious threat among antimicrobial-resistant bacteria. CPE are often resistant to multiple antimicrobials, thus reducing the antimicrobial options available. In this context, the limited therapeutic options to treat infections due to CPE requires the development of novel antimicrobial molecules, the optimization of therapeutic strategies, and an accurate description of the epidemiological pattern of the antimicrobial resistance. This Special Issue will be dedicated to the epidemiology of carbapenem-resistant Enterobacteriaceae, the emerging threat of resistance to novel antimicrobial molecules, the development of new strategies to optimize the antimicrobial treatments, and limits to the diffusion of CPE.

We invite contributors to submit original research papers, short notes, or reviews in the following areas:

(a) Emerging threat of resistance in CPE;
(b) Concepts and strategies to optimize the antimicrobial treatments for CPE infections;
(c) Management and infection control of patients with infections due to CPE;
(d) Molecular epidemiology of CPE and changing patterns of the antimicrobial resistance;
(e) Genomic characterization of CPE in difficult-to-treat infections;
(f) Characterization of the determinants of antimicrobial resistance to novel antimicrobial molecules;
(g) Description of novel in vitro diagnostic tools to optimize antimicrobial treatments.

Dr. Paolo Gaibani
Dr. Simone Ambretti
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

carbapenem-resistant Enterobacteriaceae
treatments
infection control
novel antimicrobials
genomic characterization
epidemiology

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Research

9 pages, 1179 KiB

Open AccessArticle

Successful Treatment of Bloodstream Infection due to a KPC-Producing Klebsiella Pneumoniae Resistant to Imipenem/Relebactam in a Hematological Patient

by Paolo Gaibani, Linda Bussini, Stefano Amadesi, Michele Bartoletti, Federica Bovo, Tiziana Lazzarotto, Pierluigi Viale and Simone Ambretti

Microorganisms 2022, 10(4), 778; https://doi.org/10.3390/microorganisms10040778 - 5 Apr 2022

Cited by 8 | Viewed by 1694

Abstract

Novel carbapenem-β-lactamase inhibitor combination, imipenem/relebactam (IMI-REL), has been recently approved for treatment of infections with limited or no alternative treatment options. In this study, we described the emergence of the IMI-REL-resistance in a KPC-producing Klebsiella pneumoniae (KPC-Kp) strain collected from a hematological patient with no evidence of prior colonization. Interestingly, IMI-REL-resistance was associated with meropenem/vaborbactam (MER-VAB) cross-resistance but was not associated with cross-resistance to ceftazidime/avibactam (CAZ-AVI). Although treatment with CAZ-AVI and gentamicin completely eradicated the infection due KPC-Kp cross-resistance to IMI-REL and MER-VAB, the patient became colonized subsequently by KPC-Kp strains susceptible to IMI-REL and MER-VAB. Whole-genome sequencing performed by hybrid approach using Illumina and Oxford Nanopore platforms demonstrated that all KPC-Kp strains isolated from hematological patient belonged to the ST512 and were clonally related. Analysis of antimicrobial and porins genes demonstrated that cross-resistance to IMI-REL and MER-VAB was associated with increased bla_KPC-3 copy number and truncated OmpK35 and OmpK36 with GD134-135 insertion. Phylogenetic analysis demonstrated that KPC-Kp cross-resistance to IMI-REL and MER-VAB was clonally related to a KPC-Kp resistant to IMI-REL as previously described, demonstrating the spread of this multidrug resistant clone in the hematological unit. In conclusion, the results presented in this study reported the emergence of cross-resistance to MER-VAB and IMI-REL in a KPC-Kp strain isolated from a hematological patient and highlight the potential development and diffusion of new multidrug resistance traits. Full article

(This article belongs to the Special Issue Carbapenemase Producing Enterobacteriaceae)

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12 pages, 276 KiB

Open AccessArticle

Increasing Trends of Association of 16S rRNA Methylases and Carbapenemases in Enterobacterales Clinical Isolates from Switzerland, 2017–2020

by Claudine Fournier, Laurent Poirel, Sarah Despont, Julie Kessler and Patrice Nordmann

Microorganisms 2022, 10(3), 615; https://doi.org/10.3390/microorganisms10030615 - 14 Mar 2022

Cited by 9 | Viewed by 1940

Abstract

Aminoglycosides (AGs) in combination with β-lactams play an important role in antimicrobial therapy in severe infections. Pan-resistance to clinically relevant AGs increasingly arises from the production of 16S rRNA methylases (RMTases) that are mostly encoded by plasmids in Gram-negative bacteria. The recent emergence and spread of isolates encoding RMTases is worrisome, considering that they often co-produce extended-spectrum β-lactamases (ESBLs) or carbapenemases. Our study aimed to retrospectively analyze and characterize the association of carbapenem- and aminoglycoside-resistant clinical isolates in Switzerland during a 3.5-year period between January 2017 and June 2020. A total of 103 pan-aminoglycoside- and carbapenem-resistant clinical isolates were recovered at the NARA (Swiss National Reference Center for Emerging Antibiotic Resistance) during the 2017–2020 period. Carbapenemase and RMTase determinants were identified by PCR and sequencing. The characterization of plasmids bearing resistance determinants was performed by a mating-out assay followed by PCR-based replicon typing (PBRT). Clonality of the isolates was investigated by multilocus sequence typing (MLST). Over the 991 Enterobacterales collected at the NARA during this period, 103 (10.4%) of them were resistant to both carbapenems and all aminoglycosides. Among these 103 isolates, 35 isolates produced NDM-like carbapenemases, followed by OXA-48-like (n = 23), KPC-like (n = 21), or no carbapenemase (n = 13), OXA-48-like and NDM-like co-production (n = 7), and VIM-like enzymes (n = 4). The RMTases ArmA, RmtB, RmtC, RmtF, RmtG, and RmtB + RmtF were identified among 51.4%, 13.6%, 4.9%, 24.3%, 1%, and 1%, respectively. Plasmid co-localization of the carbapenemase and the RMTase encoding genes was found among ca. 20% of the isolates. A high diversity was identified in terms of the nature of associations between RMTase and carbapenemase-encoding genes, of incompatibility groups of the corresponding plasmids, and of strain genetic backgrounds, highlighting heterogeneous importations rather than clonal dissemination. Full article

(This article belongs to the Special Issue Carbapenemase Producing Enterobacteriaceae)

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