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Calculated parenteral initial treatment of bacterial infections: Infections with multi-resistant Gram-negative rods - ESBL producers, carbapenemase-producing Enterobacteriaceae, carbapenem-resistant Acinetobacter baumannii.

ABSTRACT: This is the sixteenth chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. Infections due to multiresistant Gram-negative rods are challenging. In this chapter recommendations for targeted therapy for infections caused by ESBL-producing Enterobacteriaceae, carbapenemase-producing Enterobacteriaceae and carbapenem-resistant Acinetobacter baumannii are given, based on the limited available evidence.

SUBMITTER: Grabein B

PROVIDER: S-EPMC7186793 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Calculated parenteral initial treatment of bacterial infections: Infections with multi-resistant Gram-negative rods - ESBL producers, carbapenemase-producing Enterobacteriaceae, carbapenem-resistant Acinetobacter baumannii.

Grabein Béatrice B Ebenhoch Michael M Kühnen Ernst E Thalhammer Florian F

GMS infectious diseases 20200326

This is the sixteenth chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2<sup>nd</sup> updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. Infections due to multiresistant Gram-negative rods are challenging. In this chapter recommendations for targeted therapy for infections caused by ESBL-producing Enterobacteriaceae, c ...[more]

PMID: 32373429

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Project description:Carbapenem-resistant Enterobacteriaceae (CRE) infections, high in morbidity and mortality, pose serious clinical challenges due to limited treatment options. A previous CRE surveillance study on 1,507 patients from 43 hospitals in Osaka, Japan, revealed that 12% of patients carried CRE and that 95% of the CRE isolates were IMP-type carbapenemase producers. Here, the mechanisms for this regional dissemination of a single carbapenemase gene were investigated. Since the dissemination of CRE is primarily due to the transmission of carbapenemase genes located on plasmids, we analyzed the plasmidome of 230 CRE isolates carrying blaIMP by whole-genome sequencing and Southern blotting. blaIMP-6 was found to be predominantly disseminated among chromosomally distinct isolates through the pKPI-6 plasmid. Underlying the vast clonal dissemination of pKPI-6, various subpopulations deriving from pKPI-6 were identified, which had acquired advantages for the dissemination of CRE isolates. A cluster exhibiting heteroresistance against meropenem by the transcriptional regulation of blaIMP-6 caused an outbreak likely through covert transmission of blaIMP-6 For stable carriage of blaIMP-6, they occasionally integrated blaIMP-6 on their chromosomes. In addition, we detected one isolate that broadened the range of antimicrobial resistance through a single point mutation in blaIMP-6 on pKPI-6. Multifaceted analysis of the plasmidome granted us more accurate perspectives on the horizontal spread of CRE isolates, which is difficult to trace only by comparing the whole genomes. This study revealed the predominant spread of a specific carbapenemase-encoding plasmid accompanying the emergence of phenotypically diverse derivatives, which may facilitate further dissemination of CRE in various environments.IMPORTANCE Global dissemination of carbapenem-resistant Enterobacteriaceae (CRE) threatens human health by limiting the efficacy of antibiotics even against common bacterial infections. Carbapenem resistance, mainly due to carbapenemase, is generally encoded on plasmids and is spread across bacterial species by conjugation. Most CRE epidemiological studies have analyzed whole genomes or only contigs of CRE isolates. Here, plasmidome analysis on 230 CRE isolates carrying blaIMP was performed to shed light into the dissemination of a single carbapenemase gene in Osaka, Japan. The predominant dissemination of blaIMP-6 by the pKPI-6 plasmid among genetically distinct isolates was revealed, as well as the emergences of pKPI-6 derivatives that acquired advantages for further disseminations. Underlying vast clonal dissemination of a carbapenemase-encoding plasmid, heteroresistance was found in CRE offspring, which was generated by the transcriptional regulation of blaIMP-6, stabilization of blaIMP-6 through chromosomal integration, or broadened antimicrobial resistance due to a single point mutation in blaIMP-6.

Dataset Information

Calculated parenteral initial treatment of bacterial infections: Infections with multi-resistant Gram-negative rods - ESBL producers, carbapenemase-producing Enterobacteriaceae, carbapenem-resistant Acinetobacter baumannii.

Publications

Calculated parenteral initial treatment of bacterial infections: Infections with multi-resistant Gram-negative rods - ESBL producers, carbapenemase-producing Enterobacteriaceae, carbapenem-resistant Acinetobacter baumannii.

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