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Microorganisms
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Carbapenemase-producing Enterobacteriaceae
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Carbapenemase-producing Enterobacteriaceae

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 20072

Special Issue Editor

Dr. Hanna Sidjabat

E-Mail Website1 Website2
Guest Editor
UQ Centre for Clinical Research, The University of Queensland, Herston, QLD 4029, Australia
Interests: genome; proteome; carbapenemases; enterobacteriaceae; carbapenem antibiotics; antibiotic stewardship; infection control; nosocomial infections; probiotics; lactobacillus; alternative treatment

Special Issue Information

Dear Colleagues,

Infections by multidrug-resistant Gram-negative bacteria—in particular by carbapenemase-producing Enterobacteriaceae—result in limited options for clinically available antibiotics. Carbapenemases hydrolyze carbapenem antibiotics, which have been the antibiotics of last resort to treat infections by Enterobacteriaceae resistant to expanded-spectrum beta-lactamases. Therefore, the identification of carbapenemase-producing Enterobacteriaceae prior to providing treatment with antibiotics or through rapid detection will help to provide the appropriate treatment and help to reduce the spread of antibiotic resistance. Updates of the molecular epidemiology, genomes, the horizontal transmission of carbapenemase-encoding genes, and clinically available treatment options, as well as updates in the antibiotics pipelines for infections due to carbapenemase-producing Enterobacteriaceae will be the scope of this edition.

Dr. Hanna Sidjabat
Guest Editor

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Keywords

  • Enterobacteriaceae
  • horizontal transmission
  • plasmids, insertion element, plasmid types or replicons, plasmid sequence types
  • NDM, KPC, IMP, VIM, OXA-48
  • 16S rRNA methylases, armA, rmtB, rmtC, rmtD
  • rapid detection of carbapenemase
  • mass spectrometry for carbapenemase detection

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Published Papers (6 papers)

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Research

11 pages, 269 KiB  
Article
Does Antimicrobial Therapy Affect Mortality of Patients with Carbapenem-Resistant Klebsiella pneumoniae Bacteriuria? A Nationwide Multicenter Study in Taiwan
by Chien Chuang, Chin-Fang Su, Jung-Chung Lin, Po-Liang Lu, Ching-Tai Huang, Jann-Tay Wang, Yin-Ching Chuang, L. Kristopher Siu, Chang-Phone Fung and Yi-Tsung Lin
Microorganisms 2020, 8(12), 2035; https://doi.org/10.3390/microorganisms8122035 - 19 Dec 2020
Cited by 4 | Viewed by 2159
Abstract
Few clinical studies have previously discussed patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteriuria. This study aimed to assess the effect of antimicrobial therapy on the mortality of patients with CRKP bacteriuria. Hospitalized adults with CRKP bacteriuria were enrolled retrospectively from 16 hospitals in [...] Read more.
Few clinical studies have previously discussed patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteriuria. This study aimed to assess the effect of antimicrobial therapy on the mortality of patients with CRKP bacteriuria. Hospitalized adults with CRKP bacteriuria were enrolled retrospectively from 16 hospitals in Taiwan during 2013 and 2014. Critically ill patients were defined as those with an Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥ 20. Multivariate Cox regression analysis was used to determine independent risk factors for 14- and 28-day mortality. Of 107 patients with CRKP bacteriuria, the 14-day and 28-day mortality was 14.0% and 25.2%, respectively. Thirty-three patients received appropriate antimicrobial therapy. In the multivariate Cox regression analysis, the APACHE II score ≥ 20 was the only independent risk factor for 14-day mortality (hazard ratio [HR]: 6.15, p = 0.024). APACHE II score ≥ 20 (HR: 3.05, p = 0.018) and male sex (HR: 2.57, p = 0.037) were associated with 28-day mortality. Among critically ill patients with CRKP bacteriuria, appropriate antimicrobial therapy was not associated with 14-day or 28-day survival. In conclusion, in patients with CRKP bacteriuria, the use of appropriate antimicrobial therapy was not an independent factor associated with reduced mortality. Our findings may inform future antibiotic stewardship interventions for bacteriuria caused by multidrug resistant pathogens. Full article
(This article belongs to the Special Issue Carbapenemase-producing Enterobacteriaceae)
8 pages, 229 KiB  
Communication
Emergence of Enterobacter cloacae Complex Co-Producing IMP-10 and CTX-M, and Klebsiella pneumoniae Producing VIM-1 in Clinical Isolates in Japan
by Satoshi Nishida, Naohisa Matsunaga, Yuta Kamimura, Shinobu Ishigaki, Taiji Furukawa and Yasuo Ono
Microorganisms 2020, 8(11), 1816; https://doi.org/10.3390/microorganisms8111816 - 18 Nov 2020
Cited by 14 | Viewed by 2660
Abstract
Background: Carbapenemase-producing Enterobacteriaceae (CPE) are an emerging threat in healthcare settings worldwide. Objectives: We evaluated the presence of carbapenemase genes in CPE in a tertiary care university hospital in Tokyo, Japan. Methods: Carbapenem-resistant clinical isolates were collected in 2018 at Teikyo University Hospital [...] Read more.
Background: Carbapenemase-producing Enterobacteriaceae (CPE) are an emerging threat in healthcare settings worldwide. Objectives: We evaluated the presence of carbapenemase genes in CPE in a tertiary care university hospital in Tokyo, Japan. Methods: Carbapenem-resistant clinical isolates were collected in 2018 at Teikyo University Hospital (Tokyo, Japan). Bacterial species were identified using MALDI-TOF MS. Carbapenemase production was evaluated using a carbapenemase inactivation method. The presence of carbapenemase genes was confirmed by multiplex PCR and DNA sequencing. Results: Four CPE isolates were identified: two Enterobacter cloacae complex strains and Klebsiella oxytoca and Klebsiella pneumoniae strains. Three of the isolates (E. cloacae complex and K. oxytoca) were IMP-1-type producers, including IMP-10 in their produced metallo-β-lactamase, and are epidemic in East Japan. The IMP-10-producing E. cloacae complex strain also produced CTX-M ESBL. The other CPE isolate (K. pneumoniae) is a VIM-1 producer. VIM-1-producing K. pneumoniae is epidemic in Europe, especially in Greece. Accordingly, the VIM-1 producer was isolated from a patient with a medical history in Greece. Conclusions: This study revealed the emergence of E. cloacae complex co-producing IMP-1-type carbapenemase and CTX-M ESBL, and K. pneumoniae producing VIM-1 carbapenemase in clinical isolates in Japan. Metallo-β-lactamase was the most prevalent type of carbapenemase at Teikyo University Hospital, especially IMP-1-type carbapenemase. The detection of VIM-1-producing K. pneumoniae suggests that epidemic CPE from overseas can spread to countries with low CPE prevalence, such as Japan, highlighting the need for active surveillance. Full article
(This article belongs to the Special Issue Carbapenemase-producing Enterobacteriaceae)
5 pages, 354 KiB  
Communication
First Detection of GES-5-Producing Escherichia coli from Livestock—An Increasing Diversity of Carbapenemases Recognized from German Pig Production
by Alexandra Irrgang, Simon H. Tausch, Natalie Pauly, Mirjam Grobbel, Annemarie Kaesbohrer and Jens A. Hammerl
Microorganisms 2020, 8(10), 1593; https://doi.org/10.3390/microorganisms8101593 - 16 Oct 2020
Cited by 17 | Viewed by 2465
Abstract
Resistance to carbapenems due to carbapenemase-producing Enterobacteriaceae (CPE) is an increasing threat to human health worldwide. In recent years, CPE could be found only sporadically from livestock, but concern rose that livestock might become a reservoir for CPE. In 2019, the first GES [...] Read more.
Resistance to carbapenems due to carbapenemase-producing Enterobacteriaceae (CPE) is an increasing threat to human health worldwide. In recent years, CPE could be found only sporadically from livestock, but concern rose that livestock might become a reservoir for CPE. In 2019, the first GES carbapenemase-producing Escherichia coli from livestock was detected within the German national monitoring on antimicrobial resistance. The isolate was obtained from pig feces and was phenotypically resistant to meropenem and ertapenem. The isolate harbored three successive blaGES genes encoding for GES-1, GES-5 and GES-5B in an incomplete class-I integron on a 12 kb plasmid (pEC19-AB02908; Acc. No. MT955355). The strain further encoded for virulence-associated genes typical for uropathogenic E. coli, which might hint at an increased pathogenic potential. The isolate produced the third carbapenemase detected from German livestock. The finding underlines the importance CPE monitoring and detailed characterization of new isolates. Full article
(This article belongs to the Special Issue Carbapenemase-producing Enterobacteriaceae)
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14 pages, 3605 KiB  
Article
Elimination of Extracellular Adenosine Triphosphate for the Rapid Prediction of Quantitative Plate Counts in 24 h Time-Kill Studies against Carbapenem-Resistant Gram-Negative Bacteria
by Yiying Cai, Jonathan J. Ng, Hui Leck, Jocelyn Q. Teo, Jia-Xuan Goh, Winnie Lee, Tse-Hsien Koh, Thuan-Tong Tan, Tze-Peng Lim and Andrea L. Kwa
Microorganisms 2020, 8(10), 1489; https://doi.org/10.3390/microorganisms8101489 - 28 Sep 2020
Cited by 1 | Viewed by 2286
Abstract
Traditional in vitro time-kill studies (TKSs) require viable plating, which is tedious and time-consuming. We used ATP bioluminescence, with the removal of extracellular ATP (EC-ATP), as a surrogate for viable plating in TKSs against carbapenem-resistant Gram-negative bacteria (CR-GNB). Twenty-four-hour TKSs were conducted using [...] Read more.
Traditional in vitro time-kill studies (TKSs) require viable plating, which is tedious and time-consuming. We used ATP bioluminescence, with the removal of extracellular ATP (EC-ATP), as a surrogate for viable plating in TKSs against carbapenem-resistant Gram-negative bacteria (CR-GNB). Twenty-four-hour TKSs were conducted using eight clinical CR-GNB (two Escherichia coli, two Klebsiella spp., two Acinetobacter baumannii, two Pseudomonas aeruginosa) with multiple single and two-antibiotic combinations. ATP bioluminescence and viable counts were determined at each timepoint (0, 2, 4, 8, 24 h), with and without apyrase treatment. Correlation between ATP bioluminescence and viable counts was determined for apyrase-treated and non-apyrase-treated samples. Receiver operator characteristic curves were plotted to determine the optimal luminescence threshold to discriminate between inhibitory/non-inhibitory and bactericidal/non-bactericidal combinations, compared to viable counts. After treatment of bacteria with 2 U/mL apyrase for 15 min at 37 °C, correlation to viable counts was significantly higher compared to untreated samples (p < 0.01). Predictive accuracies of ATP bioluminescence were also significantly higher for apyrase-treated samples in distinguishing inhibitory (p < 0.01) and bactericidal (p = 0.03) combinations against CR-GNB compared to untreated samples, when all species were collectively analyzed. We found that ATP bioluminescence can potentially replace viable plating in TKS. Our assay also has applications in in vitro and in vivo infection models. Full article
(This article belongs to the Special Issue Carbapenemase-producing Enterobacteriaceae)
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7 pages, 699 KiB  
Communication
Complete Genome and Plasmids Sequences of a Clinical Proteus mirabilis Isolate Producing Plasmid Mediated NDM-1 From Italy
by Ibrahim Bitar, Vittoria Mattioni Marchetti, Alessandra Mercato, Elisabetta Nucleo, Adriano Anesi, Silvia Bracco, Vanina Rognoni, Jaroslav Hrabak and Roberta Migliavacca
Microorganisms 2020, 8(3), 339; https://doi.org/10.3390/microorganisms8030339 - 28 Feb 2020
Cited by 17 | Viewed by 3161
Abstract
Background: The spread of carbapenemase genes, such as blaNDM-1, in Proteus mirabilis poses a public health threat. The aim of the study was to characterize the genome and plasmids sequences of an NDM-1-positive strain (IBCRE14), which was isolated in 2019 from [...] Read more.
Background: The spread of carbapenemase genes, such as blaNDM-1, in Proteus mirabilis poses a public health threat. The aim of the study was to characterize the genome and plasmids sequences of an NDM-1-positive strain (IBCRE14), which was isolated in 2019 from a catheterized patient hospitalized in Italy. Methods: Whole genome sequencing (WGS) of IBCRE14 was performed on extracted genomic DNA using Sequel I platform. Genome assembly was performed using “Microbial Assembly”. Genomic analysis was conducted by uploading the contigs to ResFinder and PlasmidFinder databases from the Center for Genomic Epidemiology. Results: IBCRE14 had a genome size of 4,018,329 bp and harboured genes coding for resistance to aminoglycosides (aadA1), phenicol (cat), tetracycline (tetJ), and trimethoprim (dfrA1). A large plasmid (pIB_NDM_1) harboured antibiotic resistance genes against sulphonamide (sul1), trimethoprim (dfrA14), tetracycline (tetB), rifampicin (arr-2), aminoglycosides (aadA1, aph3-VI), and beta-lactams (blaOXA-10, blaNDM-1). Furthermore, a small plasmid (pIB_COL3M) harboured a qnrD1 gene coding for quinolone resistance. Conclusion: The ability to conjugate and the presence of a composite antibiotic resistance island suggests that pIB_NDM_1 could both acquire more resistance genes and easily disseminate. To our knowledge, this is the first report on an untypable plasmid harbouring blaNDM-1 in P. mirabilis, in Italy. Full article
(This article belongs to the Special Issue Carbapenemase-producing Enterobacteriaceae)
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16 pages, 1480 KiB  
Article
Genomic Analysis of Carbapenemase-Producing Extensively Drug-Resistant Klebsiella pneumoniae Isolates Reveals the Horizontal Spread of p18-43_01 Plasmid Encoding blaNDM-1 in South Africa
by Yogandree Ramsamy, Koleka P. Mlisana, Mushal Allam, Daniel G. Amoako, Akebe L. K. Abia, Arshad Ismail, Ravesh Singh, Theroshnie Kisten, Khine Swe Swe Han, David J. Jackson Muckart, Timothy Hardcastle, Moosa Suleman and Sabiha Y. Essack
Microorganisms 2020, 8(1), 137; https://doi.org/10.3390/microorganisms8010137 - 17 Jan 2020
Cited by 24 | Viewed by 6352
Abstract
Whole-genome sequence (WGS) analyses were employed to investigate the genomic epidemiology of extensively drug-resistant Klebsiella pneumoniae strains, focusing on the carbapenem resistance-encoding determinants, mobile genetic support, clonal and epidemiological relationships. A total of ten isolates were obtained from patients admitted to the intensive [...] Read more.
Whole-genome sequence (WGS) analyses were employed to investigate the genomic epidemiology of extensively drug-resistant Klebsiella pneumoniae strains, focusing on the carbapenem resistance-encoding determinants, mobile genetic support, clonal and epidemiological relationships. A total of ten isolates were obtained from patients admitted to the intensive care unit (ICU) in a public hospital in South Africa. Five isolates were from rectal swabs of colonized patients and five from blood cultures of patients with invasive carbapenem-resistant infections. Following microbial identification and antibiotic susceptibility tests, the isolates were subjected to WGS on the Illumina MiSeq platform. All the isolates showed genotypic resistance to tested β-lactams (NDM-1, OXA-1, CTX-M-15, TEM-1B, SHV-1) and other antibiotics. All but one isolate belonged to the ST152 with a novel sequence type, ST3136, differing by a single-locus variant. The isolates had the same plasmid multilocus sequence type (IncF[K12:A-:B36]) and capsular serotype (KL149), supporting the epidemiological linkage between the clones. Resistance to carbapenems in the 10 isolates was conferred by the blaNDM-1 mediated by the acquisition of multi-replicon [ColRNAI, IncFIB(pB171), Col440I, IncFII, IncFIB(K) and IncFII(Yp)] p18-43_01 plasmid. These findings suggest that the acquisition of blaNDM-1-bearing plasmid structure (p18-43_01), horizontal transfer and clonal dissemination facilitate the spread of carbapenemases in South Africa. This emphasizes the importance of targeted infection control measures to prevent dissemination. Full article
(This article belongs to the Special Issue Carbapenemase-producing Enterobacteriaceae)
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