scholarly journals Uncovering the gut microbiota as a reservoir of ST11 hypervirulent KPC-2-producing Klebsiella pneumoniaeUncovering the gut microbiota as a reservoir of ST11 hypervirulent KPC-2-producing Klebsiella pneumoniae

2019 ◽  
Author(s):  
Beiwen Zheng ◽  
Hao Xu ◽  
Tao Lv ◽  
Lihua Guo ◽  
Xiao Yu ◽  
...  
Keyword(s):  
Public Health ◽  
Gut Microbiota ◽  
Carbapenem Resistance ◽  
Underlying Mechanism ◽  
Public Health Issue ◽  
Virulence Plasmids ◽  
Carbapenem Resistant ◽  
Health Community ◽  
Surgical History ◽  
Genomic Characterization

Abstract Background: The emergence and spread of ST11 carbapenem-resistant, hypervirulent K. pneumonia (ST11-CR-HvKP) in China generated great concern from the public health community. The identification of ST11-CR-HvKP strain is expected to become a serious public health issue in China, considering the carbapenem resistance and virulence had converged in an epidemic clone. However, the underlying mechanism that enables its wide dissemination in China remains unclear.Results: Here, we investigate the prevalence of carbapenemase-producing Enterobacteriaceae (CPE) carriage by inpatients in a teaching hospital over a 1-year period, to identify ST11-CR-HvKP reservoirs, and to understand the transmission of these pathogens across healthcare networks. We identified a high colonization prevalence of CPE (12.4%) among inpatients with diarrhea. Correlations were detected between antibiotic exposure, surgical history, and being CPE positive. A genomic investigation of 65 CRKP isolates indicated a shared bacterial population among various wards. Maximum-likelihood phylogenetic tree demonstrated that these isolates were partitioned into three major clades. An analysis of the wzi locus revealed three different K types (KL105, KL47, and K64) among the ST11 isolates, indicating genetic diversity among these isolates. Our review of the cases showed that these patients had no contact with each other, indicating nosocomial transmission. Genetic and sequence mapping revealed complexity in the existence of virulence plasmids and resistance plasmids in the ST11-CRKP isolates. These data indicate that this process was more complicated than was earlier anticipated, as it may have involved multiple ST11 K. pneumoniae lineages and a variety of virulence plasmids. Conclusions: Collectively, this work represents the first evidence of gut microbiota may act as the source of ST11-CR-HvKP isolate. Active surveillance approaches, particularly in ICUs based on the results of this study, should be implemented to combat the spread of ST11-CR-HvKP and to improve patient outcomes. Key words: gut microbiota; hypervirulent; KPC-2; reservoir; genomic characterization

scholarly journals Stool Samples of Acute Diarrhea Inpatients as a Reservoir of ST11 Hypervirulent KPC-2-Producing Klebsiella pneumoniae

mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Beiwen Zheng ◽  
Hao Xu ◽  
Tao Lv ◽  
Lihua Guo ◽  
Yu Xiao ◽  
...  
Keyword(s):  
Public Health ◽  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Zhejiang Province ◽  
Public Health Issue ◽  
Resistant Bacteria ◽  
Phylogenetic Tree Analysis ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Stool Samples

ABSTRACT The emergence and spread of carbapenem-resistant hypervirulent Klebsiella pneumoniae sequence type 11 (ST11-CR-HvKP) in China are a great concern in the public health community. However, the underlying mechanism that enables its wide dissemination in China remains unclear. Here, we investigated the prevalence of carriage of carbapenemase-producing Enterobacteriaceae (CPE) among inpatients with diarrhea in a teaching hospital over 1 year to identify ST11-CR-HvKP reservoirs and to understand the genetic background and plasmid profiles of these pathogens. As assessed by stool analysis, the CPE colonization rate (12.4%) among the inpatients with diarrhea was high (12.4%). Antibiotic exposure, surgical history, and CPE positivity were correlated. Genomic investigation of 65 carbapenem-resistant K. pneumoniae isolates indicated a shared bacterial population in various wards. According to maximum likelihood phylogenetic tree analysis, these isolates were partitioned into three major clades. Analysis of the wzi locus revealed three different K types (KL105, KL47, and K64) among the ST11 isolates, indicating the genetic diversity of these isolates. Genetic and sequence mapping revealed the complexity of virulence and resistance plasmid sets harbored by the isolates. These observations indicate that the dissemination of resistant bacteria is more complex than initially anticipated and possibly involves multiple K. pneumoniae ST11 lineages and a variety of virulence plasmids. Collectively, we show for the first time that stool may be a source of ST11-CR-HvKP isolates. Furthermore, the findings reveal the silent dissemination of ST11-CR-HvKP bacteria in Zhejiang Province, China. Future investigations are warranted to determine the association between rectal colonization by ST11-CR-HvKP and clinical infections. IMPORTANCE China has been experiencing a rapid increase in the number of nosocomial infections caused by carbapenem-resistant Klebsiella pneumoniae ST11 (ST11-CRKP) for decades. The emergence of hypervirulent ST11-CRKP (ST11-CR-HvKP) strains is expected to become a serious public health issue in China, considering that carbapenem resistance and virulence have converged in an epidemic clone. K. pneumoniae strains that colonize the human intestinal tract may become a reservoir of virulence and carbapenemase-encoding genes. Here, we first characterized the genotypes and antimicrobial phenotypes of ST11-CR-HvKP strains isolated from diarrheal stool samples of inpatients in Zhejiang Province, China. Active surveillance approaches based on the findings of the present study should be implemented, particularly in intensive care units, to combat the spread of ST11-CR-HvKP and to improve treatment.

Emerging carbapenem resistance in ESKAPE organisms in sub-Saharan Africa and the way forward

2021 ◽  
Vol 1 (1) ◽  
pp. 3-6
Author(s):  
John Njeru
Keyword(s):  
Public Health ◽  
Carbapenem Resistance ◽  
Developed Countries ◽  
Sub Saharan Africa ◽  
Resistant Bacteria ◽  
Carbapenem Resistant ◽  
Public Health Threat ◽  
Enterobacter Species ◽  
Significant Public Health ◽  
Sub Saharan

The epidemiology of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) and their role in the development and spread of multidrug resistance (MDR) is not well characterized in sub-Saharan Africa (SSA). Carbapenems possess a broad spectrum of activity and are often reserved for the treatment of MDR infections in developed countries. However, the emergence of carbapenem resistance is increasingly being reported and therefore presents a significant public health threat. Although carbapenems are generally unavailable in African hospitals due to high cost, a small number of studies have reported the occurrence of carbapenem-resistant bacteria (CRB) in SSA. This, therefore, shows that carbapenem resistance (CR) is emerging in Africa. Thus, there is a critical need for deploying robust national and regional multidisciplinary, collaborative, and regulatory approaches aiming at elucidating the epidemiology of CR, its burden on the health care system, and strategies for compacting the development and spread of CR. This report hopes to highlight the epidemiology of carbapenem resistance and the main drivers of antibiotic resistance in SSA and proposes future strategies that can be used to combat the emergence of carbapenem resistance in the region

scholarly journals Dynamics of blaKPC-2 Dissemination from Non-CG258 Klebsiella pneumoniae to Other Enterobacterales via IncN Plasmids in an Area of High Endemicity

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Ana M. Rada ◽  
Elsa De La Cadena ◽  
Carlos Agudelo ◽  
Cesar Capataz ◽  
Nataly Orozco ◽  
...  
Keyword(s):  
Public Health ◽  
Klebsiella Pneumoniae ◽  
Neonatal Intensive Care ◽  
Carbapenem Resistance ◽  
Health Interventions ◽  
Global Public Health ◽  
Public Health Interventions ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Long Read

ABSTRACT Carbapenem-resistant Enterobacterales (CRE) pose a significant threat to global public health. The most important mechanism for carbapenem resistance is the production of carbapenemases. Klebsiella pneumoniae carbapenemase (KPC) represents one of the main carbapenemases worldwide. Complex mechanisms of blaKPC dissemination have been reported in Colombia, a country with a high endemicity of carbapenem resistance. Here, we characterized the dynamics of dissemination of blaKPC gene among CRE infecting and colonizing patients in three hospitals localized in a highly endemic area of Colombia (2013 and 2015). We identified the genomic characteristics of KPC-producing Enterobacterales recovered from patients infected/colonized and reconstructed the dynamics of dissemination of blaKPC-2 using both short and long read sequencing. We found that spread of blaKPC-2 among Enterobacterales in the participating hospitals was due to intra- and interspecies horizontal gene transfer (HGT) mediated by promiscuous plasmids associated with transposable elements that was originated from a multispecies outbreak of KPC-producing Enterobacterales in a neonatal intensive care unit. The plasmids were detected in isolates recovered in other units within the same hospital and nearby hospitals. The gene “epidemic” was driven by IncN-pST15-type plasmids carrying a novel Tn4401b structure and non-Tn4401 elements (NTEKPC) in Klebsiella spp., Escherichia coli, Enterobacter spp., and Citrobacter spp. Of note, mcr-9 was found to coexist with blaKPC-2 in species of the Enterobacter cloacae complex. Our findings suggest that the main mechanism for dissemination of blaKPC-2 is HGT mediated by highly transferable plasmids among species of Enterobacterales in infected/colonized patients, presenting a major challenge for public health interventions in developing countries such as Colombia.

scholarly journals Insights on carbapenem-resistant Acinetobacter baumannii

2021 ◽  
Vol 65 (1) ◽  
pp. 85-92
Author(s):  
Matthew Gavino Donadu ◽  
Stefania Zanetti ◽  
Ádám László Nagy ◽  
Ibrahim Barrak ◽  
Márió Gajdács
Keyword(s):  
Public Health ◽  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Public Health Issue ◽  
Carbapenem Resistant ◽  
Wide Range ◽  
Effective Choice ◽  
Phenotypic Methods ◽  
Resistance Rates ◽  
Critical Public Health

Acinetobacter baumannii (A. baumannii) is an important nosocomial pathogen, which may be a causative agent in a wide-range of human pathologies. Carbapenems are usually considered the last safe and effective choice of drugs for the treatment of Gram-negative infections. The emergence of carbapenem-resistant A. baumannii (CRAB) is a critical public health issue as they leave clinicians with limited therapeutic options. In this study, phenotypic methods were used to characterize sixty-two (n = 62) A. baumannii isolates, which were included based on their suspected non-susceptibility to meropenem. Minimum inhibitory concentrations (MICs) of meropenem, levofloxacin, gentamicin, sulfamethoxazole/trimethoprim, tigecycline were determined using E-tests, while colistin MICs were determined using broth microdilution. The isolates were subjected to the modified Hodge test (MHT), the modified carbapenem-inactivation method (mCIM) and the imipenem/EDTA combined disk test (CDT). Efflux pump overexpression was studied using agar plates containing phenylalanine-arginine β-naphthylamide (PAβN). Assessment of biofilm-formation was carried out using the crystal violet tube-adherence method. 64.5% of the strains showed meropenem MICs in the resistant range (>8 mg/L), resistance rates were similarly high to the other tested antibiotics. The MHT and mCIM assay were positive in 79.0% and 67.7% of cases, respectively; the presence of an MBL was suggested for 29.0% of isolates. Efflux-pump overexpression was seen in 12.9% of isolates. 54.8% of the isolates were characterized as strong biofilm-producers. Microbiology laboratories have an important role in differentiating the distinct mechanisms by which these pathogens develop the CRAB phenotype, as plasmid-borne carbapenemases are significant from the standpoint of public health microbiology.

scholarly journals A review on bacterial resistance to carbapenems: epidemiology, detection and treatment options

2020 ◽  
Vol 6 (3) ◽  
pp. FSO438 ◽  
Author(s):  
Ann A Elshamy ◽  
Khaled M Aboshanab
Keyword(s):  
Public Health ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Mechanisms Of Resistance ◽  
Carbapenem Resistant ◽  
Public Health Threat ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenems are a class of antimicrobial agents reserved for infections caused by multidrug-resistant microorganisms. The emergence of carbapenem resistance has become a serious public health threat. This type of antimicrobial resistance is spreading at an alarming rate, resulting in major outbreaks and treatment failure of community-acquired and nosocomial infections caused by the clinically relevant carbapenem-producing Enterobacteriaceae or carbapenem-resistant Enterobacteriaceae. This review is focused on carbapenem resistance, including mechanisms of resistance, history and epidemiology, phenotypic and genotypic detection in the clinically relevant bacterial pathogens and the possible treatment options available.

scholarly journals Characterization of a Carbapenem-Resistant Kluyvera Cryocrescens Isolate Carrying Blandm-1 from Hospital Sewage

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 149 ◽  
Author(s):  
Ying Li ◽  
Li Luo ◽  
Zhijiao Xiao ◽  
Guangxi Wang ◽  
Chengwen Li ◽  
...  
Keyword(s):  
Carbapenem Resistance ◽  
Public Health Issue ◽  
Global Public Health ◽  
Bioinformatics Analyses ◽  
Carbapenem Resistant ◽  
Antimicrobial Resistance Genes ◽  
Close Relationship ◽  
Probable Origin ◽  
Hospital Sewage ◽  
Kluyvera Cryocrescens

Carbapenem-resistant Enterobacteriaceae have been a global public health issue in recent years. Here, a carbapenem-resistant Kluyvera cryocrescens strain SCW13 was isolated from hospital sewage, and was then subjected to whole-genome sequencing (WGS). Based on WGS data, antimicrobial resistance genes were identified. Resistance plasmids were completely circularized and further bioinformatics analyses of plasmids were performed. A conjugation assay was performed to identify a self-transmissible plasmid mediating carbapenem resistance. A phylogenetic tree was constructed based on the core genome of publicly available Kluyvera strains. The isolate SCW13 exhibited resistance to cephalosporin and carbapenem. blaNDM-1 was found to be located on a ~53-kb self-transmissible IncX3 plasmid, which exhibited high similarity to the previously reported pNDM-HN380, which is an epidemic blaNDM-1-carrying IncX3 plasmid. Further, we found that SCW13 contained a chromosomal blaKLUC-2 gene, which was the probable origin of the plasmid-born blaKLUC-2 found in Enterobacter cloacae. Phylogenetic analysis showed that K. cryocrescens SCW13 exhibited a close relationship with K. cryocrescens NCTC10483. These findings highlight the further dissemination of blaNDM through clonal IncX3 plasmids related to pNDM-HN380 among uncommon Enterobacteriaceae strains, including Kluyvera in this case.

scholarly journals See and Sequence: Integrating Whole-Genome Sequencing Within the National Antimicrobial Resistance Surveillance Program in the Philippines

2019 ◽  
Author(s):  
Silvia Argimón ◽  
Melissa A. L. Masim ◽  
June M. Gayeta ◽  
Marietta L. Lagrada ◽  
Polle K. V. Macaranas ◽  
...  
Keyword(s):  
Public Health ◽  
Antimicrobial Resistance ◽  
Genome Sequencing ◽  
Genomic Data ◽  
Carbapenem Resistance ◽  
The Philippines ◽  
Surveillance Program ◽  
Whole Genome ◽  
Genomic Epidemiology ◽  
Carbapenem Resistant

AbstractDrug-resistant bacterial infections constitute a growing threat to public health globally 1. National networks of laboratory-based surveillance of antimicrobial resistance (AMR) monitor the emergence and spread of resistance and are central to the dissemination of these data to AMR stakeholders 2. Whole-genome sequencing (WGS) can support these efforts by pinpointing resistance mechanisms and uncovering transmission patterns 3, 4. However, genomic surveillance is rare in low- and middle-income countries (LMICs), which are predicted to be the most affected by AMR 5. We implemented WGS within the established Antimicrobial Resistance Surveillance Program (ARSP) of the Philippines via ongoing technology transfer, capacity building in and binational collaboration. In parallel, we conducted an initial large-scale retrospective sequencing survey to characterize bacterial populations and dissect resistance phenotypes of key bug-drug combinations, which is the focus of this article. Starting in 2010, the ARSP phenotypic data indicated increasing carbapenem resistance rates for Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Escherichia coli. We first identified that this coincided with a marked expansion of specific resistance phenotypes. By then linking the resistance phenotypes to genomic data, we revealed the diversity of genetic lineages (strains), AMR mechanisms, and AMR vehicles underlying this expansion. We discovered a previously unreported plasmid-driven hospital outbreak of carbapenem-resistant K. pneumoniae, uncovered the interplay of carbapenem resistance genes and plasmids in the geographic circulation of epidemic K. pneumoniae ST147, and found that carbapenem-resistant E. coli ST410 consisted of diverse lineages of global circulation that carried both international and local plasmids, resulting in a combination of carbapenemase genes variants previously unreported for this organism. Thus, the WGS data provided an enhanced understanding of the interplay between strains, genes and vehicles driving the dissemination of carbapenem resistance in the Philippines. In addition, our retrospective survey served both as the genetic background to contextualize local prospective surveillance, and as a comprehensive dataset for training in bioinformatics and genomic epidemiology. Continued prospective sequencing, capacity building and collaboration will strengthen genomic surveillance of AMR in the Philippines and the translation of genomic data into public-health action. We generated a blueprint for the integration of WGS and genomic epidemiology into an established national system of laboratory-based surveillance of AMR through international collaboration that can be adapted and utilized within other locations to tackle the global challenge of AMR.

scholarly journals Genomic Characterization of Carbapenemase-Producing Klebsiella pneumoniae with Chromosomally Carried blaNDM-1

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Noriko Sakamoto ◽  
Yukihiro Akeda ◽  
Yo Sugawara ◽  
Dan Takeuchi ◽  
Daisuke Motooka ◽  
...  
Keyword(s):  
Public Health ◽  
Homologous Recombination ◽  
Klebsiella Pneumoniae ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Genomic Characterization

ABSTRACT We report here Klebsiella pneumoniae strains carrying chromosomal blaNDM-1 in Thailand. The genomes of these two isolates include a 160-kbp insertion containing blaNDM-1, which is almost identical to that in the IncHI1B-like plasmid. Further analysis indicated that IS5-mediated intermolecular transposition and Tn3 transposase-mediated homologous recombination resulted in the integration of blaNDM-1 into the chromosome from an IncHI1B-like plasmid. The spread of this type of carbapenem-resistant Enterobacteriaceae may threaten public health and warrants further monitoring.

Detection and Characterization of Targeted Carbapenem-Resistant Healthcare-Associated Threats: Findings from The Antibiotic Resistance Laboratory Network, 2017–2019

2021 ◽  
Author(s):  
Sarah Sabour ◽  
Jennifer Y. Huang ◽  
Amelia Bhatnagar ◽  
Sarah E Gilbert ◽  
Maria Karlsson ◽  
...  
Keyword(s):  
Public Health ◽  
Antibiotic Resistance ◽  
Regional Differences ◽  
Carbapenem Resistance ◽  
Health Concern ◽  
Carbapenem Resistant ◽  
Laboratory Network ◽  
Carbapenemase Gene ◽  
Healthcare Associated

Carbapenemase gene-positive (CP) Gram-negative bacilli are of significant clinical and public health concern. Their rapid detection and containment are critical to preventing their spread and additional infections they can cause. To this end, CDC developed the Antibiotic Resistance Laboratory Network (AR Lab Network), in which public health laboratories across all 50 states, several cities, and Puerto Rico characterize clinical isolates of carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa (CRPA), and Acinetobacter baumannii (CRAB), and conduct colonization screens to detect the presence of mobile carbapenemase genes. In its first three years, the AR Lab Network tested 76,887 isolates and 31,001 rectal swab colonization screens. Targeted carbapenemase genes ( bla KPC , bla NDM , bla OXA-48-like , bla VIM , or bla IMP ) were detected by PCR in 35% of CRE, 2% of CRPA, <1% of CRAB, and 8% of colonization screens tested, respectively. bla KPC and bla VIM were the most common CP-CRE and CP-CRPA, respectively, but regional differences in the frequency of carbapenemase genes detected were apparent. In CRE and CRPA isolates tested for carbapenemase production and the presence of the targeted genes, 97% had concordant results; 3% of CRE and 2% of CRPA were carbapenemase production-positive but PCR-negative for those genes. Isolates harboring bla NDM showed the highest frequency of resistance across the carbapenems tested and those harboring bla IMP and bla OXA-48-like genes showed the lowest frequency of carbapenem resistance. The AR Lab Network provides a national snapshot of rare and emerging carbapenemase genes, delivering data to inform public health actions to limit the spread of these antibiotic resistance threats.

scholarly journals The Adverse Effects of Prenatal METH Exposure on the Offspring: A Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Jia-Hao Li ◽  
Jia-Li Liu ◽  
Kai-Kai Zhang ◽  
Li-Jian Chen ◽  
Jing-Tao Xu ◽  
...  
Keyword(s):  
Public Health ◽  
Adverse Effects ◽  
Gut Microbiota ◽  
Multiple Organ ◽  
Health Issue ◽  
Public Health Issue ◽  
Placental Barrier ◽  
Cardiovascular Toxicity ◽  
Exposure During Pregnancy ◽  
Abuse During Pregnancy

Abuse of methamphetamine (METH), an illicit psychostimulant, is a growing public health issue. METH abuse during pregnancy is on the rise due to its stimulant, anorectic, and hallucinogenic properties. METH can lead to multiple organ toxicity in adults, including neurotoxicity, cardiovascular toxicity, and hepatotoxicity. It can also cross the placental barrier and have long-lasting effects on the fetus. This review summarizes neurotoxicity, cardiovascular toxicity, hepatotoxicity, toxicity in other organs, and biomonitoring of prenatal METH exposure, as well as the possible emergence of sensitization associated with METH. We proposed the importance of gut microbiota in studying prenatal METH exposure. There is rising evidence of the adverse effects of METH exposure during pregnancy, which are of significant concern.

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