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

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.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01743-20 ◽

2020 ◽

Vol 64 (12) ◽

Cited By ~ 1

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.

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

German Journal of Microbiology - Special Issue: Existence Battle: Viruses vs. Creatures ◽

10.51585/gjm.2021.002 ◽

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

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Fighting Antibiotic-Resistant Klebsiella pneumoniae with “Sweet” Immune Targets

mBio ◽

10.1128/mbio.00874-18 ◽

2018 ◽

Vol 9 (3) ◽

Cited By ~ 4

Author(s):

Roberto Adamo ◽

Immaculada Margarit

Keyword(s):

Klebsiella Pneumoniae ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Therapeutic Approaches ◽

Antibiotic Resistant ◽

Content Type ◽

Carbapenem Resistant ◽

Surface Polysaccharides ◽

Resistant Strains ◽

Murine Monoclonal Antibodies

ABSTRACT Antibiotics and vaccines have greatly impacted human health in the last century by dramatically reducing the morbidity and mortality associated with infectious diseases. The recent challenge posed by the emergence of multidrug-resistant bacteria could possibly be addressed by novel immune prophylactic and therapeutic approaches. Among the newly threatening pathogens, Klebsiella pneumoniae is particularly worrisome in the nosocomial setting, and its surface polysaccharides are regarded as promising antigen candidates. The majority of Klebsiella carbapenem-resistant strains belong to the sequence type 158 (ST258) lineage, with two main clades expressing capsular polysaccharides CPS1 and CPS2. In a recent article, S. D. Kobayashi and colleagues (mBio 9:e00297-18, 2018, https://doi.org/10.1128/mBio.00297-18) show that CPS2-specific IgGs render ST258 clade 2 bacteria more sensitive to human serum and phagocytic killing. E. Diago-Navarro et al. (mBio 9:e00091-18, 2018, https://doi.org/10.1128/mBio.00091-18) generated two murine monoclonal antibodies recognizing distinct glycotopes of CPS2 that presented functional activity against multiple ST258 strains. These complementary studies represent a step toward the control of this dangerous pathogen.

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OmpK26, a Novel Porin Associated with Carbapenem Resistance in Klebsiella pneumoniae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00309-11 ◽

2011 ◽

Vol 55 (10) ◽

pp. 4742-4747 ◽

Cited By ~ 29

Author(s):

Laura García-Sureda ◽

Antonio Doménech-Sánchez ◽

Mariette Barbier ◽

Carlos Juan ◽

Joan Gascó ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Outer Membrane Proteins ◽

Systemic Infection ◽

Carbapenem Resistance ◽

Resistant Isolate ◽

Identical Result ◽

Sequencing Analysis ◽

Content Type ◽

Carbapenem Resistant

ABSTRACTClinical isolates ofKlebsiella pneumoniaeresistant to carbapenems are being isolated with increasing frequency. Loss of the expression of the major nonspecific porins OmpK35/36 is a frequent feature in these isolates. In this study, we looked for porins that could compensate for the loss of the major porins in carbapenem-resistant organisms. Comparison of the outer membrane proteins from twoK. pneumoniaeclinical isogenic isolates that are susceptible (KpCS-1) and resistant (KpCR-1) to carbapenems revealed the absence of OmpK35/36 and the presence of a new 26-kDa protein in the resistant isolate. An identical result was obtained when another pair of isogenic isolates that are homoresistant (Kpn-3) and heteroresistant (Kpn-17) to carbapenems were compared. Mass spectrometry and DNA sequencing analysis demonstrated that this new protein, designated OmpK26, is a small monomeric oligogalacturonate-specific porin that belongs to the KdgM family of porins. Insertion-duplication mutagenesis of the OmpK26 coding gene,yjhA, in the carbapenem-resistant, porin-deficient isolate KpCR-1 caused the expression of OmpK36 and the reversion to the carbapenem-susceptible phenotype, suggesting that OmpK26 is indispensable for KpCR-1 to lose OmpK36 and become resistant to these antibiotics. Moreover, loss of the major porin and expression of OmpK26 reducedin vitrofitness and attenuated virulence in a murine model of acute systemic infection. Altogether, these results indicate that expression of the oligogalacturonate-specific porin OmpK26 compensates for the absence of OmpK35/36 and allows carbapenem resistance inK. pneumoniaebut cannot restore the fitness of the microorganism.

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Carbapenem-Resistant Klebsiella pneumoniae Urinary Tract Infection following Solid Organ Transplantation

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04284-14 ◽

2014 ◽

Vol 59 (1) ◽

pp. 553-557 ◽

Cited By ~ 30

Author(s):

Kyle D. Brizendine ◽

Sandra S. Richter ◽

Eric D. Cober ◽

David van Duin

Keyword(s):

Urinary Tract ◽

Klebsiella Pneumoniae ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Carbapenem Resistance ◽

First Episode ◽

Solid Organ ◽

Content Type ◽

Carbapenem Resistant ◽

Tract Infections

ABSTRACTCarbapenem-resistantKlebsiella pneumoniae(CRKP) is an emerging pathogen with a devastating impact on organ transplant recipients (OTRs). Data describing urinary tract infections (UTIs) due to CRKP, compared to extended-spectrum β-lactamase (ESBL)-producing and susceptibleK. pneumoniae, are lacking. We conducted a retrospective cohort study comparing OTRs with a first episode of UTI due to CRKP, ESBL-producingK. pneumoniae, or susceptibleK. pneumoniae. We identified 108 individuals; 22 (20%) had UTIs due to CRKP, 22 (20%) due to ESBL-producingK. pneumoniae, and 64 (60%) due to susceptibleK. pneumoniae. Compared to susceptibleK. pneumoniae(27%), patients with UTIs due to CRKP or ESBL-producingK. pneumoniaewere more likely to have a ≥24-hour stay in the intensive care unit (ICU) before or after development of the UTI (64% and 77%, respectively;P< 0.001). Among 105/108 hospitalized patients (97%), the median lengths of stay prior to UTI with CRKP or ESBL-producingK. pneumoniae(7 and 8 days, respectively) were significantly longer than that for susceptibleK. pneumoniae(1 day;P< 0.001). Clinical failure was observed for 8 patients (36%) with CRKP, 4 (18%) with ESBL-producingK. pneumoniae, and 9 (14%) with susceptibleK. pneumoniae(P= 0.073). Microbiological failure was seen for 10 patients (45%) with CRKP, compared with 2 (9%) with ESBL-producingK. pneumoniaeand 2 (3%) with susceptibleK. pneumoniae(P< 0.001). In multivariable logistic regression analyses, CRKP was associated with greater odds of microbiological failure (versus ESBL-producingK. pneumoniae: odds ratio [OR], 9.36, 95% confidence interval [CI], 1.94 to 72.1; versus susceptibleK. pneumoniae: OR, 31.4, 95% CI, 5.91 to 264). In conclusion, CRKP is associated with ICU admission, long length of stay, and microbiological failure among OTRs with UTIs. Greater numbers are needed to determine risk factors for infection and differences in meaningful endpoints associated with carbapenem resistance.

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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

10.21203/rs.2.17648/v1 ◽

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

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Klebsiella pneumoniae Complex Harboring mcr-1, mcr-7, and mcr-8 Isolates from Slaughtered Pigs in Thailand

Microorganisms ◽

10.3390/microorganisms9122436 ◽

2021 ◽

Vol 9 (12) ◽

pp. 2436

Author(s):

Nattamol Phetburom ◽

Parichart Boueroy ◽

Peechanika Chopjitt ◽

Rujirat Hatrongjit ◽

Yukihiro Akeda ◽

...

Keyword(s):

Public Health ◽

Klebsiella Pneumoniae ◽

Continuous Monitoring ◽

One Health ◽

Public Health Issue ◽

Resistant Bacteria ◽

Colistin Resistance ◽

Amoxicillin Clavulanic Acid ◽

Monitoring And Surveillance ◽

Slaughtered Pigs

Dissemination of the mobile colistin resistance gene mcr in Enterobacterales among humans, animals, and the environment is a public health issue. We characterized mcr genes in the Klebsiella pneumoniae complex (KpnC) isolated from slaughtered pigs in Thailand. The 280 KpnCs consisted of K. pneumoniae (85%), Klebsiella quasipneumoniae (8.21%), and Klebsiella variicola (6.79%). mcr genes were detected in 6.79% (19/280) of KpnC isolates, consisting of mcr-8 (n = 9; 3.21%), mcr-7 (n = 7; 2.50%), mcr-7 + mcr-8 (n = 2; 0.71%), and mcr-1 + mcr-7 (n = 1; 0.36%). K. pneumoniae predominantly carried the mcr-7 and mcr-8 genes, while K. variicola and K. quasipneumoniae harbored mcr-7 and mcr-8, respectively. Six of the nineteen mcr-harboring KpnC isolates exhibited colistin resistance, and five had mcr-1 or mcr-8 transferable to an Escherichia coli recipient. Antimicrobial susceptibility analysis revealed that all mcr-carrying KpnC isolates were susceptible to carbapenems, cefotaxime, cefepime, amoxicillin/clavulanic acid, piperacillin/tazobactam, amikacin, and fosfomycin, and had high resistance to azithromycin. Multilocus sequence analysis demonstrated that the mcr-harboring KpnC isolates were genetically diverse. A ‘One-Health’ approach is useful to combat antimicrobial-resistant bacteria through coordinating the human, animal, and environmental sectors. Hence, continuous monitoring and surveillance of mcr-carrying KpnCs throughout the pork supply chain is crucial for ensuring public health.

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Molecular and Epidemiological Characteristics of Carbapenemase-Producing Klebsiella pneumoniae Clinical Isolates in Japan

mSphere ◽

10.1128/msphere.00490-20 ◽

2020 ◽

Vol 5 (5) ◽

Author(s):

Shinsuke Yonekawa ◽

Tomoki Mizuno ◽

Ryuichi Nakano ◽

Akiyo Nakano ◽

Yuki Suzuki ◽

...

Keyword(s):

Public Health ◽

Klebsiella Pneumoniae ◽

Virulence Genes ◽

Carbapenem Resistance ◽

Clinical Isolates ◽

Molecular Characteristics ◽

Content Type ◽

Health Threat ◽

Public Health Threat ◽

Epidemiological Characteristics

ABSTRACT Carbapenemase-producing Enterobacteriaceae represent a serious public health threat worldwide. Carbapenemase genes, harbored on a transferable plasmid, have been isolated globally with distinct geographical features. Klebsiella pneumoniae, included in Enterobacteriaceae, also produces carbapenemase and often shows hypervirulence. Overlapping carbapenem resistance and hypervirulence in K. pneumoniae have been reported, but such strains have not yet been found in Japan. Here, we screened 104 carbapenemase-producing K. pneumoniae isolates collected from 37 hospitals and outpatient clinics in Japan between September 2014 and July 2015. PCR and DNA sequencing demonstrated IMP-1 in 21 isolates and IMP-6 in 83 isolates, 77 of which coharbored CTX-M-2. Most of the isolates showed low MICs toward imipenem and meropenem but high MICs toward penicillin and cephalosporins. Conjugation experiments with an Escherichia coli J53 recipient showed that most of the plasmids in IMP-6 producers were transferable, whereas only one-half of the plasmids in IMP-1 producers were transferable. PCR-based replicon typing and multiplex PCR identified five isolates belonging to the CG258 non-tonB79 cluster and no isolate belonging to the CG258-tonB79 cluster or sequence type 307 (ST307). Four K1-ST23 isolates, 10 K2-ST65 isolates, and 7 K2-ST86 isolates were detected that harbored virulence genes. The resistance genes in 85 isolates were transferable, but the virulence genes were not transferred. These results demonstrate the acquisition of IMP-type carbapenemase genes and CTX-M-type genes among hypervirulence isolates in Japan, warranting further attention and countermeasures. In this study, we have determined the molecular characteristics and epidemiology of IMP-6 producers that coharbored various CTX-M genes in Japan. IMPORTANCE Carbapenems serve as a last resort for the clinical treatment of multidrug-resistant infections. Therefore, the rapid spread of carbapenemase-producing strains represents a serious public health threat, further limiting antibiotic choices. The current findings of hypervirulent carbapenemase-producing Klebsiella pneumoniae clinical isolates in Japan demonstrate the potential broad spread and transfer of these genes, necessitating close surveillance.

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Evolution of Carbapenem-Resistant Serotype K1 Hypervirulent Klebsiella pneumoniae by Acquisition of blaVIM-1-Bearing Plasmid

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01056-19 ◽

2019 ◽

Vol 63 (9) ◽

Cited By ~ 6

Author(s):

Ning Dong ◽

Qiaoling Sun ◽

Yonglu Huang ◽

Lingbin Shu ◽

Lianwei Ye ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Genomic Analysis ◽

Carbapenem Resistance ◽

Sequence Type ◽

Mosaic Structure ◽

Multiple Gene ◽

Content Type ◽

Carbapenem Resistant ◽

Simultaneous Expression

ABSTRACT We report the identification of a carbapenem-resistant, hypervirulent Klebsiella pneumoniae (hvKp) strain which produced the carbapenemase VIM-1. Genomic analysis showed that the strain belonged to sequence type ST23 and serotype K1, a major hvKp clone, and harbored three resistance-encoding plasmids. Among them, a blaVIM-1-bearing plasmid was found to possess a mosaic structure presumably generated by multiple gene mobilization events. This finding indicates that hvKp actively acquires mobile resistance-encoding elements, facilitating simultaneous expression of hypervirulence and carbapenem-resistance.

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Complete Nucleotide Sequence of the IncN Plasmid Encoding IMP-6 and CTX-M-2 from Emerging Carbapenem-Resistant Enterobacteriaceae in Japan

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04759-14 ◽

2014 ◽

Vol 59 (2) ◽

pp. 1356-1359 ◽

Cited By ~ 23

Author(s):

Shizuo Kayama ◽

Norifumi Shigemoto ◽

Ryuichi Kuwahara ◽

Kenshiro Oshima ◽

Hideki Hirakawa ◽

...

Keyword(s):

Multidrug Resistance ◽

Nucleotide Sequence ◽

Klebsiella Pneumoniae ◽

Dna Sequence ◽

Complete Nucleotide Sequence ◽

Carbapenem Resistance ◽

Content Type ◽

Carbapenem Resistant ◽

The Family ◽

Carbapenem Resistant Enterobacteriaceae

ABSTRACTWe have determined the DNA sequence ofKlebsiella pneumoniaemultidrug resistance plasmid pKPI-6, which is a self-transmissible IncN-type plasmid. pKPI-6 harboringblaIMP-6andblaCTX-M-2confers a stealth-type carbapenem resistance phenotype on members of the familyEnterobacteriaceaethat is not detectable with imipenem. pKPI-6 is already epidemic in Japan, favoring the dissemination of IMP-6 and CTX-M-2 in members of the familyEnterobacteriaceae.

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