Evidence of widespread endemic populations of highly multidrug-resistant Klebsiella pneumoniae seen concurrently through the lens of two hospital intensive care units in Vietnam

Background: Extended spectrum beta-lactamases-producing (ESBL-P) and/or carbapenem-resistant (CR) Klebsiella pneumoniae have severely restricted available treatment options in healthcare settings in Vietnam. Understanding the diversity and transmission mechanisms of ESBL- and carbapenemase- encoding K. pneumoniae is important in both hospital and community settings for patient management. Methods: We conducted a 6-month prospective cohort study of 69 Intensive care unit (ICU) patients from two hospitals in Hanoi, Vietnam. Longitudinally collected samples from patients and the ICU environment were cultured on selective media, and 357 K. pneumoniae colonies were whole genome sequenced. We performed phylogenetic analyses, and correlated phenotypic antimicrobial susceptibility testing with genotypic features of K. pneumoniae isolates. We constructed transmission networks of patient samples, relating ICU admission times and locations with genetic similarity of infecting K. pneumoniae. Findings: Despite being geographically and clinically separated, the two hospitals shared closely related strains carrying the same array of antimicrobial resistance genes. Many patients carried the same resistant K. pneumoniae clone from admission to discharge. 45.9% of total isolates carried both ESBL- and carbapenemase- encoding genes, with high minimum inhibitory concentrations. We found a novel co-occurrence of blaKPC-2 and blaNDM 1 in 46. 6% of samples from the globally successful ST15 lineage. Interpretation: These results highlight the high prevalence of ESBL-positive carbapenem-resistant K. pneumoniae in Vietnamese ICUs. Through studying K. pneumoniae ST15 in detail, we illustrated how important resistance genes are coalescing in stains carried broadly by patients entering the two hospitals directly or through referral.

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An Outbreak of Carbapenem-Resistant Klebsiella Pneumoniae of K57 Capsular Serotype in an Emergency Intensive Care Unit of a Teaching Hospital in China

10.21203/rs.3.rs-96882/v1 ◽

2020 ◽

Author(s):

Chunhong Shao ◽

Yan Jin ◽

Shuang Liu ◽

Meijie Jiang ◽

Shuping Zhao

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Klebsiella Pneumoniae ◽

Teaching Hospital ◽

Galleria Mellonella ◽

Pulse Field ◽

Carbapenem Resistant ◽

Surrounding Environment ◽

Antimicrobial Resistance Genes ◽

Broth Microdilution Method

Abstract Background: Klebsiella pneumoniae is a common causative pathogen of nosocomial infections. The emergence of carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) strains has further increased the threat posed by this bacterium. Here, we described an outbreak of 32 CR-hvKP isolates from the emergency intensive care unit (EICU) of a teaching hospital in China. Methods: From January 29, 2019 to March 11, 2019, 32 CRKp isolates were collected from 6 patients and their surrounding environment in EICU. Patient information including age, gender, length of EICU stay, diagnosis, treatment, and outcomes were obtained from electronic medical records. The isolates were identified using Vitek-MS system. The hypermucoviscosity phenotype was determined by the “string test”. Antimicrobial susceptibility testing was performed using VITEK 2 compact system, E-test or the broth microdilution method. All isolates were serotyped for K1, K2, K5, K20, K54, and K57 serotypes, antimicrobial resistance genes and twelve virulence-associated genes were screened using PCR and DNA sequencing. Multilocus sequence typing (MLST) and pulse-field gel electrophoresis (PFGE) were employed to characterize the genetic relationships among the CPKP isolates. The virulence capability of 11 CRKp isolates from 6 patients was evaluated through Galleria mellonella larva infection assay. Results: This outbreak involved 6 patients and lasted for 40 days. All 32 CR-hvKp isolates were obtained from 6 patients and their surrounding environment. PFGE showed that all 32 isolates belonged to one cluster, and MLST revealed that belonged to ST11. All isolates exhibited high resistance to β-lactam antibiotics, quinolones, and aminoglycosides. They were susceptible to ceftazidime/averbatan, tigecycline, and colistin. All 32 isolates harbored multiple resistance determinants, including blaKPC-2, blaSHV-11, blaTEM-1, rmtB, and qnrD. The serotype of all 32 isolates was K57 that was rarely reported. In the virulence gene analysis, all 32 isolates contained 6 virulence genes, namely, fimH, iucB, mrkD, rmpA, uge, and wabG. Infection assays demonstrated high mortality in the Galleria mellonella model. Following measures implemented by the hospital, the outbreak was controlled. The mortality rate was 83.3%.Conclusions: The epidemiology of CR-hvKP should be monitored closely to detect early indications of this emerging public health threat.

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Novel strains of Klebsiella africana and Klebsiella pneumoniae in Australian Fruit Bats (Pteropus poliocephalus)

10.1101/2021.07.12.451971 ◽

2021 ◽

Author(s):

Fiona K McDougall ◽

Kelly L Wyres ◽

Louise M Judd ◽

Wayne S J Boardman ◽

Kathryn E Holt ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Resistance Genes ◽

Multidrug Resistant ◽

Sensu Stricto ◽

The Public ◽

Fruit Bat ◽

Faecal Samples ◽

Antimicrobial Resistance Genes ◽

Pteropus Poliocephalus ◽

Sequence Types

Over the past decade human associated multidrug resistant (MDR) and hypervirulent Klebsiella pneumoniae lineages have been increasingly detected in wildlife. This study investigated the occurrence of K. pneumoniae species complex (KpSC) in grey-headed flying foxes (GHFF), an Australian fruit bat. Thirty-nine KpSC isolates were cultured from 275 GHFF faecal samples (14.2%), comprising K. pneumoniae (sensu stricto) (n=30), Klebsiella africana (n=8) and Klebsiella variicola subsp. variicola (n=1). The majority (79.5%) of isolates belonged to novel sequence types (ST), including two novel K. africana STs. This is the first report of K. africana outside of Africa and in a non-human host. A minority (15.4%) of GHFF KpSC isolates shared STs with human clinical K. pneumoniae strains, of which, none belonged to MDR clonal lineages that cause frequent nosocomial outbreaks, and no isolates were characterised as hypervirulent. The occurrence of KpSC isolates carrying acquired antimicrobial resistance genes in GHFF was low (1.1%), with three K. pneumoniae isolates harbouring both fluoroquinolone and trimethoprim resistance genes. This study indicates that GHFF are not reservoirs for MDR and hypervirulent KpSC strains, but they do carry novel K. africana lineages. The health risks associated with KpSC carriage by GHFF are deemed low for the public and GHFF.

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Emergence of DIM-1 and KPC-1 Genes Associated Carbapenem-Resistant Pseudomonas Aeruginosa Isolates in Three Major Hospitals in Hanoi, Vietnam (2010-2015)

10.21203/rs.3.rs-143498/v1 ◽

2021 ◽

Author(s):

Tran Hai Anh ◽

Tran Huy Hoang ◽

Vu Thi Ngoc Bich ◽

Trinh Son Tung ◽

Tran Dieu Linh ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Treatment Options ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Phylogenetic Tree Analysis ◽

Antibiotic Resistant ◽

Hospital Acquired Infection ◽

Healthcare Settings ◽

Carbapenem Resistant ◽

Hospital Acquired

Abstract Background: Multidrug-resistant bacteria including carbapenem resistant Pseudomonas aeruginosa are recognised as an important cause of hospital-acquired infections worldwide. To determine the molecular characterisation and antibiotic resistant genes associated with carbapenem-resistant P. aeruginosa. Methods: we conducted whole-genome sequencing and phylogenetic analysis of 72 carbapenem-resistant P. aeruginosa isolated from hospital-acquired infection patients from 2010 to 2015 in three major hospitals in Hanoi, Vietnam. Results: We identified three variants of IMP genes, among which IMP-15 gene was the most frequent (n= 34) in comparison to IMP-26 (n= 2) and IMP-51 (n=12). We observed two isolates with imipenem MIC >128mg/L that co-harboured IMP-15 and DIM-1 genes and seven isolates (imipenem MIC> 128mg/L) with KPC-1 gene from the same hospital. MLST data showed that sequence types (ST) of 72 isolates were classified into 18 STs and phylogenetic tree analysis divided these isolates into nine groups. Conclusion: Our results provide evidence that not only IMP-26, but other variants of IMPs like IMP-15 and IMP-51 genes and several STs (ST235, ST244, ST277, ST310, ST773 and ST3151) have been disseminated in health care settings in Vietnam. Also, we report the first finding in Vietnam that two isolates belonging to ST1240 and ST3340 harboured two important carbapenemase genes (IMP-15 and, DIM-1) and seven isolates belonging to ST3151 of P. aeruginosa carried the KPC-1 gene, which could be a potential cause of seriously restricted available treatment options in healthcare settings.

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Emergence and Evolution of Multidrug-Resistant Klebsiella pneumoniae with both blaKPC and blaCTX-M Integrated in the Chromosome

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00076-17 ◽

2017 ◽

Vol 61 (7) ◽

Cited By ~ 30

Author(s):

Weihua Huang ◽

Guiqing Wang ◽

Robert Sebra ◽

Jian Zhuge ◽

Changhong Yin ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Klebsiella Pneumoniae ◽

Resistance Genes ◽

De Novo ◽

Genomic Analysis ◽

Multidrug Resistant ◽

Comparative Genomic ◽

Type I ◽

Content Type ◽

Antimicrobial Resistance Genes

ABSTRACT The extended-spectrum-β-lactamase (ESBL)- and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae represent serious and urgent threats to public health. In a retrospective study of multidrug-resistant K. pneumoniae, we identified three clinical isolates, CN1, CR14, and NY9, carrying both bla CTX-M and bla KPC genes. The complete genomes of these three K. pneumoniae isolates were de novo assembled by using both short- and long-read whole-genome sequencing. In CR14 and NY9, bla CTX-M and bla KPC were carried on two different plasmids. In contrast, CN1 had one copy of bla KPC-2 and three copies of bla CTX-M-15 integrated in the chromosome, for which the bla CTX-M-15 genes were linked to an insertion sequence, ISEcp1, whereas the bla KPC-2 gene was in the context of a Tn4401a transposition unit conjugated with a PsP3-like prophage. Intriguingly, downstream of the Tn4401a-bla KPC-2-prophage genomic island, CN1 also carried a clustered regularly interspaced short palindromic repeat (CRISPR)-cas array with four spacers targeting a variety of K. pneumoniae plasmids harboring antimicrobial resistance genes. Comparative genomic analysis revealed that there were two subtypes of type I-E CRISPR-cas in K. pneumoniae strains and suggested that the evolving CRISPR-cas, with its acquired novel spacer, induced the mobilization of antimicrobial resistance genes from plasmids into the chromosome. The integration and dissemination of multiple copies of bla CTX-M and bla KPC from plasmids to chromosome depicts the complex pandemic scenario of multidrug-resistant K. pneumoniae. Additionally, the implications from this study also raise concerns for the application of a CRISPR-cas strategy against antimicrobial resistance.

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Multidrug resistance genes, including blaKPC and blaCTX-M-2, among Klebsiella pneumoniae isolated in Recife, Brazil

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86822012000500007 ◽

2012 ◽

Vol 45 (5) ◽

pp. 572-578 ◽

Cited By ~ 29

Author(s):

Adriane Borges Cabral ◽

Rita de Cássia de Andrade Melo ◽

Maria Amélia Vieira Maciel ◽

Ana Catarina Souza Lopes

Keyword(s):

Klebsiella Pneumoniae ◽

Resistance Genes ◽

Hospital Environment ◽

Enterobacterial Repetitive Intergenic Consensus ◽

Chain Reaction ◽

Carbapenem Resistant ◽

Antimicrobial Susceptibility Profile ◽

Antimicrobial Resistance Genes ◽

Polymerase Chain ◽

General Care

INTRODUCTION: The prevalence of cephalosporins and carbapenem-resistant Klebsiella pneumoniae strains is rising in Brazil, with potential serious consequences in terms of patients' outcomes and general care. METHODS: This study characterized 24 clinical isolates of K. pneumoniae from two hospitals in Recife, Brazil, through the antimicrobial susceptibility profile, analyses of β-lactamase genes (blaTEM, blaSHV,blaCTX-MblaKPC, blaVIM, blaIMP, and blaSPM), plasmidial profile and ERIC-PCR (Enterobacterial repetitive intergenic consensus-polymerase chain reaction). RESULTS: ERIC-PCR and plasmidial analysis grouped the isolates in 17 and 19 patterns, respectively. Six isolates from one hospital presented the same pattern by ERIC-PCR, indicating clonal dissemination. All isolates presented blaSHV, 62.5% presented blaCTX-M-2, 29% blaTEM, and 41.7% blaKPC. Metallo-β-lactamase genes blaand blawere not detected. Eleven isolates were identified carrying at least 3 β-lactamase studied genes, and 2 isolates carried blaSHVblaTEM, blaCTX-M-2 and blaKPC simultaneously. CONCLUSIONS: The accumulation of resistance genes in some strains, observed in this study, imposes limitations in the therapeutic options available for the treatment of infections caused by K. pneumoniae in Recife, Brazil. These results should alert the Brazilian medical authorities to establish rigorous methods for more efficiently control the dissemination of antimicrobial resistance genes in the hospital environment.

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Treatment Options for Colistin Resistant Klebsiella pneumoniae: Present and Future

Journal of Clinical Medicine ◽

10.3390/jcm8070934 ◽

2019 ◽

Vol 8 (7) ◽

pp. 934 ◽

Cited By ~ 25

Author(s):

Petrosillo ◽

Taglietti ◽

Granata

Keyword(s):

Monoclonal Antibodies ◽

Side Effects ◽

Mortality Rate ◽

Klebsiella Pneumoniae ◽

Treatment Options ◽

Multidrug Resistant ◽

Limited Range ◽

Therapeutic Strategies ◽

Colistin Resistance ◽

Carbapenem Resistant

Multidrug-resistant (MDR) Klebsiella pneumoniae represents an increasing threat to human health, causing difficult-to-treat infections with a high mortality rate. Since colistin is one of the few treatment options for carbapenem-resistant K. pneumoniae infections, colistin resistance represents a challenge due to the limited range of potentially available effective antimicrobials, including tigecycline, gentamicin, fosfomycin and ceftazidime/avibactam. Moreover, the choice of these antimicrobials depends on their pharmacokinetics/pharmacodynamics properties, the site of infection and the susceptibility profile of the isolated strain, and is sometimes hampered by side effects. This review describes the features of colistin resistance in K. pneumoniae and the characteristics of the currently available antimicrobials for colistin-resistant MDR K. pneumoniae, as well as the characteristics of novel antimicrobial options, such as the soon-to-be commercially available plazomicin and cefiderocol. Finally, we consider the future use of innovative therapeutic strategies in development, including bacteriophages therapy and monoclonal antibodies.

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Spread of ISCR1Elements ContainingblaDHA-1and Multiple Antimicrobial Resistance Genes Leading to Increase of Flomoxef Resistance in Extended-Spectrum-β-Lactamase-Producing Klebsiella pneumoniae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00259-11 ◽

2011 ◽

Vol 55 (9) ◽

pp. 4058-4063 ◽

Cited By ~ 22

Author(s):

Chen-Hsiang Lee ◽

Jien-Wei Liu ◽

Chia-Chin Li ◽

Chun-Chih Chien ◽

Ya-Fen Tang ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Resistance Genes ◽

Antimicrobial Agents ◽

Treatment Options ◽

Close Monitoring ◽

Content Type ◽

Extended Spectrum ◽

Antimicrobial Resistance Genes ◽

Multiple Resistance Genes ◽

Replicon Type

ABSTRACTIncreasing resistance to quinolones, aminoglycosides, and/or cephamycins in extended-spectrum-β-lactamase (ESBL)-producingEnterobacteriaceaeexacerbates the already limited antibiotic treatment options for infections due to these microbes. In this study, the presence of resistance determinants for these antimicrobial agents was examined by PCR among ESBL-producingKlebsiella pneumoniae(ESBL-KP) isolates that caused bacteremia. Pulsed-field gel electrophoresis was used to differentiate the clonal relationship among the isolates studied. Transferability and the location of the resistance genes were analyzed by conjugation experiments, followed by DNA-DNA hybridization. Among the 94 ESBL-KP isolates studied, 20 isolates of flomoxef-resistant ESBL-KP were identified. They all carried a DHA-1 gene and were genetically diverse. CTX-M genes were found in 18 of the isolates. Among these DHA-1/CTX-M-producingK. pneumoniaeisolates, ISCR1was detected in 13 (72%) isolates,qnrgenes (1qnrAand 17qnrBgenes) were detected in 18 (100%),aac(6′)-Ib-crwas detected in 11 (61%), and 16S rRNA methylase (allarmAgenes) was detected in 14 (78%). Four transconjugants were available for further analysis, andqnrB4,aac(6′)-Ib-cr,armA, andblaDHA-1were all identified on these self-transferableblaCTX-M-carrying plasmids. The genetic environments of ISCR1associated witharmA,blaDHA-1, andqnrB4genes in the four transconjugants were identical. Replicon-type analysis revealed a FIIA plasmid among the four self-transferable plasmids, although the other three were nontypeable. The cotransfer of multiple resistance genes with the ISCR1element-carrying plasmids has a clinical impact and warrants close monitoring and further study.

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Screening of Antimicrobial Resistance Genes and Epidemiological Features in Hospital and Community-Associated Carbapenem Resistant Pseudomonas aeruginosa Infections

10.21203/rs.3.rs-103545/v1 ◽

2020 ◽

Author(s):

ayse erturk ◽

Ayşegül Çopur ÇİÇEK ◽

Nebahat EJDER ◽

Uğur KOSTAKOĞLU ◽

İlknur Esen YILDIZ ◽

...

Keyword(s):

Resistance Genes ◽

Multidrug Resistant ◽

Gene Encoding ◽

Pfge Typing ◽

Carbapenem Resistant ◽

Antimicrobial Resistance Genes ◽

Genes Encoding ◽

Pcr Method ◽

Vitek 2 ◽

Hospital Acquired

Abstract Background: Researching carbapenem-resistant isolates and the use of antibiotics and following infection control policies enable the identification of carbapenemase-producing bacteria and prevent their spread.Methods: P. aeruginosa isolates were recovered from Medicine Faculty of Recep Tayyip Erdoğan University between April 2015 and October 2016 and identified by conventional methods and the automated Vitek 2 Compact (BioMerieux, France) system. Antimicrobial susceptibility experiments were performed in accordance with CLSI criteria and the automated Vitek 2 Compact system. The PCR method was investigated for the presence of β-lactamase resistance genes. PFGE typing was performed to show clonal relation among samples.Results: Seventy P. aeruginosa strains were isolated from seventy patients. The median age of 70 cases was found 66 with minimum 17 and maximum 92 years old. 67.1% of the patients had contact with the health service in the last 90 days and 75.7% of the patients had received antimicrobial therapy in the previous 90 days. The most common comorbidity was cardiovascular diseases. Twenty-four (34.3%) strains were carbapenem resistant, 2 strains were multidrug-resistant except colistin, and none of the samples had colistin resistance. The gene encoding β-lactamase or metallo-β-lactamase was found in a total of 36 strains. The bla VEB gene was identified in only 1 strain alone, but in combination with other resistance genes in a total of 17 strains. While the bla PER gene was detected in 5 samples alone, it was found in 13 samples in combination with other genes. Among the genes encoding metallo-β-lactamase, the most bla NDM positive was detected (n=22), followed by 14 positive samples of bla KPC . bla IMP and bla VIM were detected in 5 and 1 samples, respectively. Also, the association of bla VEB - bla PER and bla VEB - bla KPC - bla NDM was found to be very high. Much more resistance genes and associations were detected in hospital-acquired samples than community-acquired samples, both proportionally and in terms of co-occurrence. Most of the community-associated strains were collected in the F2 clade, while most of the hospital-associated strains were collected in the G1 clade. However, no difference was found between the community and hospital-associated strains according to PFGE results. Simultaneously, other microorganisms were also isolated from patients from which these 6 P. aeruginosa strains were isolated. Of these patients, 5 patients died, except the number 70.Conclusions: The median length of stay (days) was found to be significantly higher in the group with HAI than in the group with CAI. Compared to sample 28 and 37, which carried 5 β-lactamase coding genes, the death of these 5 patients with fewer or no resistance genes showed that the coexistence of other factors - especially other microorganisms in addition to resistance genes, was important.

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Tracking Nosocomial Klebsiella pneumoniae Infections and Outbreaks by Whole-Genome Analysis: Small-Scale Italian Scenario within a Single Hospital

Journal of Clinical Microbiology ◽

10.1128/jcm.00545-15 ◽

2015 ◽

Vol 53 (9) ◽

pp. 2861-2868 ◽

Cited By ~ 31

Author(s):

Raffaella Onori ◽

Stefano Gaiarsa ◽

Francesco Comandatore ◽

Stefano Pongolini ◽

Sylvain Brisse ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Treatment Options ◽

Multidrug Resistant ◽

Small Scale ◽

Phylogenomic Analysis ◽

Whole Genome ◽

Whole Genome Analysis ◽

Content Type ◽

Carbapenem Resistant ◽

Single Clone

Multidrug-resistant (MDR)Klebsiella pneumoniaeis one of the most important causes of nosocomial infections worldwide. After the spread of strains resistant to beta-lactams at the end of the previous century, the diffusion of isolates resistant to carbapenems and colistin is now reducing treatment options and the containment of infections. Carbapenem-resistantK. pneumoniaestrains have spread rapidly among Italian hospitals, with four subclades of pandemic clonal group 258 (CG258). Here we show that a single Italian hospital has been invaded by three of these subclades within 27 months, thus replicating on a small scale the “Italian scenario.” We identified a single clone responsible for an epidemic outbreak involving seven patients, and we reconstructed its star-like pattern of diffusion within the intensive care unit. This epidemiological picture was obtained through phylogenomic analysis of 16 carbapenem-resistantK. pneumoniaeisolates collected in the hospital during a 27-month period, which were added to a database of 319 genomes representing the available global diversity ofK. pneumoniaestrains. Phenotypic and molecular assays did not reveal virulence or resistance determinants specific for the outbreak isolates. Other factors, rather than selective advantages, might have caused the outbreak. Finally, analyses allowed us to identify a major subclade of CG258 composed of strains bearing the yersiniabactin virulence factor. Our work demonstrates how the use of combined phenotypic, molecular, and whole-genome sequencing techniques can help to identify quickly and to characterize accurately the spread of MDR pathogens.

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Evolution and Epidemiology of Multidrug-Resistant Klebsiella pneumoniae in the United Kingdom and Ireland

mBio ◽

10.1128/mbio.01976-16 ◽

2017 ◽

Vol 8 (1) ◽

Cited By ~ 32

Author(s):

Danesh Moradigaravand ◽

Veronique Martin ◽

Sharon J. Peacock ◽

Julian Parkhill

Keyword(s):

United Kingdom ◽

Klebsiella Pneumoniae ◽

Large Scale ◽

Multidrug Resistant ◽

Antimicrobial Treatment ◽

Whole Genome ◽

The Past ◽

Healthcare Settings ◽

The United Kingdom ◽

Antimicrobial Resistance Genes

ABSTRACT Klebsiella pneumoniae is a human commensal and opportunistic pathogen that has become a leading causative agent of hospital-based infections over the past few decades. The emergence and global expansion of hypervirulent and multidrug-resistant (MDR) clones of K. pneumoniae have been increasingly reported in community-acquired and nosocomial infections. Despite this, the population genomics and epidemiology of MDR K. pneumoniae at the national level are still poorly understood. To obtain insights into these, we analyzed a systematic large-scale collection of invasive MDR K. pneumoniae isolates from hospitals across the United Kingdom and Ireland. Using whole-genome phylogenetic analysis, we placed these in the context of previously sequenced K. pneumoniae populations from geographically diverse countries and identified their virulence and drug resistance determinants. Our results demonstrate that United Kingdom and Ireland MDR isolates are a highly diverse population drawn from across the global phylogenetic tree of K. pneumoniae and represent multiple recent international introductions that are mainly from Europe but in some cases from more distant countries. In addition, we identified novel genetic determinants underlying resistance to beta-lactams, gentamicin, ciprofloxacin, and tetracyclines, indicating that both increased virulence and resistance have emerged independently multiple times throughout the population. Our data show that MDR K. pneumoniae isolates in the United Kingdom and Ireland have multiple distinct origins and appear to be part of a globally circulating K. pneumoniae population. IMPORTANCE Klebsiella pneumoniae is a major human pathogen that has been implicated in infections in healthcare settings over the past few decades. Antimicrobial treatment of K. pneumoniae infections has become increasingly difficult as a consequence of the emergence and spread of strains that are resistant to multiple antimicrobials. To better understand the spread of resistant K. pneumoniae, we studied the genomes of a large-scale population of extensively antimicrobial-resistant K. pneumoniae in the United Kingdom and Ireland by utilizing the fine resolution that whole-genome sequencing of pathogen genomes provides. Our results indicate that the K. pneumoniae population is highly diverse and that, in some cases, resistant strains appear to have spread across the country over a few years. In addition, we found evidence that some strains have acquired antimicrobial resistance genes independently, presumably in response to antimicrobial treatment. IMPORTANCE Klebsiella pneumoniae is a major human pathogen that has been implicated in infections in healthcare settings over the past few decades. Antimicrobial treatment of K. pneumoniae infections has become increasingly difficult as a consequence of the emergence and spread of strains that are resistant to multiple antimicrobials. To better understand the spread of resistant K. pneumoniae, we studied the genomes of a large-scale population of extensively antimicrobial-resistant K. pneumoniae in the United Kingdom and Ireland by utilizing the fine resolution that whole-genome sequencing of pathogen genomes provides. Our results indicate that the K. pneumoniae population is highly diverse and that, in some cases, resistant strains appear to have spread across the country over a few years. In addition, we found evidence that some strains have acquired antimicrobial resistance genes independently, presumably in response to antimicrobial treatment.

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