Genomic Epidemiology of Carbapenem-Resistant
            <i>Klebsiella</i>
            in Qatar: Emergence and Dissemination of Hypervirulent Klebsiella pneumoniae Sequence Type 383 Strains

Tsui, Clement K. M.; Abid, Fatma Ben; Ismail, Khalil Al; McElheny, Christi L.; Maslamani, Muna Al; Omrani, Ali S.; Doi, Yohei

doi:10.1128/aac.00030-23

Cited by 12 publications

(8 citation statements)

References 60 publications

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“…Upon genomic characterization, two of the three isolates belonged to the notorious epidemic clones: K. pneumoniae ST231, which was first described in Southeast Asia and has been associated with healthcare outbreaks, as well as demonstrated diverse ARGs spanning major classes, particularly bla OXA-48 [ 22 ]. In a previous surveillance study from Qatar of 149 CREs, 8.6% of isolates were of the same epidemic clone, explaining its endemicity; which was affirmed in a recently updated and detailed study [ 13 , 23 ]. Additionally, class A extended-spectrum β-lactamases (ESBLs) were represented by bla CXM-14 and bla CXM-15 , bla SHV-1 , and bla TEM-1 .…”

Section: Discussionmentioning

confidence: 74%

“…Worryingly, recent reports highlighted the emergence of extensive and pan-drug-resistant (PDR) strains of K. pneumoniae from different countries, limiting further treatment options [ 9 , 10 , 11 , 12 ]. Previous genomic studies of K. pneumoniae in Qatar established the clonality of ST383, ST196, and ST146 in healthcare settings, where they predominately carried the carbapenem-resistant genes (CRGs) bla NDM and bla OXA 48 [ 13 ]. Furthermore, studies conducted in this field describe a large group of ARGs that impede the therapeutic function of broad-spectrum antimicrobials, such as carbapenems, as well as novel β-lactam–β-lactamase inhibitors (BLBLIs), which are considered the ultimate management agents for serious infections secondary to Gram-negative bacteria (GNB) [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Phenotypic and Genotypic Characterization of Pan-Drug-Resistant Klebsiella pneumoniae Isolated in Qatar

Sid Ahmed,

Hamid,

Hassan

et al. 2024

Antibiotics

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In secondary healthcare, carbapenem-resistant Enterobacterales (CREs), such as those observed in Klebsiella pneumoniae, are a global public health priority with significant clinical outcomes. In this study, we described the clinical, phenotypic, and genotypic characteristics of three pan-drug-resistant (PDR) isolates that demonstrated extended resistance to conventional and novel antimicrobials. All patients had risk factors for the acquisition of multidrug-resistant organisms, while microbiological susceptibility testing showed resistance to all conventional antimicrobials. Advanced susceptibility testing demonstrated resistance to broad agents, such as ceftazidime-avibactam, ceftolozane–tazobactam, and meropenem–vaborbactam. Nevertheless, all isolates were susceptible to cefiderocol, suggested as one of the novel antimicrobials that demonstrated potent in vitro activity against resistant Gram-negative bacteria, including CREs, pointing toward its potential therapeutic role for PDR pathogens. Expanded genomic studies revealed multiple antimicrobial-resistant genes (ARGs), including blaNMD-5 and blaOXA derivative types, as well as a mutated outer membrane porin protein (OmpK37).

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Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Phenotypic and Genotypic Characterization of Pan-Drug-Resistant Klebsiella pneumoniae Isolated in Qatar

Sid Ahmed,

Hamid,

Hassan

et al. 2024

Antibiotics

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“…A study reported that among 1052 CRKP strains isolated during 2015–2017 from 56 centres across China, only 72 (6.8%) strains carried all of the four virulence genes [ 34 ]. In recent years, the highest prevalence of a single virulence gene in CRKP isolates was approximately 20% in China and Vietnam, followed by 10% in Qatar, and less than 10% in the USA and the UK [ 21 , 35 – 37 ]. Thus, the mechanism underlying the simultaneous presence of all four of these virulence genes at high rates in K. pneumoniae , CRKP and ST11- KPC-2 isolates is currently unknown and needs to be investigated in the future.…”

Section: Discussionmentioning

confidence: 99%

“…It was also shown that the occurrence of the virulence genes rmpA , rmpA2 , iroN and iucA was correlated with the presence of the virulence plasmid pLVPK [ 18 – 20 ]. Furthermore, an increasing occurrence of hv-CRKP is also being observed in other sequence types (STs), including ST15 and ST147 [ 21 – 24 ]. Therefore, this study aimed to find the risk factors for and mortality associated with CRKP infection by comparing the clinical characteristics of CRKP infection cases with those of CSKP infection cases and to identify the molecular characteristics, namely, the presence of carbapenem resistance genes ( bla KPC-2 , bla NDM like and bla OXA-48 like) and four virulence genes ( rmpA , rmpA2 , iroN and iucA ), that are correlated with the resistance and virulence of CRKP isolates.…”

Section: Introductionmentioning

confidence: 99%

Clinical and molecular characteristics of Klebsiella pneumoniae infection in a tertiary general hospital of Wuhan, China

Xiang,

Tian,

Chen

et al. 2023

Eur J Clin Microbiol Infect Dis

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Objectives The aim of this study was to investigate the clinical and molecular characteristics of Klebsiella pneumoniae infection from a tertiary general hospital in Wuhan, China. Methods From December 2019 to August 2022, 311 non-duplicate isolates of K. pneumoniae were collected from a tertiary hospital in Wuhan. These comprised 140 carbapenem-resistant K. pneumoniae (CRKP) isolates and 171 carbapenem-susceptible K. pneumoniae (CSKP) isolates. The clinical characteristics of patients with K. pneumoniae infection were retrospectively collected. Polymerase chain reaction (PCR) assays were used to identify the main carbapenem resistance genes, virulence genes and multi-locus sequence typing (MLST) profiles of the isolates, and the Galleria mellonella infection model was used to determine their virulence phenotypes. Results Independent risk factors for CRKP infection were hypertension, neurological disorders, being admitted to the intensive care unit (ICU) and prior use of antibiotics. Patient with CRKP infection had higher mortality than those with CSKP infection (23.6% vs 14.0%, P < 0.05). One hundred and two sequence types (STs) were identified among the K. pneumoniae isolates, and the most prevalent ST type was ST11 (112/311, 36.0%). All of the ST11 isolates were CRKP. Among the 112 ST11 isolates, 105 (93.8%) harboured the carbapenem resistance gene blaKPC-2 (ST11-KPC-2), and of these isolates, 78 (74.3%, 78/105) contained all of the four virulence genes, namely rmpA, rmpA2, iroN and iucA, suggesting that these genes were widespread among the isolates responsible for K. pneumoniae infections. Conclusion In this study, ST11-KPC-2 was responsible for most of the K. pneumoniae infection cases. Carbapenem resistance rather than the co-occurrence of the virulence genes rmpA, rmpA2, iroN and iucA was associated with K. pneumoniae infection-related mortality during hospitalisation. Furthermore, a high proportion of ST11-KPC-2 isolates carried all of the four virulence genes.

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“…The first hybrid virulence/resistance plasmid was described in an isolate of K. pneumoniae ST147 collected in 2016, which also carried bla NDM-1 in a separate plasmid [11]. Subsequently, isolates carrying both bla NDM-5 and virulence elements in the same plasmid were described [12, 13]. At that time, hybrid resistance/virulence plasmids were remarkable, but they are now becoming common, especially, in our experience, among representatives of ST147.…”

Section: Introductionmentioning

confidence: 99%

Klebsiella pneumoniae sequence type 147: a high-risk clone increasingly associated with plasmids carrying both resistance and virulence elements

Turton,

Perry,

McGowan

et al. 2024

Journal of Medical Microbiology

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Introduction. The first hybrid resistance/virulence plasmid, combining elements from virulence plasmids described in hypervirulent types of Klebsiella pneumoniae with those from conjugative resistance plasmids, was described in an isolate of sequence type (ST) 147 from 2016. Subsequently, this type has been increasingly associated with these plasmids. Hypothesis or gap statement. The extent of carriage of hybrid virulence/resistance plasmids in nosocomial isolates of K. pneumoniae requires further investigation. Aim. To describe the occurrence of virulence/resistance plasmids among isolates of K. pneumoniae received by the UK reference laboratory, particularly among representatives of ST147, and to compare their sequences. Methodology. Isolates received by the laboratory during 2022 and the first half of 2023 (n=1278) were screened for virulence plasmids by PCR detection of rmpA/rmpA2 and typed by variable-number tandem repeat analysis. Twenty-nine representatives of ST147 (including a single-locus variant) from seven hospital laboratories were subjected to long-read nanopore sequencing using high-accuracy q20 chemistry to provide complete assemblies. Results. rmpA/rmpA2 were detected in 110 isolates, of which 59 belonged to hypervirulent K1-ST23, K2-ST86 and K2-ST65/375. Of the remainder, representatives of ST147 formed the largest group, with 22 rmpA/rmpA2-positive representatives (out of 47 isolates). Representatives were from 19 hospital laboratories, with rmpA/rmpA2-positive isolates from 10. Nanopore sequencing of 29 representatives of ST147 divided them into those with no virulence plasmid (n=12), those with non-New Delhi metallo-β-lactamase (NDM) virulence plasmids (n=6) and those carrying bla NDM-5 (n=9) or bla NDM-1 (n=2) virulence plasmids. These plasmids were of IncFIB(pNDM-Mar)/IncHI1B(pNDM-MAR) replicon types. Most of the non-NDM virulence plasmids were highly similar to the originally described KpvST147L_NDM plasmid. Those carrying bla NDM-5 were highly similar to one another and to previously described plasmids in ST383 and carried an extensive array of resistance genes. Comparison of the fully assembled chromosomes indicated multiple introductions of ST147 in UK hospitals. Conclusion. This study highlights the high proportion of representatives of ST147 that carry IncFIB(pNDM-Mar)/IncHI1B(pNDM-MAR) hybrid resistance virulence plasmids. It is important to be aware of the high probability that representatives of this type carry these plasmids combining resistance and virulence determinants and of the consequent increased risk to patients.

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Genomic Epidemiology of Carbapenem-Resistant Klebsiella in Qatar: Emergence and Dissemination of Hypervirulent Klebsiella pneumoniae Sequence Type 383 Strains

Abstract: The emergence of carbapenem-resistant, hypervirulent Klebsiella pneumoniae is a new threat to health care. We studied the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae isolates in Qatar using whole-genome sequence data.

Cited by 12 publications

References 60 publications

Phenotypic and Genotypic Characterization of Pan-Drug-Resistant Klebsiella pneumoniae Isolated in Qatar

Phenotypic and Genotypic Characterization of Pan-Drug-Resistant Klebsiella pneumoniae Isolated in Qatar

Clinical and molecular characteristics of Klebsiella pneumoniae infection in a tertiary general hospital of Wuhan, China

Klebsiella pneumoniae sequence type 147: a high-risk clone increasingly associated with plasmids carrying both resistance and virulence elements

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