Detecting KPC-2 and NDM-1 Coexpression in Klebsiella pneumoniae Complex from Human and Animal Hosts in South America

Vásquez-Ponce, Felipe; Dantas, Karine; Becerra, Johana; Melocco, Gregory; Esposito, Fernanda; Cardoso, Brenda; Rodrigues, Liana Álvares; Lima, Keli; Andrade-Lima, Aluísio; Sellera, Fábio P.; Mattos, Renata; Trevisoli, Lucas; Vianello, Marco A.; Sincero, Thaís Cristine Marques; Conza, José Alejandro Di; Vespero, Eliana Carolina; Gutkind, Gabriel; Sampaio, Julliane Messias Cordeiro; Lincopán, Nilton

doi:10.1128/spectrum.01159-22

“…All NDM-1-producing CPE showed resistance to β-lactams, including aztreonam, often due to AmpC and ESBL genes, with the blaCTX-M-15 gene being particularly prevalent in our data set ( 14 , 15 ). The co-production of carbapenemases NDM-1 and KPC-2 in K. pneumoniae has been previously described in South America, including Brazil, Argentina, Uruguay, Ecuador, and Paraguay ( 16 ). Our report provides further evidence of this occurrence and regional dispersion of CPE co-producing NDM-1 and KPC-2 carbapenemases.…”

Section: Discussionmentioning

confidence: 89%

Molecular characterization of carbapenemase-producing Enterobacterales in a tertiary hospital in Lima, Peru

Cuicapuza,

Loyola,

Velásquez

et al. 2024

Microbiol Spectr

3

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Carbapenemase-producing Enterobacterales (CPE) are a growing threat to global health and the economy. Understanding the interactions between resistance and virulence mechanisms of CPE is crucial for managing difficult-to-treat infections and informing outbreak prevention and control programs. Here, we report the characterization of 21 consecutive, unique clinical isolates of CPE collected in 2018 at a tertiary hospital in Lima, Peru. Isolates were characterized by phenotypic antimicrobial susceptibility testing and whole-genome sequencing to identify resistance determinants and virulence factors. Seven Klebsiella pneumoniae isolates were classified as extensively drug-resistant. The remaining Klebsiella , Enterobacter hormaechei, and Escherichia coli isolates were multidrug-resistant. Eighteen strains carried the metallo-β-lactamase NDM-1, two the serine-carbapenemase KPC-2, and one isolate had both carbapenemases. The bla NDM-1 gene was located in the truncated ΔISAba125 element, and the bla KPC-2 gene was in the Tn4401a transposon. ST147 was the most frequent sequence type among K. pneumoniae isolates. Our findings highlight the urgent need to address the emergence of CPE and strengthen control measures and antibiotic stewardship programs in low- and middle-income settings. IMPORTANCE Genomic surveillance of antimicrobial resistance contributes to monitoring the spread of resistance and informs treatment and prevention strategies. We characterized 21 carbapenemase-producing Enterobacterales collected at a Peruvian tertiary hospital in 2018, which exhibited very high levels of resistance and carried numerous resistance genes. We detected the coexistence of carbapenemase-encoding genes ( bla NDM-1 and bla KPC-2 ) in a Klebsiella pneumoniae isolate that also had the PmrB(R256G) mutation associated with colistin resistance. The bla KPC-2 genes were located in Tn4401a transposons, while the bla NDM-1 genes were in the genetic structure Tn125 (ΔISAba125). The presence of high-risk clones among Klebsiella pneumoniae (ST11 and ST147) and Escherichia coli (ST410) isolates is also reported. The study reveals the emergence of highly resistant bacteria in a Peruvian hospital, which could compromise the effectiveness of current treatments and control.

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“…Therefore, most likely R264_A265insG and S181_P182insSS mutations confer protein conformations leading to inefficient binding of immobilized monoclonal antibodies targeted to recognize KPC-type enzymes inhibited by avibactam, consequently resulting in the failure of the detection method. On the other hand, CZA-resistant isolates displaying susceptibility to meropenem could not be identified as KPC producers ( 32 ), leading to a misleading detection by diagnostic laboratories. Thus, since CZA has become the first-line option for the treatment of infections due to KPC-2 producers, it is imperative to improve screening methods for the detection of KPC variants displaying resistance to CZA, in order to facilitate its rapid and accurate detection.…”

Section: Observationmentioning

confidence: 99%

Emergence of KPC-113 and KPC-114 variants in ceftazidime-avibactam-resistant Klebsiella pneumoniae belonging to high-risk clones ST11 and ST16 in South America

Vásquez-Ponce,

Bispo,

Becerra

et al. 2023

Microbiol Spectr

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Two novel variants of Klebsiella pneumoniae carbapenemase (KPC) associated with resistance to ceftazidime-avibactam (CZA) and designated as KPC-113 and KPC-114 by NCBI were identified in 2020, in clinical isolates of Klebsiella pneumoniae in Brazil. While K. pneumoniae of ST16 harbored the bla KPC-113 variant on an IncFII-IncFIB plasmid, K. pneumoniae of ST11 carried the bla KPC-114 variant on an IncN plasmid. Both isolates displayed resistance to broad-spectrum cephalosporins, β-lactam inhibitors, and ertapenem and doripenem, whereas K. pneumoniae producing KPC-114 showed susceptibility to imipenem and meropenem. Whole-genome sequencing and in silico analysis revealed that KPC-113 presented a Gly insertion between Ambler positions 264 and 265 (R264_A265insG), whereas KPC-114 displayed two amino acid insertions (Ser-Ser) between Ambler positions 181 and 182 (S181_P182insSS) in KPC-2, responsible for CZA resistance profiles. Our results confirm the emergence of novel KPC variants associated with resistance to CZA in international clones of K. pneumoniae circulating in South America. IMPORTANCE KPC-2 carbapenemases are endemic in Latin America. In this regard, in 2018, ceftazidime-avibactam (CZA) was authorized for clinical use in Brazil due to its significant activity against KPC-2 producers. In recent years, reports of resistance to CZA have increased in this country, limiting its clinical application. In this study, we report the emergence of two novel KPC-2 variants, named KPC-113 and KPC-114, associated with CZA resistance in Klebsiella pneumoniae strains belonging to high-risk clones ST11 and ST16. Our finding suggests that novel mutations in KPC-2 are increasing in South America, which is a critical issue deserving active surveillance.

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“…6 CRKP, which produces both KPC and NDM, confers resistance to nearly all β-lactams and β-lactamase inhibitors, and presents a significant challenge in clinical treatment owing to extremely limited options. In recent years, the co-production of KPC and NDM (mainly KPC-2 and NDM-1) has become a severe threat to public health, with increasing reports worldwide, [7][8][9][10][11][12] and has been documented in other Enterobacteriaceae. [13][14][15] A nationwide survey in China revealed an increased prevalence of CRKP coproducing KPC-2 and NDM-1 in recent years.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of a Novel Hybrid IncFIIpHN7A8:IncR:IncN Plasmid Co-Harboring blaNDM-5 and blaKPC-2 from a Clinical ST11 Carbapenem-Resistant Klebsiella pneumoniae Strain

Sun,

Chen,

Qu

et al. 2023

IDR

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Purpose We aimed to characterize a novel bla NDM-5 and bla KPC-2 co-carrying hybrid plasmid from a clinical carbapenem-resistant Klebsiella pneumoniae (CRKP) strain. Methods Antimicrobial susceptibility was determined by the broth microdilution method. Plasmid size and localization were estimated using S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting. Plasmid transfer ability was evaluated by conjugation experiments. Whole genome sequencing (WGS) was performed using Illumina NovaSeq6000 and Oxford Nanopore MinION platforms. Genomic characteristics were analyzed using bioinformatics methods. Results Strain ZY27320 was a multidrug-resistant (MDR) clinical ST11 K. pneumoniae strain that confers high-level resistance to carbapenems (meropenem, MIC 128 mg/L; imipenem, MIC 64 mg/L) and ceftazidime/avibactam (MIC >128/4 mg/L). Both S1-PFGE–Southern blotting and whole genome sequencing revealed that the carbapenemase genes bla KPC-2 and bla NDM-5 were carried by the same IncFII pHN7A8 :IncR:IncN hybrid plasmid (pKPC2_NDM5). Conjugation experiments indicated that pKPC2_NDM5 was a non-conjugative plasmid. Conclusion This is the first report of a hybrid plasmid carrying both carbapenemase genes bla NDM-5 and bla KPC-2 in a clinical K. pneumoniae ST11 isolate that confers resistance to both ceftazidime/avibactam and carbapenems, thereby presenting a serious threat to treatment in clinical practice.

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Detecting KPC-2 and NDM-1 Coexpression in Klebsiella pneumoniae Complex from Human and Animal Hosts in South America

Cited by 14 publications

References 52 publications

Molecular characterization of carbapenemase-producing Enterobacterales in a tertiary hospital in Lima, Peru

Molecular characterization of carbapenemase-producing Enterobacterales in a tertiary hospital in Lima, Peru

Emergence of KPC-113 and KPC-114 variants in ceftazidime-avibactam-resistant Klebsiella pneumoniae belonging to high-risk clones ST11 and ST16 in South America

Characterisation of a Novel Hybrid IncFIIpHN7A8:IncR:IncN Plasmid Co-Harboring blaNDM-5 and blaKPC-2 from a Clinical ST11 Carbapenem-Resistant Klebsiella pneumoniae Strain

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