OXA-181-Like Carbapenemases in Klebsiella pneumoniae ST14, ST15, ST23, ST48, and ST231 from Septicemic Neonates: Coexistence with NDM-5, Resistome, Transmissibility, and Genome Diversity

Naha, Sharmi; Sands, Kirsty; Mukherjee, Subhankar; Saha, Bijan; Basu, Sulagna

doi:10.1128/msphere.01156-20

Cited by 41 publications

(26 citation statements)

References 46 publications

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“…Numerous high-risk K. pneumoniae clones, among them ST14, have now been identified [2]. ST14 strains have been reported to produce a wide range of carbapenemases: apart from being the sequence type from which the bla NDM-1 gene was first identified [18], various bla KPC [9,19,20], bla NDM [21,22], and bla OXA-48-like [6,[23][24][25][26] alleles or double carbapenemase producers have been reported from different parts of the world, including the Middle East [7,8,[27][28][29][30][31]. Furthermore, ST14 strains appear to be one of the most wide-spread, highly resistant CRE clones in Dubai [8].…”

Section: Discussionmentioning

confidence: 99%

Diversity of carbapenem-resistant Klebsiella pneumoniae ST14 and emergence of a subgroup with KL64 capsular locus in the Arabian Peninsula

Mouftah

Pál

Higgins

et al. 2021

Eur J Clin Microbiol Infect Dis

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To understand the reasons of successful spread of carbapenem-resistant Klebsiella pneumoniae ST14 (CRKP-ST14) in countries of the Arabian Peninsula, the resistome, capsular locus, carbapenemase carrying plasmid types, and core genome of isolates from the region were compared to global isolates. Thirty-nine CRKP-ST14 strains isolated from 13 hospitals in the United Arab Emirates, Bahrain, and Saudi Arabia were selected for whole genome sequencing on Illumina MiSeq platform based on the variety of carbapenemase genes carried and plasmids bearing these genes. Their resistome, capsular locus, and core genome MLST were compared to 173 CRKP-ST14 genomes available in public databases. The selected 39 CRKP-ST14 produced either NDM-1, OXA-48, OXA-162, OXA-232, KPC-2, or co-produced NDM-1 and an OXA-48-like carbapenemase. cgMLST revealed three clusters: 16 isolates from five UAE cities (C1), 11 isolates from three UAE cities and Bahrain (C2), and 5 isolates from Saudi Arabia (C3), respectively, and seven singletons. Resistance gene profile, carbapenemase genes, and their plasmid types were variable in both C1 and C2 clusters. The majority of CRKP-ST14 had KL2, but members of the C2 cluster and two further singletons possessed KL64 capsular locus. Based on cgMLST comparison of regional and global isolates, CRKP-ST14 with KL64 from four continents formed a distinct cluster, suggesting a recent emergence and spread of this variant. Our findings confirmed clonal transmission coupled with likely horizontal gene transfer in carbapenem-resistant Klebsiella pneumoniae ST14. Dissemination of this genetically flexible, highly resistant clone warrants further monitoring.

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Section: Discussionmentioning

confidence: 99%

Diversity of carbapenem-resistant Klebsiella pneumoniae ST14 and emergence of a subgroup with KL64 capsular locus in the Arabian Peninsula

Mouftah

Pál

Higgins

et al. 2021

Eur J Clin Microbiol Infect Dis

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“…By feature selection, we proposed a top 40 feature-based regression model, which had the best predictive performance of 91%. First, according to Naha et al (2021) and Okanda et al (2020), we found that gene mutations may affect drug resistance of Klebsiella; thus, we tried to find the relevant sites affecting resistance by calling SNPs. After pre-processing the raw data by using biogenetics tools BWA, BCFTools, and SamTools, we obtained a matrix of mutation site and sample list.…”

Section: Discussionmentioning

confidence: 99%

Prediction of Minimal Inhibitory Concentration of Meropenem Against Klebsiella pneumoniae Using Metagenomic Data

Tan¹,

Yu²,

Liu

et al. 2021

Front. Microbiol.

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Minimal inhibitory concentration (MIC) is defined as the lowest concentration of an antimicrobial agent that can inhibit the visible growth of a particular microorganism after overnight incubation. Clinically, antibiotic doses for specific infections are determined according to the fraction of MIC. Therefore, credible assessment of MICs will provide a physician valuable information on the choice of therapeutic strategy. Early and precise usage of antibiotics is the key to an infection therapy. Compared with the traditional culture-based method, the approach of whole genome sequencing to identify MICs can shorten the experimental time, thereby improving clinical efficacy. Klebsiella pneumoniae is one of the most significant members of the genus Klebsiella in the Enterobacteriaceae family and also a common non-social pathogen. Meropenem is a broad-spectrum antibacterial agent of the carbapenem family, which can produce antibacterial effects of most Gram-positive and -negative bacteria. In this study, we used single-nucleotide polymorphism (SNP) information and nucleotide k-mers count based on metagenomic data to predict MICs of meropenem against K. pneumoniae. Then, features of 110 sequenced K. pneumoniae genome data were combined and modeled with XGBoost algorithm and deep neural network (DNN) algorithm to predict MICs. We first use the XGBoost classification model and the XGBoost regression model. After five runs, the average accuracy of the test set was calculated. The accuracy of using nucleotide k-mers to predict MICs of the XGBoost classification model and XGBoost regression model was 84.5 and 89.1%. The accuracy of SNP in predicting MIC was 80 and 81.8%, respectively. The results show that XGBoost regression is better than XGBoost classification in both nucleotide k-mers and SNPs to predict MICs. We further selected 40 nucleotide k-mers and 40 SNPs with the highest correlation with MIC values as features to retrain the XGBoost regression model and DNN regression model. After 100 and 1,000 runs, the results show that the accuracy of the two models was improved. The accuracy of the XGBoost regression model for k-mers, SNPs, and k-mers & SNPs was 91.1, 85.2, and 91.3%, respectively. The accuracy of the DNN regression model was 91.9, 87.1, and 91.8%, respectively. Through external verification, some of the selected features were found to be related to drug resistance.

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“…It is noteworthy that earlier studies reported the presence of a single carbapenemase in K. pneumoniae but in recent years reports of co-occurrence of multiple carbapenemases are emerging (16,75,82). In a recent study from India OXA-181/OXA-232 was concomitantly present with NDM-5 in K. pneumoniae causing neonatal septicemia (82).…”

Section: Drug-resistant Bug and The Newbornmentioning

confidence: 98%

Neonatal Sepsis: The Impact of Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae

et al. 2021

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The convergence of a vulnerable population and a notorious pathogen is devastating, as seen in the case of sepsis occurring during the first 28 days of life (neonatal period). Sepsis leads to mortality, particularly in low-income countries (LICs) and lower-middle-income countries (LMICs). Klebsiella pneumoniae, an opportunistic pathogen is a leading cause of neonatal sepsis. The success of K. pneumoniae as a pathogen can be attributed to its multidrug-resistance and hypervirulent-pathotype. Though the WHO still recommends ampicillin and gentamicin for the treatment of neonatal sepsis, K. pneumoniae is rapidly becoming untreatable in this susceptible population. With escalating rates of cephalosporin use in health-care settings, the increasing dependency on carbapenems, a “last resort antibiotic,” has led to the emergence of carbapenem-resistant K. pneumoniae (CRKP). CRKP is reported from around the world causing outbreaks of neonatal infections. Carbapenem resistance in CRKP is largely mediated by highly transmissible plasmid-encoded carbapenemase enzymes, including KPC, NDM, and OXA-48-like enzymes. Further, the emergence of a more invasive and highly pathogenic hypervirulent K. pneumoniae (hvKP) pathotype in the clinical context poses an additional challenge to the clinicians. The deadly package of resistance and virulence has already limited therapeutic options in neonates with a compromised defense system. Although there are reports of CRKP infections, a review on neonatal sepsis due to CRKP/ hvKP is scarce. Here, we discuss the current understanding of neonatal sepsis with a focus on the global impact of the CRKP, provide a perspective regarding the possible acquisition and transmission of the CRKP and/or hvKP in neonates, and present strategies to effectively identify and combat these organisms.

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OXA-181-Like Carbapenemases in Klebsiella pneumoniae ST14, ST15, ST23, ST48, and ST231 from Septicemic Neonates: Coexistence with NDM-5, Resistome, Transmissibility, and Genome Diversity

Cited by 41 publications

References 46 publications

Diversity of carbapenem-resistant Klebsiella pneumoniae ST14 and emergence of a subgroup with KL64 capsular locus in the Arabian Peninsula

Diversity of carbapenem-resistant Klebsiella pneumoniae ST14 and emergence of a subgroup with KL64 capsular locus in the Arabian Peninsula

Prediction of Minimal Inhibitory Concentration of Meropenem Against Klebsiella pneumoniae Using Metagenomic Data

Neonatal Sepsis: The Impact of Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae

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