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. 2020 Oct 23;71(7):e141-e150.
doi: 10.1093/cid/ciz1095.

An Emerging Clone, Klebsiellapneumoniae Carbapenemase 2-Producing K. pneumoniae Sequence Type 16, Associated With High Mortality Rates in a CC258-Endemic Setting

Diego O Andrey  1   2 , Priscila Pereira Dantas  3 , Willames B S Martins  1   4 , Fabíola Marques De Carvalho  5 , Luiz Gonzaga Paula Almeida  5 , Kirsty Sands  1 , Edward Portal  1 , Julien Sauser  6 , Rodrigo Cayô  4 , Marisa F Nicolas  5 , Ana Tereza R Vasconcelos  5 , Eduardo A Medeiros  3 , Timothy R Walsh  1 , Ana C Gales  4
Affiliations

An Emerging Clone, Klebsiellapneumoniae Carbapenemase 2-Producing K. pneumoniae Sequence Type 16, Associated With High Mortality Rates in a CC258-Endemic Setting

Diego O Andrey et al. Clin Infect Dis. .

Abstract

Background: Carbapenemase-producing Klebsiella pneumoniae has become a global priority, not least in low- and middle-income countries. Here, we report the emergence and clinical impact of a novel Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) sequence type (ST) 16 clone in a clonal complex (CC) 258-endemic setting.

Methods: In a teaching Brazilian hospital, a retrospective cohort of adult KPC-KP bloodstream infection (BSI) cases (January 2014 to December 2016) was established to study the molecular epidemiology and its impact on outcome (30-day all-cause mortality). KPC-KP isolates underwent multilocus sequence typing. Survival analysis between ST/CC groups and risk factors for fatal outcome (logistic regression) were evaluated. Representative isolates underwent whole-genome sequencing and had their virulence tested in a Galleria larvae model.

Results: One hundred sixty-five unique KPC-KP BSI cases were identified. CC258 was predominant (66%), followed by ST16 (12%). The overall 30-day mortality rate was 60%; in contrast, 95% of ST16 cases were fatal. Patients' severity scores were high and baseline clinical variables were not statistically different across STs. In multivariate analysis, ST16 (odds ratio [OR], 21.4; 95% confidence interval [CI], 2.3-202.8; P = .008) and septic shock (OR, 11.9; 95% CI, 4.2-34.1; P < .001) were independent risk factors for fatal outcome. The ST16 clone carried up to 14 resistance genes, including blaKPC-2 in an IncFIBpQIL plasmid, KL51 capsule, and yersiniabactin virulence determinants. The ST16 clone was highly pathogenic in the larvae model.

Conclusions: Mortality rates were high in this KPC-KP BSI cohort, where CC258 is endemic. An emerging ST16 clone was associated with high mortality. Our results suggest that even in endemic settings, highly virulent clones can rapidly emerge demanding constant monitoring.

Keywords: Klebsiella pneumoniae; CC258; KPC; bloodstream infections; carbapenem-resistant Enterobacteriaceae.

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Figures

Figure 1.
Figure 1.
Kaplan-Meier plots showing the survival of patients following bacteremia due to Klebsiella pneumoniae carbapenemase–producing K. pneumoniae (KPC-KP) belonging to sequence type (ST) 16 vs clonal complex (CC) 258 vs other STs (A) and ST16 vs ST11, ST258, and ST437 (B), over 30 days. C, Pie chart showing multilocus sequence typing distribution of KPC-KP isolates. Survival curves were plotted using the Kaplan-Meier method (GraphPad Prism version 5 software), and P values were calculated by log-rank (Mantel-Cox) test. One patient (ST258 group) was censored. One patient (ST258 group) was censored and is signaled on by*. Abbreviations: CC, clonal complex; NA, isolates unavailable for multilocus sequence typing analysis; ST, sequence type.
Figure 2.
Figure 2.
Virulence, antibiotic resistance genes, and plasmid replicons of 64 sequenced Klebsiella pneumoniae carbapenemase–producing K. pneumoniae strains. The heatmap was generated after aligning the contigs of sequenced genomes of each strain to our virulence gene dataset, to Resfinder, and to PlasmidFinder. Chromosomally encoded oqxAB genes were found in all K. pneumoniae genomes and were not displayed. None of these genomes was found to harbor MCR genes. Abbreviation: MCR, mobile colistin resistance.
Figure 3.
Figure 3.
A, Kaplan-Meier plots showing the percentage survival of Galleria mellonella over 72 hours postinfection with clinical isolates representative of sequence type (ST) 16 (KL51), ST11 (KL64 or KL15), ST258 (KL107), and ST437 (KL36), at 10E4 (A), 10E5 (B), and 10E6 CFU (C). A58300 is a ST23 K1 rmpA2-positive hypermucoviscous positive control. Survival curves were plotted using the Kaplan-Meier method, and P values were calculated by log-rank (Mantel-Cox) test. Each line represents a single isolate. Data on all tested isolates are available in Supplementary Figure 6; a subset is shown here for clarity. Abbreviation: CFU, colony-forming units.
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