Molecular epidemiology of virulence and antimicrobial resistance determinants in Klebsiella pneumoniae from hospitalised patients in Kilimanjaro, Tanzania

Sonda, Tolbert; Kumburu, Happiness; Zwetselaar, Marco van; Alifrangis, Michael; Mmbaga, Blandina T.; Lund, Ole; Kibiki, Gibson; Aarestrup, Frank Møller

doi:10.1007/s10096-018-3324-5

Cited by 21 publications

(26 citation statements)

References 54 publications

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“…However, phenotypic prediction based on the genotype cannot replace phenotypic testing, as the present understanding of the genetic basis of resistance and the associated databases are not comprehensive [85]. This limitation was shown during a WGS-based surveillance of antimicrobial resistant determinants in Klebsiella pneumonia where the phenotypically determined resistance was higher than the sequenced-based resistance [86].…”

Section: Resultsmentioning

confidence: 99%

“…Although WGS data has the potential to support phenotypic predictions of virulence and resistance based on the genotype, phenotypic data will still be needed to identify new resistance/virulence mechanisms and to keep the databases up-to-date [12, 85, 86, 157, 166, 167]. Therefore, phenotypic testing results and clinical data have to be collected in a standardized manner alongside the sequence data to feed the databases from which associations between genotype and phenotype can be observed [160].…”

Section: Discussionmentioning

confidence: 99%

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Status and potential of bacterial genomics for public health practice: a scoping review

et al. 2019

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Background Next-generation sequencing (NGS) is increasingly being translated into routine public health practice, affecting the surveillance and control of many pathogens. The purpose of this scoping review is to identify and characterize the recent literature concerning the application of bacterial pathogen genomics for public health practice and to assess the added value, challenges, and needs related to its implementation from an epidemiologist’s perspective. Methods In this scoping review, a systematic PubMed search with forward and backward snowballing was performed to identify manuscripts in English published between January 2015 and September 2018. Included studies had to describe the application of NGS on bacterial isolates within a public health setting. The studied pathogen, year of publication, country, number of isolates, sampling fraction, setting, public health application, study aim, level of implementation, time orientation of the NGS analyses, and key findings were extracted from each study. Due to a large heterogeneity of settings, applications, pathogens, and study measurements, a descriptive narrative synthesis of the eligible studies was performed. Results Out of the 275 included articles, 164 were outbreak investigations, 70 focused on strategy-oriented surveillance, and 41 on control-oriented surveillance. Main applications included the use of whole-genome sequencing (WGS) data for (1) source tracing, (2) early outbreak detection, (3) unraveling transmission dynamics, (4) monitoring drug resistance, (5) detecting cross-border transmission events, (6) identifying the emergence of strains with enhanced virulence or zoonotic potential, and (7) assessing the impact of prevention and control programs. The superior resolution over conventional typing methods to infer transmission routes was reported as an added value, as well as the ability to simultaneously characterize the resistome and virulome of the studied pathogen. However, the full potential of pathogen genomics can only be reached through its integration with high-quality contextual data. Conclusions For several pathogens, it is time for a shift from proof-of-concept studies to routine use of WGS during outbreak investigations and surveillance activities. However, some implementation challenges from the epidemiologist’s perspective remain, such as data integration, quality of contextual data, sampling strategies, and meaningful interpretations. Interdisciplinary, inter-sectoral, and international collaborations are key for an appropriate genomics-informed surveillance. Electronic supplementary material The online version of this article (10.1186/s13012-019-0930-2) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Status and potential of bacterial genomics for public health practice: a scoping review

et al. 2019

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“…TEM-1 is the main TEM-type of K. pneumoniae isolated from Tanzania, India, and Iran. [41][42][43] OXA-1 and SHV-108 are rarely detected from K. pneumoniae.…”

Section: Discussionmentioning

confidence: 99%

Genomic Epidemiology of an Outbreak of Klebsiella pneumoniae ST471 Producing Extended-Spectrum β-Lactamases in a Neonatal Intensive Care Unit

Wang¹,

Luo²,

Du³

et al. 2020

IDR

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Purpose: Klebsiella pneumoniae producing extended-spectrum β-lactamases (ESBLs) causes nosocomial infections worldwide. The present study aimed to determine the molecular subtyping characteristics and antibiotic resistance mechanisms of ESBL-producing K. pneumoniae strains collected during an outbreak. Moreover, we attempted to reveal the fine transmission route of the strains within this outbreak using whole-genome sequencing (WGS). Methods: Collecting cases and strain information were carried out. Outbreak-related strains were identified using pulsed-field gel electrophoresis (PFGE). The antibiotic susceptibility, drug-resistant genes, and molecular subtype characteristics of ESBL-producing K. pneumoniae were analyzed. The fine transmission route of the strains within this outbreak was revealed using WGS and minimum core genome (MCG) sequence typing. Results: In mid-January, 2015, five cases of neonatal pneumonia caused by ESBLproducing K. pneumoniae were observed in the neonatal intensive care unit (NICU) of the Affiliated Hospital of Chifeng University, China. Eight ESBL-producing K. pneumoniae were isolated from these five cases, and two additional strains from another two cases were identified using PFGE. All ten isolates harbored bla CTX-M-15 , bla TEM-1 , bla SHV-108 , and bla OXA-1 genes, and belonged to the sequence type 471 (ST471) clone. A putative transmission map was constructed via comprehensive consideration of genomic and epidemiological information. WGS identified the initial case and the "superspreader". The genomic epidemiological investigation revealed that the outbreak was caused by the introduction of the bacteria one month before the first case appeared. Conclusion: As far as we know, this is the first report to describe the characteristics of an ST471 ESBL-producing K. pneumoniae outbreak. The data showed that epidemiological inferences could be greatly improved by interpretation in the context of WGS and that K. pneumoniae strains isolated from the same outbreak contain sufficient genomic differences to refine epidemiological linkages on the basis of genetic lineage. These findings suggested that integration of genomic and epidemiological data can help us to have a clearer understanding of when and how outbreaks occur, so as to better control nosocomial transmission.

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“…The complex synthesized can be described using the following general formula: [Ir(C^N)2(N^N)](PF6), where N^N is the ancillary ligand; and C^N corresponds to a cyclometalating ligand. In this study PSIR-3 is [Ir(ppy)2(ppdh)]PF6 where ppdh is pteridino [7,6-f] [1,10]phenanthroline-1,13(10H,12H)-dihydroxy and ppy is 2-phenylpyridine [41]. The structure and purities of the compound were confirmed by nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), and mass spectroscopy (MALDI-MS) measurements.…”

Section: Synthesis Of the Psir-3 Compoundmentioning

confidence: 94%

“…The high MDR shown by strains of K. pneumoniae does not fully explain its notable success as one of the most important agents of HAIs, suggesting the participation of other factors [9]. An increasing number of authors suggest that increased bacterial survival during infections is related to virulence factors [1,3,[9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Effective Photodynamic Therapy with Ir(III) for Virulent Clinical Isolates of Extended-Spectrum Beta-lactamase Klebsiella pneumoniae

Núñez

Palavecino

González

et al. 2021

Preprint

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Background: The extended-spectrum beta-lactamase (ESBL) Klebsiella pneumoniae is one of the leading causes of health-associated infections (HAI), whose antibiotic treatments have been severely reduced. Besides, HAI bacteria may harbor pathogenic factors such as siderophores, enzymes, or capsules, which increase the virulence of these strains. Thus, new therapies such as antimicrobial photodynamic inactivation (aPDI) are needed. Method: A collection of 118 clinical isolates of K. pneumoniae were characterized susceptibility and virulence through the determination of the minimum inhibitory concentration (MIC) of Amk, Cfx, Cfz, Imp, Mer, and Pip-taz, and by PCR, the frequency of the virulence genes, K2, magA, rmpA, entB, ybtS, and allS. Susceptibility to innate immunity, such as human serum, macrophages, and polymorphonuclear cells, was tested. All the strains were tested for sensitivity to the photosensitizer PSIR-3 (4µg/mL) in a 17µW/cm2 for 30 min aPDI. Results: A significantly higher frequency of virulence genes in ESBL than non-ESBL bacteria were observed. The isolates of the genotype K2+, ybtS+, and allS+ display enhanced virulence since they showed higher resistance to human serum as well as to phagocytosis. All strains are susceptible to the aPDI with PSIR-3 decreasing viability in 3log10. The combined treatment with Cfx improved the aPDI to 6log10 for the ESBL strains. The combined treatment is synergistic as it showed an FIC index value of 0.15. Conclusions: The aPDT effectively inhibits clinical isolates of K. pneumoniae, including the more risky strains of ESBL-producing bacteria and the K2+, ybtS+, and allS+ genotype. The aPDI with PSIR-3 is synergistic with Cfx.

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Molecular epidemiology of virulence and antimicrobial resistance determinants in Klebsiella pneumoniae from hospitalised patients in Kilimanjaro, Tanzania

Cited by 21 publications

References 54 publications

Status and potential of bacterial genomics for public health practice: a scoping review

Status and potential of bacterial genomics for public health practice: a scoping review

<p>Genomic Epidemiology of an Outbreak of <em>Klebsiella pneumoniae</em> ST471 Producing Extended-Spectrum β-Lactamases in a Neonatal Intensive Care Unit</p>

Effective Photodynamic Therapy with Ir(III) for Virulent Clinical Isolates of Extended-Spectrum Beta-lactamase <em>Klebsiella pneumoniae</em>

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