Within-Host Genotypic and Phenotypic Diversity of Contemporaneous Carbapenem-Resistant Klebsiella pneumoniae from Blood Cultures of Patients with Bacteremia

Cheng, Shaoji; Fleres, Giuseppe; Chen, Liang; Liu, Guojun; Hao, Binghua; Newbrough, Anthony; Driscoll, Eileen; Shields, Ryan K.; Squires, Kevin; Chu, Tingyu; Kreiswirth, Barry N.; Clancy, Cornelius J.

doi:10.1128/mbio.02906-22

Cited by 12 publications

(12 citation statements)

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“…Genotypically and phenotypically diverse bacterial populations are increasingly recognized during colonization and chronic infections of non-sterile sites, including GI tract, lungs, and skin [13][14][15] . Aside from our recent demonstration that positive blood cultures of patients with carbapenem-resistant K. pneumoniae BSIs were comprised of genetically variant, clonal strains that differed in antibiotic susceptibility and virulence 16 , there are scant data on microbial diversity during acute infections of putatively sterile sites. 31 Numbers of nucleotide differences (i.e., SNPs, indels) between contemporaneous C. glabrata BSI strains here (pairwise average per-patient: ~3,500)…”

Section: Discussionmentioning

confidence: 99%

“…At present, it is unknown if BSIs are commonly caused by genetically diverse populations, rather than single organisms. We recently demonstrated, for the first time, that positive blood cultures from individual patients with monomicrobial bacterial BSI (carbapenem-resistant Klebsiella pneumoniae) were comprised of mixed populations of genetically and phenotypically diverse strains, including those demonstrating differences in antibiotic susceptibility and virulence 16 .…”

Section: Introductionmentioning

confidence: 99%

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Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures

Badrane

Cheng

Dupont

et al. 2023

Preprint

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The longstanding paradigm is that most bloodstream infections (BSIs) are caused by a single organism. We performed whole genome sequencing of five-to-ten strains from blood culture (BC) bottles in each of ten patients with Candida glabrata BSI. We demonstrated that BCs contained mixed populations of clonal but genetically diverse strains. Genetically distinct strains from two patients exhibited phenotypes that were potentially important during BSIs, including differences in susceptibility to antifungal agents and phagocytosis. In both patients, the clinical microbiology lab recovered a fluconazole-susceptible index strain, but we identified mixed fluconazole-susceptible and –resistant populations. Diversity in drug susceptibility was likely clinically relevant, as fluconazole-resistant strains were subsequently recovered by the clinical laboratory during persistent or relapsing infections. In one patient, unrecognized respiration-deficient small colony variants were fluconazole-resistant and significantly attenuated for virulence during murine candidiasis. Our data suggest a new population-based paradigm of C. glabrata genotypic and phenotypic diversity during BSIs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures

Badrane

Cheng

Dupont

et al. 2023

Preprint

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“…aureus incidence can vary substantially within and between countries, and population structures such as dominant lineages vary geographically [25]. In particular, extending into the adult populations and comparing hospitals with overlapping patient networks would improve generalizability and understanding of how such diversity may be transmitted across hospital networks, as well as expanding to other key clinical pathogens [63–67].…”

Section: Discussionmentioning

confidence: 99%

Quantifying patient- and hospital-level antimicrobial resistance dynamics in Staphylococcus aureus from routinely collected data

Leclerc

Clements

Dunn

et al. 2023

Journal of Medical Microbiology

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Introduction. Antimicrobial resistance (AMR) to all antibiotic classes has been found in the pathogen Staphylococcus aureus . The reported prevalence of these resistances varies, driven by within-host AMR evolution at the patient level, and between-host transmission at the hospital level. Without dense longitudinal sampling, pragmatic analysis of AMR dynamics at multiple levels using routine surveillance data is essential to inform control measures. Gap Statement. The value and limitations of routinely collected hospital data to gain insight into AMR dynamics at the hospital and individual levels simultaneously are unclear. Methodology. We explored S. aureus AMR diversity in 70 000 isolates from a UK paediatric hospital between 2000–2021, using electronic datasets containing multiple routinely collected isolates per patient with phenotypic antibiograms and information on hospitalization and antibiotic consumption. Results. At the hospital level, the proportion of isolates that were meticillin-resistant (MRSA) increased between 2014–2020 from 25–50 %, before sharply decreasing to 30%, likely due to a change in inpatient demographics. Temporal trends in the proportion of isolates resistant to different antibiotics were often correlated in MRSA, but independent in meticillin-susceptible S. aureus . Ciprofloxacin resistance in MRSA decreased from 70–40 % of tested isolates between 2007–2020, likely linked to a national policy to reduce fluoroquinolone usage in 2007. At the patient level, we identified frequent AMR diversity, with 4 % of patients ever positive for S. aureus simultaneously carrying, at some point, multiple isolates with different resistances. We detected changes over time in AMR diversity in 3 % of patients ever positive for S. aureus . These changes equally represented gain and loss of resistance. Conclusion. Within this routinely collected dataset, we found that 65 % of changes in resistance within a patient’s S. aureus population could not be explained by antibiotic exposure or between-patient transmission of bacteria, suggesting that within-host evolution via frequent gain and loss of AMR genes may be responsible for these changing AMR profiles. Our study highlights the value of exploring existing routine surveillance data to determine underlying mechanisms of AMR. These insights may substantially improve our understanding of the importance of antibiotic exposure variation, and the success of single S. aureus clones.

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“…10 Previous studies have used WGS to characterize CRPK isolates from local hospitals and their susceptibility to commonly used antibiotics are urgently needed for improved clinical guidance. [11][12][13] However, the reports from Wuhan China are limited. Our study explored the antibiotic resistance genes, virulence factors and action mechanisms of CRKP through antimicrobial susceptibility tests and WGS technology, to screen common antibiotic resistance genes, so as to further guide the rational and standardized use of antibiotics in the clinic, which hopefully to effectively reduce and control CRKP occurrence.…”

Section: Introductionmentioning

confidence: 99%

Molecular and Clinical Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Isolates at a Tertiary Hospital in Wuhan, China

Fan¹,

Lin²,

Mou³

et al. 2023

IDR

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Background: Carbapenem resistant Klebsiella pneumoniae (CRKP) is an independent risk factor for nosocomial infection which poses a serious threat to human health. How to prevent and suppress CRKP infection and explore its drug resistance mechanisms have become a huge challenge and possesses immediate significance. Methods: A total of 45 CRKP strains isolated from hospitalized patients in Zhongnan Hospital of Wuhan University were collected from August 2018-December 2020. The strain's identification and antimicrobial susceptibility tests were performed using the VITEK 2 automated identification instrument. Single molecule DNA sequencing of 45 CRKP isolates was performed by the third generation high-throughput sequencing technology. Results:The results were analyzed by multi locus sequence typing (MLST) and phylogenetic analysis. Antimicrobial susceptibility showed that 45 CRKP isolates were multi-drug resistant strains, and the resistance rates to common antibiotics were as high as 68%. Whole genome sequencing results showed that the CRKP strains carried multiple drug resistance genes and virulence factors. MLST analysis found two different sequence types (ST), of which 44 were ST11 and 1 was ST1049. Conclusion: Through whole genome sequencing (WGS), we found multiple drug-resistant genes and virulence factors, and there was obvious dominant microbiota. The source was mainly related to nosocomial infection. The ST11-KPC Klebsiella pneumoniae was the main type, which was consistent with the most common type in China. We identified several dominant microbiotas which may serve as a target in the clinical prevention and treatment of severe bacterial infections. Our finding may have a role for guiding clinical antibiotic choosing.

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Within-Host Genotypic and Phenotypic Diversity of Contemporaneous Carbapenem-Resistant Klebsiella pneumoniae from Blood Cultures of Patients with Bacteremia

Cited by 12 publications

References 60 publications

Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures

Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures

Quantifying patient- and hospital-level antimicrobial resistance dynamics in Staphylococcus aureus from routinely collected data

Molecular and Clinical Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Isolates at a Tertiary Hospital in Wuhan, China

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