Duration of Carbapenemase-Producing <i>Enterobacteriaceae</i> Carriage in Hospital Patients

Yin, Mingli; Hernández-Koutoucheva, Anastasia; Musicha, Patrick; Bertrand, Denis; Lye, David C.; Ng, Oon Tek; Fenlon, Shannon N.; Chen, Swaine L.; Ling, Moi Lin; Tang, Wen; Barkham, Timothy; Nagarajan, Niranjan; Cooper, Ben; Marimuthu, Kalisvar

doi:10.3201/eid2609.190592

Cited by 16 publications

(21 citation statements)

References 8 publications

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“…Leveraging the observation that CPE carriage in hospital patients can be resolved within 3 months, with 98.5% probability within a year for our cohort 24 (though other cohorts have reported longer durations 25,26 ), we tracked gut microbiome composition in this cohort of individuals for a year to understand ecological changes associated with decolonization (up to 12 timepoints, 361 samples in total; Table 1, Supplementary File 1 ). Specifically, stool samples were obtained from hospital patients who screened positive for CPE carriage (n=29, index subjects), as well as their non-CPE-colonized family members (n=17, serving as home environment-matched controls) and characterized via deep shotgun metagenomic sequencing (>50 million Illumina 2×100bp reads, on average; Methods ).…”

Section: Resultsmentioning

confidence: 99%

“…Specifically, stool samples were obtained from hospital patients who screened positive for CPE carriage (n=29, index subjects), as well as their non-CPE-colonized family members (n=17, serving as home environment-matched controls) and characterized via deep shotgun metagenomic sequencing (>50 million Illumina 2×100bp reads, on average; Methods ). Principal coordinates analysis with average-linkage clustering based on taxonomic profiling of the data showed that there are multiple distinct community configurations (I, II, III, IV), where CPE positive samples (based on stool culture and qPCR 24 ) were less commonly seen in configurations I and II, and more commonly seen in configurations III and IV ( Figure 1a, Supplementary Figure 1, Supplementary File 2 ). This statistically significant shift of CPE positive samples along PCoA1 (Wilcoxon rank-sum p-value<1.4×10 −8 , Supplementary Figure 2a ) is defined by a gradient of relative abundances that are most strongly correlated for the genera Escherichia (negative i.e.…”

Section: Resultsmentioning

confidence: 99%

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Long-term ecological and evolutionary dynamics in the gut microbiomes of carbapenemase-producing Enterobacteriaceae colonized subjects

Kang

Teo

Bertrand

et al. 2022

Preprint

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Long-term colonization of the gut microbiome by carbapenemase-producing Enterobacteriaceae (CPE) is a growing area of public health concern as it can lead to community transmission and rapid increase in cases of life-threatening CPE infections. Leveraging the observation that many subjects are decolonized without interventions within a year, we used longitudinal shotgun metagenomics (up to 12 timepoints) for detailed characterization of ecological and evolutionary dynamics in the gut microbiome of a cohort of CPE-colonized subjects and family members (n=46; 361 samples). Subjects who underwent decolonization exhibited a distinct ecological shift marked by recovery of microbial diversity, key commensals and anti-inflammatory pathways. In addition, colonization was marked by elevated but unstable Enterobacteriaceae abundances, which exhibited distinct strain-level dynamics for different species (Escherichia coli and Klebsiella pneumoniae). Finally, comparative analysis with whole genome sequencing data from CPE isolates (n=159) helped identify sub-strain variation in key functional genes and the presence of highly similar E. coli and K. pneumoniae strains with variable resistance profiles and plasmid sharing. These results provide an enhanced view into how colonization by multi-drug resistant bacteria associates with altered gut ecology and can enable transfer of resistance genes, even in the absence of overt infection and antibiotic usage.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Long-term ecological and evolutionary dynamics in the gut microbiomes of carbapenemase-producing Enterobacteriaceae colonized subjects

Kang

Teo

Bertrand

et al. 2022

Preprint

Self Cite

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“…Transient or intermittent patient carriage of CPOs could also be a contributing factor. 34 It is also important to note that a complex interplay of factors can affect carbapenemase-mediated carbapenem resistance, including plasmid and carbapenemase gene copy numbers, as well as alterations in the promoter regions of carbapenemase genes. For instance, Kitchel et al 35 reported that increased bla KPC gene expression levels coupled with dual porin loss in Klebsiella pneumoniae isolates led to the highest minimum inhibitory concentrations to carbapenem antibiotics.…”

Section: Discussionmentioning

confidence: 99%

“…Although CPOs were not recovered from a subset of carbapenemase gene‐positive specimens in our PPS, this is likely due to the high sensitivity of the PCR assays that were performed in combination with a low colonizing burden of CPOs in patients, limiting recovery by culture. Transient or intermittent patient carriage of CPOs could also be a contributing factor 34 . It is also important to note that a complex interplay of factors can affect carbapenemase‐mediated carbapenem resistance, including plasmid and carbapenemase gene copy numbers, as well as alterations in the promoter regions of carbapenemase genes.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of carbapenemase‐producing organisms among hospitalized solid organ transplant recipients, five US hospitals, 2019–2020

Chan

Nazarian

Musser

et al. 2022

Transplant Infectious Dis

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Background: Passive reporting to the Centers for Disease Control and Prevention has identified carbapenemase-producing organisms (CPOs) among solid organ transplant (SOT) recipients, potentially representing an emerging source of spread. We analyzed CPO prevalence in wards where SOT recipients receive inpatient care to inform public health action to prevent transmission.Methods: From September 2019 to June 2020, five US hospitals conducted consecutive point prevalence surveys (PPS) of all consenting patients admitted to transplant units, regardless of transplant status. We used the Cepheid Xpert Carba-R assay to identify carbapenemase genes (bla KPC , bla NDM , bla VIM , bla IMP , bla OXA-48 ) from rectal swabs. Laboratory-developed molecular tests were used to retrospectively test for a wider range of bla IMP and bla OXA variants.Results: In total, 154 patients were screened and 92 (60%) were SOT recipients. CPOs were detected among 7 (8%) SOT recipients, from two of five screened hospitals: four bla KPC , one bla NDM , and two blaOXA -23 . CPOs were detected in two (3%) of 62 nontransplant patients. In three of five participating hospitals, CPOs were not identified among any patients admitted to transplant units. Conclusions:Longitudinal surveillance in transplant units, as well as PPS in areas with diverse CPO epidemiology, may inform the utility of routine screening in SOT units to prevent the spread of CPOs.

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“…Gut colonization often precedes and serves as a reservoir for transmission to other body sites resulting in the development of subsequent infections [ 13 ]. The duration of gut colonization with multi-drug resistant (MDR) bacteria, such as carbapenem-resistant K. pneumoniae varies from 43 to 387 days [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Polyclonal Endemicity of Carbapenemase-Producing Klebsiella pneumoniae in ICUs of a Greek Tertiary Care Hospital

et al. 2022

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Carbapenemase-producing Klebsiella pneumoniae (CPKP) emerged in Greece in 2002 and became endemic thereafter. Driven by a notable variability in the phenotypic testing results for carbapenemase production in K. pneumoniae isolates from the intensive care units (ICUs) of our hospital, we performed a study to assess the molecular epidemiology of CPKP isolated between 2016 and 2019 using pulse-field gel electrophoresis (PFGE) including isolates recovered from 165 single patients. We investigated the molecular relatedness among strains recovered from rectal surveillance cultures and from respective subsequent infections due to CPKP in the same individual (48/165 cases). For the optimal interpretation of our findings, we carried out a systematic review regarding the clonality of CPKP isolated from clinical samples in ICUs in Europe. In our study, we identified 128 distinguishable pulsotypes and 17 clusters that indicated extended dissemination of CPKP within the hospital ICU setting throughout the study period. Among the clinical isolates, 122 harbored KPC genes (74%), 2 harbored KPC+NDM (1.2%), 38 harbored NDM (23%), 1 harbored NDM+OXA-48 (0.6%), 1 harbored NDM+VIM (0.6%) and 1 harbored the VIM (0.6%) gene. Multiple CPKP strains in our hospital have achieved sustained transmission. The polyclonal endemicity of CPKP presents a further threat for the selection of pathogens resistant to last-resort antimicrobial agents.

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Duration of Carbapenemase-Producing Enterobacteriaceae Carriage in Hospital Patients

Cited by 16 publications

References 8 publications

Long-term ecological and evolutionary dynamics in the gut microbiomes of carbapenemase-producing Enterobacteriaceae colonized subjects

Long-term ecological and evolutionary dynamics in the gut microbiomes of carbapenemase-producing Enterobacteriaceae colonized subjects

Prevalence of carbapenemase‐producing organisms among hospitalized solid organ transplant recipients, five US hospitals, 2019–2020

Polyclonal Endemicity of Carbapenemase-Producing Klebsiella pneumoniae in ICUs of a Greek Tertiary Care Hospital

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