The Gastrointestinal Load of Carbapenem-Resistant Enterobacteriacea Is Associated With the Transition From Colonization to Infection by Klebsiella pneumoniae Isolates Harboring the blaKPC Gene

Migliorini, Letícia Busato; Leaden, Laura; Sales, Romário Oliveira de; Correa, Nathalia Pellegrini; Marins, Maryana Mara; Koga, Paula Célia Mariko; Toniolo, Alexandra do Rosario; Menezes, Fernando Gatti de; Martino, Marinês Dalla Valle; Mingorance, Jesús; Severino, Patrícia

doi:10.3389/fcimb.2022.928578

Cited by 13 publications

(8 citation statements)

References 38 publications

(50 reference statements)

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“…ST11 is a monolocus variant of ST258 within the same clonal complex, 39 which is considered to be responsible for the global spread of KPC over the past 20 years, with KPC-2 and KPC-3 being the dominant subtypes. 40 Therefore, our study concluded that carbapenemase types were closely related to specific STs and that the risk of BSI in KPC-carrying K. pneumoniae rectal carriers was much higher than in NDM-carrying K. pneumoniae carriers. While our molecular results support the association between CRKP colonization and BSI, suggesting that hospitalized patients are infected with their colonized strains, our study highlights the importance of screening for specific carbapenemase types with rectal colonization.…”

Section: Discussionmentioning

confidence: 70%

Bloodstream Infections in Patients with Rectal Colonization by Carbapenem-Resistant Enterobacteriaceae: A Prospective Cohort Study

Chu¹,

Hang²,

Li³

et al. 2022

IDR

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Purpose Carbapenem-resistant Enterobacteriaceae (CRE) infection has become a concerning threat, especially in hospital settings; however, its phenotypic characterization, association with rectal colonization and subsequent bloodstream infections (BSI) remain to be clarified. This study aimed to investigate the incidence and risk factors of CRE infection in rectal CRE carriers and to understand the clonality of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains and their association with subsequent BSI in these patients. Patients and Methods This was a prospectively designed cohort study. Hospitalized patients treated at our institution from April 2019 to October 2020 with intestinal CRE carriage were screened at admission and weekly thereafter until death or discharge from the hospital. Stool and blood samples were obtained for strain growth and mass spectrometry. The colonization and clinical infection isolates were analyzed by antimicrobial susceptibility testing to identify CRE. The clonality of the CRE strains and their corresponding clinical infection strains was studied by whole-genome sequencing to explore the mechanism of drug resistance and evaluate possible transmission. CRE-associated risk factors were analyzed in combination with epidemiological data. Results Of the 1203 patients, 85 were colonized by CRE and 21 developed CRE infection, of whom 13 developed CRE bloodstream infection (BSI). Ninety-one CRE strains were isolated from the rectal specimens of the 85 patients. Tracheotomy and chemotherapy in the past three months were independent risk factors for CRE infection in intestinal CRE carriers. ST11-KL64 (92.3%, 24/26) was the most dominant capsule and multilocus sequence typing (MLST) type among clonal CRKP isolates. Single-nucleotide polymorphism clustering showed homology of representative colonization and infection CRKP strain pairs (n=13) in the same patient. One group of leading clones was endemic in surgical intensive care units (ICUs). Twenty-four CRKP strains carried β-lactamase K. pneumonia carbapenemase 2, and 73.1% (19 strains) of CRKP carried mucoid phenotype regulator genes A2 and iucABCD. Conclusion In summary, intestinal CRE colonization was detectable at an elevated rate among hospitalized patients and prevalent in ICU patients, with potential rapid horizontal transmission, providing evidence that CRE BSI infection in hospitalized patients might be due to their colonized strains and indicates the correlation between intestinal colonization and BSI.

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Section: Discussionmentioning

confidence: 70%

Bloodstream Infections in Patients with Rectal Colonization by Carbapenem-Resistant Enterobacteriaceae: A Prospective Cohort Study

Chu¹,

Hang²,

Li³

et al. 2022

IDR

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“…Gastrointestinal carriage of AMR bacteria may precede infection and, without active surveillance, can serve as a hidden reservoir for drug-resistant organisms' transmission in hospital environments [11] [12] [13]. Yet, few studies have focused on faecal carriage of MDR bacteria and risk factors for colonization in Kenya, including faecal carriage of CRE in adults and children (1%) [14], carbapenemase-producing organisms (62.4%) in hospitalized newborns [15], and ESBL Enterobacteriales among neonates before (10%) and after admission (55%) [13].…”

Section: Introductionmentioning

confidence: 99%

Faecal carriage and risk factors of carbapenemase-producing gram-negative bacteria resistant to third-generation cephalosporins in hospitalized and non- hospitalized patients, Kenya

Maina,

Maingi,

Mutuma

et al. 2023

Preprint

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Background carbapenem-resistant Gram-negative bacteria (CR-GNB), especially the carbapenemase-producing strains, are growing public health concerns globally; however, epidemiological data to inform prevention and control interventions in line with AMR global and national action plans in our study setting are limited. We assessed carbapenem-resistant and carbapenemase-producing Gram-negative bacteria (CR/CP- GNB) faecal carriage and associated risk factors among hospitalized and non-hospitalized patients in a county referral hospital, Kenya. Methods We adopted a cross-sectional study design, from June to September 2022. By systematic random sampling, we recruited 310 adult patients, equally from hospitalized and non-hospitalized patients, excluding those presenting with diarrhoea, ≤ 48 hours-antibiotic history, admitted for < 72 hours, and declining consent. We collected sociodemographic and clinical data using structured questionnaire, and stool samples in sterile containers and transported in an icebox to Kenya Medical Research Institute, Nairobi, and analysed, within 4–6 hours, using the standard and automated bacteriological methods. Results Overall CR-GNB carriage rate was 5.8%, predominantly among hospitalized (4.8%) patients. Acinetobacter baumannii and Enterobacter cloacae subsp. dissolvens (33.3% respectively) were the predominant isolates. All CR-GNB were MDR, carbapenemase producers, and third-generation cephalosporins resistant (100% ceftriaxone- and cefotaxime-resistant). Factors associated with CR/CP-GNB carriage were: occupation (aOR = 21, Cl = 95%,p = 0.007), travel history (aOR = 151.4, Cl = 95%,p = 0.002), water source (aOR = 163.7, Cl = 95%, p = 0.033) and treatment method (aOR = 0.0041, Cl = 95%, p = 0.025), and toilet type: pit (aOR = 0.027, Cl = 95%,p = 0.01) or pit and flush (aOR = 0.0332, Cl = 95%,p = 0.025). Conclusion This study highlights a public health risk posed by the faecal carriage of multidrug-resistant CP-GNB, dominated by third-generation cephalosporins resistant strains in community and hospital settings, with participant’s occupation, travel history, water source and treatment type, type of toilet as risk factors for carriage. Our finding calls for urgent and stringent prevention and control interventions through regular and continuous surveillance to mitigate further spread of the CR/CP-GNB ‘superbugs’, and strengthen antibiotic stewardship programs in this study area and beyond.

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“…Recent studies have shown that the degree of intestinal colonization by opportunistic pathogens, especially ESBL- and carbapenemase-producers, can have a direct effect on infection and mortality rates ( Dahdouh et al., 2021 ; Migliorini et al., 2022 ; Pérez-Nadales et al., 2022 ). Moreover, this colonization can be occult, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…present at such low amounts that it is not detected by traditional culture media, but has the potential to quickly expand and dominate the intestinal microbiome in response to antibiotic pressure ( Sim et al., 2022 ). Previous studies have shown associations between high intestinal Relative Loads (RLs) of carbapenemase-producing Klebsiella pneumoniae , antibiotic consumption, and development of infections in hospitalized adult patient populations ( Migliorini et al., 2022 ;, Lázaro-Perona et al., 2020 ), and in pediatric liver transplant patients ( Dahdouh et al., 2022 ). The aim of this study is to use the qPCR assay developed and validated in these previous studies to determine the relationship between the intestinal RLs of selected ESBL and carbapenemase genes, antibiotic consumption, occult colonization, gut microbiome dysbiosis, and extra-intestinal spread of MDROs among critically ill pediatric patients.…”

Section: Introductionmentioning

confidence: 99%

Intestinal loads of extended-spectrum beta-lactamase and Carbapenemase genes in critically ill pediatric patients

Cendejas-Bueno

Ruiz‐Carrascoso

Schüffelmann

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionIntestinal colonization by Multi-Drug Resistant Organisms (MDROs) can pose a threat on the health of critically ill patients. The extent of colonization by these organisms is related to previous antibiotic treatments and their ability to cause infections among adult patients. The aim of this study is to determine the relationship between the intestinal Relative Loads (RLs) of selected antibiotic resistance genes, antibiotic consumption and extra-intestinal spread among critically ill pediatric patients.MethodsRLs of blaCTX-M-1-Family, blaOXA-1, blaOXA-48 and blaVIM were determined in 382 rectal swabs obtained from 90 pediatric critically ill patients using qPCRs. The RLs were compared to the patients’ demographics, antibiotic consumption, and detection of MDROs from extra-intestinal sites. 16SrDNA metagenomic sequencing was performed for 40 samples and clonality analyses were done for representative isolates.Results and discussion76 (74.45%) patients from which 340 (89.01%) rectal swabs were collected had at least one swab that was positive for one of the tested genes. Routine cultures did not identify carbapenemases in 32 (45.1%) and 78 (58.2%) swabs that were positive by PCR for blaOXA-48 and blaVIM, respectively. RLs of above 6.5% were associated with extra-intestinal spread of blaOXA-48-harboring MDROs. Consumption of carbapenems, non-carbapenem β-lactams, and glycopeptides were statistically associated with testing negative for blaCTX-M-1-Family and blaOXA-1 while the consumption of trimethoprim/sulfamethoxazole and aminoglycosides was associated with testing negative for blaOXA-48 (P<0.05). In conclusion, targeted qPCRs can be used to determine the extent of intestinal dominance by antibiotic resistant opportunistic pathogens and their potential to cause extra-intestinal infections among a critically ill pediatric population.

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The Gastrointestinal Load of Carbapenem-Resistant Enterobacteriacea Is Associated With the Transition From Colonization to Infection by Klebsiella pneumoniae Isolates Harboring the blaKPC Gene

Cited by 13 publications

References 38 publications

Bloodstream Infections in Patients with Rectal Colonization by Carbapenem-Resistant Enterobacteriaceae: A Prospective Cohort Study

Bloodstream Infections in Patients with Rectal Colonization by Carbapenem-Resistant Enterobacteriaceae: A Prospective Cohort Study

Faecal carriage and risk factors of carbapenemase-producing gram-negative bacteria resistant to third-generation cephalosporins in hospitalized and non- hospitalized patients, Kenya

Intestinal loads of extended-spectrum beta-lactamase and Carbapenemase genes in critically ill pediatric patients

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