Characterizing carbapenemase-producing Escherichia coli isolates from Spain: high genetic heterogeneity and wide geographical spread.

Introduction: Carbapenemase-Producing Escherichia coli (CP-Eco) isolates, though less prevalent than other CP-Enterobacterales, have the capacity to rapidly disseminate antibiotic resistance genes (ARGs) and cause serious difficult-to-treat infections. The aim of this study is phenotypically and genotypically characterizing CP-Eco isolates collected from Spain to better understand their resistance mechanisms and population structure. Methods: Ninety representative isolates received from 2015 to 2020 from 25 provinces and 59 hospitals Spanish hospitals were included. Antibiotic susceptibility was determined according to EUCAST guidelines and whole-genome sequencing was performed. Antibiotic resistance and virulence-associated genes, phylogeny and population structure, and carbapenemase genes-carrying plasmids were analyzed. Results and discussion: The 90 CP-Eco isolates were highly polyclonal, where the most prevalent was ST131, detected in 14 (15.6%) of the isolates. The carbapenemase genes detected were bla OXA-48 (45.6%), bla VIM-1 (23.3%), bla NDM-1 (7.8%), bla KPC-3 (6.7%), and bla NDM-5 (6.7%). Forty (44.4%) were resistant to 6 or more antibiotic groups and the most active antibiotics were colistin (98.9%), plazomicin (92.2%) and cefiderocol (92.2%). Four of the seven cefiderocol-resistant isolates belonged to ST167 and six harbored bla NDM. Five of the plazomicin-resistant isolates harbored rmt. IncL plasmids were the most frequent (45.7%) and eight of these harbored bla VIM-1. bla OXA-48 was found in IncF plasmids in eight isolates. Metallo-ß-lactamases were more frequent in isolates with resistance to six or more antibiotic groups, with their genes often present on the same plasmid/integron. ST131 isolates were associated with sat and pap virulence genes. This study highlights the genetic versatility of CP-Eco and its potential to disseminate ARGs and cause community and nosocomial infections.

Candida auris inpatient screening in collaboration with the public health department.

Candida auris is a multidrug-resistant fungal pathogen that is associated with nosocomial outbreaks in patients with extensive health care exposure and treatment outside the United States. The Ohio Department of Health recommends C auris screening in high-risk patients. However, this can be operationally difficult for many health care facilities. This report describes a C auris and carbapenem-resistant Enterobacterales inpatient screening program done in collaboration with state public health.

Expansion and transmission dynamics of high risk carbapenem-resistant Klebsiella pneumoniae subclones in China: An epidemiological, spatial, genomic analysis.

AIMS: Carbapenem-resistant Klebsiella pneumonia (CRKP) is a global threat that varies by region. The global distribution, evolution, and clinical implications of the ST11 CRKP clone remain obscure. METHODS: We conducted a multicenter molecular epidemiological survey using isolates obtained from 28 provinces and municipalities across China between 2011 and 2021. We integrated sequences from public databases and performed genetic epidemiology analysis of ST11 CRKP. RESULTS: Among ST11 CRKP, KL64 serotypes exhibited considerable expansion, increasing from 1.54% to 46.08% between 2011 and 2021. Combining our data with public databases, the phylogenetic and phylogeography analyses indicated that ST11 CRKP appeared in the Americas in 1996 and spread worldwide, with key clones progressing from China's southeastern coast to the inland by 2010. Global phylogenetic analysis showed that ST11 KL64 CRKP has evolved to a virulent, resistant clade with notable regional spread. Single-nucleotide polymorphism (SNP) analysis identified BMPPS (bmr3, mltC, pyrB, ppsC, and sdaC) as a key marker for this clade. The BMPPS SNP clade is associated with high mortality and has strong anti-phagocytic and competitive traits in vitro. CONCLUSIONS: The high-risk ST11 KL64 CRKP subclone showed strong expansion potential and survival advantages, probably owing to genetic factors.

A practical approach to screening for carbapenemase-producing Enterobacterales- views of a group of multidisciplinary experts from English hospitals.

INTRODUCTION: Carbapenemase-producing Enterobacterales (CPE) are an important public health threat, with costly operational and economic consequences for NHS Integrated Care Systems and NHS Trusts. UK Health Security Agency guidelines recommend that Trusts use locally developed risk assessments to accurately identify high-risk individuals for screening, and implement the most appropriate method of testing, but this presents many challenges. METHODS: A convenience sample of cross-specialty experts from across England met to discuss the barriers and practical solutions to implementing UK Health Security Agency framework into operational and clinical workflows. The group derived responses to six key questions that are frequently asked about screening for CPE. KEY FINDINGS: Four patient groups were identified for CPE screening: high-risk unplanned admissions, high-risk elective admissions, patients in high-risk units, and known positive contacts. Rapid molecular testing is a preferred screening method for some of these settings, offering faster turnaround times and more accurate results than culture-based testing. It is important to stimulate action now, as several lessons can be learnt from screening during the COVID-19 pandemic, as well as from CPE outbreaks. CONCLUSION: Further decisive and instructive information is needed to establish CPE screening protocols based on local epidemiology and risk factors. Local management should continually evaluate local epidemiology, analysing data and undertaking frequent prevalence studies to understand risks, and prepare resources- such as upscaled screening- to prevent increasing prevalence, clusters or outbreaks. Rapid molecular-based methods will be a crucial part of these considerations, as they can reduce unnecessary isolation and opportunity costs.

A predictive score for the result of carbapenem-resistant Enterobacterales and vancomycin-resistant enterococci screening.

BACKGROUND: The duration of extensively drug-resistant bacteria (XDR) carriage depends on several factors for which the information can be difficult to recover. AIM: To determine whether past screening and clinical results of patients can predict the results of subsequent screening. METHODS: In total, 256 patients were retrospectively included from 10 healthcare centres in France from January 2014 to January 2022. We created a predictive clearance score, ranging from -5 to +7, that included the number of XDR species and the type of resistance detected in the sample, as well as the time from the last positive sample, the number of previous consecutive negative samples, and obtaining at least one negative PCR result in the collection. This score could be used for the upcoming rectal screening of a patient carrying an XDR as soon as the last screening sample was negative. FINDINGS: The negative predictive value was >99% for score ≤0. The median time to achieve XDR clearance was significantly shorter for a score of 0 (443 days (259-705)) than that based on previously published criteria. CONCLUSION: This predictive score shows high performance for the assessment of XDR clearance. Relative to previous guidelines, it could help to lift specific infection prevention and control measures earlier. Nevertheless, the decision should be made according to other factors, such as antimicrobial use and adherence to hand hygiene.

The Natural History of Carbapenemase-Producing Enterobacterales: Progression From Carriage of Various Carbapenemases to Bloodstream Infection.

BACKGROUND: Little is known about the risk of progression from carbapenemase-producing Enterobacterales (CPE) carriage to CPE bloodstream infection (BSI) outside of high-risk settings. We aimed to determine the incidence of CPE BSI among CPE carriers and to assess whether the incidence differs by carbapenemase, species, and setting. METHODS: We conducted a nationwide population-based retrospective cohort study using national databases. The cohort consisted of all patients in Israel with CPE detected by screening from 1 January 2020 to 10 October 2022. We calculated the cumulative incidence of CPE BSI within 1 year among CPE carriers. We used a competing-risks model with BSI as the outcome and death as the competing risk. RESULTS: The study included 6828 CPE carriers. The cumulative incidence of CPE BSI was 2.4% (95% confidence interval [CI], 2.1-2.8). Compared with Klebsiella pneumoniae carbapenemase (KPC), the subhazard of BSI was lower for New Delhi metallo-ß-lactamase (NDM) (adjusted subhazard ratio [aSHR], 0.72; 95% CI, .49-1.05) and oxacillinase-48-like (OXA-48-like) (aSHR, 0.60; 95% CI, .32-1.12) but these differences did not reach statistical significance. Compared with K. pneumoniae, the subhazard of BSI was lower for carriers of carbapenemase-producing Escherichia coli (aSHR, 0.33; 95% CI, .21-.52). The subhazard of BSI was higher among patients with CPE carriage first detected in intensive care units (aSHR, 2.10; 95% CI, 1.27-3.49) or oncology/hematology wards (aSHR, 3.95; 95% CI, 2.51-6.22) compared with medical wards. CONCLUSIONS: The risk of CPE BSI among CPE carriers is lower than previously reported in studies that focused on high-risk patients and settings. The risk of BSI differs significantly by bacterial species and setting, but not by carbapenemase.

Colistin versus polymyxin B for the treatment of carbapenem-resistant Klebsiella pneumoniae bloodstream infections.

BACKGROUND: To assess the effectiveness of colistin (administered as colistimethate sodium-CMS) and polymyxin B (PMB) for the treatment of bloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). MATERIALS AND METHODS: This retrospective cohort included hospitalized adult patients with CRKP BSIs from a single tertiary-care hospital. A univariate analysis comparing CMS and PMB groups was carried out and an inverse-probability propensity score (IPPS) was created. An IPPS-adjusted Cox regression model for 30-day mortality was performed including covariates potentially associated with mortality. RESULTS: A total of 100 patients with CRKP BSI (87 were KPC-producing isolates) were included. The 30-day mortality was 42.0 %:17/46 (38.8 %) and 25/54 (44.6 %) patients of CMS and PMB groups, respectively, P = 0.54 (incidence rate, 18.9 and 21.7/1000 patients-day in CMS and PMB groups, respectively, P = 0.62). No statistically significant difference in 30-day mortality rate was observed in a model adjusted for Pitt bacteremia score, high-risk primary site and IPPS, which included age, intensive care unit admission, minimal inhibitory concentration, previous colonization by CRKP, diabetes mellitus, malignancy, neutropenia, meropenem use before BSI, adjuvant therapy with meropenem and amikacin, and time to start polymyxin. Acute kidney injury (AKI) occurred in 52.0 % of patients, with no significant differences between groups (47.8 % and 57.4 % for CMS and PMB, respectively, P = 0.83). In-hospital mortality was 47,7 % and 50.0 % in CMS and PMB groups, respectively, P = 0.82. CONCLUSION: There was no difference in 30-day mortality and AKI rates among patients with CRKP BSI treated with PMB or CMS.

Enterobacterales resistentes a carbapenemes: estudio epidemiológico de aislamientos en un hospital público de Santa Fe / Carbapenem-resistant Enterobacterales: Epidemiological study of isolates in a public hospital in Santa Fe

Introducción: La incidencia de Enterobacterales resistentes a carbapenemes (ERC) se elevó en la última década, y en especial durante la pandemia de COVID-19. Objetivo: Conocer el perfil de resistencia antimicrobiana, así como la frecuencia y tipo de carbapenemasas presen-tes en los aislamientos de ERC en un hospital regional.Materiales y métodos: Estudio epidemiológico, observa-cional y retrospectivo. Incluyó ERC aislados en muestras clínicas durante 2021 en un hospital regional de Santa Fe, Argentina. El cálculo de la incidencia (aislamientos/pacien-tes-día) e intervalo de confianza 95% (IC 95%), y las pruebas estadísticas se realizaron con OpenEpi.Resultados: 348 ERC aislados (11,9 aislamientos/1000 pacientes-día; IC95% 10,7-13,2). La incidencia se correla-cionó con los casos de COVID-19 (rho=0,874, p<0,001) y fue a expensas de la Unidad de Cuidados Intensivos (76,4%). El principal ERC aislado fue Klebsiella pneumoniae (71,4%, n=260). KPC fue el principal mecanismo de resistencia (61,2%). Se aislaron dos doble productores de carbapene-masas. La tasa global de resistencia a los antibióticos no betalactámicos evaluados fue superior en Klebsiella pneu-moniae que en el resto de los aislamientos resistentes a carbapenemes (60,6% vs. 38,5%, p<0,001). En KPC hubo mayor resistencia a colistin (44,6% vs. 23,9%, p=0,001) y menor a amikacina (23,9% vs. 72,6%, p<0,001).Conclusión: Frente a las escasas opciones terapéuticas en infecciones por ERC se destaca la importancia de conocer los mecanismos de resistencia implicados y la epidemiología local

Introduction: The incidence of carbapenem-resistant Enterobacterales (CRE) rose in the last decade, and especially during the COVID-19 pandemic.Objective: To identify the antimicrobial resistance profile, as well as the frequency and type of carbapenems that were present in CRE isolations in a tertiary care hospital.Materials and methods: Epidemiological, observational and retrospective study. It included CRE isolated in clinical samples during 2021 in a tertiary care hospital in Argentina. Incidences (isolations/patients-day), confidence intervals of 95% (CI 95%) and statistical comparisons were made with OpenEpi.Results: 348 CRE were isolated (11.9 isolations/1,000 patients-day, IC95% 10.7-13.2). Incidence correlated to COVID-19 cases (rho=0.874, p<0.001). Most isolations were from the Intensive Care Unit (76.4%) and the from respiratory samples (27.6%, n=96) and blood cultures (24.4%, n=92). The main isolated CRE was Klebsiella pneumoniae (71.4%, n=260), with a general carbapenem resistance of 53.4%. KPC was the main resistance mechanism (61.2%). Two double carbapenemase-producing Enterobacterales were isolated. Klebsiella pneumoniae presented a higher overall resistance rate to non-betalactam antibiotics (60.6% vs 38.5%, p<0.001). Among CRE, a higher colistin resistance rate was found in KPC isolations (44.6% vs 23.9%, p=0.001) and lower resistance to amikacin (23.9% vs 72.6%, p<0.001).Conclusion: The difficulty in the selection of antibiotic regimens for CRE forces the treating physicians to put emphasis on the knowledge of resistance mechanisms to optimize them

Rapid Detection of Carbapenemase-producing Enterobacteriaceae From Blood Culture Bottles of Known CPE Carriers: Real-world Experience.

We used a rapid antigen test for the detection of carbapenemases directly from positive blood culture bottles of pediatric hemato-oncologic patients, known carriers of carbapenemase-producing enterobacteriaceae. Resistance mechanism was detected within 15 minutes of observing Gram-negative bacilli from a positive bottle, leading to treatment modification. This simple-to-use, inexpensive assay shortens the interval between empiric to tailored antimicrobial therapy.

Enterobacterales productores de carbapenemasas en sifones de lavamanos de una Unidad de Paciente Crítico / Carbapenemase-producing Enterobacterales in the sink traps of a Critical Patient Unit

INTRODUCCIÓN: Enterobacterales productores de carbapenemasas (EPC) son una importante causa de infecciones asociadas a la atención en salud (IAAS). El principal reservorio de EPC lo constituyen pacientes infectados y colonizados, sin embargo, también se han identificado reservorios ambientales. OBJETIVO: Detectar la presencia de EPC en los sifones de lavamanos de la unidad de cuidados críticos de pacientes quemados adultos (UPC QMD) y unidad de cuidados críticos de pacientes pediátricos crónicos (UCEP). MÉTODO: Se recolectaron cuatro muestras de sifones de los lavamanos ubicados en el interior de las unidades de pacientes en UCEP y 10 de UPC QMD. A las muestras se les realizó estudio fenotípico y molecular para detección de carbapenemasas en el Instituto de Salud Pública de Chile. RESULTADOS: En los sifones estudiados de UCEP no se aislaron cepas de EPC. En UPC QMD, 50% de los sifones estudiados se aislaron cepas de EPC. CONCLUSIONES: En UPC QMD se objetivó la presencia de EPC en una alta proporción de los sifones de lavamanos testeados, lo que demuestra un reservorio ambiental de bacterias multi-resistentes.

INTRODUCTION: Carbapenemase-producing Enterobacterales (CPE) are an important cause of health care associated infections (HAI). The main reservoir is constituted by infected and colonized patients; however, environmental reservoirs have also been identified. OBJECTIVE: To detect the presence of CPE in the sink traps of the critical care unit for adult burn patients (UPC QMD) and the critical care unit for chronic pediatric patients (UCEP). MATERIAL AND METHOD: Four samples of trap were collected from the sinks located inside the patient units at PICU and 10 at UPC QMD. The samples underwent a phenotypic and molecular study for the detection of carbapenemases at the Institute of Public Health of Chile. RESULTS: In the UCEP no EPC strains were isolated. In UPC QMD, CPE was detected in 50% of the traps. CONCLUSIONS: In UPC QMD, the presence of CPE was observed in a high proportion of the tested sinks traps, which shows an environmental reservoir of multi-resistant bacteria.

Effectiveness of surveillance cultures for high priority multidrug-resistant bacteria in hematopoietic stem cell transplant units.

Surveillance strategies to detect colonization are an important tool to prevent and control the spread of microorganisms in hematopoietic stem cell transplant (HSCT) units. The aim of this study was to evaluate routine surveillance cultures for screening colonization and infection by carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPa), and vancomycin-resistant enterococci (VRE). Surveillance cultures were collected (1,323 samples) from 200 patients admitted to an HSCT unit over one year; swabs were taken on admission and then weekly. We compared the positivity of cultures for each site, agent, clinical and epidemiological data according to the colonization status. Infection due to multidrug-resistant organisms (MDROs) occurred in 52 (21.5%) patients, 45 (86.5%) due to blood stream infection; 12 (23%) patients had a positive surveillance culture before the infection. Cultures of 554 (41.8%) samples were performed for CRPa, 413 (31.2%) for VRE and 356 (27%) for CRE. Of these, 179 (13.5%) were positive. Colonization by any MDRO, CRE or CRPa was associated with increased risk of infection (P < 0.05), but not with death. Previous colonization by an MDRO was a significant risk for infection by these pathogens, specially by CRE. Overall, rectal swabs had the highest positivity rate compared with other sites, oropharynx swabs were an option for CRPa, and fecal cultures showed low positivity. Although the impact of the strategy on the mortality of patients undergoing HSCT is not clear, routine VRE surveillance should be questioned with regard to patients undergoing auto-HSCT due to the additional cost and little impact on survival rates.

Carbapenem-resistant Klebsiella pneumoniae colonization and infection is associated with lower overall survival in a cohort of haematopoietic stem-cell transplantation patients: mechanism of resistance and virulence by whole-genome sequencing.

Carbapenem-resistant Klebsiella pneumoniae (CRK) infections are a growing concern in immunocompromised patients. The aim of the present study was to evaluate the impact of CRK colonization and infection in overall mortality for haematopoietic stem-cell transplant (HSCT) patients. We also aimed to investigate resistance and virulence profiles of CRK isolates and assess their epidemiological and genetic relatedness. Patients in the HSCT unit were screened for colonization with CRK with weekly rectal swab or stool cultures and placed under contact precautions. We defined CRK colonization as positive culture from a swab or stool sample grown in MacConkey agar with meropenem at 1 µg ml-1. Demographic and clinical data were retrieved from the patients' charts and electronic records. According to resistance mechanisms and pulsed field gel electrophoresis profile, isolates were selected based on whole-genome sequencing (WGS) using MiSeq Illumina. Outcomes were defined as overall mortality (death up to D+100), and infection-related death (within 14 days of infection). We report a retrospective cohort of 569 haematopoietic stem-cell transplant patients with 105 (18.4 %) CRK colonizations and 30 (5.3 %) infections. blaKPC was the most frequent carbapenemase in our cohort with three isolates co-harbouring blaKPC and blaNDM. We found no difference in virulence profiles from the CRK isolates. There were also no significant differences in virulence profiles among colonization and infection isolates regarding genes encoding for type 1 and 3 fimbriae, siderophores, lipopolysaccharide and colibactin. In clonality analysis by PFGE and WGS, isolates were polyclonal and ST340 was the most prevalent. Overall survival at D+100 was 75.4 % in in CRK-colonized (P=0.02) and 35.7 % in infected patients and significantly lower than non-colonized patients (85.8 %; P<0.001). We found a higher overall mortality associated with colonization and infection; KPC was the main resistance mechanism for carbapenems. The polyclonal distribution of isolates and findings of CRK infection in patients not previously colonized suggest the need to reinforce antibiotic stewardship.

Epidemiology, risk factors, and prediction score of carbapenem resistance among inpatients colonized or infected with 3rd generation cephalosporin resistant Enterobacterales.

In this study, we determined the incidence and risk factors of Carbapenem-resistant Enterobacterales (CRE) acquisition in inpatients with 3rd generation cephalosporin-resistant (3GCR) Enterobacterales at a tertiary-care hospital in Lebanon, and suggested a risk prediction score for it. This is a retrospective matched case-control study of inpatients with 3GCR Enterobacterales that are carbapenem resistant (cases) versus those with carbapenem-sensitive isolates (controls). Data analysis was performed on IBM SPSS program, version 23.0 (Armonk, NY, USA: IBM Corp.). Categorical variables were compared between cases and controls through bivariate analysis and those with statistical significance (P < 0.05) were included in the forward stepwise multiple logistic regression analysis. To develop the CRE acquisition risk score, variables that maintained statistical significance in the multivariate model were assigned a point value corresponding to the odds ratio (OR) divided by the smallest OR identified in the regression model, and the resulting quotient was multiplied by two and rounded to the nearest whole number. Summation of the points generated by the calculated risk factors resulted in a quantitative score that was assigned to each patient in the database. Predictive performance was determined by assessing discrimination and calibration. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for different cutoffs of the score. The incidence of CRE acquisition significantly increased with time from 0.21 cases/1000 patient-days (PD) in 2015 to 1.89 cases/1000PD in 2019 (r2 = 0.789, P = 0.041). Multivariate analysis of matched data revealed that the history of cerebrovascular disease (OR 1.96; 95% CI 1.04-3.70; P = 0.039), hematopoietic cells transplantation (OR 7.75; 95% CI 1.52-39.36; P = 0.014), presence of a chronic wound (OR 3.38; 95% CI 1.73-6.50; P < 0.001), endoscopy done during the 3 months preceding the index hospitalization (OR 2.96; 95% CI 1.51-4.73; P = 0.01), nosocomial site of acquisition of the organism in question (OR 2.68; 95% CI 1.51-4.73; P = 0.001), and the prior use of meropenem within 3 months of CRE acquisition (OR 5.70; 95% CI 2.61-12.43; P < 0.001) were independent risk factors for CRE acquisition. A risk score ranging from 0 to 25 was developed based on these independent variables. At a cut-off of ≥ 5 points, the model exhibited a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 64.5%, 85.8%, 82%, 70.7% and 75%, respectively. We also showed that only meropenem consumption intensity and CRE acquisition incidence density showed a strong positive correlation(r = 0.798, P = 0.106), unlike imipenem (r = - 0.868, P = 0.056) and ertapenem (r = 0.385, P = 0.522). Patients with a score of ≥ 5 points in our model were likely to acquire CRE. Only meropenem was associated with CRE carriage. Our proposed risk prediction score would help target surveillance screening for CRE amongst inpatients at the time of hospital admission and properly guide clinicians on using anti-CRE therapy.

Preliminary exploration on the serum biomarkers of bloodstream infection with carbapenem-resistant Klebsiella pneumoniae based on mass spectrometry.

BACKGROUND: Carbapenem-resistant K. pneumoniae (CRKP) bloodstream infections (BSI) must be rapidly identified to improve patient survival rates. This study investigated a new mass spectrometry-based method for improving the identification of CRKP BSI and explored potential biomarkers that could differentiate CRKP BSI from sensitive. METHODS: Mouse models of BSI were first established. MALDI-TOF MS was then used to profile serum peptides in CRKP BSI versus normal samples before applying BioExplorer software to establish a diagnostic model to distinguish CRKP from normal. The diagnostic value of the model was then tested against 32 clinical CRKP BSI and 27 healthy serum samples. Finally, the identities of the polypeptides used to establish the diagnostic model were determined by secondary mass spectrometry. RESULTS: 107 peptide peaks were shared between the CRKP and normal groups, with 18 peaks found to be differentially expressed. Five highly expressed peptides in the CRKP group (m/z 1349.8, 2091.3, 2908.2, 4102.1, and 8129.5) were chosen to establish a diagnostic model. The accuracy, specificity and sensitivity of the model were determined as 79.66%, 81.48%, and 78.12%, respectively. Secondary mass spectrometry identified the Fibrinogen alpha chain (FGA), Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and Serum amyloid A-2 protein (SAA2) as the source of the 5 serum peptides. CONCLUSIONS: We successfully established a serum peptide-based diagnostic model that distinguished clinical CRKP BSI samples from normal healthy controls. The application of MALDI-TOF MS to measure serum peptides, therefore, represents a promising approach for early BSI diagnosis of BSI, especially for multidrug-resistant bacteria where identification is urgent.

Tandem fecal microbiota transplantation cycles in an allogeneic hematopoietic stem cell transplant recipient targeting carbapenem-resistant Enterobacteriaceae colonization: a case report and literature review.

BACKGROUND: Due to limited antibiotic options, carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with high non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Also, intestinal CRE colonization is a risk factor for subsequent CRE infection. Several clinical studies have reported successful fecal microbiota transplantation (FMT) for the gut decontamination of a variety of multidrug-resistant bacteria (MDRB), even in immunosuppressed patients. Similarly, other studies have also indicated that multiple FMTs may increase or lead to successful therapeutic outcomes. CASE PRESENTATION: We report CRE colonization in an allo-HSCT patient with recurrent CRE infections, and its successful eradication using tandem FMT cycles at 488 days after allo-HSCT. We also performed a comprehensive microbiota analysis. No acute or delayed adverse events (AEs) were observed. The patient remained clinically stable with CRE-negative stool culture at 26-month follow-up. Our analyses also showed some gut microbiota reconstruction. We also reviewed the current literature on decolonization strategies for CRE. CONCLUSIONS: CRE colonization led to a high no-relapse mortality after allo-HSCT; however, well-established decolonization strategies are currently lacking. The successful decolonization of this patient suggests that multiple FMT cycles may be potential options for CRE decolonization.

Incidence and risk factors of carbapenem-resistant Enterobacteriaceae infection in intensive care units: a matched case-control study.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) infection is associated with intensive care admissions, morbidity, and mortality. Our study aimed to determine the incidence, risk factors, and patient outcomes of CRE in the ICU units. METHODS: This was a retrospective matched case-control study of patients admitted to ICUs. Patients who have positive cultures of CRE and carbapenem-susceptible Enterobacteriaceae (CSE) were included in the study. Patients were randomly selected from a pool of CSE subjects in a ratio of 1:1 of CRE to CSE as control patients. RESULTS: The infection rate with CRE among all patients admitted to ICUs was 7.6% and the incidence of CRE infection was 5.6 per 1,000 person-day. The risk factors independently associated with CRE infection were: Higher Sequential Organ Failure Assessment (SOFA) and Nutrition Risk in Critically ill (NUTRIC) scores, prolonged ICU length of stay (LOS), previous surgery, dialysis and mechanical ventilation during ICU stay, and previous use of aminoglycoside and carbapenems. CONCLUSION: In this retrospective study, the incidence of CRE infection was relatively elevated in patients admitted to ICU. Patients with high SOFA and NUTRIC scores, prolonged ICU LOS, previous surgery, dialysis and mechanical ventilation, and prior aminoglycosides and carbapenems use, may have an increased risk of CRE infection.

Epidemiology and risk factors of rectal colonization of carbapenemase-producing Enterobacteriaceae among high-risk patients from ICU and HSCT wards in a university hospital.

BACKGROUND: Nosocomial carbapenemase-producing Enterobacterieceae (CPE) infections constitute a major global health concern and are associated with increased morbidity and mortality. Rectal colonization with CPE is a risk factor for bacterial translocation leading to subsequent endogenous CPE infections. This prospective observational study was aimed to investigate the prevalence and epidemiology of rectal colonization of CPE, the carbapenemase genotypes, and to identify the independent risk factors for the acquisition of CPE colonization in high-risk patients from ICU and HSCT wards in a university hospital in China. METHODS: In a prospective cohort study, 150 fecal samples from rectal swabs were consecutively obtained for inpatients from the intensive care unit (ICU) and hematopoietic stem cell transplantation (HSCT) wards from November 2018 to May 2019, and screening test for CPE was conducted by using prepared in-house trypsin soybean broth (TSB) selective media and MacConkey agar. Antimicrobial susceptibility was determined by the broth microdilution method and carbapenemase genes were characterized by both the GeneXpert Carba-R and PCR for blaKPC, blaNDM, blaIMP, blaVIM and blaOXA. Multi-locus sequence typing (MLST) was employed to characterize the genetic relationships among the carbapenemase-producing K. Pneumonia (CPKP) isolates. In order to further investigate the risk factors and clinical outcomes of CPE colonization, a prospective case-control study was also performed. RESULTS: Twenty-six suspected CPE strains, including 17 Klebsiella pneumoniae, 6 Escherichia coli, 1 Citrobacter freundii, 1 Enterobacter Kobe, and 1 Raoultella ornithinolytica, were identified in 25 non-duplicated rectal swab samples from 25 patients, with a carriage rate of 16.67% (25/150). Through GeneXpert Carba-R and subsequent PCR and sequencing, all the suspected CPE isolates were identified to be positive for the carbapenemase genes, of which 17 were blaKPC-carriers, and another 9 were blaNDM-producers. MLST designated all the CPKP isolates to be ST11 clone. Multivariate analysis indicated that urinary system diseases, operation of bronchoscopy, and combined use of antibiotics were independent risk factors for acquiring CPE colonization in high-risk patients from the ICU and HSCT wards. CONCLUSIONS: This study revealed a high prevalence of rectal CPE colonization in high-risk patients from ICU and HSCT wards, and a predominant colonization of the KPC-producing K. pneumoniae clone ST11. Stricter infection control measures are urgently needed to limit the dissemination of CPE strains, especially in patients who were afflicted by urinary system diseases, have underwent bronchoscopy, and were previously exposed to combined antibiotic use.

[Clinical characteristics of carbapenem-resistant Enterobacteriaceae infection in pediatric liver transplantation recipients].

Objective: To explore the clinical features and treatment of carbapenem-resistant Enterobacteriaceae (CRE) infection in pediatric liver transplantation recipients and discuss the significance of CRE colonization by screening with rectal swabs. Methods: A total of 286 cases of pediatic liver transplantation recipients, who came from Tianjin First Central Hospital during August 1,2017 to August 1, 2018, were retrospectively investigated. The clinical characteristics, antibiotic susceptibity test, treatment outcomes and prognosis of CRE infection patients were analyzed. CRE colonization were screened by rectal swabs after liver transplantation. All cases were divided into CRE colonization group and non-CRE colonization group based on CRE colonization results. The high risk factors of CRE colonization and its relationship with CRE infection were investigated. χ(2) test was used for the comparison between groups.The single-factor analysis was used to screen risk factors. Results: The 286 cases included 132 male and 154 female cases. The age was (8±4) months.CRE infection rate after liver transplantation was 7.3% (21/286). The time of CRE infection was the 5(th) (1(th)-14(th)) days after transplantation. Abdominal infection was the most common (95.2%, 20/21), followed by bloodstream infection (12 cases) and pulmonary infection (8 cases). Infection in two or more sites accounted for 71.4% (15/21); 27 CRE strains, in which 24 strains were carbapenem-resistant Klebsiella pneumonia (88.9%), 2 strains were carbapenem-resistant Escherichia coli (7.4%) and one strain was carbapenem-resistant Enterobacter aerogenes (3.7%). The drug resistance rate of CRE strains to carbapenems, penicillin antibiotics, second-and third-generation cephalosporin was 100.0%. Medication treatment included meropenem+fosfomycin (13 cases) and meropenem+tegacycline (8 cases). The treatment was effective in 16 cases and the time was 19 (1-27) d. The 1-year survival rate among CRE infection group and non-CRE infection group were 71.4% (15/21) and 98.1% (260/265), respectively (χ(2)=37.460, P<0.01). CRE infection rate among CRE colonization group and non-CRE colonization group were 26.4% (19/72) and 0.9% (2/214), respectively (χ(2)=51.300, P<0.01). Factors before transplantation, including third-generation cephalosporin or carbapenems exposure, prolonged hospital stay within 3 months, CRE infection, and factors after transplantation, including emergency surgery, mechanical ventilation more than 24 hours (χ(2)=20.570, 6.411, 13.960, 14.600, 9.560, all P<0.01) were high risk factors for CRE colonization. Conclusions: The prognosis of CRE infection after pediatric liver transplantation is poor. Timely diagnosis and treatment are of great importance. Much attention should be paid on CRE rectal colonization and its risk factors. Screening of CRE colonization is important for early warning and control of CRE infection.

Five-year change of prevalence and risk factors for infection and mortality of carbapenem-resistant Klebsiella pneumoniae bloodstream infection in a tertiary hospital in North China.

BACKGROUND: There are few studies focused on carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI). The aim of this study is to identify the prevalence and risk factors for infection and mortality of CRKP BSI. METHODS: Susceptibility of Klebsiella pneumoniae (KP) isolated from blood samples and the proportion of CRKP were recorded annually. One hundred sixty-four patients with CRKP and 328 with carbapenem-susceptible Klebsiella pneumoniae (CSKP) BSI were categorized as the case group and control group to identify risk factors for CRKP infection and mortality by univariable analysis and multivariable logistic-regression analysis. RESULTS: The proportion and mortality of CRKP BSI increased significantly, with the percentage of KP in BSI increasing from 7 to 12% from 2014 to 2019 with a concomitant resistance to meropenem increasing from 16.7 to 41.8%. Compared with CSKP group, patients in CRKP group had longer hospitalization time before bacteremia (median 14 vs 4, P < 0.001) and longer total hospitalization time (median 31 vs 19, P < 0.001). The proportion of admission to ICU was higher (70.7% vs 17.7%, P < 0.001), and APACHE II score was higher (median 12 vs 8, P < 0.001). The mortality in CRKP group was 43.9% (72/164), while 14.9% (49/328) in CSKP group (p < 0.001). KP detection in other sites(P = 0.036, OR 1.964), blood purification(P = 0.018, OR 3.326), bronchoscopy(P = 0.011, OR 5.423), surgery (P = 0.001, OR 3.084), carbapenem use(P = 0.001, OR 3.395), tigecycline use(P = 0.006, OR 4.595) were independent risk factors for CRKP BSI. Previous hospitalization (P = 0.048, OR 2.755), long hospitalization (P = 0.003, OR 1.035), bone marrow puncture (P = 0.037, OR3.856), use of ß-lactamase inhibitor (P = 0.005, OR 3.890) were independent risk factors for mortality in CRKP BSI. CONCLUSION: The prevalence and mortality of CRKP BSI are still increasing. Timely treatment of KP infection in other site, strengthening the hospital infection control of blood purification, bronchoscopy and surgery, control the use of carbapenem and tigecycline, may help to prevent CRKP BSI. More preventative hospital resources are needed for severely ill patients with prolonged hospitalizations and intensive care.

Different screening frequencies of carbapenem-resistant Enterobacteriaceae in patients undergoing hematopoietic stem cell transplantation: which one is better?

BACKGROUND: A consensus has been reached that carbapenem-resistant Enterobacteriaceae (CRE) screening in immunosuppressed individuals can reduce the incidence of CRE bloodstream infection (BSI). METHODS: We retrospectively studied the clinical data of 395 consecutive HSCT patients from September 2017 to April 2019. From September 2017 to June 2018 (period 1), 200 patients received single CRE screening before transplantation. From July 2018 to April 2019 (period 2), 195 patients received continuous weekly CRE screening after admission. For patients colonized with CRE, targeted managements were received: (1) contact precautions and (2) preemptive CRE-targeted treatment if necessary. RESULTS: During period 1, 3 patients with CRE colonization were detected (1.5%). The CRE BSI rate was 2.0% (4 patients), and the related 30-day mortality was 50.0% (2 out of 4 patients). During period 2, 21 patients with CRE colonization were detected, and the detection rate was significantly higher than that in period 1 (P < 0.001). Of the 21 colonized patients, 4 (19.0%) patients were identified as positive for CRE at the first screening, 5 (23.8%) were identified at the second screening, and the remaining 12 (57.1%) were identified at the third or later screening. The CRE BSI rate decreased to 0.5% (1/195), and there were no CRE-related death. Fifteen colonized patients developed neutropenic fever. Thirteen colonizers were preemptively treated with tigecycline within 24 h of fever onset, and they achieved rapid temperature control. One colonizer received tigecycline later than 48 h after fever onset and ultimately survived due to the addition of polymyxin. The other received tigecycline later than 72 h after fever onset and died of septic shock. CONCLUSION: The increase in screening frequency contributed to the detection of patients with CRE colonization. Targeted managements for these colonized patients may contribute to reducing the incidence and mortality of CRE BSI, therefore improving the prognosis of patients.