Colistin-resistant Klebsiella pneumoniae bloodstream infection: old drug, bad bug.

Multi-drug-resistant (MDR) Enterobacteriaceae pose a global threat to hospitalized patients. We report a series of colistin-resistant Klebsiella pneumoniae blood isolates from Israel and explore their resistance mechanisms using whole genome sequencing (WGS). Patients with colistin-resistant K. pneumoniae bloodstream infection (BSI) were identified during the period between 2006 and 2018. Demographic and clinical data were collected, and antibiotic susceptibility testing (AST) was performed using three commercial platforms. Long and short read sequencing were performed on a PacBio RS II (Pacific Biosciences) and an Illumina Miseq (Illumina), respectively. Thirteen patients with colistin-resistant K. pneumoniae BSI were identified, and seven isolates from seven different patients were successfully revived. Patient records indicated that five of the patients were previously treated with colistin. AST indicated that six of the seven isolates were colistin resistant and four of these isolates were resistant to carbapenems. WGS assigned the isolates to four distinct clusters that corresponded to in silico-derived multi-locus sequence types (MLST). Three isolates carried blaKPC-3 on two different plasmids and one carried blaOXA-48 on a novel IncL/M plasmid. All colistin-resistant isolates carried a variety of different mutations that inactivated the mgrB gene. We report the first comprehensive analysis of a series of colistin-resistant K. pneumoniae from Israel. A diverse set of isolates were obtained and colistin resistance was found to be attributed to different mechanisms that ablated the mgrB gene. Notably, carbapenemase genes were identified in four isolates and were carried on novel plasmids.

Rapid detection method of carbapenemase-producing Enterobacteriaceae by MALDI-TOF MS with imipenem/cilastatin (KB) disc and zinc sulfate solution.

INTRODUCTION: Carbapenemase-producing Enterobacteriaceae (CPE) is a major global health threat, and development of rapid detection methods is desired. Here, we established a cost-effective and relatively rapid CPE detection method using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). METHODS: We examined 134 CPE strains (IMP-type, NDM-type, VIM-type, KPC-type, OXA-48-like-type, and GES-type) and 107 non-CPE strains, previously confirmed by genetic tests. The proposed MALDI-TOF MS method involves mixing of a carbapenem drug [here, the commercially available imipenem (IPM) KB disc] and the bacterial strains to be tested, and the consequent drug hydrolysis owing to bacterial carbapenemase activity is confirmed by a waveform spectrum before and after 2 h of the mixing. As metallo-beta-lactamases require zinc in their active site, the false-negatives obtained from our method were cultured in presence of zinc sulfate solution and tested again. RESULTS: Based on the presence or absence of the IPM (+cyano-4-hydroxy-cinnamic acid)-specific waveform peak near 489.45 m/z (±500 ppm), the detection sensitivity and specificity of our method for CPE were determined to be 94.8% and 91.6%, respectively. Seven false-negatives of IMP-type (4), VIM-type (2), and GES-type (1) were found, of which the IMP- and VIM-types tested positive as CPE after culture with zinc sulfate solution. Thus, the overall detection sensitivity improved to 99.3%. CONCLUSION: Our study proposes a new approach for CPE detection using MALDI-TOF MS. Moreover, we propose cultivation of test strains with zinc sulfate solution for efficient detection of IMP-type CPE, not only for MALDI-TOF MS, but also for other detection methods.

Blood-Modified Carbapenem Inactivation Method: a Phenotypic Method for Detecting Carbapenemase-Producing Enterobacteriaceae Directly from Positive Blood Culture Broths.

A variant of the modified carbapenem inactivation method (mCIM) was developed to detect carbapenemase activity directly from positive blood culture broths. The method, termed "Blood-mCIM," was evaluated using Bactec blood culture bottles (Becton, Dickinson and Company, Franklin Lakes, NJ) inoculated with 27 different carbapenemase-producing Enterobacteriaceae (CPE) isolates and 34 different non-CPE isolates. The assay was positive for all blood culture broths inoculated with CPE isolates and negative for all blood culture broths inoculated with non-CPE isolates, corresponding to a diagnostic sensitivity and specificity of 100%, respectively. This assay is inexpensive using "off the shelf" reagents, does not require centrifugation or mechanical lysis, and can be readily implemented in any clinical microbiology laboratory. The Blood-mCIM should facilitate expedient administration of antimicrobial therapy targeted toward CPE bloodstream infections and assist infection control and public health surveillance.

Risk factors for carbapenem-resistant Enterobacteriaceae infections: a French case-control-control study.

This study aimed to assess characteristics associated with infections due to carbapenem-resistant Enterobacteriaceae (CRE), producing (CPE) or not producing (non-CPE) carbapenemase, among hospitalised patients in 2014-2016 in France. Case-patients with CRE were compared to two control populations. In multivariate analysis comparing 160 CRE cases to 160 controls C1 (patients with a clinical sample positive for carbapenem-susceptible Enterobacteriaceae), five characteristics were linked to CRE: male gender (OR = 1.9; 95% CI = 1.3-3.4), travel in Asia (OR = 10.0; 95% CI = 1.1-91.2) and hospitalisation in (OR = 2.4; 95% CI = 1.3-4.4) or out of (OR = 4.4; 95% CI = 0.8-24.1) France in the preceding 12 months, infection in the preceding 3 months (OR = 3.0; 95% CI = 1.5-5.9), and antibiotic receipt between admission and inclusion (OR = 1.9; 95% CI = 1.0-3.3). In multivariate analysis comparing 148 CRE cases to 148 controls C2 [patients with culture-negative sample(s)], four characteristics were identified: prior infection (OR = 3.3; 95% CI = 1.6-6.8), urine drainage (OR = 3.0; 95% CI = 1.5-6.1) and mechanical ventilation (OR = 3.7; 95% CI = 1.1-13.0) during the current hospitalisation, and antibiotic receipt between admission and inclusion (OR = 6.6; 95% CI = 2.8-15.5). Univariate analyses comparing separately CPE cases to controls (39 CPE vs C1 and 36 CPE vs C2) and non-CPE cases to controls (121 non-CPE vs C1 and 112 non-CPE vs C2), concomitantly with comparison of CPE to non-CPE cases showed that only CPE cases were at risk of previous travel and hospitalisation abroad. This study shows that, among CRE, risk factors are different for CPE and non-CPE infection, and suggests that question patients about their medical history and lifestyle should help for early identification of patients at risk of CPE among patients with CRE.

Environmental pollution with antimicrobial agents from bulk drug manufacturing industries in Hyderabad, South India, is associated with dissemination of extended-spectrum beta-lactamase and carbapenemase-producing pathogens.

PURPOSE: High antibiotic and antifungal concentrations in wastewater from anti-infective drug production may exert selection pressure for multidrug-resistant (MDR) pathogens. We investigated the environmental presence of active pharmaceutical ingredients and their association with MDR Gram-negative bacteria in Hyderabad, South India, a major production area for the global bulk drug market. METHODS: From Nov 19 to 28, 2016, water samples were collected from the direct environment of bulk drug manufacturing facilities, the vicinity of two sewage treatment plants, the Musi River, and habitats in Hyderabad and nearby villages. Samples were analyzed for 25 anti-infective pharmaceuticals with liquid chromatography-tandem mass spectrometry and for MDR Gram-negative bacteria using chromogenic culture media. In addition, specimens were screened with PCR for bla VIM, bla KPC, bla NDM, bla IMP-1, and bla OXA-48 resistance genes. RESULTS: All environmental specimens from 28 different sampling sites were contaminated with antimicrobials. High concentrations of moxifloxacin, voriconazole, and fluconazole (up to 694.1, 2500, and 236,950 µg/L, respectively) as well as increased concentrations of eight other antibiotics were found in sewers in the Patancheru-Bollaram industrial area. Corresponding microbiological analyses revealed an extensive presence of extended-spectrum beta-lactamase and carbapenemase-producing Enterobacteriaceae and non-fermenters (carrying mainly bla OXA-48, bla NDM, and bla KPC) in more than 95% of the samples. CONCLUSIONS: Insufficient wastewater management by bulk drug manufacturing facilities leads to unprecedented contamination of water resources with antimicrobial pharmaceuticals, which seems to be associated with the selection and dissemination of carbapenemase-producing pathogens. The development and global spread of antimicrobial resistance present a major challenge for pharmaceutical producers and regulatory agencies.

Carbapenemase-producing Enterobacteriaceae in Europe: assessment by national experts from 38 countries, May 2015.

In 2012, the European Centre for Disease Prevention and Control (ECDC) launched the 'European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE)' project to gain insights into the occurrence and epidemiology of carbapenemase-producing Enterobacteriaceae (CPE), to increase the awareness of the spread of CPE, and to build and enhance the laboratory capacity for diagnosis and surveillance of CPE in Europe. Data collected through a post-EuSCAPE feedback questionnaire in May 2015 documented improvement compared with 2013 in capacity and ability to detect CPE and identify the different carbapenemases genes in the 38 participating countries, thus contributing to their awareness of and knowledge about the spread of CPE. Over the last two years, the epidemiological situation of CPE worsened, in particular with the rapid spread of carbapenem-hydrolysing oxacillinase-48 (OXA-48)- and New Delhi metallo-beta-lactamase (NDM)-producing Enterobacteriaceae. In 2015, 13/38 countries reported inter-regional spread of or an endemic situation for CPE, compared with 6/38 in 2013. Only three countries replied that they had not identified one single case of CPE. The ongoing spread of CPE represents an increasing threat to patient safety in European hospitals, and a majority of countries reacted by establishing national CPE surveillances systems and issuing guidance on control measures for health professionals. However, 14 countries still lacked specific national guidelines for prevention and control of CPE in mid-2015.

Colistin resistance in ESBL- and Carbapenemase-producing Escherichia coli and Klebsiella pneumoniae clinical isolates in Cambodia.

OBJECTIVES: Despite the critical importance of colistin as a last-resort antibiotic, limited studies have investigated colistin resistance in human infections in Cambodia. This study aimed to investigate the colistin resistance and its molecular determinants among Extended-spectrum beta-lactamase (ESBL)- and carbapenemase-producing (CP) Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) isolated in Cambodia between 2016 and 2020. METHODS: E. coli (n = 223) and K. pneumoniae (n = 39) were tested for colistin minimum inhibitory concentration (MIC) by broth microdilution. Resistant isolates were subjected to polymerase chain reaction (PCR) for detection of mobile colistin resistance genes (mcr) and chromosomal mutations in the two-component system (TCS). RESULTS: Eighteen isolates (10 K. pneumoniae and 8 E. coli) revealed colistin resistance with a rate of 5.9% in E. coli and 34.8% in K. pneumoniae among ESBL isolates, and 1% in E. coli and 12.5% in K. pneumoniae among CP isolates. The resistance was associated with mcr variants (13/18 isolates, mcr-1, mcr-3, and mcr-8.2) and TCS mutations within E. coli and K. pneumoniae, with the first detection of mcr-8.2 in Cambodia, the discovery of new mutations potentially associated to colistin resistance in the TCS of E. coli (PhoP I47V, PhoQ N352K, PmrB G19R, and PmrD G85R) and the co-occurrence of mcr genes and colistin resistance conferring TCS mutations in 11 of 18 isolates. CONCLUSIONS: The findings highlight the presence of colistin resistance in ESBL- and CP- Enterobacteriaceae involved in human infections in Cambodia as well as chromosomal mutations in TCS and the emergence of mcr-8.2 in E. coli and K. pneumoniae. It underscores the need for continuous surveillance, antimicrobial stewardship, and control measures to mitigate the spread of colistin resistance.

Epidemiology of Carbapenem-Resistant Enterobacteriaceae Bacteremia in Gyeonggi Province, Republic of Korea, between 2018 and 2021.

The incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing since 2008, with Gyeonggi Province in South Korea being particularly vulnerable due to its large number of healthcare facilities. This study examines the trends of CRE occurrence in Gyeonggi Province over the past four years and the epidemiological characteristics of the infected patients. Patients with positive CRE blood cultures admitted to healthcare facilities in Gyeonggi Province from January 2018 to December 2021 were evaluated in this study. Risk factors for CRE-related death were analyzed using data from patients who died within 30 days of the last blood sampling. Older adults aged 70 years and above constituted the majority of patients with CRE bacteremia. Antibiotic use did not significantly affect mortality risk. Non-survivors were more common in tertiary hospitals and intensive care units and included patients with hypertension, malignant tumors, and multiple underlying diseases. Klebsiella pneumoniae was the most common CRE strain, with Klebsiella pneumoniae carbapenemase being the predominant carbapenemase. Our study suggests the endemicity of CRE in Gyeonggi Province and highlights the increasing isolation of CRE strains in South Korean long-term care hospitals within the province. Further, infection control measures and government support specific to each healthcare facility type are crucial.

Bacterial Outer Membrane Permeability Increase Underlies the Bactericidal Effect of Fatty Acids From Hermetia illucens (Black Soldier Fly) Larvae Fat Against Hypermucoviscous Isolates of Klebsiella pneumoniae.

Behind expensive treatments, Klebsiella pneumoniae infections account for extended hospitalization's high mortality rates. This study aimed to evaluate the activity and mechanism of the antimicrobial action of a fatty acid-containing extract (AWME3) isolated from Hermetia illucens (HI) larvae fat against K. pneumoniae subsp. pneumoniae standard NDM-1 carbapenemase-producing ATCC BAA-2473 strain, along with a wild-type hypermucoviscous clinical isolate, strain K. pneumoniae subsp. pneumoniae KPi1627, and an environmental isolate, strain K. pneumoniae subsp. pneumoniae KPM9. We classified these strains as extensive multidrug-resistant (XDR) or multiple antibiotic-resistant (MDR) demonstrated by a susceptibility assay against 14 antibiotics belonging to ten classes of antibiotics. Antibacterial properties of fatty acids extracted from the HI larvae fat were evaluated using disk diffusion method, microdilution, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), half of the inhibitory concentration (MIC50), and bactericidal assays. In addition, the cytotoxocity of AWME3 was tested on human HEK293 cells, and AWME3 lipid profile was determined by gas chromatography-mass spectrometry (GC-MS) analysis. For the first time, we demonstrated that the inhibition zone diameter (IZD) of fatty acid-containing extract (AWME3) of the HI larvae fat tested at 20 mg/ml was 16.52 ± 0.74 and 14.23 ± 0.35 mm against colistin-resistant KPi1627 and KPM9, respectively. It was 19.72 ± 0.51 mm against the colistin-susceptible K. pneumoniae ATCC BAA-2473 strain. The MIC and MBC were 250 µg/ml for all the tested bacteria strains, indicating the bactericidal effect of AWME3. The MIC50 values were 155.6 ± 0.009 and 160.1 ± 0.008 µg/ml against the KPi1627 and KPM9 isolates, respectively, and 149.5 ± 0.013 µg/ml against the ATCC BAA-2473 strain in the micro-dilution assay. For the first time, we demonstrated that AWME3 dose-dependently increased bacterial cell membrane permeability as determined by the relative electric conductivity (REC) of the K. pneumoniae ATCC BAA-2473 suspension, and that none of the strains did not build up resistance to extended AWME3 treatment using the antibiotic resistance assay. Cytotoxicity assay showed that AWME3 is safe for human HEK293 cells at IC50 266.1 µg/ml, while bactericidal for all the strains of bacteria at the same concentration. Free fatty acids (FFAs) and their derivatives were the significant substances among 33 compounds identified by the GC-MS analysis of AWME3. Cis-oleic and palmitoleic acids represent the most abundant unsaturated FAs (UFAs), while palmitic, lauric, stearic, and myristic acids were the most abundant saturated FAs (SFAs) of the AWME3 content. Bactericidal resistant-free AWM3 mechanism of action provides a rationale interpretations and the utility of HI larvae fat to develop natural biocidal resistance-free formulations that might be promising therapeutic against Gram-negative MDR bacteria causing nosocomial infections.

A high prevalence of blaOXA-48 in Klebsiella (Raoultella) ornithinolytica and related species in hospital wastewater in South West England.

Klebsiella species occupy a wide range of environmental and animal niches, and occasionally cause opportunistic infections that are resistant to multiple antibiotics. In particular, Klebsiella pneumoniae (Kpne) has gained notoriety as a major nosocomial pathogen, due principally to the rise in non-susceptibility to carbapenems and other beta-lactam antibiotics. Whilst it has been proposed that the urban water cycle facilitates transmission of pathogens between clinical settings and the environment, the level of risk posed by resistant Klebsiella strains in hospital wastewater remains unclear. We used whole genome sequencing (WGS) to compare Klebsiella species in contemporaneous samples of wastewater from an English hospital and influent to the associated wastewater treatment plant (WWTP). As we aimed to characterize representative samples of Klebsiella communities, we did not actively select for antibiotic resistance (other than for ampicillin), nor for specific Klebsiella species. Two species, Kpne and K. (Raoultella) ornithinolytica (Korn), were of equal dominance in the hospital wastewater, and four other Klebsiella species were present in low abundance in this sample. In contrast, despite being the species most closely associated with healthcare settings, Kpne was the dominant species within the WWTP influent. In total, 29 % of all isolates harboured the blaOXA-48 gene on a pOXA-48-like plasmid, and these isolates were almost exclusively recovered from the hospital wastewater. This gene was far more common in Korn (68 % of isolates) than in Kpne (3.4 % of isolates). In general plasmid-borne, but not chromosomal, resistance genes were significantly enriched in the hospital wastewater sample. These data implicate hospital wastewater as an important reservoir for antibiotic-resistant Klebsiella, and point to an unsuspected role of species within the Raoultella group in the maintenance and dissemination of plasmid-borne blaOXA-48. This article contains data hosted by Microreact.

Multidrug-resistant enterobacteriaceae in coastal water: an emerging threat.

BACKGROUND: The environmental role of carbapenemase-producing Enterobacteriaceae (CPE) acquisition and infection in human disease has been described but not thoroughly investigated. We aimed to assess the occurrence of CPE in nearshore aquatic bodies. METHODS: Enterobacteriaceae were cultured from coastal and estuary water near Netanya, Israel in June and July of 2018. Bacteria were identified by VITEK2® and their antimicrobial susceptibility was tested according to the CLSI guidelines. Enterobacteriaceae genomes were sequenced to elucidate their resistome and carbapenemase types. RESULTS: Among other clinically relevant bacteria, four CPE (three Enterobacter spp and one Escherichia coli isolate) were isolated from two river estuaries (Poleg and Alexander Rivers) and coastal water at a popular recreational beach (Beit Yanai). Molecular analysis and genome sequencing revealed the persistent presence of rare beta-lactamase resistance genes, including blaIMI-2 and a previously unknown blaIMI-20 allele, which were not found among the local epidemiological strains. Genome comparisons revealed the high identity of riverine and marine CPE that were cultivated one month apart. CONCLUSIONS: We show that CPE contamination was widespread in nearshore marine and riverine habitats. The high genome-level similarity of riverine and marine CPEs, isolated one month apart, hints at the common source of infection. We discuss the clinical implications of these findings and stress the urgent need to assess the role of the aquatic environment in CPE epidemiology.

Performance of modified carbapenem inactivation method and inhibitor-based combined disk test in the detection and distinguishing of carbapenemase producing Enterobacteriaceae.

BACKGROUND: This study aimed to evaluate the performance of modified carbapenem inactivation method (mCIM) combined EDTA-carbapenem inactivation method (eCIM), and inhibitor-based combined disk test (CDT) in the detection and distinguishing of carbapenemase production in Enterobacteriaceae. METHODS: A total of 101 nonrepetitive carbapenem insensitive Enterobacteriaceae [minimal inhibitory concentration (MIC) ≥2 µg/mL] were tested by mCIM, eCIM and CDT respectively, and the major carbapenemase genes including blaKPC, blaNDM, blaIMP, blaVIM and blaOXA-48-like genes were detected by polymerase chain reaction (PCR) as control. RESULTS: Seventy-nine (78.2%) of isolates were found to harbour one or more carbapenemase genes by PCR, with blaKPC and blaNDM being the most common genes. OXA-48-like genes were undetectable. The coincidence rate of mCIM combined eCIM and CDT was 97.5% (77/79) and 96.2% (76/79) respectively, compared with gene detection. Both assays had a misclassification in two blaKPC+NDM-producing isolates of Klebsiella oxytoca. The sensitivity and specificity of two assays above were 100.0% vs. 95.0% and 98.4% vs. 98.4%, respectively in distinguishing serine-carbapenemase, while they were 95.1% vs. 97.6% and 100% vs. 100.0%, respectively in distinguishing metallo-carbapenemase. CONCLUSIONS: mCIM combined eCIM and the CDT are both useful tools for the reliable detection and distinguishing single serine-carbapenemase or metallo-carbapenemase, but not for mixed types.

Audit of the management of patients at high risk of carbapenemase-producing enterobacteriaceae (CPE): Are we ready?

BACKGROUND: Incidence of carbapenemase-producing enterobacteriaceae (CPE) in the UK is increasing. In 2013, Public Health England (PHE) published a toolkit to control spread of CPE within healthcare settings. AIM: To assess compliance to hospital CPE policy (adapted from PHE) in the identification, isolation and screening of suspected CPE patients. METHODS: Admission booklets of 150 patients were evaluated to see whether the relevant section had been completed to identify high-risk CPE patients. Where necessary, patients were interviewed or their GPs were contacted to assess their CPE risk. Additionally, 28 patients screened for CPE were audited to assess compliance to screening and isolation. FINDINGS: Only 23 patients out of 147 (15.6%) were risk assessed on admission. Risk status of 27 (18.4%) patients could not be assessed due to lack of data. Fifteen patients out of 28 (54%) screened for CPE were identified and isolated on admission. Ten out of 19 patients (53%) had three screens 48 h apart. DISCUSSION: This audit highlights difficulties in screening based on individual risk factors as the majority of patients were not screened on admission and documentation on isolation and screening was poor. More needs to be done to raise awareness of the requirements for routine assessment, isolation and screening.

Verification of the Cepheid Xpert Carba-R assay for the detection of carbapenemase genes in bacterial isolates cultured on alternative solid culture media.

The Xpert Carba-R (Cepheid) is a polymerase chain reaction (PCR) assay for detection and differentiation of five common carbapenemase genes. If used according to manufacturer's instructions, bacterial isolates tested must be cultured on blood or MacConkey agar. This study confirms that the assay performs well against a diverse panel of bacterial isolates with known carbapenemase genes. It also demonstrates that the assay performs well using three solid agar culture media that have not been recommended by the PCR assay's manufacturer: CLED (cystine-, lactose-, and electrolyte-deficient), ChromID CARBA-SMART, and a nutrient slope. By testing isolates directly from any of these media, delays in laboratory reporting can be avoided.

Infection control implications of heterogeneous resistance mechanisms in carbapenem-resistant Enterobacteriaceae (CRE).

The Centers for Disease Control and Prevention (CDC) defines carbapenem-resistant Enterobacteriaceae (CRE) based upon a phenotypic demonstration of carbapenem resistance. However, considerable heterogeneity exists within this definitional umbrella. CRE may mechanistically differ by whether they do or do not produce carbapenemases. Moreover, patients can acquire CRE through multiple pathways: endogenously through antibiotic selective pressure on intestinal microbiota, exogenously through horizontal transmission or through a combination of these factors. Some evidence suggests that non-carbapenemase-producing CRE may be more frequently acquired by antibiotic exposure and carbapenemase-producing CRE via horizontal transmission, but definitive data are lacking. This review examines types of CRE resistance mechanisms, antibiotic exposure and horizontal transmission pathways of CRE acquisition, and the implications of these heterogeneities to the development of evidence-based CRE healthcare epidemiology policies. In our Expert Commentary & Five-Year View, we outline specific nosocomial CRE knowledge gaps and potential methodological approaches for their resolution.

Antimicrobial treatment and outcomes of critically ill patients with OXA-48like carbapenemase-producing Enterobacteriaceae infections.

We report on the clinical characteristics, antimicrobial therapy, and outcomes of 20 critically ill patients with severe OXA-48like infections. Carbapenem-based therapy demonstrated improved survival (odds ratio = 5.0) as compared with non-carbapenem therapy. Risk factors for mortality included Acute Physiology and Chronic Health Evaluation III score and length of stay, highlighting the significant influence of comorbidities and severity of underlying illness on outcomes.

French recommendations for the prevention of 'emerging extensively drug-resistant bacteria' (eXDR) cross-transmission.

Controlling the spread of multi- or extensively drug-resistant bacteria (MDR or XDR) includes a dual strategy for reducing antibiotic prescriptions and preventing their spread from patient carriers. Standard precautions are applicable to all health professionals caring for any patients; additional barrier precautions (isolation) are recommended for patients carrying transmissible infectious diseases or MDR bacteria in sporadic or epidemic situations. Moreover, additional precautions may be required for populations at particular risk of infection or colonization by emerging XDR (eXDR), defined in our country as carbapenemase-producing Enterobacteriaceae and vancomycin-resistant enterococci. Our ability to detect and identify eXDR carriers early and ensure their follow-up, through effective communication between all those involved, is a significant challenge for controlling their spread. Thus, the French High Committee for Public Health has updated and standardized all French existing recommendations concerning the prevention of the cross-transmission of these bacteria, and these recommendations are summarized in this review. The recommendations are based on scientific and operational knowledge up to 2013. Different preventive strategies are recommended for patients found to be carrying eXDR and those who are considered to be at risk of having eXDR because of a history of contact. The local context, the experience of the infection control team, the different times at which detection of eXDR takes place (during admission, hospitalization, etc.) and the epidemiological situation (sporadic cases, clusters, outbreaks, widespread epidemic) must be included in risk assessments that in turn inform the control measures that should be applied in each clinical circumstance.