Transmission Of Carbapenemase-producing Enterobacteriaceae Research Articles

Successful control of an environmental reservoir of NDM-producing Klebsiella pneumoniae associated with nosocomial transmissions in a low-incidence setting

BackgroundThe hospital wastewater system has been reported as a source of nosocomial acquisition of carbapenemase producing Enterobacteriaceae (CPE) in various settings. Cleaning and disinfection protocols or replacement of contaminated equipment often fail to eradicate these environmental reservoirs, which can lead to long-term transmission of CPE. We report a successful multimodal approach to control a New Delhi metallo-beta-lactamase positive Klebsiella pneumoniae (NDM-KP) nosocomial outbreak implicating contamination of sink traps in a low-incidence setting.MethodsFollowing the incidental identification of NDM-KP in a urine culture of an inpatient, we performed an epidemiological investigation, including patient and environmental CPE screening, and whole genome sequencing (WGS) of strains. We also implemented multimodal infection prevention and control (IPC) measures, namely the isolation of cases, waterless patient care, replacement of contaminated P-traps and connecting pieces, and bleach and steam disinfection of sinks for 6 months, followed by patient and environmental screenings for eradication.ResultsBetween February and May 2022, five NDM-KP cases were identified in an eight-bed neurosurgical intermediate care unit. Among the eight sink traps of the unit, three were positive for NDM-KP. Patient and environmental isolates belonged to multilocus sequence typing ST-268. All isolate genomes were genetically very similar suggesting cross-transmission and a potential role of the environment as the source of transmissions. Following the introduction of combined IPC measures, no new case was subsequently detected and sink traps remained negative for NDM-KP within 6 months after the intervention.ConclusionThe implementation of multimodal IPC measures, including waterless patient care combined with the replacement and disinfection of P-traps and connecting pieces, was successful in the control of NDM-KP after eight months. In a low-incidence setting, this approach has made it possible to pursue the objective of zero transmission of carbapenemase-producing Enterobacteriaceae (CPE).

Carbapenemase-Producing Enterobacteriaceae detected in a Large Canadian Tertiary Care Hospital: Five-year retrospective study

Background: The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) is increasing worldwide. In Canada, where rates of healthcare-associated (HA) transmission of CPE remains relatively low, there is a need to share early experience of universal screening programs and risk factors for HA acquisition. Method: In 2018, universal screening was introduced throughout our large Canadian tertiary care hospital across, all critical care and oncology units. Additionally, risk-factor based screening was applied in all other inpatient units, with further targeted screening of roommate exposures or all inpatients on unit following identification of a single HA case. A retrospective cohort study was carried out on CPE cases detected between January 2018 and December 2023. We assessed the proportion of HA CPE cases, defined as CPE identified in patients with prior admission to our facility or after >72 hours after admission. HA cases were examined for relevant risk factors, including known roommate with CPE, the presence of other CPE on the unit, exposure to outbreak units, prior travel history, travel by a family member, and antibiotic exposure within the past 90 days. Result: A total of 150 CPE cases were identified, with 66 (44%) classified as HA. Among these HA cases, 14 (21%) were associated with presence of known case on the unit. The remaining 52 (79%) represented sporadic nosocomial cases without a known exposure or further transmission on the unit. Upon further retrospective review, 6 (9.2%) HA cases had documented travel history or exposure to a family member with recent travel to China, India, Sri Lanka, or the United States within the past year. Nearly all HA cases (62, 95.4%) had antibiotic exposure within 90 days of CPE detection; specifically, 47 (72.3%) received beta-lactams, 42 (64.6%) cephalosporin, 25 (38.5%) glycopeptide, 20 (30.8%) carbapenem, and 8 (12.3%) macrolide. Conclusion: HA CPE acquisition identified during the first 5-years of universal screening were mostly sporadic and not associated with known exposures or other risk factors. Receipt of prior antibiotics was present in nearly all cases.

Best practices for flexible endoscope high-level disinfection-an integrative review

Background: Flexible endoscopes have a complicated design which includes several small lumen channels intended to facilitate the flow of fluids, tissue, and tools through the length of the device. This complex design leads to reprocessing challenges for high-level disinfection (HLD) to ensure endoscopes are free from contaminants that could lead to hospital-acquired infections. The aim of this project was to identify optimal strategies and obstacles for each stage of flexible endoscope HLD through an integrative review with the goal of achieving reprocessing excellence. Methods: A literature search was conducted using PubMed/Medline and CINAHL databases. A total of 32 articles and six guidelines were included in the review. Results: Ten elements with best-practice recommendations of flexible endoscope HLD have been identified. The HLD elements that received the most literature support include quality assurance/process monitoring and manual cleaning/decontamination. Several barriers to the adequate performance of HLD elements were also identified. Conclusion: This integrative review applied varying levels of rigour to identify and synthesize best practices for the following HLD elements: point-of-use treatment, transport, leak testing, manual cleaning/decontamination, visual inspection, manual or automated HLD, rinsing/drying, storage/hang time, record keeping, and quality assurance/process monitoring.

Sink-traps are a major source for carbapenemase-producing Enterobacteriaceae transmission.

We studied the extent of carbapenemase-producing Enterobacteriaceae (CPE) sink contamination and transmission to patients in a nonoutbreak setting. During 2017-2019, 592 patient-room sinks were sampled in 34 departments. Patient weekly rectal swab CPE surveillance was universally performed. Repeated sink sampling was conducted in 9 departments. Isolates from patients and sinks were characterized using pulsed-field gel electrophoresis (PFGE), and pairs of high resemblance were sequenced by Oxford Nanopore and Illumina. Hybrid assembly was used to fully assemble plasmids, which are shared between paired isolates. In total, 144 (24%) of 592 CPE-contaminated sinks were detected in 25 of 34 departments. Repeated sampling (n = 7,123) revealed that 52%-100% were contaminated at least once during the sampling period. Persistent contamination for >1 year by a dominant strain was common. During the study period, 318 patients acquired CPE. The most common species were Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. In 127 (40%) patients, a contaminated sink was the suspected source of CPE acquisition. For 20 cases with an identical sink-patient strain, temporal relation suggested sink-to-patient transmission. Hybrid assembly of specific sink-patient isolates revealed that shared plasmids were structurally identical, and SNP differences between shared pairs, along with signatures for potential recombination events, suggests recent sharing of the plasmids. CPE-contaminated sinks are an important source of transmission to patients. Although traditionally person-to-person transmission has been considered the main route of CPE transmission, these data suggest a change in paradigm that may influence strategies of preventing CPE dissemination.

Comparing the transmission of carbapenemase-producing and extended-spectrum beta-lactamase-producing Escherichia coli between broiler chickens.

The emergence of carbapenemase-producing Enterobacteriaceae (CPE) is a threat to public health, because of their resistance to clinically important carbapenem antibiotics. The emergence of CPE in meat-producing animals is particularly worrying because consumption of meat contaminated with resistant bacteria comparable to CPE, such as extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, contributed to colonization in humans worldwide. Currently, no data on the transmission of CPE in livestock is available. We performed a transmission experiment to quantify the transmission of CPE between broilers to fill this knowledge gap and to compare the transmission rates of CPE and other antibiotic-resistant E. coli. A total of 180 Ross 308 broiler chickens were distributed over 12 pens on the day of hatch (day 0). On day 5, half of the 10 remaining chickens in each pen were orally inoculated with 5·102 colony-forming units of CPE, ESBL, or chloramphenicol-resistant E. coli (catA1). To evaluate the effect of antibiotic treatment, amoxicillin was given twice daily in drinking water in 6 of the 12 pens from days 2-6. Cloacal swabs of all animals were taken to determine the number of infectious broilers. We used a Bayesian hierarchical model to quantify the transmission of the E. coli strains. E. coli can survive in the environment and serve as a reservoir. Therefore, the susceptible-infectious transmission model was adapted to account for the transmission of resistant bacteria from the environment. In addition, the caecal microbiome was analyzed on day 5 and at the end of the experiment on day 14 to assess the relationship between the caecal microbiome and the transmission rates. The transmission rates of CPE were 52 - 68 per cent lower compared to ESBL and catA1, but it is not clear if these differences were caused by differences between the resistance genes or by other differences between the E. coli strains. Differences between the groups in transmission rates and microbiome diversity did not correspond to each other, indicating that differences in transmission rates were probably not caused by major differences in the community structure in the caecal microbiome. Amoxicillin treatment from day 2-6 increased the transmission rate more than three-fold in all inoculums. It also increased alpha-diversity compared to untreated animals on day 5, but not on day 14, suggesting only a temporary effect. Future research could incorporate more complex transmission models with different species of resistant bacteria into the Bayesian hierarchical model.

Risk Factors and Prevalence of Mother to New-Born Transmission of Carbapenemase Producing Enterobacteriaceae in Two Hospitals in Yaounde, Cameroon

Background: In African countries, where the burden of neonatal sepsis is the highest, the spread of Carbapenemases Producing Enterobacteriaceae (CPE) in the community, potentially contributing to neonatal mortality, is a public health concern. The transmission routes are not well defined, particularly the possible key role played by pregnant women. The aim of this study was to understand the neonatal acquisition of CPE in Yaounde, Cameroon. Methods: A transversal analytical study was conducted in an urban area. Maternal stool samples during delivery and the first stool from their new-born were collected and cultured to isolate Enterobacteria. After isolation, characterization using API20E identification system, and antibiotic susceptibility testing were performed according to the Antibiogram Committee of the French Society of Microbiology. Carbapenemases detection was done on each carbapenem-resistant strain using the Modified Hodge Test (MHT) and their classification using the synergy tests with different inhibitors. Results: Out of the 55 CPE isolates identified, Escherichia coli was the most encountered bacteria both in mothers (n = 18, 50.00%) and infants (n = 11, 57.89%). Class B and D carbapenemases were found both in mothers and infants. The estimated prevalence of vertical transmission in our study, was 10% (n = 12). Logistic regression showed that CPE carriage in mothers and CPE acquisition in their new-borns were independently associated with the presence of greenish amniotic fluid (OR = 7.33, p 0.0001 in mothers and OR = 4.09, p = 0.0086 in new-borns). Conclusion: Our results highlight the non-negligeable role played by pregnant women in the neonatal acquisition of CPE.

Audit and feedback as a tool to increase compliance with carbapenemase-producing Enterobacteriaceae (CPE) screening and decrease CPE transmission in the hospital.

To increase compliance with carbapenemase-producing Enterobacteriaceae (CPE) screening through real-time audit and feedback in our hospital and decrease CPE transmissions. A before-and-after trial, using active enhanced surveillance of CPE carriers. A 500-bed, secondary, university-affiliated hospital that serves a population of 450,000 in a northern district in Israel. The study was conducted during 2016-2019 and included patients who were admitted to the hospital and fulfilled CPE screening criteria upon admission and during prolonged hospitalizations. On January 1, 2017, the infection control team implemented a new strategy of real-time feedback toward compliance with in-hospital screening guidelines. Other infection control measurements were performed without interventions. The primary outcome was compliance with appropriate CPE screening. Secondary outcomes included CPE acquisition and compliance with hand hygiene and contact precaution practices. Data were analyzed to calculate differences between compliance with CPE screening during the study period and to test the correlation between contact precautions and hand hygiene practices according to compliance with CPE screening. During the study period, 3,131 patients were eligible for CPE screening. We detected a statistically significant increase in compliance to CPE screening from 74% during 2017 to 92% in 2018 and 95% in 2019 (P < .0001 for both comparisons). We detected a decrease in CPE transmission from 12% in 2017 to 2% in 2019 (P < .0001). We did not find any correlation between other infection control interventions and CPE screening and acquisition. Audit and feedback can improve appropriate CPE screening and may reduce CPE transmission in the hospital.

Epidemiology and Transmission of Carbapenemase-Producing Enterobacteriaceae in a Health Care Network of an Acute-Care Hospital and Its Affiliated Intermediate- and Long-Term-Care Facilities in Singapore.

ABSTRACTMovement of patients in a health care network poses challenges for the control of carbapenemase-producing Enterobacteriaceae (CPE). We aimed to identify intra- and interfacility transmission events and facility type-specific risk factors of CPE in an acute-care hospital (ACH) and its intermediate-term and long-term-care facilities (ILTCFs). Serial cross-sectional studies were conducted in June and July of 2014 to 2016 to screen for CPE. Whole-genome sequencing was done to identify strain relatedness and CPE genes (blaIMI, blaIMP-1, blaKPC-2, blaNDM-1, and blaOXA-48). Multivariable logistic regression models, stratified by facility type, were used to determine independent risk factors. Of 5,357 patients, half (55%) were from the ACH. CPE prevalence was 1.3% in the ACH and 0.7% in ILTCFs (P = 0.029). After adjusting for sociodemographics, screening year, and facility type, the odds of CPE colonization increased significantly with a hospital stay of ≥3 weeks (adjusted odds ratio [aOR], 2.67; 95% confidence interval [CI], 1.17 to 6.05), penicillin use (aOR, 3.00; 95% CI, 1.05 to 8.56), proton pump inhibitor use (aOR, 3.20; 95% CI, 1.05 to 9.80), dementia (aOR, 3.42; 95% CI, 1.38 to 8.49), connective tissue disease (aOR, 5.10; 95% CI, 1.19 to 21.81), and prior carbapenem-resistant Enterobacteriaceae (CRE) carriage (aOR, 109.02; 95% CI, 28.47 to 417.44) in the ACH. For ILTCFs, presence of wounds (aOR, 5.30; 95% CI, 1.01 to 27.72), respiratory procedures (aOR, 4.97; 95% CI, 1.09 to 22.71), vancomycin-resistant enterococcus carriage (aOR, 16.42; 95% CI, 1.52 to 177.48), and CRE carriage (aOR, 758.30; 95% CI, 33.86 to 16,982.52) showed significant association. Genomic analysis revealed only possible intra-ACH transmission and no evidence for ACH-to-ILTCF transmission. Although CPE colonization was predominantly in the ACH, risk factors varied between facilities. Targeted screening and precautionary measures are warranted.

Household transmission of carbapenemase-producing Enterobacteriaceae: a prospective cohort study.

To estimate the transmission rate of carbapenemase-producing Enterobacteriaceae (CPE) in households with recently hospitalized CPE carriers. We conducted a prospective case-ascertained cohort study. We identified the presence of CPE in stool samples from index subjects, household contacts and companion animals and environmental samples at regular intervals. Linked transmissions were identified by WGS. A Markov model was constructed to estimate the household transmission potential of CPE. Ten recently hospitalized index patients and 14 household contacts were included. There were seven households with one contact, two households with two contacts, and one household with three contacts. Index patients were colonized with blaOXA-48-like (n = 4), blaKPC-2 (n = 3), blaIMP (n = 2), and blaNDM-1 (n = 1), distributed among divergent species of Enterobacteriaceae. After a cumulative follow-up time of 9.0 years, three family members (21.4%, 3/14) acquired four different types of CPE in the community (hazard rate of 0.22/year). The probability of CPE transmission from an index patient to a household contact was 10% (95% CI 4%-26%). We observed limited transmission of CPE from an index patient to household contacts. Larger studies are needed to understand the factors associated with household transmission of CPE and identify preventive strategies.

Importance of the Respiratory Tract in Carbapenemase-Producing Enterobacteriaceae Spread

Background: Carbapenemase-producing Enterobacteriaceae (CPE) causes infections associated with high mortality rates among hospitalized patients. CPE transmission occurs frequently, and prevention of patient-to-patient transmission is a priority. However, transmission pathways are not yet completely understood. The colonization of the respiratory tract with a CPE may lead to a higher risk of contamination of the patient’s environment increasing the spread of CPE. Objective: We estimated the rate of CPE spread when respiratory tract infection or colonization is present. Methods: We studied CPE dissemination analyzing a cohort of patients admitted between January 2013 and December 2018 at the university hospital complex of A Corua, a tertiary-care hospital. All patients who were hospitalized in the same room as a patient colonized or infected with a CPE (index case) for at least 24 hours were screened for CPE carriage. The microbiological screening was performed with conventional culture or polymerase chain reaction (PCR) to identified possible CPE patient-to-patient transmission. The screening test included several samples: rectal swab, perineal swab, wound or drainage swab, and low respiratory tract sample. Results: Active screening for CPE carriage was performed in 84 contact patients. Men represent 57.1% of the sample, and the mean age was 78.5 years (men, 68.0 years and women, 80.8 years), with significant differences between sexes (12.9; 95% CI, 19.6 to 6.1). The major group of cases (86.9%) were hospitalized in medical wards. Transmission confirmed by PCR occurred in 13 (15.5%) of 84 contact patients, after a mean exposure to the index case of 13.3 days. No significant differences were detected in terms of mean exposure to index cases between those contact patients who result negative and those who result positive. The 35 index cases (41.7%) tested positive for CPE on the respiratory sample, and exposure to them led to 8 positive contact patients (61.5%). Conclusions: CPE transmission in a tertiary-care hospital occurred frequently. The spread rate is even higher when CPE is present at the respiratory level. Understanding the mode of spread is important for designing effective control measures and adding a respiratory sample to CPE screening could be a key consideration.Funding: NoneDisclosures: None

Sink and Drain Monitoring and Decontamination Protocol for Carbapenemase-producing Enterobacteriaceae (CPE)

Background Carbapenemase-producing Enterobacteriaceae (CPE) can colonize hospital drains and spread from drain to patient. The optimal approach to preventing drain colonization is unknown. We present our hospital's experience with a drain decontamination protocol. Methods Our facility is a 450 bed academic hospital in Toronto. Between 2017 and 2019, we identified 32 CPE positive inpatients 24 of whom were known to carry CPE or were CPE screen positive on admission. We implemented a sink drain protocol to prevent plumbing colonization. CPE patients admitted >48 hours have all drains in their room disinfected weekly and when transferred or discharged. Hydrogen peroxide gel (4.5%) is poured into the drain and flushed after 10 minutes. Drain swabs are collected >48 after disinfection; some rooms were also tested pre-disinfection. If post-disinfection swabs were positive, enhanced disinfection methods were used. Results 4.7% (18/387) sink/drain swabs were CPE positive. Eight positive swabs were collected before and ten after disinfection. These 18 positive swabs were from drains in 8 patient rooms and 2 communal showers. Enterobacter species predominated (5/10) and CPE enzymes included KPC(4), NDM(3), OXA-48(2), and mixed NDM&KPC(1). Positive room drains matched the patient's CPE enzyme for 7 of 8 positive rooms. Drain disinfection was successful for 70% (7/10) of positive sinks/drains. Three drains failed disinfection and required the enhanced disinfection protocol. After successful disinfection, all room drains have remained negative on at least one additional swab performed >1 month after successful disinfection but two communal shower drains reverted to positive with the same CPE enzyme on retesting >6 months post-disinfection. Conclusions Sink drains can become contaminated with CPE. Our disinfection protocol was largely successful in eradicating CPE from drains, although two communal shower drains reverted to positive. Disinfection of drains in CPE rooms routinely and at discharge may prevent drain colonization and reduce CPE transmission risk. Carbapenemase-producing Enterobacteriaceae (CPE) can colonize hospital drains and spread from drain to patient. The optimal approach to preventing drain colonization is unknown. We present our hospital's experience with a drain decontamination protocol. Our facility is a 450 bed academic hospital in Toronto. Between 2017 and 2019, we identified 32 CPE positive inpatients 24 of whom were known to carry CPE or were CPE screen positive on admission. We implemented a sink drain protocol to prevent plumbing colonization. CPE patients admitted >48 hours have all drains in their room disinfected weekly and when transferred or discharged. Hydrogen peroxide gel (4.5%) is poured into the drain and flushed after 10 minutes. Drain swabs are collected >48 after disinfection; some rooms were also tested pre-disinfection. If post-disinfection swabs were positive, enhanced disinfection methods were used. 4.7% (18/387) sink/drain swabs were CPE positive. Eight positive swabs were collected before and ten after disinfection. These 18 positive swabs were from drains in 8 patient rooms and 2 communal showers. Enterobacter species predominated (5/10) and CPE enzymes included KPC(4), NDM(3), OXA-48(2), and mixed NDM&KPC(1). Positive room drains matched the patient's CPE enzyme for 7 of 8 positive rooms. Drain disinfection was successful for 70% (7/10) of positive sinks/drains. Three drains failed disinfection and required the enhanced disinfection protocol. After successful disinfection, all room drains have remained negative on at least one additional swab performed >1 month after successful disinfection but two communal shower drains reverted to positive with the same CPE enzyme on retesting >6 months post-disinfection. Sink drains can become contaminated with CPE. Our disinfection protocol was largely successful in eradicating CPE from drains, although two communal shower drains reverted to positive. Disinfection of drains in CPE rooms routinely and at discharge may prevent drain colonization and reduce CPE transmission risk.

Increased detection of carbapenemase-producing Enterobacteriaceae on post-clean sampling of a burns unit's wet surfaces

Wet surface biofilms are a potential reservoir for multidrug-resistant Gram-negative organisms, including carbapenemase-producing Enterobacteriaceae (CPE). Recognition of environmental sources is important in reducing secondary patient transmission. We report the increased detection of blaIMP-4+ CPE in environmental samples from floor drains in burns unit shower rooms, when collected following cleaning as compared to pre-cleaning. We propose that disruption of biofilms during cleaning may account for the increased detection of multi-resistant organisms. The results highlight the role of the wet environment as an under-recognized potential source of CPE transmission. Environmental screening focusing on pre-cleaning samples alone will likely underestimate environmental contamination.

Emergence of Carbapenemase-Producing Enterobacteriaceae, South-Central Ontario, Canada1.

We analyzed population-based surveillance data from the Toronto Invasive Bacterial Diseases Network to describe carbapenemase-producing Enterobacteriaceae (CPE) infections during 2007–2015 in south-central Ontario, Canada. We reviewed patients’ medical records and travel histories, analyzed microbiologic and clinical characteristics of CPE infections, and calculated incidence. Among 291 cases identified, New Delhi metallo-β-lactamase was the predominant carbapenemase (51%). The proportion of CPE-positive patients with prior admission to a hospital in Canada who had not received healthcare abroad or traveled to high-risk areas was 13% for patients with oxacillinase-48, 24% for patients with New Delhi metallo-β-lactamase, 55% for patients with Klebsiella pneumoniae carbapenemase, and 67% for patients with Verona integron-encoded metallo-β-lactamase. Incidence of CPE infection increased, reaching 0.33 cases/100,000 population in 2015. For a substantial proportion of patients, no healthcare abroad or high-risk travel could be established, suggesting CPE acquisition in Canada. Policy and practice changes are needed to mitigate nosocomial CPE transmission in hospitals in Canada.

Assessing the role of a patient transfer network in the spread of carbapenemase-producing Enterobacteriaceae: The case of France between 2012 and 2015

Introduction The spread of carbapenemase-producing Enterobacteriaceae (CPE) is a major public health threat that has been associated with cross-border and local transfer of patients between healthcare facilities. However, the impact of healthcare transfer networks on CPE spread dynamics may vary in time and between countries. In this context, our study aimed to assess the contribution of the patient transfer network on CPE spread in France from 2012 to 2015. Methods Using the French healthcare network of 2.3 million patients, we extended a previously proposed statistical method and tested the ability of this network to support observed CPE incidence episodes. First, using 2237 CPE episodes that occurred from 2012 to 2015, we identified the most likely infector for the 1251 non-imported episodes using network-supported paths (NSPs). We then compared the observed NSP distances to those expected by chance, using random permutations of the CPE data. The impact of the assumed time window between infector episode and CPE episode was investigated in a sensitivity analysis. Results More than half of all CPE episodes were linked, either as infectors or incident episodes. The percentage of episodes with identified potential infectors over the network increased with time, from 57% in 2012 to 66% in 2015. NSP distances from 2013 to 2015 were significantly shorter in the observed data than expected by chance, indicating a role of the transfer network in CPE spread dynamics in France. In 2012 however, this result was not found. Over the entire study period, linked episodes tended to occur in the same administrative department or within close geographic distances. The 3-to-4 weeks baseline window between infector and episode was supported by the sensitivity analysis, where the strongest evidence for network-supported CPE transmission was observed for 2014 and 2015 episodes. Conclusions We observed a transition in 2013 from an epidemic sustained by importation to local transmission events sustaining the epidemic. As a result of a growing contribution of transfers in CPE spread over time, coordinated prevention and infection control strategies in France should focus on at-risk patient transfers to reduce regional and inter-regional transmission of CPE.

Colonization and infection due to carbapenemase-producing Enterobacteriaceae in liver and lung transplant recipients and donor-derived transmission: a prospective cohort study conducted in Italy

ObjectivesA prospective cohort study was conducted in Italy in order to describe the microbiologic aspects of colonization/infection by carbapenemase-producing Enterobacteriaceae (CPE) in donors and recipients of lung and liver transplants and the possible CPE transmission from donors to recipients. MethodsBetween 15 January 2014 and 14 January 2015, all recipients of solid organ transplants (SOT) at ten lung and eight liver transplantation centres and the corresponding donors were enrolled. Screening cultures to detect CPE were performed in donors, and screening and clinical cultures in recipients with a 28-day microbiologic follow-up after receipt of SOT. Detection of carbapenemase genes by PCR, genotyping by multilocus sequence typing, and pulsed-field gel electrophoresis and whole-genome sequencing were performed. ResultsOf 588 screened donors, 3.4% were colonized with CPE. Of the liver first transplant recipients (n = 521), 2.5% were colonized before receipt of SOT and 5% acquired CPE during follow-up. CPE colonization was higher in lung first transplant recipients (n = 111, 2.7% before SOT and 14.4% after SOT). CPE infections occurred in 1.9% and 5.3% of liver or lung recipients, respectively. CPE isolates were mostly Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae belonging to CG258. Three events of donor–recipient CPE transmission, confirmed by whole-genome sequencing and/or pulsed-field gel electrophoresis, occurred in lung recipients: two involving K. pneumoniae sequence type 512 and one Verona integron-encoded metallo-β-lactamase (VIM)-producing Enterobacter aerogenes. ConclusionsThis study showed a low risk of donor–recipient CPE transmission, indicating that donor CPE colonization does not necessarily represent a contraindication for donation unless colonization regards the organ to be transplanted. Donor and recipient screening remains essential to prevent CPE transmission and cross-infection in transplantation centres.

Is cohorting the only solution to control carbapenemase-producing Enterobacteriaceae outbreaks? A single-centre experience

Carbapenemase-producing Enterobacteriaceae (CPE) are a major health issue. Cohorting may help to control spread of CPEs in hospitals, but is expensive and hard to implement. To identify ward variables associated with CPE in-hospital transmission in a hospital where cohorting has never been implemented. Cohort prospective study, comparing 14-consecutive-day periods regarding in-hospital transmission. Each period met the two following conditions: (i) CPE carriers/infected admitted for ≥48h; (ii) 80% of relative contact patients were screened at least twice. Periods (a) with no acquired CPE case among relative contact patients were compared to periods (b) during which one or more CPE case acquisition was identified. Variables potentially associated with CPE transmission were assessed: colonization pressure, caregiver:patient ratio, hand hygiene compliance, hydro-alcoholic product consumption, antibiotic consumption, and infection control team (ICT) involvement on the ward. Sixty-eight periods of two consecutive weeks were included, 18 (26.5%) included at least one CPE case acquisition. By multivariate analysis, colonization pressure (odds ratio: 1.12; 95% confidence interval: 1.0-1.25; P=0.042) and antibiotic consumption (2.41; 1.02-5.66; P=0.044) were associated with CPE in-hospital transmission. Caregiver:patient ratio potentiated both these variables, suggesting a role for understaffing in CPE transmission. Understanding ward variables associated with CPE spread can help design suitable solutions. Colonization pressure and antibiotic consumption seems to be driving in-hospital transmission, along with caregiver:patient ratio. In presence of high colonization pressure, dedicated healthcare workers for managing CPE patients should be implemented. Co-ordination between ICT and antimicrobial stewardship team is also crucial to prevent CPE spread.

MASTDISCS combi Carba plus, a simple method for discriminating carbapenemase-producing Enterobacteriaceae, including OXA-48-type producers.

Accurate and rapid detection of carbapenemases and identification of their types in Enterobacteriaceae are both still major challenges for clinical laboratories in attempting to prevent the intrusion and transmission of carbapenemase-producing Enterobacteriaceae. This study aimed to evaluate the performance of the MASTDISCS combi Carba plus disc system in identification of different carbapenemase types, including OXA-48-type carbapenemase, for which no specific enzyme inhibitors have so far been available. The simple disc system discriminates carbapenemases, including OXA-48-types exhibiting low carbapenem minimum inhibitory concentrations, by targeting Enterobacteriaceae isolates with a EUCAST meropenem screening cut-off of ≥0.25 mg/L.

Recommendations for the control of carbapenemase-producing Enterobacteriaceae (CPE): A guide for acute care health facilities

Gram-negative bacteria that are resistant to antimicrobials, including carbapenems, have emerged as a significant global public health threat. Multidrug-resistant gram-negative bacteria, including carbapenemase-producing Enterobacteriaceae (CPE), place patients at risk of potentially untreatable infection. Australia has not reported a large number of CPE cases compared to Europe, North America, and the Middle East, creating an opportunity to prevent CPE from becoming established in Australia.An outbreak of Klebsiella pneumoniae carbapenemase in 2014 demonstrated there was variable testing, reporting, response to and communication of CPE. In response, the Australian Commission on Safety and Quality in Health Care formed a taskforce to assist health facilities to respond to the threat of CPE. Recommendations for state and territory health departments include coordinating a risk assessment, undertaking epidemiological and microbiological investigations, determining the requirement for control measures, and coordinating risk-communication activities. The response should take advice from experts in infectious diseases, microbiology, public health, infection prevention and control and epidemiologists.The guide aims to:•Alert healthcare professionals, health departments and hospital executives to the emerging threat of CPE in Australia•Recommend strategies to prevent, detect and contain CPE•Provide information and resources for hospital executives, healthcare professionals and consumers•Recommend laboratory screening and confirmation methods.The recommendations with rationale and commentary have been structured into sections depending on the burden of CPE in the health facility. The sections include: planning, preparing and prevention; CPE screening and surveillance; strategies to reduce CPE transmission; outbreak management; laboratory screening and confirmation methods.

Clinical and Molecular Epidemiology of Carbapenem-Resistant Enterobacteriaceae Among Adult Inpatients in Singapore.

Since 2010, the incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing in Singapore. We analyzed the clinical and molecular epidemiology of CRE among adult inpatients in Singapore. Quarterly incidence of unique subjects (per 100000 patient-days) with positive clinical and surveillance cultures for CRE were estimated based on mandatory data submitted to the National Public Health Laboratory by public hospitals between 2010 and 2015. CRE-positive adult inpatients were prospectively recruited from 6 public sector hospitals between December 2013 and April 2015. Subjects answered a standardized epidemiologic questionnaire and provided samples for this study. Further clinical information was extracted from subjects' electronic medical records. Whole-genome sequencing was performed on study isolates to determine transmission clusters. Incidence of CRE clinical cultures among adult inpatients plateaued from 2013 (range: 7.73 to 10.32 per 100000 patient-days) following an initial increase between 2010 and end-2012. We prospectively recruited 249 subjects. Their median age was 65 years, 108 (43%) were female, and 161 (64.7%) had carbapenemase-producing Enterobacteriaceae (CPE). On multivariate analysis, prior carbapenem exposure (OR: 3.23; 95% CI: 1.67-6.25) and hematological malignancies (OR: 2.85; 95% CI: 1.10-7.41) were associated with non-carbapenemase-producing CRE (NCPE) (n = 88) compared with CPE (n = 161) subjects. Among 430 CRE isolates from the 249 subjects, 307(71.3%) were CPE, of which 154(50.2%) were blaKPC-positive, 97(31.6%) blaNDM-positive, and 42 (13.7%) blaOXA-positive. Klebsiella pneumoniae (n = 180, 41.9%), Escherichia coli (n = 129, 30.0%) and Enterobacter cloacae (n = 62, 14.4%) were the main Enterobacteriaceae species. WGS (n = 206) revealed diverse bacterial strain type (STs). The predominant blaKPC-positive plasmid was pHS102707 (n = 62, 55.4%) and the predominant blaNDM-positive plasmid was pNDM-ECS01 (n = 46, 48.9%). Five transmission clusters involving 13 subjects were detected. Clinical CRE trend among adult inpatients showed stabilization following a rapid rise since introduction in 2010 potentially due to infection prevention measures and antimicrobial stewardship. More work is needed on understanding CPE transmission dynamics.

Persisting transmission of carbapenemase-producing Klebsiella pneumoniae due to an environmental reservoir in a university hospital, France, 2012 to 2014.

In France, the proportion of episodes of carbapenemase-producing Enterobacteriaceae (CPE) with no recent stay or hospitalisation abroad is increasing. In this study, we investigate epidemiological links between apparently unrelated cases of OXA-48-producing Klebsiella pneumoniae (Kp OXA-48) colonisation or infection. We genotyped detected organisms by repetitive sequence-based PCR, and used a dynamic registry of cases and contacts to cross-reference patients' hospital stays. Between 1 November 2012 and 28 February 2014, 23 Kp OXA-48 cases were detected in a university hospital in Montpellier, of which 15 were involved in three outbreaks: outbreaks I and II occurred in November 2012 and outbreak III in October 2013. Molecular comparison of bacterial strains revealed clonal identity between cases involved in outbreaks II and III and four single cases. Cross-referencing of hospital stays revealed that these single cases and the index case of outbreak III had occupied the same room. Active case search among former occupants of that room found an additional Kp OXA-48 carrier. A clonal strain was isolated from the sink of that room. The epidemiological link between the contaminated room and outbreak II remained undetected. This study is a reminder that environmental reservoirs should be considered as a source of CPE transmission.