Spread Of Carbapenem-resistant Enterobacteriaceae Research Articles

Carbapenem-resistant Enterobacteriaceae infections among patients admitted to intensive care units in Kano, Nigeria

Background: Globally, intensive care units (ICUs) are encountering emergence and spread of antibiotic-resistant pathogens, and for some pathogens, there are few therapeutic options available. Objectives: The study assessed prevalence, susceptibility pattern, and risk factors of carbapenem-resistant Enterobacteriaceae (CRE) infections among ICU patients in Kano, Nigeria. Materials and Methods: A descriptive cross-sectional study was used to study 190 patients admitted to the ICUs of two tertiary hospitals in Kano. Antibiotic susceptibility of isolated organisms was determined by disc diffusion technique. Suspected carbapenemase producers were further subjected to the modified Hodge test (MHT) method for confirmation. Results: A total of 76 out of the 190 samples yielded clinical isolates of Enterobacteriaceae as follows: 34 (44.7%) Escherichia coli, 19 (25%) Klebsiella pneumoniae, 3 (3.9%) Proteus mirabilis, 4 (5.3%) Enterobacter aerogenes, 3 (3.9%) Proteus vulgaris, 2 (2.6%) Citrobacter freundii, 2 (2.6%) Klebsiella ozaenae, 2 (2.6%) Klebsiella oxytoca, 2 (2.6%) Salmonella subsp. 3b, 2 (2.6%) Enterobacter agglomerans, 2 (2.6%) Enterobacter cloacae, and 1 (1.3%) Serratia odorifera. Screening the Enterobacteriaceae-positive samples for carbapenem resistance using ertapenem disc (10 μg) showed 8 samples (10.5%) as resistant while MHT gave a carbapenem resistance prevalence of 7.9% (6 out of 76). Based on multiplex polymerase chain reaction; the distributions of genotypes of the carbapenemase producers were as follows: Verona Integron Metallo-beta-lactamase (VIM) genes only (4 [50%]) New Delhi Metallo-beta-lactamase (NDM) genes only (2 [25%]), and 1 (12.5%) had Klebsiella pneumoniae carbapenemase (KPC) and VIM gene coexisting. Surgical procedure (P = 0.009) and history of recent admission (P = 0.001) were found to be risk factors for CRE. Conclusion: The study provided evidence of the presence of CRE infections among patients admitted to ICUs in the study centers. This underscores the need for effective infection prevention and control measures to avoid the spread of CRE in hospital setting.

Pattern of Carbapenem Resistance in Enterobacteriaceae in Rajshahi Medical College Hospital

The global emergence and spread of Carbapenem Resistant Enterobacteriaceae have been threatening the ability to treat an infection. Hence the present study was carried out with the aim to isolate important members of Enterobacteriaceae family with identification of carbapenem resistant isolates among them. The study was done in the Department of Microbiology, Rajshahi Medical College with collaboration of different disciplines of RMCH from January 2019 to December 2019. Samples were collected purposively. Causative organisms were isolated by culture and identified by colonial morphology, gram staining and relevant biochemical tests. Identified Enterobacteriaceae those showed resistance to carbapenem (imipenem, meropenem) were tested phenotypically by Modified Hodge Test (MHT) to see carbapenemase production. A total of 97 Enterobacteriaceae were isolated from 275 samples. E. coli (54.64%) was the most frequent isolate. By Modified Hodge Test, 19(19.59%) bacteria were phenotypically confirmed as Carbapenem Resistant Enterobacteriaceae (CRE). This study signifies that carbapenem resistance is increasing at an alarming rate.
 TAJ 2020; 33(2): 63-68

Carbapenem –resistant Enterobacteriaceae : Prevalence and bacteriological profile in a tertiary teaching hospital from rural western India

Introduction: In last few years, Gram-negative bacilli are isolated capable of producing various classes of carbapenemases with ability of hydrolyzing the ?-lactam antimicrobial. Carbapenem Resistant Enterobacteriaceae (CRE) have been reported worldwide. There is a serious threat to public health due to the emergence and rapid spread of CRE. Aims: To find prevalence and bacterial profile of CRE in clinical isolates in indoor patients from a rural tertiary care centre. Materials and Methods: The study was conducted in a tertiary care teaching hospital in Western India, June 2016 to April 2018. The clinical specimens received in microbiology laboratory were processed by the standard method. Bacteria were identified by VITEK 2 compact (Biomerieux) automation system, and antimicrobial susceptibility testing was done with the same system to detect minimum inhibitory concentrations for carbapenem group of antimicrobials. CLSI 2016 guidelines were used to detect CRE. Results: Total 535 Enterobactericaeae clinical isolates were included in the study. Of these, 31.77% (n=170) were CRE. Specimens like urine, pus/ wound swab and endotracheal tube secretion were the major contributors for CRE isolates.82% of CRE were Klebsiella pneumoniae (63%) and E.coli (19%). Conclusions: A high prevalence of 31.77% carbapenem resistance was observed among Enterobacteriaceae isolates. Early detection, isolation and contact precaution of CRE patients will help to prevent rapid dissemination of CRE infection. Keywords: Carbapenem Resistant Enterobacteriaceae, CRE, Carbapenemase, Klebsiella pneumoniae.

Carbapenem resistant Enterobacteriaceae neonatal gut colonization: A future concern in healthcare settings

Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) isolates are resistant to carbapenem and other beta-lactam drugs. Infections with these CREs have been reported in different age groups and are difficult to treat because of their resistant pattern and thus, they have become epidemiologically important. Materials and Methods: Rectal swabs from 150 term/ late preterm neonates (> 35 weeks) and 150 preterm neonates ( 3 days. Three rectal swabs were taken; 1st within 24hrs of birth (day 0), 2nd on day 3 and 3rd before discharge (day 4-10). They were screened for CRE in stool/rectal swab according to CDC criteria. These were further confirmed by following CLSI guidelines (MHT) to observe the carbapenemases production and real-time PCR for blaNDM-1, blaIMP, blaVIM, blaKPC. Results: A total of 8.7% (26/300) possible CREs were isolated in term/late preterm (15/26, 57.7%) and preterm neonates (11/26, 42.3%). Klebsiella pneumoniae was the commonest organism. In total, 22/26 (84.6%) possible CREs were MHT positive and rest 4 were MHT negative. The majority of MHT positive CREs were multidrug-resistant whereas MHT negative CREs was sensitive to tested carbapenem drugs. Carbapenemases genes (blaNDM-1=10, blaVIM=8, blaIMP=1, blaKPC=0) were identified in 19/26 of possible CREs, but multiple carbapenemases genes were not found. Conclusions: In this study, neonates were colonized with CRE within their gut as early as 72 hours after birth. This can cause infection in the postnatal period and may lead to spread of CRE in the community. Keywords: Carbapenem-Resistant Enterobacteriaceae, Neonatal Intensive care Unit, Modified Hodge Test.

How Long-Term Acute Care Hospitals Can Play an Important Role in Controlling Carbapenem-Resistant Enterobacteriaceae in a Region: A Simulation Modeling Study.

Typically, long-term acute care hospitals (LTACHs) have less experience in and incentives to implementing aggressive infection control for drug-resistant organisms such as carbapenem-resistant Enterobacteriaceae (CRE) than acute care hospitals. Decision makers need to understand how implementing control measures in LTACHs can impact CRE spread regionwide. Using our Chicago metropolitan region agent-based model to simulate CRE spread and control, we estimated that a prevention bundle in only LTACHs decreased prevalence by a relative 4.6%-17.1%, averted 1,090-2,795 new carriers, 273-722 infections and 37-87 deaths over 3 years and saved $30.5-$69.1 million, compared with no CRE control measures. When LTACHs and intensive care units intervened, prevalence decreased by a relative 21.2%. Adding LTACHs averted an additional 1,995 carriers, 513 infections, and 62 deaths, and saved $47.6 million beyond implementation in intensive care units alone. Thus, LTACHs may be more important than other acute care settings for controlling CRE, and regional efforts to control drug-resistant organisms should start with LTACHs as a centerpiece.

An Outbreak of New Delhi Metallo--Lactamase-5 (blaNDM-5)–Producing Escherichia coli in Companion Animals in the United States

Background: The emergence of carbapenem-resistant Enterobacteriaceae (CRE) in companion animals will be a game changer for infection prevention and control strategies in veterinary and human healthcare facilities. CRE have emerged as an important cause of human healthcare-associated infections and are a major clinical and public health problem. Although reports of CRE from animals are still very rare, they have been documented in China, Europe, and the United States. Methods: In April 2019, a passive veterinary surveillance system identified the blaNDM-5 gene in an E. coli isolated from a dog in Philadelphia in July 2018. CRE are reportable to the Philadelphia Department of Public Health (PDPH), and in May 2019, the Matthew J. Ryan Veterinary Hospital at the University of Pennsylvania (MJRVH) reported a cluster of carbapenem-resistant E. coli (CR-E. coli) isolated from 14 animals to the PDHP. This cluster of 17 isolates, that all contained a blaNDM-5 gene, was the first report of a CR-E. coli outbreak at a US veterinary facility. The first isolate, E. coli 24213-18, was sequenced on the Pacific Biosciences (PacBio) Sequel Sequencer and has been uploaded to GenBank. Whole genome sequencing was performed on all 17 isolates using the Illumina MiSeq platform. Antimicrobial resistance genes were identified from the National Center for Biotechnology Information Pathogen Detection Isolates Browser using AMRFinder. Results: PacBio sequencing confirmed E. coli ST167 and identified a circular IncFII plasmid of 139,547 bp that contained the blaNDM-5 gene, along with many additional resistance genes. In June 2019, a retrospective review of hospital records was completed and showed that, from July 2018, 17 CR- E. coli were isolated from 14 animals. Conclusions: Control of CRE infections in human healthcare settings is challenging because the organisms colonize the gastrointestinal tract and can go undetected. The same issue is to be expected with companion animals. Healthcare-associated spread of CRE E. coli in a veterinary facility emphasizes the importance of rapidly identifying and characterizing carbapenem-resistant isolates from animals. Methods to control the spread of CRE in veterinary medical settings have not yet been studied, and related investigations will be critically important to limit the transmission of these pathogens in animal populations. The risk of transmission of CRE from animals to people is currently poorly understood. CRE will be a major challenge across all health fields as these organisms become more prevalent in the community. It is likely that a ‘One Health’ approach to surveillance, infection prevention, and antimicrobial stewardship will be required to limit the spread and potential global dominance of CRE.Funding: NoneDisclosures: None

Multiscale Modeling of Patient Movement to Determine Effects of Surveillance on Healthcare-Associated Infections

Background: The transmission of pathogenic organisms in healthcare settings is a major cause of healthcare-associated infections (HAIs). In recent years, infections with carbapenem-resistant Enterobacteriaceae (CRE) have become a significant public health threat, in part because many patients are arriving at the hospital already colonized, and colonization is a major risk factor for infection. Reducing transmission requires understanding how patient movement drives the spread of CRE; however, analysis of this issue has mostly been modeled at a hospital-level without much consideration for the population dynamics that occur outside of the hospital setting and how patients move between healthcare settings. Patients move between hospitals, other healthcare settings, such as long-term care facilities (LTCFs), and the community, all of which pose different colonization risks. Thus, studying each environment in isolation fails to realistically address the consequences of large-scale policy interventions. One such intervention is a statewide electronic registry to track patients who are known to be colonized or have had a CRE infection. Understanding the potential for reducing CRE morbidity and mortality requires consideration of small- and large-scale effects on patients’ movement and transmission. Methods: We developed a multiscale, metapopulation model for hospitals, communities, and LTCFs in the state of Maryland. In our computational simulation, we included a regional- as well as a local-scale model that were informed by the patient-mix data from the Maryland Health Service Cost Review Commission. We examined the impact of implementing a registry compared to less coordinated scenarios. Results: The most effective policy was the implementation of an electronic registry which resulted in 9.6% median reduction in CRE HAIs in Maryland for simulated outcomes (Fig. 1). Other interventions included colonization screening at various or all hospitals and using a predictive algorithm to determine at-risk patients that need to be screened. These interventions only resulted in ~1%–3% reductions in HAIs. We also observed that coupling other interventions with an electronic registry does not aid in reducing more HAIs.Funding: NoneDisclosures: NoneBoxplot of simulated outcomes of all scenarios compared to the baseline scenario. The scenarios include (1) complete screening with no electronic registry, (2) selective screening with no electronic registry, (3) predictive screening with no electronic registry, (4) baseline with an electronic registry, (5) complete screening with an electronic registry, (6) selective screening with an electronic registry, and (7) predictive screening with an electronic registry. Scenarios 5-7 include the same interventions as 1–3 coupled with an electronic registry.

Carbapenem-resistant enterobacteriaceae: don’t trust your neighbour

Abstract Background The spread of carbapenem-resistant enterobacteriaceae (CRE) outbreaks consists not only of germs producing KPC and OXA-48, endemic already, but also metallo-beta-lactamase such as NDM or VIM. In Tuscany, Italy, a multidisciplinary regional task force has extended, since NDM alert spread out, from 1st Oct 2019 the CRE screening programme, via molecular testing, to newly admitted patients in high risk settings (medical, intensive care, oncology, transplant, infectious diseases, cardiac surgery units) to fight cross-contamination. The aim of the study is to assess levels and types of CRE in an italian teaching hospital (615 beds) after the programme became effective. Methods The surveillance team began recording daily all the CRE positive cases, defined as laboratory confirmed colonizations/infections with CRE. Our retrospective, descriptive study covers the time span between 30th Sep - 16th Dec 2019. Cases were classified by infected apparatus and by resistance phenotype, and we calculated descriptive statistics. Results In total we identified 97 cases (male 60.82%, mean (+/-SD) age 71.58+/-17.34 years, 74.23% in medical wards); 5 patients had two body districts infected and 9 carried two different phenotypes. Out of 102 positive samples, 92.16% were bowel colonization, 1.96% BSI, 3.92% urinary and 1.96% respiratory. Among these, 21 were NDM (19.81%), 29 KPC (27.36%), 4 OXA-48 (3.77%), 52 VIM (49.06%). The most detected germ was Klebsiella pneumoniae (30.19%), followed by Escherichia coli (2.83%), Enterobacter cloacae (2.83%), Citrobacter freundii and braakii (2.83%), Klebsiella oxytoca (1.89%). 61 agents were unspecified (57.55%). Among the 21 NDM, 76.19% were K. pneumoniae, only one was a BSI. Conclusions CREs continue to be present despite constant surveillance. Although high levels of KPC-producing agents persist, the new spread of VIM phenotype is significant, highlighting, however, that the pathogen wasn't detected in over 50% of the samples. Key messages Despite increased surveillance, there is still a consistent portion of patients colonized with unidentified CRE. A surveillance mainly focused on NDM-producing CREs had incidentally highlighted an unexpected spread of VIM phenotype.

Efficacy of meropenem and amikacin combination therapy against carbapenemase-producing Klebsiella pneumoniae mouse model of pneumonia

BackgroundThe emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) is a global health problem due to its high mortality and limited treatment options. Combination antimicrobial therapy is reported to be effective against CRE in vitro; however, its efficacy in vivo has not been thoroughly evaluated. Thus, this study assessed the efficacy of combination therapy of meropenem (MEPM) and amikacin (AMK) in a carbapenem-resistant Klebsiella pneumoniae (CR-Kp) mouse model of pneumonia. Materials and methodsAgar-based bacterial suspension of CR-Kp clinical isolates was inoculated into the trachea of BALB/c mice. Treatment was initiated 6 h post infection, with 100 mg/kg MEPM every 6 h, 100 mg/kg AMK every 12 h, or in combination; survival was evaluated for 7 days. The number of viable bacteria in the lungs, lung histopathology, and neutrophil counts in broncho-alveolar lavage fluid (BALF) were evaluated 42 h after infection. ResultsAll mice in the untreated control group died in 48 h, while all the mice in treatment groups survived past 7 days following infection. The bacterial count in the lungs (log10 CFU/mL, mean ± SEM) in the combination group (2.00 ± 0.00) decreased significantly compared to that in control (10.19 ± 0.11, p < 0.0001), MEPM (6.38 ± 0.17, p < 0.0001), and AMK (6.17 ± 0.16, p < 0.0001) groups. BALF neutrophil count reduced only in the combination therapy group. Combination therapy prevented the progression of lung inflammation, including alveolar neutrophil infiltration and hemorrhage. ConclusionsThis study demonstrates in vivo efficacy of MEPM and AMK combination therapy against CR-Kp pneumonia.

Rising Threat of OXA-48 and other Carbapenemase Encoding Genes among Carbapenem Resistant Enterobacteriaceae in India

Members of Enterobacteriaceae family are responsible for both community and hospital acquired infections. Because of development of antimicrobial resistance carbapenem has remained as last resort of drug for treatment of infections caused by these bacteria.Mechanism for development of this resistance in carbapenem resistant Enterobacteriaceae (CRE) may due to production of carbapenemases, efflux mechanism or loss of outer membrane porins.The most common carbapenemase enzymes are Class A – KPC, Class B – NDM, VIM and IMP and Class D oxacillinase(OXA-48 like enzymes).In India, most prevalent carbapenemase encoding gene is NDM-1but there is rising threat of OXA-48 prevalence. Unlike the phenotypic methods, the genotypic methods are useful to discriminate the type of carbapenemase enzyme, specifically for OXA-48 like enzymes. Total 170 CRE isolates were subjected for multiplex PCR study for their molecular characterization. Of the 170 CRE isolates,68.2 % (n=116) were positive for NDM-1 gene while 44.1 % (n= 75) of the isolates showed presence of OXA-48 gene. VIM (2.3%), KPC (1.7 %) were responsible for carbapenemase production while none of the isolates showed presence of IMP gene. NDM-1 and OXA-48 coexisted in 21.2 % (n=36) of the total isolates. OXA-48 causes weak hydrolysis of carbapenem because of which it is under reported with routine diagnostic methods. Early detection of OXA-48 and other carbapenemase encoding genes, helps for contact precautions and effective therapy which prevents further escalation and horizontal spread of CRE.

Co-occurrence of a novel VIM-1 and FosA3-encoding multidrug-resistant plasmid and a KPC-2-encoding pKP048-like plasmid in a clinical isolate of Klebsiella pneumoniae sequence type 11

The spread of carbapenem-resistant Enterobacteriaceae (CRE) worldwide remains a major threat to public health. Notably, carbapenemase-encoding genes are usually located in plasmids harboring other resistance determinants, and isolates having multiple plasmids are often highly resistant to carbapenems. In this study, we characterized the genetic context of coproduction of KPC-2, VIM-1, and FosA3 via two plasmids in the multidrug-resistant Klebsiella pneumoniae sequence type 11 (ST11) isolate JS187, recovered during an outbreak of KPC-2-producing K. pneumoniae in a Chinese teaching hospital in 2008. Plasmid p187–1, coharboring blaVIM-1 and fosA3, consisted of a pKOX-R1-like backbone and two multidrug resistant (MDR) regions separated by pKHS1-like backbone sequences involving plasmid replication and stability. The MDR region 1 was a chimera composed of the blaVIM-1-bearing In916-like integron and Tn1721-like transposon, and was disrupted by sequential insertion of an IS26-based transposition unit carrying blaCTX-M-3 and a ΔTn3-like transposon bearing blaTEM-1. MDR region 2 was an IS26-array structure with fosA3 and blaSHV-12. Plasmid p187–2 harboring blaKPC-2 was closely related to pKP048. blaKPC-2 in p187–2 was carried by a Tn1721 variant, which differed from the prototype Tn1721-blaKPC-2 transposon observed in pKP048 by disruption of an IS26 at Tn3 and deletion of a 31-kb MDR fragment. Co-existence of the novel VIM-1- and FosA3-encoding MDR plasmid p187–1 and the KPC-2-encoding pKP048-like plasmid p187–2 made K. pneumoniae JS187 highly resistant to carbapenems. Moreover, p187–1 still carried genes conferring resistance to cephalosporins, fosfomycin, chloramphenicol, and quaternary ammonium, posing substantial challenges for the treatment of Enterobacteriaceae infections. Thus, monitoring the prevalence and evolution of these plasmids and/or strains is critical.

What are acute NHS trusts in England doing to prevent the cross-border spread of carbapenem-resistant Enterobacteriaceae?

Carbapenem-resistant Enterobacteriaceae (CRE) pose a significant threat to global public health as these organisms have the potential to cause infections which are easily spread and are associated with high mortality rates. The aim of this study was to establish which screening strategies acute NHS trusts in England have chosen to adopt and whether or not that strategy has prevented or is likely to prevent the cross-border spread of CRE. All acute NHS trusts in England were invited to participate in a multicentre quantitative study. Participants were asked to complete a questionnaire relating to their local CRE screening protocol. Of the 91 participating trusts, 83 (91.2%) adhere to Public Health England (2013) guidance. However, only 22 (24.2%) trusts have adopted the European Centre for Disease Prevention and Control (2016) recommendations. In total, 31 (34.1%) trusts reported incidences of person-to-person transmission, of which 45.2% were related to foreign travel. Furthermore, 31 (34.1%) trusts reported that patients who have had an admission to a hospital in the UK not known to have a high prevalence of healthcare-associated CRE in the last 12 months had screened positive. This study has demonstrated that inter-hospital transmission is as much of a concern as cross-border spread. Mandatory participation in enhanced surveillance could provide PHE with the epidemiological evidence required to support this stance and help to develop new national guidance.

Carbapenem Resistant Enterobacteriaceae in Africa

Carbapenems are regarded as unique among the �-lactam antibiotics due to their broad spectrum of activity and ability to resist �-lactamase hydrolysis. Carbapenems are the only �-lactam antibiotics with efficacy in severe infections caused by extended-spectrum beta-lactamase (ESBL) producing bacteria. However, recent reports of carbapenem resistance particularly among members of Enterobacteriaceae that are responsible for diseases such as gastrointestinal infections, septicemia, pneumonia, meningitis, peritonitis as well as urinary tract infections, call for concerns. In Africa, the problem of carbapenem-resistant Enterobacteriaceae (CRE) is aggravated by factors such as the high rate of infections, poor diagnostic tools, sub-optimal disease surveillance, and abuse of antibiotics. Besides, the problem of CRE in Africa is understudied. This review distills available literature on the spread of CRE in Africa, CRE genes in circulation, and the need to pay attention to this emerging threat to lives in developing countries.

Inactivation of mgrB gene regulator and resistance to colistin is becoming endemic in carbapenem-resistant Klebsiella pneumoniae in Greece: A nationwide study from 2014 to 2017

IntroductionIn Greece, the spread of carbapenem-resistant Enterobacteriaceae in humans has led to the reintroduction of colistin as a therapeutic agent. Unfortunately, colistin resistance with different mechanisms has emerged. The present work aims to determine the prevalence of carbapenem and colistin resistance and the corresponding mechanisms in Klebsiella pneumoniae clinical isolates from Greece. MethodsFrom 2014 to 2017, 288 carbapenem-resistant K. pneumoniae clinical strains were gathered from a collection of 973 isolates from eight different hospitals in Greece. Antibiotic susceptibility testing was performed using three different methods. Screening of carbapenem and colistin resistance genes was conducted using polymerase chain reaction (PCR) amplification and sequencing. ResultsAmong the 288 (29.6 %) carbapenem-resistant isolates, 213 (73.9%) were colistin-resistant (minimum inhibitory concentration [MIC] >2 mg/L). The KPC type was the most common carbapenemase gene (116; 40.3%), followed by VIM (41; 14.2%), NDM (33; 11.5%) and OXA-48 (22; 7.6%). Moreover, 44 (15.3%) strains co-produced two types of carbapenemases. No mcr genes were detected for colistin resistance but mutations in chromosomal genes were found. These included inactivation of the mgrB gene for 148 (69.5%) strains, including insertion sequences for 94 (44.1%), nonsense mutations for 4 (1.9%) and missense mutations for 24 (11.3%). Moreover, PCR amplification of mgrB gene was negative for 26 (12.2%) strains. Finally, 65 (30.5%) colistin-resistant strains exhibited a wild-type mgrB, the mechanisms of which remain to be elucidated. ConclusionThis study shows that K. pneumoniae clinical strains in Greece are resistant to both carbapenems and colistin and this is endemic and is likely chromosomally encoded.

How to Choose Target Facilities in a Region to Implement Carbapenem-resistant Enterobacteriaceae Control Measures.

When trying to control regional spread of antibiotic-resistant pathogens such as carbapenem-resistant Enterobacteriaceae (CRE), decision makers must choose the highest-yield facilities to target for interventions. The question is, with limited resources, how best to choose these facilities. Using our Regional Healthcare Ecosystem Analyst-generated agent-based model of all Chicago metropolitan area inpatient facilities, we simulated the spread of CRE and different ways of choosing facilities to apply a prevention bundle (screening, chlorhexidine gluconate bathing, hand hygiene, geographic separation, and patient registry) to a resource-limited 1686 inpatient beds. Randomly selecting facilities did not impact prevalence, but averted 620 new carriers and 175 infections, saving $6.3 million in total costs compared to no intervention. Selecting facilities by type (eg, long-term acute care hospitals) yielded a 16.1% relative prevalence decrease, preventing 1960 cases and 558 infections, saving $62.4 million more than random selection. Choosing the largest facilities was better than random selection, but not better than by type. Selecting by considering connections to other facilities (ie, highest volume of discharge patients) yielded a 9.5% relative prevalence decrease, preventing 1580 cases and 470 infections, and saving $51.6 million more than random selection. Selecting facilities using a combination of these metrics yielded the greatest reduction (19.0% relative prevalence decrease, preventing 1840 cases and 554 infections, saving $59.6 million compared with random selection). While choosing target facilities based on single metrics (eg, most inpatient beds, most connections to other facilities) achieved better control than randomly choosing facilities, more effective targeting occurred when considering how these and other factors (eg, patient length of stay, care for higher-risk patients) interacted as a system.

Evaluation of patient risk factors for infection with carbapenem-resistant Enterobacteriaceae

To evaluate risk factors for infection or colonization with carbapenem-resistant Enterobacteriaceae (CRE) to develop an algorithm for targeted CRE screening. We conducted a case-control study of 50 CRE-positive cases and 100 CRE-negative controls to identify risk factors that were significant for CRE infection or colonization. The setting was at an acute care academic hospital. Patients who tested positive for CRE or other microbiological laboratory tests during the study period were included. We reviewed medical records of 50 patients who were CRE-positive and 100 matched controls who had a non-CRE culture at a similar anatomic site within the closest time period to the case's culture date. Risk factors were assessed using logistic regression with SAS 9.4, observing the 95% confidence interval (CI) to determine significance. Significant risk factors for CRE infection or colonization included the use of fluoroquinolones (odds ratio [OR], 3.75; 95% CI, 1.35, 10.38) and cephalosporins (OR, 2.37; 95% CI, 1.17, 4.86). In addition, undergoing an invasive procedure with a scope device was also a significant risk factor for our participants (OR, 4.57; 95% CI, 1.31, 16.02). Significance of these risk factors varied within the community-acquired and hospital-acquired cases. Our results suggest that exposure to certain antimicrobials and invasive procedures with a scope device (endoscopic retrograde cholangiopancreatography, duodenal endoscope) are risk factors for CRE. The findings of significant differences in antimicrobials received highlight the necessity to understand antimicrobial stewardship in the development of CRE colonization and infection. Along with antibiotics, inaccessibility to components within scope devices may be increasing the risk of CRE spread.

Comparison of Four Commercial Screening Assays for the Detection of blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA48 in Rectal Secretion Collected by Swabs.

The spread of carbapenem-resistant Enterobacteriaceae (CRE) has been enabled by the lack of control measures directed at carriers of multidrug-resistant organisms in healthcare settings. Screening patients for asymptomatic colonization on the one hand, and implementation of contact precautions on the other hand, reduces patient-to-patient transmission. Screening plates represents a relatively low-cost method for isolating CRE from rectal swabs; however, molecular assays have become widely available. This study compared the performance of four commercial molecular platforms in detecting clinically significant carbapenemase genes versus routine screening for CRE. A total of 1015 non-duplicated rectal swabs were cultured on a chromogenic carbapenem-resistant selective medium. All growing Enterobacteriaceae strains were tested for carbapenemase-related genes. The same specimens were processed using the following molecular assays: Allplex™ Entero-DR, Amplidiag® CarbaR + MCR, AusDiagnostics MT CRE EU, and EasyScreen™ ESBL/CPO. The prevalence of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae detected by swab culture was 2.2%, while organisms producing oxacillinase (OXA)-48 and metallo-β-lactamases were infrequent. The cost of CRE-related infection control precautions, which must be kept in place while waiting for screening results, are significant, so the molecular tests could become cost-competitive, especially when the turnaround time is decreased dramatically. Molecular assays represent a powerful diagnostic tool as they allow the rapid detection of the most clinically relevant carbapenemases.

Knowing More of the Iceberg: How Detecting a Greater Proportion of Carbapenem-Resistant Enterobacteriaceae Carriers Influences Transmission.

Clinical testing detects a fraction of carbapenem-resistant Enterobacteriaceae (CRE) carriers. Detecting a greater proportion could lead to increased use of infection prevention and control measures but requires resources. Therefore, it is important to understand the impact of detecting increasing proportions of CRE carriers. We used our Regional Healthcare Ecosystem Analyst-generated agent-based model of adult inpatient healthcare facilities in Orange County, California, to explore the impact that detecting greater proportions of carriers has on the spread of CRE. Detecting and placing 1 in 9 carriers on contact precautions increased the prevalence of CRE from 0% to 8.0% countywide over 10 years. Increasing the proportion of detected carriers from 1 in 9 up to 1 in 5 yielded linear reductions in transmission; at proportions >1 in 5, reductions were greater than linear. Transmission reductions did not occur for 1, 4, or 5 years, varying by facility type. With a contact precautions effectiveness of ≤70%, the detection level yielding nonlinear reductions remained unchanged; with an effectiveness of >80%, detecting only 1 in 5 carriers garnered large reductions in the number of new CRE carriers. Trends held when CRE was already present in the region. Although detection of all carriers provided the most benefits for preventing new CRE carriers, if this is not feasible, it may be worthwhile to aim for detecting >1 in 5 carriers.

539. Canaries in a Coal Mine?: Early Identification of Regional Spread of Novel Multidrug-resistant Organisms (MDROs) Using Sentinel Surveillance in Skilled Nursing Facilities Caring For Ventilated Patients (vSNFs)

BackgroundRegional containment of novel or targeted MDROs depends on detecting their presence as soon as possible following their introduction. Prior modeling studies suggest that after importation to a region, novel MDROs appear relatively quickly in certain high-risk post-acute long-term care facilities via patient movement. Sentinel surveillance in such facilities might facilitate early detection of emergent MDROs, thereby enhancing the effectiveness of containment efforts.MethodsWe simulated the introduction and spread of carbapenem-resistant Enterobacteriaceae (CRE) in a region using an adaptation of a previously described susceptible-infectious-susceptible model (Clin Infect Dis. 2019 March 28 doi: 10.1093/cid/ciz248). The model includes the patient sharing network among healthcare facilities in an exemplar US state, using claims data and the Minimum Data Set from the Centers for Medicare & Medicaid Services for 2015. Disease progression, transmission and testing rates were estimated for CRE using data from the literature. Each simulated outbreak was initiated with a single importation to a Dartmouth Atlas of Health Care hospital referral region. The predicted timing of first CRE detection using two different data sources was compared: (1) real-time monitoring of clinical microbiology test results, or (2) results from quarterly point prevalence colonization surveys (PPSs). For each data source, the timing of earliest detection was compared according to availability of data from: (a) all healthcare facilities statewide, (b) only long-term acute care hospitals, (c) only vSNFs, or (d) only the largest acute care hospitals in the state (n = 23).ResultsCompared with real-time monitoring of clinical microbiology testing results from all facilities statewide, quarterly PPSs at all facilities detected CRE 446 days (median; range 312–608 days) earlier, while PPSs at only vSNFs (representing 4.4% of inpatient beds statewide) detected CRE 385 days (range 194–553 days) earlier (figures).ConclusionRegular point prevalence surveys in vSNFs may detect new MDROs in a region approximately one year sooner than real-time monitoring of clinical microbiology results, and may be an efficient strategy for early regional detection and subsequent containment. Disclosures All authors: No reported disclosures.

Carbapenem-Resistant Enterobacteriaceae Posing a Dilemma in Effective Healthcare Delivery.

The emergence and spread of Carbapenem-resistant Enterobacteriaceae (CRE) is seriously posing threats in effective healthcare delivery. The aim of this study was to ascertain the emergence of CRE at Chukwuemeka Odumegwu Ojukwu University Teaching Hospital (COOUTH) Awka. Biological samples were collected from 153 consenting patient from 5 clinics in the hospital. The isolates were identified using standard microbiological protocols. Susceptibility to meropenem was done using Kirby-Bauer disc diffusion method on Mueller Hinton Agar. A total of 153 patients were recruited in this study. About one half of those from rural, 63.64% from Sub-urban and 42.27% from urban areas had significant E. coli and Klebsiella spp infections. The male: female ratio of the Enterobacteriaceae infection was 1:1. Almost as much inpatient as outpatient study participants had the infections. The infections were observed mostly on participants with lower educational status. The unmarried individuals were most infected compared to their married counterparts. Enterobacteriaceae infection rate was 50.98%. Of this, 28.21% had CRE infection while the overall prevalence of the CRE in the studied population was 14.38% (22/153). This study shows that CRE is quickly emerging in both community and hospital environments. Klebsiella spp was the most common CRE in this hospital especially Klebsiella oxytoca. Hospitalization was a strong risk factor in the CRE infections. Rapid and accurate detection is critical for their effective management and control.