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Success of a National Intervention in Controlling Carbapenem-resistant Enterobacteriaceae in Israel’s Long-term Care Facilities

Success of a National Intervention in Controlling Carbapenem-resistant Enterobacteriaceae in... Abstract Background Long-term care facilities (LTCFs) are a major reservoir of carbapenem-resistant Enterobacteriaceae (CRE) in healthcare facilities, contributing to rapid regional dissemination of CRE. Methods In 2008, The Israeli National Center for Infection Control (NCIC) initiated a coordinated, comprehensive intervention in Israel’s LTCFs, encompassing approximately 25000 beds in over 300 institutions. The intervention included implementation of population-tailored contact precautions and early detection of carriers. The NCIC established a real-time repository of all CRE carriers and events of acquisition, supervised information exchange between healthcare facilities and directed intervention at the institutional level during local outbreaks. CRE incidence was determined based on detection of CRE, either during LTFC stay or on admission to another facility. Prevalence was determined by a series of 5 cross-sectional surveys commenced between 2008 and 2015. Results From January 2009 through December 2015, 5265 patients acquired CRE in LTCFs. During the study period, incidence of acquisition declined in all facility types, to approximately 50% of the baseline (P < .001). The number of skilled nursing facilities and nursing homes experiencing ≥ 5 CRE acquisitions annually decreased from 35 to 11 during this period. The point prevalence of newly detected CRE carriage in post-acute care hospitals decreased from 12.3% in the survey commenced in 2008 to 0.8% in that begun in 2015 (P < .001). Conclusions A national, coordinated intervention resulted in a sustained decrease in CRE incidence and prevalence in LTCFs. These results support the assumption that centrally coordinated intervention is an essential public health tool in reducing CRE in healthcare facilities. carbapenem-resistant Enterobacteriaceae, intervention, long-term care facilities Carbapenem-resistant Enterobacteriaceae (CRE) are spreading globally and are of major concern to clinicians and public health authorities. These organisms are at highest priority for both drug development and prevention activities by the Centers for Disease Control and Prevention and the World Health Organization [1, 2]. The rapidity of CRE spread within and between healthcare facilities is unprecedented [3, 4]. The annual number of serious CRE infections is estimated at over 25000 in North America [1] and over 68000 in Europe [5, 6]. The rapid regional and inter-regional spread combined with the severe outcomes of these infections threaten the ability of the healthcare system to provide patient care safely [7]. High degrees of CRE prevalence have been described in several investigations involving patients from long-term care facilities, predominantly long-term acute care hospitals (LTACHs) [8–10]. Mounting evidence suggests that outbreaks in LTCFs may be a driving force behind regional dissemination of CRE, facilitated by extensive patient transfer between acute and long-term care facilities [11]. Yet despite increasing knowledge of the central role of LTCFs in regional dissemination, most reported interventions have been conducted in individual, mostly acute care facilities [12]. Given the degree of patient movement between healthcare facilities in a given region and the demonstrated efficiency of CRE spread in the inpatient setting [11], it is increasingly apparent that coordinated, regional interventions including all types of inpatient healthcare facilities may have a key role in containing regional spread of CRE [1, 13, 14]. The Israeli CRE outbreak has been described in several reports [15, 16]. Briefly, since 2006, Israel has faced nationwide dissemination of CRE. The percentage of Klebsiella pneumoniae invasive isolates resistant to carbapenems rose from less than 1%, to over 22% within 2 years [17]. In response, a nationally directed infection control intervention was undertaken in early 2007 by the Israeli National Center for Infection Control (NCIC), implemented initially in acute care hospitals. This intervention led to a substantial decrease in the incidence of nosocomial CRE in acute care [18]. Shortly after initiating the national intervention, we noted that approximately 40% of carriers in acute care hospitals were discharged to LTCFs, resulting in a large CRE reservoir in these facilities. Moreover, some acute care hospital outbreaks were traced to carriers admitted from LTCFs. In response to these epidemiological observations, in 2008 the NCIC extended its nationwide intervention targeting CRE spread to LTCFs. Here we describe and report on the impact of this ongoing national LTCF intervention. METHODS Setting LTCFs in Israel comprise 3 facility types: 15 post-acute care hospitals (PACHs), 15 skilled nursing facilities (SNFs) and roughly 300 nursing homes (NHs), with an approximate overall total of 25000 beds (Table 1). The PACHs, which comprise about 10% of LTCF beds, provide continued intensive treatment after hospital discharge to patients with conditions that result in reduced ability to perform activities of daily living. Wards in PACHs are classified as skilled nursing care, chronic mechanically ventilated, subacute medical and rehabilitation. Included among the patient populations in PACHs are those found in LTACHs in the United States. SNFs include patients requiring ongoing nursing care and medical observation. NHs include patients requiring nursing care without continuous medical observation. Table 1. Long-term Care Facilities and Population-based Infection Control Measures for Prevention of Carbapenem-resistant Enterobacteriaceae Spread Facility Type Post-acute Care Hospital (N = 15) Ward Types Skilled Nursing Facilities (N = 15) Nursing Homes (N~300) Skilled Nursing Care Chronic Mechanically Ventilated Sub-acute Medical Rehabilitation Facility characteristics Number of beds 850 500 300 1100 2500 20000 Patient population Require intensive nursing care and medical observation Stable, mechanically ventilated >30 days Complex medical conditions requiring longer hospitalization than provided in acute care Require rehabilitation, mostly following hospitalization involving immobilization Mixed, require nursing care at varying levels of intensity and medical observation Stable, require assistance in activities of daily living Average length of stay Months to years Months to years Weeks Weeks to months Months to years Years Infection control measures for CRE carriers Use of single-use gowns and gloves and dedicated medical equipment Required Dedicated nursing staff Not required Private room/ cohort Required Required Required Not required Requirement depends on specific ward population Not required Active surveillance of high-risk patientsa Required Required Required Not required Requirement depends on specific ward population Not required Participation in group activities Permitted Implementation of national carrier isolation discontinuation protocol 3 months from last positive CRE culture Recommended Facility Type Post-acute Care Hospital (N = 15) Ward Types Skilled Nursing Facilities (N = 15) Nursing Homes (N~300) Skilled Nursing Care Chronic Mechanically Ventilated Sub-acute Medical Rehabilitation Facility characteristics Number of beds 850 500 300 1100 2500 20000 Patient population Require intensive nursing care and medical observation Stable, mechanically ventilated >30 days Complex medical conditions requiring longer hospitalization than provided in acute care Require rehabilitation, mostly following hospitalization involving immobilization Mixed, require nursing care at varying levels of intensity and medical observation Stable, require assistance in activities of daily living Average length of stay Months to years Months to years Weeks Weeks to months Months to years Years Infection control measures for CRE carriers Use of single-use gowns and gloves and dedicated medical equipment Required Dedicated nursing staff Not required Private room/ cohort Required Required Required Not required Requirement depends on specific ward population Not required Active surveillance of high-risk patientsa Required Required Required Not required Requirement depends on specific ward population Not required Participation in group activities Permitted Implementation of national carrier isolation discontinuation protocol 3 months from last positive CRE culture Recommended Abbreviation: CRE, carbapenem-resistant Enterobacteriaceae. aRelates not to known CRE carriers but to patients at risk of carriage View Large Table 1. Long-term Care Facilities and Population-based Infection Control Measures for Prevention of Carbapenem-resistant Enterobacteriaceae Spread Facility Type Post-acute Care Hospital (N = 15) Ward Types Skilled Nursing Facilities (N = 15) Nursing Homes (N~300) Skilled Nursing Care Chronic Mechanically Ventilated Sub-acute Medical Rehabilitation Facility characteristics Number of beds 850 500 300 1100 2500 20000 Patient population Require intensive nursing care and medical observation Stable, mechanically ventilated >30 days Complex medical conditions requiring longer hospitalization than provided in acute care Require rehabilitation, mostly following hospitalization involving immobilization Mixed, require nursing care at varying levels of intensity and medical observation Stable, require assistance in activities of daily living Average length of stay Months to years Months to years Weeks Weeks to months Months to years Years Infection control measures for CRE carriers Use of single-use gowns and gloves and dedicated medical equipment Required Dedicated nursing staff Not required Private room/ cohort Required Required Required Not required Requirement depends on specific ward population Not required Active surveillance of high-risk patientsa Required Required Required Not required Requirement depends on specific ward population Not required Participation in group activities Permitted Implementation of national carrier isolation discontinuation protocol 3 months from last positive CRE culture Recommended Facility Type Post-acute Care Hospital (N = 15) Ward Types Skilled Nursing Facilities (N = 15) Nursing Homes (N~300) Skilled Nursing Care Chronic Mechanically Ventilated Sub-acute Medical Rehabilitation Facility characteristics Number of beds 850 500 300 1100 2500 20000 Patient population Require intensive nursing care and medical observation Stable, mechanically ventilated >30 days Complex medical conditions requiring longer hospitalization than provided in acute care Require rehabilitation, mostly following hospitalization involving immobilization Mixed, require nursing care at varying levels of intensity and medical observation Stable, require assistance in activities of daily living Average length of stay Months to years Months to years Weeks Weeks to months Months to years Years Infection control measures for CRE carriers Use of single-use gowns and gloves and dedicated medical equipment Required Dedicated nursing staff Not required Private room/ cohort Required Required Required Not required Requirement depends on specific ward population Not required Active surveillance of high-risk patientsa Required Required Required Not required Requirement depends on specific ward population Not required Participation in group activities Permitted Implementation of national carrier isolation discontinuation protocol 3 months from last positive CRE culture Recommended Abbreviation: CRE, carbapenem-resistant Enterobacteriaceae. aRelates not to known CRE carriers but to patients at risk of carriage View Large The LTCF Intervention We began the intervention in 2008 with site visits at the PACHs, followed by a cross-sectional point prevalence survey, conducted to assess prevalence and risk factors associated with CRE carriage [19]. High proportions of carriage were observed, ranging from 27% in skilled nursing wards to 2% in rehabilitation wards. We developed the subsequent components of the PACH intervention in accordance with our findings. We have previously reported results of the first 3 years of the intervention in the PACHs [20]. In 2009 we formalized and extended the ongoing nationally coordinated multimodal intervention in all types of LTCFs, focusing on improving general infection control practices and intensifying CRE containment measures. NCIC professionals developed a curriculum and provided training in infection control principles specific to the LTCF setting to designated infection control personnel, responsible in turn for the transfer of knowledge within the institutions. This training consisted of a 36-hour course and periodic workshops, supported by the Ministry of Health. The CRE-specific prevention program was tailored to the ward setting. Based on the results of our 2008 survey [19] and observations from site visits and professional communications, we stratified wards into risk categories: high risk (mechanical ventilation, skilled nursing and subacute medical wards) and low risk (rehabilitation and general nursing wards). Table 1 summarizes the infection control measures prescribed for CRE carriers in each ward type. Rehabilitation and social activities, such as group dining, games and entertainment, were allowed in all wards. In PACHs, the national prevention program included the use of a 16-element infection control score for the measurement of implementation of infection control measures, as previously described [20]. All LTCFs with CRE carriers were required to send periodic reports to the NCIC, weekly in the case of PACHs, and in the others upon changes in carrier census. These reports included a census of all CRE carriers hospitalized in the facility and an update on transfers of CRE carriers from or to other healthcare facilities, and were supplemented by concomitant reports from other facilities associated with the transfers and from laboratories identifying CRE in patient samples. By mandate, new acquisitions were reported promptly, and these reports triggered implementation of NCIC requirements regarding isolation measures and contact screening. In the case of acquisition traced to another hospital prior to the present admission, the local infection control practitioner was notified immediately and instructed to conduct an epidemiologic investigation. Early identification of local outbreaks, at the ward or facility level, defined based on time clusters of CRE acquisitions, led to intensified control measures overseen by the NCIC. Coordination of the national intervention, including regular interaction with the facilities, site visits and educational sessions, was managed by a dedicated infection control nurse. Measurement of Outcomes In accordance with national guidelines for transfer between healthcare institutions, a new detection of CRE was classified as LTCF acquired if it occurred > 72 hours after admission (based on LTCF reports), or within 72 hours of transfer from an LTCF to an acute care hospital (based on acute care hospital reports) [21]. At SNFs and NHs, we examined the number of institutions experiencing at least 5 acquisitions yearly, which we characterized as an outbreak, reflecting our observation that fewer than 5 acquisitions in 1 year at a single institution are more likely to represent sporadic occurrences than epidemiologically related events. We conducted 5 cross-sectional prevalence surveys in the PACHs during the study period. The first 2 were conducted in 12 of 13 centers (1 center declined to participate), and subsequent surveys included in addition 2 newly classified PACHs. In each facility, 1 of each ward type was selected randomly for participation in screening. Screening cultures were obtained from all patients hospitalized in each included ward. We measured CRE prevalence among all patients, as well as among the subset of patients with no known history of CRE. Microbiological Methods Microbiological methods used for the samples from prevalence surveys have been previously described [20]. Briefly, rectal swabs were collected and transferred on the same day to the NCIC laboratory. Specimens were screened for CRE on selective media. Isolates suspected as CRE were identified and antimicrobial susceptibilities determined using the Vitek 2 system, and polymerase chain reaction was conducted for the presence of blaKPC, blaNDM, and blaOXA-48. Statistical Analysis We used an ecological approach in data analysis, focusing on the healthcare facilities or wards. Thus, we aggregated the data at one of these levels. The one exception regarded CRE prevalence in the cross-sectional PACH surveys, which we calculated as total number of newly identified CRE-positive patients divided by all patients screened. The trend in CRE acquisition incidence for each facility type over time was calculated as the incidence rate ratio (IRR). For each facility type, we used bivariate Poisson regression to test for change over time in the annual CRE acquisition rate per 10000 patient-days. We analyzed the relationship between the number of acquired cases of CRE and the degree of influx of CRE carriers into LTCFs from other hospitals using mixed-effects Poisson regression, with facility type as a random effect. We used bivariate Poisson regression to test for change in the annual number of outbreaks over time in NHs and SNFs, and linear regression to test for a change in the mean number of patients per outbreak over time. To compare CRE carrier prevalence in the prevalence surveys conducted in the PACHs, we used mixed-effects logistic regression using patient-level data and PACH as a random effect. We used mixed-effects linear regression using hospital-level data and PACH as a random effect to compare infection control score over time and determine the association between infection control score and CRE prevalence. All analyses were performed with Stata version 14.2 (Stata Corporation, College Station, Texas). For all analyses, P < .05 was considered significant. The study was approved by the jurisdictional institutional review board RESULTS Complete data regarding CRE acquisitions in LTCFs are available as of 2009. From January 2009 through December 2015, 5265 patients acquired CRE in LTCFs. A higher incidence was detected in PACHs (2139 acquisitions, 2.4/10000 patient-days) and SNFs (944 acquisitions, 2.5/10000 patient-days), compared with NHs (2182 acquisitions, 0.5/10000 patient-days). A large proportion (60.6%) of the acquisitions attributed to LTCFs were detected on transfer to acute care hospitals, via active surveillance carried out in patients admitted from long-term care. The remaining acquisitions were detected through surveillance or clinical cultures at the LTCFs. Between January 2008 and December 2015, LTCFs had 9932 CRE carrier transfers from acute care facilities. The number of CRE carrier admissions was associated with a slightly increased risk of CRE acquisition within LTCFs (P < .001). The effect of the intervention on CRE acquisition rates became apparent in SNFs after one year and in PACHs and NHs after 2–3 years. Following the launch of the intervention, the CRE acquisition rate, expressed as cases per 10000 patient-days, initially increased in all facility types: in PACHs from 2.5 to 3.2, in SNFs from 2 to 4.1, and in NHs from 0.5 to 0.7. From the year acquisition peaked in each facility type onward, a persistent decrease was observed in CRE acquisition rates, approaching the 2009 baseline by 2013, and continuing to decrease thereafter, reaching approximately 50% of the baseline value by 2015 (1.2, 0.8, and 0.3 per 10000 patient-days in PACHs, SNFs, and NHs, respectively). The incidence of CRE acquisition declined between 2009 and 2015 in all facility types, as expressed by an IRR of <1/year (PACHs: 0.90, 95% CI 0.88–0.92, P < .001; SNFs: 0.87, 95% CI 0.85—0.90, P < .001; NHs: 0.93, 95% CI 0.91–0.95, P < .001). The decline remained significant after controlling for the effect of influx of carriers into LTCFs (IRR for all types of facilities combined: 0.91, 95% CI 0.89–0.92, P < .001). Figure 1 shows the percent change in incidence by institution type compared with the reference year (2009). Figure 1. View largeDownload slide Percent change in the incidence of CRE acquisitions in Israeli long-term care facilities, by type of facility, compared to the reference year, 2009. Error bars represent 95% confidence intervals. Abbreviation: CRE, carbapenem-resistant Enterobacteriaceae. Figure 1. View largeDownload slide Percent change in the incidence of CRE acquisitions in Israeli long-term care facilities, by type of facility, compared to the reference year, 2009. Error bars represent 95% confidence intervals. Abbreviation: CRE, carbapenem-resistant Enterobacteriaceae. An additional outcome measure is the number of SNFs and NHs experiencing an outbreak. The total number of these facilities experiencing ≥5 CRE acquisitions annually decreased from 35 to 11 during the period 2012–2015. Figure 2 shows the change in numbers of CRE acquisitions and outbreaks per year, and patients per outbreak. In both types of institutions, the decrease in number of acquisitions was statistically significant (P < .001). There was a significant decrease in the number of outbreaks in SNFs (P < .001) but not in NHs. No significant change in outbreak size was found in either facility type. Figure 2. View largeDownload slide Annual number of Carbapenem-resistant Enterobacteriaceae acquisitions and outbreaks and average number of patients per outbreak, 2012-2015. (a) Nursing homes; (b) skilled nursing facilities. Figure 2. View largeDownload slide Annual number of Carbapenem-resistant Enterobacteriaceae acquisitions and outbreaks and average number of patients per outbreak, 2012-2015. (a) Nursing homes; (b) skilled nursing facilities. A third outcome is found in the results of the serial point prevalence surveys conducted in the PACHs. In 5 surveys commenced between 2008 and 2015 (the final survey concluded in 2016), a total of 6785 patients were screened. Of these patients, 5718 (84.3%) had no known prior history of CRE, while 1067 patients (15.7%) were known carriers. A consistent decline in detection of CRE carriage among those with no prior history was observed: newly detected CRE carriage decreased from 12.3% in the survey commenced in 2008 to 0.8% in that begun in 2015 (P < .001). A significant decrease was observed in all ward types (P < .001 for all wards combined and for chronic ventilation, skilled nursing, and subacute wards; P = .02 for rehabilitation wards; Figure 3). Among all patients (including those with prior known CRE carriage), prevalence decreased from 16.9% in the first survey to 3.3% in the fifth (P < 0.001). During the study period, we observed a persistent increase in the implementation of infection control measures. The average infection control score increased from 6.9/16 in 2008 to 15.3/16 in 2015 (P < .001). A significant association between the score and CRE prevalence was found: for each 1-point increase in infection control score, prevalence decreased by 1.1% (95% CI 0.7%–1.5%, P < .001). Figure 3. View largeDownload slide Percentage of patients with positive results on screening for CRE carriage among patients with no CRE history in 5 cross-sectional surveys, by type of ward. Abbreviation: CRE, carbapenem-resistant Enterobacteriaceae. Figure 3. View largeDownload slide Percentage of patients with positive results on screening for CRE carriage among patients with no CRE history in 5 cross-sectional surveys, by type of ward. Abbreviation: CRE, carbapenem-resistant Enterobacteriaceae. DISCUSSION We report results from an intervention conducted in Israeli LTCFs aiming to control CRE spread across healthcare facilities nationwide. The LTCF intervention was implemented approximately 2 years after the introduction of CRE into Israeli hospitals. By the time of implementation, it is estimated that over 10000 patients had already acquired CRE in acute care hospitals [22], approximately 40% of whom were discharged to LTCFs. Despite the delay in intervention and the high prevalence at its initiation, we demonstrated that a comprehensive, multimodal, nationwide strategy focusing on improved infection control, early carrier detection and contact isolation succeeded in reducing CRE incidence in LTCFs by over 50%, and almost eliminating CRE prevalence 8 years into implementation. Moreover, consistent with earlier findings [20], in PACHs we demonstrated a positive correlation between implementation and reduction in CRE acquisition. Rising proportions of CRE carriage among LTCF residents are widely reported. In the absence of focused preventative efforts, the pathogen spreads extensively [23]. Moreover, LTCFs are components of larger healthcare networks, and have been shown to contribute to rapid regional dissemination of CRE by serving as a reservoir and amplifier of the pathogen while bridging between multiple acute care hospitals [11]. The extensive sharing of complex patients among healthcare facilities within a region suggests that successful control of CRE requires a coordinated regional effort of all acute and long-term healthcare facilities, similar to what has been demonstrated in control of other multidrug-resistant enteric bacteria [24]. A recent model predicted that a coordinated response to prevent CRE spread across interconnected healthcare facilities will result in a 55% reduction in CRE acquisitions over 15 years [25]. Our experience supports the assertion that regional interventions are the most effective strategy in preventing the spread of CRE. We found that most CRE acquisitions in LTCFs were detected upon transfer to an acute care hospital. A key element in the Israeli intervention was real-time notification of healthcare facilities upon detection of such cases, enabling timely contact tracing and local preventive measures. In parallel to the reduction in LTCFs, a marked reduction in CRE acquisition was also observed in acute care hospitals [22]. Reversing the rise in new acquisitions in LTCFs occurred gradually after initiating the intervention. The intervention was initiated well after CRE had spread extensively throughout all healthcare facilities in the country. As was demonstrated in a recent model, delayed intervention is expected to result in a delay in impact but will ultimately achieve a marked reduction in transmission [26]. Additionally, increased incidence soon after initiating an intervention could be associated with a high influx of CRE carriers from acute care hospitals, resulting in high colonization pressure. Colonization pressure in the ward has been found in several studies to be an independent risk factor for CRE acquisition [27, 28]. During the last decade, several acute care facilities have reported a sustained decrease in CRE acquisitions following implementation of preventive measures [29–31]. Active surveillance cultures and cohorting of patients and staff were found to be an essential element in acute care facilities [32]. Implementing identical strategies in the long-term care setting may not be suitable due to differences in patient populations and hospitalization goals. LTCFs may serve as longstanding homes for their residents, making restrictions on residents’ activities untenable. Thus, interventions in LTCFs should be tailored to the unique features of these facilities. Moreover, not every control measure required in acute care facilities is necessary in the LTCF setting, as we have demonstrated regarding staff cohorting in Israeli LTCFs [19]. Our study has a number of limitations. First, as this is not a controlled trial, bias and confounding may have played a role in the findings. Of greatest concern would be regression to the mean, since such bias is often seen in determination of multi-drug resistant pathogen incidence rates [33]. However, data from several countries demonstrate continuous increase in incidence once CRE is introduced into a region [17, 34]. Therefore, the persistent decrease observed in hundreds of healthcare facilities is unlikely due to chance. Second, although we have controlled for the influence of the success of the acute care intervention on our findings in LTCFs by including influx of carriers from acute care in our model, we cannot exclude some residual confounding in this regard. Third, although we have systematically obtained data across the study period from point prevalence surveys conducted in the PACHs, our data obtained from other LTCFs are obtained by passive rather than active surveillance. Nevertheless, these data are composed of mandatory reports from both the LTCFs and the clinical microbiology laboratories nationwide to the NCIC, and therefore the likelihood of significant underreporting is low. Finally, although we know the starting points of the various elements of the intervention, the uptake and implementation may have varied across institutions. Because these data were not available to us at all facility types, we could correlate between implementation and success only at PACHs. In conclusion, this study demonstrates that a national coordinated intervention implemented in LTCFs led to a sustained decrease in CRE incidence and prevalence. Establishing a national network that enables daily communication between all facilities in a region is an essential element in national strategies for CRE control, in conjunction with attention to basic infection control and early identification of carriers. Note Potential conflicts of interest. Y. C. reports grants and personal fees from MSD, grants and personal fees from AstraZeneca, personal fees from DaVoltera, personal fees from Intercell AG, grants and personal fees from Allecra Therapeutics, personal fees from BioMerieux SA, personal fees from Rempex Pharmaceuticals, personal fees from Nariva, grants and personal fees from Achoagen, personal fees from Roche, grants and personal fees from Pfizer, grants from Shionogi, outside the submitted work. All other authors have no conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. 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Carbapenem-resistant Enterobacteriaceae: a strategic roadmap for infection control . Infect Control Hosp Epidemiol 2017 ; 38 : 580 – 94 . Google Scholar PubMed 33. Cooper BS , Stone SP , Kibbler CC , et al. Systematic review of isolation policies in the hospital management of methicillin-resistant Staphylococcus aureus: a review of the literature with epidemiological and economic modelling . Health Technol Assess 2003 ; 7 : 1 – 194 . Google Scholar PubMed 34. Sudan S , Cherian C , Goldstein E , Hines DW , Glenn G , Chopra T . Trends in carbapenem susceptibility of Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae isolates from long-term acute care hospitals across the United States: an analysis of antibiograms . Open Forum Infect Dis 2015 ; 2 : 177 . Google Scholar PubMed APPENDIX Israel Long-Term Care Facility Carbapenem-Resistant Enterobacteriaceae Working Group Name Institution Shiri Navon-Venezia, PhD Bacterial Pathogens and Antibiotic Resistance Lab, Department of Molecular Biology, Faculty of Natural Sciences, Ariel University Moria Atun, RN Amal Jerusalem Geriatric Hospital Natalia Zaigraykin, MD Bait Balev Nesher Geriatric Rehabilitation Center Angela Shamunov, RN, BA Beit Rivka Geriatric Medical Center Ludmila Zaidenberg, MD Beit Rivka Geriatric Medical Center Gideon Friedman, MD Beit Hadar, Medical Rehabilitation and Nursing Center Evgeny Frodin, RN, BA Beit Hadar, Medical Rehabilitation and Nursing Center Margalit Ben-Zimon, MA Dorot Geriatric Rehabilitation Center Elena Aidinoff, MD Loewenstein Rehabilitation Hospital Ilana Or, RN, MA Loewenstein Rehabilitation Hospital Dov Albukrek, MD Reut Rehabilitation Hospital David Dvir, MD, MPH Reut Rehabilitation Hospital Irina Weinberg, RN, MOcc.H Reut Rehabilitation Hospital Vera Rosenfeld, MD Shmuel Harofe Geriatric Medical Center Shoshi Taichman, RN, BA Shmuel Harofe Geriatric Medical Center Sarit Nissan, MD Shoham Geriatric Medical Center Tania Boguslavsky, MD Shoham Geriatric Medical Center Ester Granot, RN, MA Shoham Geriatric Medical Center Aaron Cohen, MD Geriatrics Branch, Ministry of Health Pinhas Berkman, MD Geriatrics Branch, Ministry of Health Irit Laxer Assael, MD Geriatrics Branch, Ministry of Health Name Institution Shiri Navon-Venezia, PhD Bacterial Pathogens and Antibiotic Resistance Lab, Department of Molecular Biology, Faculty of Natural Sciences, Ariel University Moria Atun, RN Amal Jerusalem Geriatric Hospital Natalia Zaigraykin, MD Bait Balev Nesher Geriatric Rehabilitation Center Angela Shamunov, RN, BA Beit Rivka Geriatric Medical Center Ludmila Zaidenberg, MD Beit Rivka Geriatric Medical Center Gideon Friedman, MD Beit Hadar, Medical Rehabilitation and Nursing Center Evgeny Frodin, RN, BA Beit Hadar, Medical Rehabilitation and Nursing Center Margalit Ben-Zimon, MA Dorot Geriatric Rehabilitation Center Elena Aidinoff, MD Loewenstein Rehabilitation Hospital Ilana Or, RN, MA Loewenstein Rehabilitation Hospital Dov Albukrek, MD Reut Rehabilitation Hospital David Dvir, MD, MPH Reut Rehabilitation Hospital Irina Weinberg, RN, MOcc.H Reut Rehabilitation Hospital Vera Rosenfeld, MD Shmuel Harofe Geriatric Medical Center Shoshi Taichman, RN, BA Shmuel Harofe Geriatric Medical Center Sarit Nissan, MD Shoham Geriatric Medical Center Tania Boguslavsky, MD Shoham Geriatric Medical Center Ester Granot, RN, MA Shoham Geriatric Medical Center Aaron Cohen, MD Geriatrics Branch, Ministry of Health Pinhas Berkman, MD Geriatrics Branch, Ministry of Health Irit Laxer Assael, MD Geriatrics Branch, Ministry of Health View Large Name Institution Shiri Navon-Venezia, PhD Bacterial Pathogens and Antibiotic Resistance Lab, Department of Molecular Biology, Faculty of Natural Sciences, Ariel University Moria Atun, RN Amal Jerusalem Geriatric Hospital Natalia Zaigraykin, MD Bait Balev Nesher Geriatric Rehabilitation Center Angela Shamunov, RN, BA Beit Rivka Geriatric Medical Center Ludmila Zaidenberg, MD Beit Rivka Geriatric Medical Center Gideon Friedman, MD Beit Hadar, Medical Rehabilitation and Nursing Center Evgeny Frodin, RN, BA Beit Hadar, Medical Rehabilitation and Nursing Center Margalit Ben-Zimon, MA Dorot Geriatric Rehabilitation Center Elena Aidinoff, MD Loewenstein Rehabilitation Hospital Ilana Or, RN, MA Loewenstein Rehabilitation Hospital Dov Albukrek, MD Reut Rehabilitation Hospital David Dvir, MD, MPH Reut Rehabilitation Hospital Irina Weinberg, RN, MOcc.H Reut Rehabilitation Hospital Vera Rosenfeld, MD Shmuel Harofe Geriatric Medical Center Shoshi Taichman, RN, BA Shmuel Harofe Geriatric Medical Center Sarit Nissan, MD Shoham Geriatric Medical Center Tania Boguslavsky, MD Shoham Geriatric Medical Center Ester Granot, RN, MA Shoham Geriatric Medical Center Aaron Cohen, MD Geriatrics Branch, Ministry of Health Pinhas Berkman, MD Geriatrics Branch, Ministry of Health Irit Laxer Assael, MD Geriatrics Branch, Ministry of Health Name Institution Shiri Navon-Venezia, PhD Bacterial Pathogens and Antibiotic Resistance Lab, Department of Molecular Biology, Faculty of Natural Sciences, Ariel University Moria Atun, RN Amal Jerusalem Geriatric Hospital Natalia Zaigraykin, MD Bait Balev Nesher Geriatric Rehabilitation Center Angela Shamunov, RN, BA Beit Rivka Geriatric Medical Center Ludmila Zaidenberg, MD Beit Rivka Geriatric Medical Center Gideon Friedman, MD Beit Hadar, Medical Rehabilitation and Nursing Center Evgeny Frodin, RN, BA Beit Hadar, Medical Rehabilitation and Nursing Center Margalit Ben-Zimon, MA Dorot Geriatric Rehabilitation Center Elena Aidinoff, MD Loewenstein Rehabilitation Hospital Ilana Or, RN, MA Loewenstein Rehabilitation Hospital Dov Albukrek, MD Reut Rehabilitation Hospital David Dvir, MD, MPH Reut Rehabilitation Hospital Irina Weinberg, RN, MOcc.H Reut Rehabilitation Hospital Vera Rosenfeld, MD Shmuel Harofe Geriatric Medical Center Shoshi Taichman, RN, BA Shmuel Harofe Geriatric Medical Center Sarit Nissan, MD Shoham Geriatric Medical Center Tania Boguslavsky, MD Shoham Geriatric Medical Center Ester Granot, RN, MA Shoham Geriatric Medical Center Aaron Cohen, MD Geriatrics Branch, Ministry of Health Pinhas Berkman, MD Geriatrics Branch, Ministry of Health Irit Laxer Assael, MD Geriatrics Branch, Ministry of Health View Large © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Infectious Diseases Oxford University Press

Success of a National Intervention in Controlling Carbapenem-resistant Enterobacteriaceae in Israel’s Long-term Care Facilities

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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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1058-4838
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1537-6591
DOI
10.1093/cid/ciy572
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Abstract

Abstract Background Long-term care facilities (LTCFs) are a major reservoir of carbapenem-resistant Enterobacteriaceae (CRE) in healthcare facilities, contributing to rapid regional dissemination of CRE. Methods In 2008, The Israeli National Center for Infection Control (NCIC) initiated a coordinated, comprehensive intervention in Israel’s LTCFs, encompassing approximately 25000 beds in over 300 institutions. The intervention included implementation of population-tailored contact precautions and early detection of carriers. The NCIC established a real-time repository of all CRE carriers and events of acquisition, supervised information exchange between healthcare facilities and directed intervention at the institutional level during local outbreaks. CRE incidence was determined based on detection of CRE, either during LTFC stay or on admission to another facility. Prevalence was determined by a series of 5 cross-sectional surveys commenced between 2008 and 2015. Results From January 2009 through December 2015, 5265 patients acquired CRE in LTCFs. During the study period, incidence of acquisition declined in all facility types, to approximately 50% of the baseline (P < .001). The number of skilled nursing facilities and nursing homes experiencing ≥ 5 CRE acquisitions annually decreased from 35 to 11 during this period. The point prevalence of newly detected CRE carriage in post-acute care hospitals decreased from 12.3% in the survey commenced in 2008 to 0.8% in that begun in 2015 (P < .001). Conclusions A national, coordinated intervention resulted in a sustained decrease in CRE incidence and prevalence in LTCFs. These results support the assumption that centrally coordinated intervention is an essential public health tool in reducing CRE in healthcare facilities. carbapenem-resistant Enterobacteriaceae, intervention, long-term care facilities Carbapenem-resistant Enterobacteriaceae (CRE) are spreading globally and are of major concern to clinicians and public health authorities. These organisms are at highest priority for both drug development and prevention activities by the Centers for Disease Control and Prevention and the World Health Organization [1, 2]. The rapidity of CRE spread within and between healthcare facilities is unprecedented [3, 4]. The annual number of serious CRE infections is estimated at over 25000 in North America [1] and over 68000 in Europe [5, 6]. The rapid regional and inter-regional spread combined with the severe outcomes of these infections threaten the ability of the healthcare system to provide patient care safely [7]. High degrees of CRE prevalence have been described in several investigations involving patients from long-term care facilities, predominantly long-term acute care hospitals (LTACHs) [8–10]. Mounting evidence suggests that outbreaks in LTCFs may be a driving force behind regional dissemination of CRE, facilitated by extensive patient transfer between acute and long-term care facilities [11]. Yet despite increasing knowledge of the central role of LTCFs in regional dissemination, most reported interventions have been conducted in individual, mostly acute care facilities [12]. Given the degree of patient movement between healthcare facilities in a given region and the demonstrated efficiency of CRE spread in the inpatient setting [11], it is increasingly apparent that coordinated, regional interventions including all types of inpatient healthcare facilities may have a key role in containing regional spread of CRE [1, 13, 14]. The Israeli CRE outbreak has been described in several reports [15, 16]. Briefly, since 2006, Israel has faced nationwide dissemination of CRE. The percentage of Klebsiella pneumoniae invasive isolates resistant to carbapenems rose from less than 1%, to over 22% within 2 years [17]. In response, a nationally directed infection control intervention was undertaken in early 2007 by the Israeli National Center for Infection Control (NCIC), implemented initially in acute care hospitals. This intervention led to a substantial decrease in the incidence of nosocomial CRE in acute care [18]. Shortly after initiating the national intervention, we noted that approximately 40% of carriers in acute care hospitals were discharged to LTCFs, resulting in a large CRE reservoir in these facilities. Moreover, some acute care hospital outbreaks were traced to carriers admitted from LTCFs. In response to these epidemiological observations, in 2008 the NCIC extended its nationwide intervention targeting CRE spread to LTCFs. Here we describe and report on the impact of this ongoing national LTCF intervention. METHODS Setting LTCFs in Israel comprise 3 facility types: 15 post-acute care hospitals (PACHs), 15 skilled nursing facilities (SNFs) and roughly 300 nursing homes (NHs), with an approximate overall total of 25000 beds (Table 1). The PACHs, which comprise about 10% of LTCF beds, provide continued intensive treatment after hospital discharge to patients with conditions that result in reduced ability to perform activities of daily living. Wards in PACHs are classified as skilled nursing care, chronic mechanically ventilated, subacute medical and rehabilitation. Included among the patient populations in PACHs are those found in LTACHs in the United States. SNFs include patients requiring ongoing nursing care and medical observation. NHs include patients requiring nursing care without continuous medical observation. Table 1. Long-term Care Facilities and Population-based Infection Control Measures for Prevention of Carbapenem-resistant Enterobacteriaceae Spread Facility Type Post-acute Care Hospital (N = 15) Ward Types Skilled Nursing Facilities (N = 15) Nursing Homes (N~300) Skilled Nursing Care Chronic Mechanically Ventilated Sub-acute Medical Rehabilitation Facility characteristics Number of beds 850 500 300 1100 2500 20000 Patient population Require intensive nursing care and medical observation Stable, mechanically ventilated >30 days Complex medical conditions requiring longer hospitalization than provided in acute care Require rehabilitation, mostly following hospitalization involving immobilization Mixed, require nursing care at varying levels of intensity and medical observation Stable, require assistance in activities of daily living Average length of stay Months to years Months to years Weeks Weeks to months Months to years Years Infection control measures for CRE carriers Use of single-use gowns and gloves and dedicated medical equipment Required Dedicated nursing staff Not required Private room/ cohort Required Required Required Not required Requirement depends on specific ward population Not required Active surveillance of high-risk patientsa Required Required Required Not required Requirement depends on specific ward population Not required Participation in group activities Permitted Implementation of national carrier isolation discontinuation protocol 3 months from last positive CRE culture Recommended Facility Type Post-acute Care Hospital (N = 15) Ward Types Skilled Nursing Facilities (N = 15) Nursing Homes (N~300) Skilled Nursing Care Chronic Mechanically Ventilated Sub-acute Medical Rehabilitation Facility characteristics Number of beds 850 500 300 1100 2500 20000 Patient population Require intensive nursing care and medical observation Stable, mechanically ventilated >30 days Complex medical conditions requiring longer hospitalization than provided in acute care Require rehabilitation, mostly following hospitalization involving immobilization Mixed, require nursing care at varying levels of intensity and medical observation Stable, require assistance in activities of daily living Average length of stay Months to years Months to years Weeks Weeks to months Months to years Years Infection control measures for CRE carriers Use of single-use gowns and gloves and dedicated medical equipment Required Dedicated nursing staff Not required Private room/ cohort Required Required Required Not required Requirement depends on specific ward population Not required Active surveillance of high-risk patientsa Required Required Required Not required Requirement depends on specific ward population Not required Participation in group activities Permitted Implementation of national carrier isolation discontinuation protocol 3 months from last positive CRE culture Recommended Abbreviation: CRE, carbapenem-resistant Enterobacteriaceae. aRelates not to known CRE carriers but to patients at risk of carriage View Large Table 1. Long-term Care Facilities and Population-based Infection Control Measures for Prevention of Carbapenem-resistant Enterobacteriaceae Spread Facility Type Post-acute Care Hospital (N = 15) Ward Types Skilled Nursing Facilities (N = 15) Nursing Homes (N~300) Skilled Nursing Care Chronic Mechanically Ventilated Sub-acute Medical Rehabilitation Facility characteristics Number of beds 850 500 300 1100 2500 20000 Patient population Require intensive nursing care and medical observation Stable, mechanically ventilated >30 days Complex medical conditions requiring longer hospitalization than provided in acute care Require rehabilitation, mostly following hospitalization involving immobilization Mixed, require nursing care at varying levels of intensity and medical observation Stable, require assistance in activities of daily living Average length of stay Months to years Months to years Weeks Weeks to months Months to years Years Infection control measures for CRE carriers Use of single-use gowns and gloves and dedicated medical equipment Required Dedicated nursing staff Not required Private room/ cohort Required Required Required Not required Requirement depends on specific ward population Not required Active surveillance of high-risk patientsa Required Required Required Not required Requirement depends on specific ward population Not required Participation in group activities Permitted Implementation of national carrier isolation discontinuation protocol 3 months from last positive CRE culture Recommended Facility Type Post-acute Care Hospital (N = 15) Ward Types Skilled Nursing Facilities (N = 15) Nursing Homes (N~300) Skilled Nursing Care Chronic Mechanically Ventilated Sub-acute Medical Rehabilitation Facility characteristics Number of beds 850 500 300 1100 2500 20000 Patient population Require intensive nursing care and medical observation Stable, mechanically ventilated >30 days Complex medical conditions requiring longer hospitalization than provided in acute care Require rehabilitation, mostly following hospitalization involving immobilization Mixed, require nursing care at varying levels of intensity and medical observation Stable, require assistance in activities of daily living Average length of stay Months to years Months to years Weeks Weeks to months Months to years Years Infection control measures for CRE carriers Use of single-use gowns and gloves and dedicated medical equipment Required Dedicated nursing staff Not required Private room/ cohort Required Required Required Not required Requirement depends on specific ward population Not required Active surveillance of high-risk patientsa Required Required Required Not required Requirement depends on specific ward population Not required Participation in group activities Permitted Implementation of national carrier isolation discontinuation protocol 3 months from last positive CRE culture Recommended Abbreviation: CRE, carbapenem-resistant Enterobacteriaceae. aRelates not to known CRE carriers but to patients at risk of carriage View Large The LTCF Intervention We began the intervention in 2008 with site visits at the PACHs, followed by a cross-sectional point prevalence survey, conducted to assess prevalence and risk factors associated with CRE carriage [19]. High proportions of carriage were observed, ranging from 27% in skilled nursing wards to 2% in rehabilitation wards. We developed the subsequent components of the PACH intervention in accordance with our findings. We have previously reported results of the first 3 years of the intervention in the PACHs [20]. In 2009 we formalized and extended the ongoing nationally coordinated multimodal intervention in all types of LTCFs, focusing on improving general infection control practices and intensifying CRE containment measures. NCIC professionals developed a curriculum and provided training in infection control principles specific to the LTCF setting to designated infection control personnel, responsible in turn for the transfer of knowledge within the institutions. This training consisted of a 36-hour course and periodic workshops, supported by the Ministry of Health. The CRE-specific prevention program was tailored to the ward setting. Based on the results of our 2008 survey [19] and observations from site visits and professional communications, we stratified wards into risk categories: high risk (mechanical ventilation, skilled nursing and subacute medical wards) and low risk (rehabilitation and general nursing wards). Table 1 summarizes the infection control measures prescribed for CRE carriers in each ward type. Rehabilitation and social activities, such as group dining, games and entertainment, were allowed in all wards. In PACHs, the national prevention program included the use of a 16-element infection control score for the measurement of implementation of infection control measures, as previously described [20]. All LTCFs with CRE carriers were required to send periodic reports to the NCIC, weekly in the case of PACHs, and in the others upon changes in carrier census. These reports included a census of all CRE carriers hospitalized in the facility and an update on transfers of CRE carriers from or to other healthcare facilities, and were supplemented by concomitant reports from other facilities associated with the transfers and from laboratories identifying CRE in patient samples. By mandate, new acquisitions were reported promptly, and these reports triggered implementation of NCIC requirements regarding isolation measures and contact screening. In the case of acquisition traced to another hospital prior to the present admission, the local infection control practitioner was notified immediately and instructed to conduct an epidemiologic investigation. Early identification of local outbreaks, at the ward or facility level, defined based on time clusters of CRE acquisitions, led to intensified control measures overseen by the NCIC. Coordination of the national intervention, including regular interaction with the facilities, site visits and educational sessions, was managed by a dedicated infection control nurse. Measurement of Outcomes In accordance with national guidelines for transfer between healthcare institutions, a new detection of CRE was classified as LTCF acquired if it occurred > 72 hours after admission (based on LTCF reports), or within 72 hours of transfer from an LTCF to an acute care hospital (based on acute care hospital reports) [21]. At SNFs and NHs, we examined the number of institutions experiencing at least 5 acquisitions yearly, which we characterized as an outbreak, reflecting our observation that fewer than 5 acquisitions in 1 year at a single institution are more likely to represent sporadic occurrences than epidemiologically related events. We conducted 5 cross-sectional prevalence surveys in the PACHs during the study period. The first 2 were conducted in 12 of 13 centers (1 center declined to participate), and subsequent surveys included in addition 2 newly classified PACHs. In each facility, 1 of each ward type was selected randomly for participation in screening. Screening cultures were obtained from all patients hospitalized in each included ward. We measured CRE prevalence among all patients, as well as among the subset of patients with no known history of CRE. Microbiological Methods Microbiological methods used for the samples from prevalence surveys have been previously described [20]. Briefly, rectal swabs were collected and transferred on the same day to the NCIC laboratory. Specimens were screened for CRE on selective media. Isolates suspected as CRE were identified and antimicrobial susceptibilities determined using the Vitek 2 system, and polymerase chain reaction was conducted for the presence of blaKPC, blaNDM, and blaOXA-48. Statistical Analysis We used an ecological approach in data analysis, focusing on the healthcare facilities or wards. Thus, we aggregated the data at one of these levels. The one exception regarded CRE prevalence in the cross-sectional PACH surveys, which we calculated as total number of newly identified CRE-positive patients divided by all patients screened. The trend in CRE acquisition incidence for each facility type over time was calculated as the incidence rate ratio (IRR). For each facility type, we used bivariate Poisson regression to test for change over time in the annual CRE acquisition rate per 10000 patient-days. We analyzed the relationship between the number of acquired cases of CRE and the degree of influx of CRE carriers into LTCFs from other hospitals using mixed-effects Poisson regression, with facility type as a random effect. We used bivariate Poisson regression to test for change in the annual number of outbreaks over time in NHs and SNFs, and linear regression to test for a change in the mean number of patients per outbreak over time. To compare CRE carrier prevalence in the prevalence surveys conducted in the PACHs, we used mixed-effects logistic regression using patient-level data and PACH as a random effect. We used mixed-effects linear regression using hospital-level data and PACH as a random effect to compare infection control score over time and determine the association between infection control score and CRE prevalence. All analyses were performed with Stata version 14.2 (Stata Corporation, College Station, Texas). For all analyses, P < .05 was considered significant. The study was approved by the jurisdictional institutional review board RESULTS Complete data regarding CRE acquisitions in LTCFs are available as of 2009. From January 2009 through December 2015, 5265 patients acquired CRE in LTCFs. A higher incidence was detected in PACHs (2139 acquisitions, 2.4/10000 patient-days) and SNFs (944 acquisitions, 2.5/10000 patient-days), compared with NHs (2182 acquisitions, 0.5/10000 patient-days). A large proportion (60.6%) of the acquisitions attributed to LTCFs were detected on transfer to acute care hospitals, via active surveillance carried out in patients admitted from long-term care. The remaining acquisitions were detected through surveillance or clinical cultures at the LTCFs. Between January 2008 and December 2015, LTCFs had 9932 CRE carrier transfers from acute care facilities. The number of CRE carrier admissions was associated with a slightly increased risk of CRE acquisition within LTCFs (P < .001). The effect of the intervention on CRE acquisition rates became apparent in SNFs after one year and in PACHs and NHs after 2–3 years. Following the launch of the intervention, the CRE acquisition rate, expressed as cases per 10000 patient-days, initially increased in all facility types: in PACHs from 2.5 to 3.2, in SNFs from 2 to 4.1, and in NHs from 0.5 to 0.7. From the year acquisition peaked in each facility type onward, a persistent decrease was observed in CRE acquisition rates, approaching the 2009 baseline by 2013, and continuing to decrease thereafter, reaching approximately 50% of the baseline value by 2015 (1.2, 0.8, and 0.3 per 10000 patient-days in PACHs, SNFs, and NHs, respectively). The incidence of CRE acquisition declined between 2009 and 2015 in all facility types, as expressed by an IRR of <1/year (PACHs: 0.90, 95% CI 0.88–0.92, P < .001; SNFs: 0.87, 95% CI 0.85—0.90, P < .001; NHs: 0.93, 95% CI 0.91–0.95, P < .001). The decline remained significant after controlling for the effect of influx of carriers into LTCFs (IRR for all types of facilities combined: 0.91, 95% CI 0.89–0.92, P < .001). Figure 1 shows the percent change in incidence by institution type compared with the reference year (2009). Figure 1. View largeDownload slide Percent change in the incidence of CRE acquisitions in Israeli long-term care facilities, by type of facility, compared to the reference year, 2009. Error bars represent 95% confidence intervals. Abbreviation: CRE, carbapenem-resistant Enterobacteriaceae. Figure 1. View largeDownload slide Percent change in the incidence of CRE acquisitions in Israeli long-term care facilities, by type of facility, compared to the reference year, 2009. Error bars represent 95% confidence intervals. Abbreviation: CRE, carbapenem-resistant Enterobacteriaceae. An additional outcome measure is the number of SNFs and NHs experiencing an outbreak. The total number of these facilities experiencing ≥5 CRE acquisitions annually decreased from 35 to 11 during the period 2012–2015. Figure 2 shows the change in numbers of CRE acquisitions and outbreaks per year, and patients per outbreak. In both types of institutions, the decrease in number of acquisitions was statistically significant (P < .001). There was a significant decrease in the number of outbreaks in SNFs (P < .001) but not in NHs. No significant change in outbreak size was found in either facility type. Figure 2. View largeDownload slide Annual number of Carbapenem-resistant Enterobacteriaceae acquisitions and outbreaks and average number of patients per outbreak, 2012-2015. (a) Nursing homes; (b) skilled nursing facilities. Figure 2. View largeDownload slide Annual number of Carbapenem-resistant Enterobacteriaceae acquisitions and outbreaks and average number of patients per outbreak, 2012-2015. (a) Nursing homes; (b) skilled nursing facilities. A third outcome is found in the results of the serial point prevalence surveys conducted in the PACHs. In 5 surveys commenced between 2008 and 2015 (the final survey concluded in 2016), a total of 6785 patients were screened. Of these patients, 5718 (84.3%) had no known prior history of CRE, while 1067 patients (15.7%) were known carriers. A consistent decline in detection of CRE carriage among those with no prior history was observed: newly detected CRE carriage decreased from 12.3% in the survey commenced in 2008 to 0.8% in that begun in 2015 (P < .001). A significant decrease was observed in all ward types (P < .001 for all wards combined and for chronic ventilation, skilled nursing, and subacute wards; P = .02 for rehabilitation wards; Figure 3). Among all patients (including those with prior known CRE carriage), prevalence decreased from 16.9% in the first survey to 3.3% in the fifth (P < 0.001). During the study period, we observed a persistent increase in the implementation of infection control measures. The average infection control score increased from 6.9/16 in 2008 to 15.3/16 in 2015 (P < .001). A significant association between the score and CRE prevalence was found: for each 1-point increase in infection control score, prevalence decreased by 1.1% (95% CI 0.7%–1.5%, P < .001). Figure 3. View largeDownload slide Percentage of patients with positive results on screening for CRE carriage among patients with no CRE history in 5 cross-sectional surveys, by type of ward. Abbreviation: CRE, carbapenem-resistant Enterobacteriaceae. Figure 3. View largeDownload slide Percentage of patients with positive results on screening for CRE carriage among patients with no CRE history in 5 cross-sectional surveys, by type of ward. Abbreviation: CRE, carbapenem-resistant Enterobacteriaceae. DISCUSSION We report results from an intervention conducted in Israeli LTCFs aiming to control CRE spread across healthcare facilities nationwide. The LTCF intervention was implemented approximately 2 years after the introduction of CRE into Israeli hospitals. By the time of implementation, it is estimated that over 10000 patients had already acquired CRE in acute care hospitals [22], approximately 40% of whom were discharged to LTCFs. Despite the delay in intervention and the high prevalence at its initiation, we demonstrated that a comprehensive, multimodal, nationwide strategy focusing on improved infection control, early carrier detection and contact isolation succeeded in reducing CRE incidence in LTCFs by over 50%, and almost eliminating CRE prevalence 8 years into implementation. Moreover, consistent with earlier findings [20], in PACHs we demonstrated a positive correlation between implementation and reduction in CRE acquisition. Rising proportions of CRE carriage among LTCF residents are widely reported. In the absence of focused preventative efforts, the pathogen spreads extensively [23]. Moreover, LTCFs are components of larger healthcare networks, and have been shown to contribute to rapid regional dissemination of CRE by serving as a reservoir and amplifier of the pathogen while bridging between multiple acute care hospitals [11]. The extensive sharing of complex patients among healthcare facilities within a region suggests that successful control of CRE requires a coordinated regional effort of all acute and long-term healthcare facilities, similar to what has been demonstrated in control of other multidrug-resistant enteric bacteria [24]. A recent model predicted that a coordinated response to prevent CRE spread across interconnected healthcare facilities will result in a 55% reduction in CRE acquisitions over 15 years [25]. Our experience supports the assertion that regional interventions are the most effective strategy in preventing the spread of CRE. We found that most CRE acquisitions in LTCFs were detected upon transfer to an acute care hospital. A key element in the Israeli intervention was real-time notification of healthcare facilities upon detection of such cases, enabling timely contact tracing and local preventive measures. In parallel to the reduction in LTCFs, a marked reduction in CRE acquisition was also observed in acute care hospitals [22]. Reversing the rise in new acquisitions in LTCFs occurred gradually after initiating the intervention. The intervention was initiated well after CRE had spread extensively throughout all healthcare facilities in the country. As was demonstrated in a recent model, delayed intervention is expected to result in a delay in impact but will ultimately achieve a marked reduction in transmission [26]. Additionally, increased incidence soon after initiating an intervention could be associated with a high influx of CRE carriers from acute care hospitals, resulting in high colonization pressure. Colonization pressure in the ward has been found in several studies to be an independent risk factor for CRE acquisition [27, 28]. During the last decade, several acute care facilities have reported a sustained decrease in CRE acquisitions following implementation of preventive measures [29–31]. Active surveillance cultures and cohorting of patients and staff were found to be an essential element in acute care facilities [32]. Implementing identical strategies in the long-term care setting may not be suitable due to differences in patient populations and hospitalization goals. LTCFs may serve as longstanding homes for their residents, making restrictions on residents’ activities untenable. Thus, interventions in LTCFs should be tailored to the unique features of these facilities. Moreover, not every control measure required in acute care facilities is necessary in the LTCF setting, as we have demonstrated regarding staff cohorting in Israeli LTCFs [19]. Our study has a number of limitations. First, as this is not a controlled trial, bias and confounding may have played a role in the findings. Of greatest concern would be regression to the mean, since such bias is often seen in determination of multi-drug resistant pathogen incidence rates [33]. However, data from several countries demonstrate continuous increase in incidence once CRE is introduced into a region [17, 34]. Therefore, the persistent decrease observed in hundreds of healthcare facilities is unlikely due to chance. Second, although we have controlled for the influence of the success of the acute care intervention on our findings in LTCFs by including influx of carriers from acute care in our model, we cannot exclude some residual confounding in this regard. Third, although we have systematically obtained data across the study period from point prevalence surveys conducted in the PACHs, our data obtained from other LTCFs are obtained by passive rather than active surveillance. Nevertheless, these data are composed of mandatory reports from both the LTCFs and the clinical microbiology laboratories nationwide to the NCIC, and therefore the likelihood of significant underreporting is low. Finally, although we know the starting points of the various elements of the intervention, the uptake and implementation may have varied across institutions. Because these data were not available to us at all facility types, we could correlate between implementation and success only at PACHs. In conclusion, this study demonstrates that a national coordinated intervention implemented in LTCFs led to a sustained decrease in CRE incidence and prevalence. Establishing a national network that enables daily communication between all facilities in a region is an essential element in national strategies for CRE control, in conjunction with attention to basic infection control and early identification of carriers. Note Potential conflicts of interest. Y. C. reports grants and personal fees from MSD, grants and personal fees from AstraZeneca, personal fees from DaVoltera, personal fees from Intercell AG, grants and personal fees from Allecra Therapeutics, personal fees from BioMerieux SA, personal fees from Rempex Pharmaceuticals, personal fees from Nariva, grants and personal fees from Achoagen, personal fees from Roche, grants and personal fees from Pfizer, grants from Shionogi, outside the submitted work. All other authors have no conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. 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Google Scholar PubMed APPENDIX Israel Long-Term Care Facility Carbapenem-Resistant Enterobacteriaceae Working Group Name Institution Shiri Navon-Venezia, PhD Bacterial Pathogens and Antibiotic Resistance Lab, Department of Molecular Biology, Faculty of Natural Sciences, Ariel University Moria Atun, RN Amal Jerusalem Geriatric Hospital Natalia Zaigraykin, MD Bait Balev Nesher Geriatric Rehabilitation Center Angela Shamunov, RN, BA Beit Rivka Geriatric Medical Center Ludmila Zaidenberg, MD Beit Rivka Geriatric Medical Center Gideon Friedman, MD Beit Hadar, Medical Rehabilitation and Nursing Center Evgeny Frodin, RN, BA Beit Hadar, Medical Rehabilitation and Nursing Center Margalit Ben-Zimon, MA Dorot Geriatric Rehabilitation Center Elena Aidinoff, MD Loewenstein Rehabilitation Hospital Ilana Or, RN, MA Loewenstein Rehabilitation Hospital Dov Albukrek, MD Reut Rehabilitation Hospital David Dvir, MD, MPH Reut Rehabilitation Hospital Irina Weinberg, RN, MOcc.H Reut Rehabilitation Hospital Vera Rosenfeld, MD Shmuel Harofe Geriatric Medical Center Shoshi Taichman, RN, BA Shmuel Harofe Geriatric Medical Center Sarit Nissan, MD Shoham Geriatric Medical Center Tania Boguslavsky, MD Shoham Geriatric Medical Center Ester Granot, RN, MA Shoham Geriatric Medical Center Aaron Cohen, MD Geriatrics Branch, Ministry of Health Pinhas Berkman, MD Geriatrics Branch, Ministry of Health Irit Laxer Assael, MD Geriatrics Branch, Ministry of Health Name Institution Shiri Navon-Venezia, PhD Bacterial Pathogens and Antibiotic Resistance Lab, Department of Molecular Biology, Faculty of Natural Sciences, Ariel University Moria Atun, RN Amal Jerusalem Geriatric Hospital Natalia Zaigraykin, MD Bait Balev Nesher Geriatric Rehabilitation Center Angela Shamunov, RN, BA Beit Rivka Geriatric Medical Center Ludmila Zaidenberg, MD Beit Rivka Geriatric Medical Center Gideon Friedman, MD Beit Hadar, Medical Rehabilitation and Nursing Center Evgeny Frodin, RN, BA Beit Hadar, Medical Rehabilitation and Nursing Center Margalit Ben-Zimon, MA Dorot Geriatric Rehabilitation Center Elena Aidinoff, MD Loewenstein Rehabilitation Hospital Ilana Or, RN, MA Loewenstein Rehabilitation Hospital Dov Albukrek, MD Reut Rehabilitation Hospital David Dvir, MD, MPH Reut Rehabilitation Hospital Irina Weinberg, RN, MOcc.H Reut Rehabilitation Hospital Vera Rosenfeld, MD Shmuel Harofe Geriatric Medical Center Shoshi Taichman, RN, BA Shmuel Harofe Geriatric Medical Center Sarit Nissan, MD Shoham Geriatric Medical Center Tania Boguslavsky, MD Shoham Geriatric Medical Center Ester Granot, RN, MA Shoham Geriatric Medical Center Aaron Cohen, MD Geriatrics Branch, Ministry of Health Pinhas Berkman, MD Geriatrics Branch, Ministry of Health Irit Laxer Assael, MD Geriatrics Branch, Ministry of Health View Large Name Institution Shiri Navon-Venezia, PhD Bacterial Pathogens and Antibiotic Resistance Lab, Department of Molecular Biology, Faculty of Natural Sciences, Ariel University Moria Atun, RN Amal Jerusalem Geriatric Hospital Natalia Zaigraykin, MD Bait Balev Nesher Geriatric Rehabilitation Center Angela Shamunov, RN, BA Beit Rivka Geriatric Medical Center Ludmila Zaidenberg, MD Beit Rivka Geriatric Medical Center Gideon Friedman, MD Beit Hadar, Medical Rehabilitation and Nursing Center Evgeny Frodin, RN, BA Beit Hadar, Medical Rehabilitation and Nursing Center Margalit Ben-Zimon, MA Dorot Geriatric Rehabilitation Center Elena Aidinoff, MD Loewenstein Rehabilitation Hospital Ilana Or, RN, MA Loewenstein Rehabilitation Hospital Dov Albukrek, MD Reut Rehabilitation Hospital David Dvir, MD, MPH Reut Rehabilitation Hospital Irina Weinberg, RN, MOcc.H Reut Rehabilitation Hospital Vera Rosenfeld, MD Shmuel Harofe Geriatric Medical Center Shoshi Taichman, RN, BA Shmuel Harofe Geriatric Medical Center Sarit Nissan, MD Shoham Geriatric Medical Center Tania Boguslavsky, MD Shoham Geriatric Medical Center Ester Granot, RN, MA Shoham Geriatric Medical Center Aaron Cohen, MD Geriatrics Branch, Ministry of Health Pinhas Berkman, MD Geriatrics Branch, Ministry of Health Irit Laxer Assael, MD Geriatrics Branch, Ministry of Health Name Institution Shiri Navon-Venezia, PhD Bacterial Pathogens and Antibiotic Resistance Lab, Department of Molecular Biology, Faculty of Natural Sciences, Ariel University Moria Atun, RN Amal Jerusalem Geriatric Hospital Natalia Zaigraykin, MD Bait Balev Nesher Geriatric Rehabilitation Center Angela Shamunov, RN, BA Beit Rivka Geriatric Medical Center Ludmila Zaidenberg, MD Beit Rivka Geriatric Medical Center Gideon Friedman, MD Beit Hadar, Medical Rehabilitation and Nursing Center Evgeny Frodin, RN, BA Beit Hadar, Medical Rehabilitation and Nursing Center Margalit Ben-Zimon, MA Dorot Geriatric Rehabilitation Center Elena Aidinoff, MD Loewenstein Rehabilitation Hospital Ilana Or, RN, MA Loewenstein Rehabilitation Hospital Dov Albukrek, MD Reut Rehabilitation Hospital David Dvir, MD, MPH Reut Rehabilitation Hospital Irina Weinberg, RN, MOcc.H Reut Rehabilitation Hospital Vera Rosenfeld, MD Shmuel Harofe Geriatric Medical Center Shoshi Taichman, RN, BA Shmuel Harofe Geriatric Medical Center Sarit Nissan, MD Shoham Geriatric Medical Center Tania Boguslavsky, MD Shoham Geriatric Medical Center Ester Granot, RN, MA Shoham Geriatric Medical Center Aaron Cohen, MD Geriatrics Branch, Ministry of Health Pinhas Berkman, MD Geriatrics Branch, Ministry of Health Irit Laxer Assael, MD Geriatrics Branch, Ministry of Health View Large © The Author(s) 2018. 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Clinical Infectious DiseasesOxford University Press

Published: Mar 5, 2019

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