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The impact of enhanced screening for carbapenemase-producing Enterobacterales in an acute care hospital in South Korea

The impact of enhanced screening for carbapenemase-producing Enterobacterales in an acute care... Background Carbapenemase-producing Enterobacterales (CPE) poses a significant challenge to infection control in healthcare settings. Active screening is recommended to prevent intra-hospital CPE transmission. Methods CPE screening was initiated at a 660-bed hospital in South Korea in September 2018, targeting patients previously colonized/infected or admitted to outside healthcare facilities (HCFs) within 1 month. Universal intensive care unit (ICU) screening was performed at the time of admission. After a hospital-wide CPE outbreak in July- September 2019, the screening program was enhanced by extending the indications (admission to any HCF within 6 months, receipt of hemodialysis) with weekly screening of ICU patients. The initial screening method was changed from screening cultures to the Xpert Carba-R assay. The impact was assessed by comparing the CPE incidence per 1000 admissions before (phase 1, September 2018-August 2019) and after instituting the enhanced screening program (phase 2, September 2019-December 2020). Results A total of 13,962 (2,149 and 11,813 in each phase) were screened as indicated, among 49,490 inpatients, and monthly screening compliance increased from 18.3 to 93.5%. Compared to phase 1, the incidence of screening positive patients increased from 1.2 to 2.3 per 1,000 admissions (P = 0.005) during phase 2. The incidence of newly detected CPE patients was similar (3.1 vs. 3.4, P = 0.613) between two phases, but the incidence of hospital-onset CPE patients decreased (1.9 vs. 1.1, P = 0.018). A significant decrease was observed (0.5 to 0.1, P = 0.014) in the incidence of patients who first confirmed CPE positive through clinical cultures without a preceding positive screening. Compared to phase 1, the median exposure duration and number of CPE contacts were also markedly reduced in phase 2: 10.8 days vs. 1 day (P < 0.001) and 11 contacts vs. 1 contact (P < 0.001), respectively. During phase 2, 42 additional patients were identified by extending the admission screening indications (n = 30) and weekly in-ICU screening (n = 12). Conclusions The enhanced screening program enabled us to identify previously unrecognized CPE patients in a rapid manner and curtailed a hospital-wide CPE outbreak. As CPE prevalence increases, risk factors for CPE *Correspondence: Sun Hee Park sh.park@catholic.ac.kr Full list of author information is available at the end of the article © The Author(s) 2023. 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The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 2 of 11 colonization can broaden, and hospital prevention strategies should be tailored to the changing local CPE epidemiology. Keywords Carbapenemase-producing Enterobacterales, Active screening, Periodic screening, Infection prevention and control Background limited indications, including previous CPE colonization/ Carbapenemase-producing Enterobacterales (CPE) poses infection, previous admission to outside HCFs within the a significant threat to global health, and the prevalence of past month, transfer from outside HCFs, and ICU admis- CPE has increased worldwide. In South Korea, the preva- sion. Screening was performed using two consecutive lence of CPE has steadily increased since 2010, after the rectal swabs sampled on chromogenic agar. Between July first identification of imported case [ 1], and mandatory and September 2019, a CPE outbreak occurred in several notification of carbapenem-resistant Enterobacterales wards. Thus, as of mid-August 2019, an enhanced screen - (CRE) infection/colonization to the Korea Disease Con- ing program was implemented by broadening the screen- trol and Prevention Agency (KDCA) was initiated in June ing indications and updating the screening protocol to 2017. Since then, the number of reported CRE cases has include a rapid polymerase chain reaction (PCR) method, increased substantially from 5,717 to 2017 to 23,311 in the Xpert-Carba-R assay, with culture-based methods. 2021, with CPE accounting for 63.3% of the CRE cases in This study aimed to evaluate the impact of changes in 2021 [1, 2]. CPE screening strategies on the spread of CPE and devel- Early detection and isolation of patients infected or col- opment of clinical infections. We explored the trend of onized with CPE are the main infection control strategies CPE colonization/infection over time and compared to contain the spread of CPE in healthcare settings. For CPE incidence in screening cultures and clinical cul- this purpose, many countries have developed national tures before and after the introduction of the enhanced infection control guidelines based on the active screening screening program. We also investigated the effect of the of patients at high risk of CPE colonization or hospital- enhanced screening program on intra-hospital transmis- ized patients in high-risk units [3–8]. However, it is the sion of CPE. responsibility of individual facilities to make decisions regarding whom to screen and how to screen. This has Methods led to variability in CPE screening strategies among hos- Ethics pitals [9]. The KDCA guidance recommends screening of This study was approved by the Institutional Review patients who are at risk of CPE colonization at the time Board at the Catholic University of Korea, Daejeon St. of admission; suggested risk factors include a history of Mary’s Hospital, and the need for informed consent was contact with a CPE patient or admission to healthcare waived (DC21ENSI0040). facilities (HCFs) where CPE outbreaks have occurred, or previous CPE colonization or infection. However, in the Hospital settings KDCA guidance, the duration of risk is not specified, and This retrospective observational cohort study was con - CPE screening policy primarily depends on the health- ducted at the Catholic University of Korea, Daejeon St. care facilities’ decisions [10]. In South Korea, most hospi- Mary’s Hospital from April 2017 to December 2020. tals have multi-occupancy rooms with shared bathrooms The study population included all hospitalized patients and open-bay design intensive care units (ICUs). In hos- aged ≥ 18 years and those who stayed in the ICU for pital settings, where patient isolation is difficult owing to > 24 h. Our hospital is a 660-bed, university-affiliated sec - the shortage of single rooms, active surveillance is often ondary care hospital in Daejeon, South Korea. Daejeon discouraged. Rapid detection is essential for effectively has a population of 1.5  million people, and this hospital reducing the duration of exposure to CPE when pre- has an average of 24,300 admissions per year. Hospital emptive isolation is difficult. However, conventional and general wards are composed of 95% multi-occupancy commonly-used screening methods, such as culturing rooms with shared bathrooms, 5% en-suite single rooms, samples on selective media, require 24–48 h for growth, and four airborne infection isolation rooms. There are and molecular methods are required for confirmation [ 4]. two ICUs (medical and surgical) that have an open bay Therefore, containment of CPE is a challenge in Korean design and two isolation rooms per ICU. Each ICU healthcare facilities. accommodates 18 patients. In 2017, the first case of CPE was identified at Daejeon St Mary’s Hospital in Daejeon, South Korea. In Septem- Microbiology tests ber 2018, we launched an admission CPE screening pro- For screening cultures, ChromID CARBA agar (bioMéri- gram targeting patients at risk of CPE colonization with eux, France) was used to culture rectal swab specimens. Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 3 of 11 The Xpert Carba-R assay was used to detect carbapen - methods (Table  1). If the Xpert Carba-R test was posi- emases. CPE positivity was defined as both the Xpert tive, the patients were isolated until two consecutives Carba-R assay and screening culture being positive. screening cultures were negative. If CPE colonization Carbapenemase genes were further subtyped using PCR was confirmed, isolation was continued. During phase2, and sequencing as previously described [11]. When the in addition to universal ICU admission screening, ICU Xpert Carba-R assay was negative but the cultures were patients were screened weekly during their stay, using positive, the isolates were considered CRE. Species iden- cultures. Throughout the study period, preemptive isola - tification was performed using matrix-assisted laser tion was performed only for patients with documented desorption/ionization time-of-flight mass spectrom - history of previous CPE colonization/infection. Previous etry (Bruker, Daltonics, Germany), and antimicrobial CPE colonization/infection was verified through flags in susceptibilities were determined according to Clinical electronic medical records and microbiology results at and Laboratory Standards Institute guidelines using the this hospital, and through inter-facility communication. MicroScan WalkAway 96 Plus system and Neg Combo Management of CPE positive patients was as follows. If Panel Type 72 (Beckman Coulter, Brea, California). CPE was confirmed, patients continued to be isolated in a single room until discharge. In case of a shortage of single CPE screening programs and patient management rooms, CPE patients were cohorted in multi-occupancy CPE screening programs and patient management strat- rooms according to carbapenemase gene and organism egies have changed over time, as shown in Table  1. In type. Other infection prevention measures included (1) brief, CPE screening was not performed during phase 0 the signage on isolation room doors and flags in elec - (April 2017-August 2018). During phase 1 (September tronic medical records, (2) the use of personal protective 2018-August 2019), we performed the screening program equipment (PPE) including single-use gloves and gowns with limited indications using only culture-based screen- whenever entering the room, (3) the use of disposable ing. If the screening culture was positive, the patients or dedicated patient care equipment, (4) cohorting of were isolated in a single room. During phase 2 (Septem- nursing and cleaning staff in the event of an outbreak, ber 2019-December 2020), the indications for admis- and (5)  environmental cleaning (twice daily) of isolation sion screening were expanded, the Xpert Carba-R assay rooms and terminal cleaning with hypochlorite solution was used for initial testing, along with culture-based after patient discharge. Table 1 Changes in carbapenemase-producing Enterobacterales control strategy during the entire study period (2017–2020) Phase 0 Phase 1 Phase 2 General ward Ad- None Colonization/infection with CPE within 6 months Colonization/infection with CPE within 6 months prior mission screening prior to admission to admission 1 1 Previous admission to outside healthcare facility Previous admission to any healthcare facility within within the past 1 month the past 6 months Transfer from long-term care facilities or acute care Transfer from long-term care facilities, acute care hos- hospitals pitals, rehabilitation centers or nursing homes Receipt of hemodialysis ICU Admission None Universal screening for all patients admitted to ICU Universal screening for all patients admitted to ICU screening ICU Periodic None None Weekly screening during the ICU stay screening Screening method None Two consecutive rectal swab cultures on chromo- Xpert Carba R assay, followed by two consecutive genic agar with a 24-hour interval, followed by rectal swab cultures on ChromID CARBA agar with a Xpert Carba R assay if cultures are positive 24-hour interval Patient Isolation Patient isolation Patient isolation once cultures reported as positive Patient isolation once Xpert Carba R assay reported as once clinical positive until the following two rectal swab cultures cultures reported reported negative. as positive Isolation continued if cultures reported as positive Patient De-isolation De-isolation De-isolation when 3 consecutive cultures with 1 De-isolation when 3 consecutive cultures with 1 week when 3 con- week interval reported negative interval reported negative and at least 6 months have secutive cultures elapsed since the first negative conversion with 1 week interval reported negative Abbreviation: ICU, intensive care unit 1 2 Footnote: Acute care hospitals, long-term care hospitals, nursing homes and rehabilitation hospitals were included. Preemptive isolation was performed only for patients with previous CPE colonization/infection Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 4 of 11 Contact management was similar during the study (HO): infection detected > 2 days after admission to this period. When any new CPE patients were identified, all hospital. contacts were traced and screened using cultures. The CPE isolates obtained from a single patient were con- Xpert-Carba-R assay was also used for contact screen- sidered duplicates if they were the same species/car- ing of ICU patients during phase  2. CPE contacts were bapenemase combination, regardless of the source of cohorted until they were cleared after obtaining two neg- culture specimens. Otherwise, CPE isolates without such ative swabs > 24 h apart. concordance were considered as non-duplicates. CPE- positive clinical cultures included CPE isolates which Staff education on CPE management were detected in clinical specimens either before or after Since 2017, the hospital’s healthcare workers (HCWs) screening cultures, or in cases where CPE screening was have received regular education and updates on CPE not conducted. management according to the changes in the hospital policies. The CPE screening program was communi - Data collection and analysis cated to the staff before its launch in September 2018. In We collected data on patient demographics and the risk response to the outbreak, comprehensive training was factors described above, the timing of specimen sam- conducted in in-person meetings, with active involve- pling and reporting, exposure duration, number of con- ment of the hospital leadership, to educate all relevant tacts, and CPE screening results. To assess the impact of HCWs in CPE management. Education programs were the enhanced screening program, the incidence of CPE customized to suit the specific requirements and roles colonization/infection per 1,000 admissions was calcu- of each department in containing the outbreak. The lated during phases 1 and 2 and compared using Pois- hospital-wide campaign was initiated and continued to son regression. Given the outbreak period coincided reinforce the enhanced CPE screening program. The per - with parts of both phase 1 and phase2, further analysis formance of hand hygiene, implementation of contact was conducted by dividing the study period into three precaution measures, and adherence to CPE screening periods: pre-outbreak (September 2018-June 2019), out- protocols were monitored and communicated to both break (July-September 2019), and post-outbreak (Octo- HCWs and leadership. ber 2019-December 2020), in order to assess the impact of the enhanced screening program in an endemic set- Definitions ting. The Chi-squared test or Fisher’s exact test was used Compliance with admission screening was calculated by to compare categorical variables. The Student’s t-test dividing the number of patients who were screened ≤ 48 h or Wilcoxon rank-sum test was used to compare con- after admission by the number of patients who were indi- tinuous variables. Risk factors for positive admission cated for screening. Compliance with weekly ICU screen- screening were evaluated using log-binomial regression. ing was calculated by dividing the number of patients Multivariate analyses were conducted, adjusting for age, screened weekly by the number of patients who stayed in sex and patient characteristics which were found signifi - the ICU for ≥ 7 days. cant in the bivariate analysis (P < 0.1). All analyses were The CPE exposure duration was defined as the period performed using Stata (version 17.0; StataCorp, LP, Col- from either the admission date or the date when the most lege Station, TX, US). P < 0.05 was considered statistically recent rectal swab culture was negative during admission significant. to the date of initiation of contact isolation. Patients were considered CPE contacts if they shared a room with a Results CPE patient during the exposure period. Patient demographics and compliance to the enhanced CPE patients were epidemiologically categorized based program on timing of specimen sampled and the presence of risk During the study period, 80,348 patients (30,858, 22,228, factors as follows: (1) community-associated (CA): infec- and 27,262 during phases 0, 1, and 2, respectively) were tion detected ≤ 2 days after admission to this hospital and admitted to this hospital, and 7,413 episodes of ICU with no known exposure to healthcare facilities; (2) com- admission were identified among 6,555 patients. Over munity-onset, healthcare associated (CO-HA): infection time, there was a steady increase in the proportion of detected ≤ 2 days after admission, with a history of hos- patients who had been hospitalized in acute care hos- pitalization, long-term care facility (LTCF) residence, or pitals (ACHs) or resided in LTCFs during the previous hemodialysis within the previous 6 months; (3) Health- 6 months and who were transferred from outside HCFs care-onset, outside healthcare facilities (HO-OHCF): (Table  2). The proportion of patients with comorbidities infection detected ≤ 2 days from admission after transfer such as malignancy, diabetes, dementia, and congestive from outside healthcare facilities; (4) healthcare-onset heart failure increased as well. The mean age of inpa - tients increased from 61.7 to 63.3 years over the study Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 5 of 11 Table 2 Comparisons of patient eligible for screenings, new CPE patients by sample and screen, and the incidence of CPE colonization or infection before (Phase 1) and after (Phase 2) the enhanced screening program Phase 1 Phase 2 P-value Number of patients with risk factors (%) Previous colonization/infection 12 (0.05) 111 (0.4) Previous admission to HCFs within 6 months 6,662 (30.0) 8,889 (32.6) < 0.001 Receipt of hemodialysis 620 (2.8) 798 (2.9) < 0.001 Transfer from outside HCFs 1406 (6.3) 2111 (7.7) < 0.001 Number of ICU patients eligible for screening (%) ICU universal admission screening 2,376 (10.7) 2,652 (9.7) < 0.001 ICU weekly screening NA 765 (2.8) Positive screening per 1,000 screens IRR (95% CI) P-value Admission screening 11.7 5.3 0.45 (0.29–0.71) 0.001 ICU universal admission screening 9.4 4.4 0.47 (0.19–1.14) 0.07 ICU weekly screening 18.8 Positive screening per 1,000 admissions IRR (95% CI) P-value Admission screening 1.2 2.3 1.90 (1.21–2.99) 0.005 ICU universal admission screening 5.5 4.2 0.76 (0.31–1.83) 0.507 ICU weekly screening 15.7 Incidence of CPE colonization/infection per 1,000 admissions IRR (95% CI) P-value Total new CPE patients 3.1 3.4 1.08 (0.79–1.48) 0.613 New CPE from screening samples 2.6 3.3 1.27 (0.91–1.76) 0.162 New CPE from clinical samples 0.5 0.1 0.20 (0.06–0.72) 0.014 Hospital-onset CPE patients 1.9 1.1 0.57 (0.36–0.91) 0.018 Patients with CPE-positive clinical cultures 0.7 0.4 0.65 (0.31–1.39) 0.270 Abbreviations: CI, confidence interval; CPE, carbapenemase-producing Enterobacterales; ICU, intensive care unit; IRR, incidence rate ratio; HCF, healthcare facility; NA, not applicable Footnote: Patients with CPE isolates detected in clinical samples before or after the identification of CPE colonization through screening, or in cases where CPE screening was not conducted, were included period, and those aged ≥ 70 years accounted for 39.6% previously colonized with NDM-1-producing Klebsi- of all inpatients in phase 2 (Supplementary Table  1). The ella oxytoca was found to carry a different CPE isolate mean age of patients who were transferred from out- (KPC-2-producing Klebsiella pneumoniae). A total of 24 side HCFs was higher than those who were not (72.4 CPE cases were identified through universal ICU admis - vs. 62.2 years, P < 0.001). During phase 1 and 2, 13,962 sion screening, and 10 of them (41.7%) had no indica- patients were screened for indications (2,149 in phase tions other than ICU admission. There were 30 patients 1 and 11,813 in phase 2), and 1,851 patients for other with clinical cultures positive for CPE (3 in phase 0, 15 in purposes. The proportion of admitted patients meeting phase 1, and 12 in phase 2), the most common site being screening criteria increased from 14.6% (n = 3,250) in urine (n = 16), followed by sputum (n = 8), wounds (n = 3), Phase 1 to 44.4% (n = 12,100) in Phase 2. Over the study and blood (n = 3). period, the monthly compliance with the CPE screening In terms of epidemiologic categorization, there were program markedly increased from 18.3 to 93.5% (Fig.  1). three HO cases and one CO-HA case during phase 0. On average, compliance with the screening program sig- During phases 1 and 2, there were 47 CO-HA patients nificantly increased between phase 1 and 2, from 59.3 to (42 associated with this hospital and five associated with 86.3% (P < 0.001). Weekly ICU screening was performed other facilities) and 39 HO-OHCF patients, including 21 in 83.7% of the ICU-admitted patients (640/765). from ACHs and 18 from LTCFs or nursing homes. Four CPE cases were considered to be community-associated. Trends in CPE colonization/infection and epidemiological There were 73 HO cases associated with this hospital, characteristics of CPE cases including 29 cases detected during the outbreak period The annual incidence of CPE-colonization/infections (Fig. 1). substantially increased from 0.10 to 4.2 per 1,000 admis- In terms of CPE isolates, there were 175 non-duplicate sions over the 4-year study period. A total of 167 CPE CPE isolates identified, including 8 non-duplicate isolates cases were newly identified during the study period, from 4 patients. Species of CPE isolates and carbapen- including 149 cases from surveillance testing and 18 emase genes were diverse throughout the study period cases from clinical cultures. One patient who was (Fig.  2). Nonetheless, 47.4% (n = 83) of cultures were K. Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 6 of 11 Fig. 1 Trend in newly detected CPE cases according to epidemiological category and compliance to the screening program (2017–2020) Abbreviation: CA, community-associated; CO-HA, community-onset, healthcare-associated; CPE, carbapenemase-producing Enterobacterales; HO, hos- pital-onset; HO-OHCF, hospital-onset at outside healthcare facilities (transferred from outside healthcare facilities). Fig. 2 Trend in non-duplicate CPE isolates by bacterial species and carbapenemase genes (2017–2020) Abbreviations: CPE, carbapenemase-producing Enterobacterales; KPN, Klebsiella pneumoniae; ECO, Escherichia coli; CF, Citrobacter freundii; KO, Klebsiella oxytoca. 1 2 Footnote: Other Enterobacterales are as follows: other includes Citrobacter, E. coli, K. oxytoca, and K. pneumoniae; other includes K. pneumoniae and E. coli; 3 4 5 other includes Citrobacter and K. aerogenes; other includes C. freundii and K. pneumoniae; other includes K. pneumoniae, E. coli, and E. asburiae Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 7 of 11 pneumoniae, and NDM-1 (39.4%, 69/175) and KPC-2 (31.4%, 55/175) were the most commonly identified car - bapenemases. These genes were also frequently detected in patients who were transferred from outside HCFs with NDM-1 accounting for 33.3% (13/39) and KPC-2 accounting for 35.9% (14/39). Impact of the enhanced screening program Compared to phase 1, the incidence of CPE increased from 1.2 to 1,000 admissions to 2.3 per 1,000 admis- sions in phase 2. The total number of patients eligible for admission screening increased from 3,250 in phase 1 to 12,100 in phase 2, and the proportion of positive admis- sion screens decreased during phase 2 (Table 2). Although the incidence of newly detected cases was higher during phase 2, a significant decrease was observed in the inci - dence of newly detected CPE cases from clinical sam- ples without a preceding positive screening, from 0.54 to 1,000 admissions to 0.11 per 1,000 admissions (inci- dence rate ratio [IRR] 0.20; 95% confidence interval [CI] 0.06–0.72; P = 0.014) (Table  2), and CPE-positive clinical cultures per 1000 admissions did not change significantly (IRR 0.65; 95% CI 0.31–1.39; P = 0.27). The incidence of HO cases also decreased during phase 2 (IRR 0.57; 95% CI 0.36–0.91; P = 0.018) (Table 3). Overall, 42 additional patients were identified during phase 2 by extending the admission screening indica- tions (n = 30) and weekly in-ICU screening (n = 12). These accounted for 45.2% (42/93) of the newly detected CPE cases during phase 2. In comparison to phase 1, the median exposure dura- tion to CPE was significantly reduced during phase 2, from 10.8 days (interquartile range [IQR] 2.6–21.0) to 1  day (IQR 0.5–2.6) (P < 0.001). The median number of CPE contacts was also reduced during phase 2, from 11 contacts (IQR 4–19) to 1 contact (IQR 0–5) (P < 0.001). During phase 2, no widespread outbreaks occurred, although there were small clusters or sporadic CPE cases. When analyzing the pre-outbreak, outbreak and post- outbreak periods, similar findings were observed. Com - pared to the pre-outbreak period, a significant reduction was observed in the incidence of newly detected CPE cases from clinical samples (0.5 vs. 0.1 per 1,000 admis- sions, P = 0.033), the exposure duration (7.6 days vs. 1.0 days, P < 0.001), and the number of CPE contacts (9.0 vs. 1.0, P < 0.001) during the post-outbreak period. The incidence of HO cases was similar between the pre-and post-outbreak period (0.8 vs. 0.9; P = 0.528) despite a sub- fi stantial increase in overall CPE incidence (1.4 vs. 3.1 per 1,000 admissions, P < 0.001) (Supplementary Table 2). Risk associated with CPE colonization at admission The risks of CPE-positive admission screening are sum - marized in Table  3. The risk of CPE positive admission Table 3 The relative risk of factors associated with CPE-positive admission screening during the study period after the initiation of screening program (September 2018-December 2020) Proportion of CPE positive screening (%) RR (95% CI, P-value) aRR (95% CI, P-value) Previous colonization/infection No 90 (0.6) Yes 39 (31.7) 53.30 (38.36–74.07, P < 0.001) 37.25 (25.68–54.04, P < 0.001) Transfer from acute care hospitals No 108 (0.9) Yes 21 (1.3) 1.52 (0.95–2.42, P = 0.078) 3.09 (1.93–4.95, P < 0.001) Transfer from long-term care facilities No 107 (0.8) Yes 22 (1.8) 2.15 (1.36–3.39, P = 0.001) 1.66 (1.05–2.61, P = 0.029) Previous hospitalization within 6 months No 29 (0.5) Yes 100 (1.2) 2.53 (1.67–3.82, P < 0.001) 2.30 (1.44–3.68, P = 0.001) Receipt of hemodialysis No 109 (0.8) Yes 20 (2.6) 3.18 (1.98–5.09, P < 0.001) 1.68 (1.09–2.60, P = 0.020) Abbreviations: CI, condence interval; CPE, carbapenemase-producing Enterobacterales; RR, relative risk; aRR, adjusted relative risk Footnote: Adjusted for risk factors above, age and sex Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 8 of 11 screening was the highest in patients with previous increased from 2017 to 2021, as did the number of CPE- CPE colonization/infection with the proportion of posi- colonized patients. In studies conducted before 2017, tive screening upon readmission being 31.7% (39/123) none of the screened patients were positive for CPE [14], (adjusted relative risk [aRR] 37.25, 95% confidence inter - whereas after 2017, 1.4–1.8% of screened patients were val [CI] 25.68–54.04; P < 0.001). Among patients without CPE-positive at the time of admission [15]. In our study, previous CPE colonization/infection, the risk of having the proportion of CPE positivity among the screened a positive CPE screening was highest among patients patients was lower than that reported in previous stud- transferred form ACHs or LTCFs. Also, receipt of hemo- ies because of the extended indications for CPE screen- dialysis was identified as an independent risk factor with ing. However, the incidence of patients positive for CPE the proportion of CPE positive admission screening screening per 1000 admissions increased from 1.2 in being 1.7% (13/784) (Supplementary Table 3). The risk of phase 1 to 2.3 in phase 2, which indicates an increasing CPE screening positivity did not differ between patients risk of carrying CPE among inpatients in South Korea receiving HD at other hospitals compared to those and highlights the importance of active CPE screening. receiving HD at this hospital (RR 1.10, 95%CI 0.36–3.32, In this study, the mean age of inpatients at this hospi- P = 0.869). tal steadily increased over the study period. This aging demographics of the inpatients at this hospital may also Discussion have influenced the high detection rate at admission This study showed that previously unrecognized CPE screening during phase 2. As South Korea is an aging carriers were detected using the enhanced screening society, the number of elderly patients staying at long- program. More than 45% of CPE cases were additionally term care hospitals or nursing homes has increased [16]. detected through the enhanced screening program and The movement of elderly patients between ACHs and increased compliance. Application of the Xpert Carba- LTCFs may increase the risk of acquisition of CPE. In a R assay in combination with screening cultures reduced study examining CPE acquisition rates in LTCFs in South the exposure duration and number of close contacts in Korea, the positivity rate was 22.5% for patients shar- hospital settings. These factors may have prevented wide - ing a room with a CPE-positive patient [17]. In LTCFs, spread CPE outbreaks and reduced the incidence of CPE patients are at an increased risk of persistent coloniza- clinical infections. Universal screening of ICU patients at tion due to frequent admissions and readmissions to admission and weekly thereafter was useful for detecting ACHs, comorbidities, and dependency on nursing care CPE colonization early and potentially reducing the risk [18]. Transfer from ACHs also poses a high risk of CPE of clinical infections in critically ill patients. In particu- colonization [18–20]. The findings of this study provide lar, weekly ICU screening is considered as an important additional evidence that patients transferred from both component of the surveillance program as the positiv- LTCFs and ACHs are at increased risk of CPE carriage ity rate among patients undergoing weekly ICU screen- compared to those from the community. However, not ing was higher than those undergoing ICU admission all healthcare facilities perform CPE screening, and the screening. CPE status of transferred patients is not always commu- In South Korea, the prevalence of CRE has increased nicated. Thus, CPE screening is required to verify CPE rapidly since 2017, and CPE constitutes 73.9% of the CRE colonization status in patients transferred from outside collected from 2017 to 2020 [12]. Among them, KPC-2 HCFs, which possibly poses the risk of covert transmis- was the predominant carbapenemase (KPC-2 73.8%), sion before detection. Interfacility patient transfer plays followed by NDM-1 (12.9%) and OXA-181 (1.8%). KPC- an important role in the spread of CPE [21] and clonal 2-producing K. pneumoniae accounted for 58.7% of CPE spread of CPE within a region and across the country [12]. This increasing trend correlates with the findings has been identified in South Korea [ 12, 22]. Thus, active of this study, and the high prevalence of bacteria with screening is recommended for patients transferred from the KPC-2 and NDM-1 genes in our hospital reflects either LTCFs or ACH, and interfacility communication the nationwide spread of KPC-2- or NDM-1-carrying should be improved for the timely identification of CPE- Enterobacterales in South Korea. However, in this study, colonized patients [23]. the prevalence of NDM-1 (39.4%) was higher than that As CPE endemicity increases and population demo- of KPC-2 (31.4%) despite KPC-2 being more commonly graphics change, the risk factors for CPE colonization identified at the national level. This finding indicates the can broaden. CPE acquisition is more likely to be caused possibility of intra-hospital transmission of NDM-1 car- by within-hospital transmission and interfacility spread rying Enterobacterales in this hospital. within the same country rather than by international Among the CRE cases reported to the KDCA, > 90% travel [21, 24]. Consistent with the evolving risk factors, were colonized cases [13], suggesting that the number this study also showed considerable intra-hospital trans- of healthcare facilities performing active surveillance mission. The CPE positivity among the weekly screened Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 9 of 11 ICU patients was higher than that of patients screened to contain CPE [33]. Even with the implementation of upon ICU admission and that HO CPE colonization/ active screening, it is challenging to preemptively iso- infection continued to occur in the post-outbreak period, late patients in healthcare settings with a shortage of despite the implementation of the enhanced admission single rooms. Therefore, in such healthcare settings, as screening program in Phase 2. In our hospital, the initial an alternative to preemptive isolation, rapid detection CPE screening program with narrow indications failed to with the Xpert-Carba-R assay can reduce the exposure effectively detect CPE-colonized patients, which allowed duration. This study showed that the exposure dura - an undetected influx of CPE patients into the hospital tion and number of patients exposed to CPE cases were and subsequent dissemination of CPE. In this study, the markedly reduced after incorporating the Xpert Carba-R prevalence of newly detected CPE colonization among assay for screening. Furthermore, increased awareness dialysis patients was relatively high at the time of admis- of CPE among leaders and HCWs plays a crucial role in sion (1.7%). Although the prevalence of CPE among the successful implementation of active screening. In our dialysis patients has not been widely studied, hemodialy- hospital, the importance of CPE prevention was widely sis patients are considered at risk of CPE colonization as recognized during the CPE outbreak, and compliance they are repeatedly exposed to healthcare settings [3, 18, with CPE screening increased over time through col- 25]. One study in Korea showed that approximately 8.4% laborative efforts by IPC units, laboratory department, (14/165) carried CRE and 85.7% (12/14) of those iso- HCWs, and leadership. During the CPE outbreak, the lates harbored KPC-type carbapenemase [26]. In South education on CPE management was reinforced among Korea, the number of dialysis patients has increased HCWs, and their compliance with infection prevention annually, reaching 108,873 patients in 2019, more than measures and the screening program was continued to be 50% of whom were over 65 years of age [27]. Therefore, monitored and communicated even after the outbreak. appropriate infection prevention measures should be These concerted efforts led to the significant improve - implemented in hemodialysis units, and the risk of CPE ment in compliance between phase 1 and phase 2, which colonization among dialysis patients should be studied was critical in containing the CPE outbreak. further. This study has a few limitations. Due to the retrospec - The ICU is a high-risk unit for CPE transmission with tive nature of the study, medical histories from other hos- a detrimental impact on clinical outcomes. Thus, most pitals may have been incomplete. Despite this, our study guidelines recommend the active screening of ICU- had high compliance and well-designed screening plans admitted patients. However, screening strategies for ICU during phase 2. Secondly, cost-effectiveness was not con - patients vary, including universal or targeted screening sidered. The enhanced screening program led to more with or without periodic follow-up screening. Also, the testing and higher expenses in terms of contact precau- CPE positivity among ICU patients vary depending on tion measures. However, preventing CPE infections and the screening strategies. Previous studies reported that outbreaks could decrease the costs of additional care the CPE positivity among ICU patients ranged from 0.6% and longer hospital stays. Cost-effectiveness studies in using universal screening to 7.5% using targeted screen- other countries have concluded that screening is more ing for patients transferred from outside facilities [23, economical overall than not screening in CPE-prevalent 28–31]. From the perspective of test efficiency, universal settings with a colonization prevalence of > 0.015% [34, screening may be labor-intensive and less cost effective-, 35]. In South Korea, the estimated prevalence of CPE but many patients would be missed if targeted screening was approximately 0.029% in 2023, based on the number was used [32]. Our study showed a relatively low CPE of CPE cases reported to the KDCA and the estimated positivity (0.48%) among ICU patients who underwent Korean population of 51.4  million in the given year [2, universal screening. However, it is notable that a sub- 36]. Therefore, CPE screening can be cost-effective in stantial proportion of CPE-positive ICU patients (41.7%) South Korea. Thirdly, the impact of the enhanced screen - were solely identified through universal screening. As the ing program itself may be overestimated. The observed acquisition of CPE is frequent during the ICU stay, peri- significant reduction in HO CPE cases during phase 2, odic CPE screening among ICU patients is important for in comparison to phase  1, could have been attributed to detecting patients with CPE colonization and prompt- suboptimal compliance during phase 1. With increased ing timely infection prevention and control (IPC) mea- compliance during phase 1, the incidence of HO CPE sures. In our study, 12 patients with CPE were discovered cases would have decreased, even in the absence of the through weekly screening, which potentially contributed additional CPE screening measures. to preventing widespread CPE dissemination in ICUs. Potential barriers to active CPE screening include a shortage of single rooms, limited availability of screen- ing tests, and a lack of leadership and government efforts Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 10 of 11 Consent for publication Conclusions Not applicable. This study showed that an enhanced CPE screening pro - Author details gram with high compliance enabled us to identify previ- Infection Prevention and Control Unit, Daejeon St. Mary’s Hospital, The ously unrecognized CPE-colonized patients in a timely Catholic University of Korea, Daejeon, Republic of Korea Division of Infectious Diseases, Department of Internal Medicine, College manner and to rapidly institute contact precaution mea- of Medicine, The Catholic University of Korea, Seoul, Republic of Korea sures that reduced CPE transmission and curtailed a Vaccine Bio Research Institute, College of Medicine, The Catholic widespread CPE outbreak. As CPE endemicity increases, University of Korea, Seoul, Republic of Korea Department of Pediatrics, College of Medicine, The Catholic University of the risk factors for CPE colonization may broaden, and Korea, Seoul, Republic of Korea hospital prevention strategies need to be tailored to Department of Laboratory Medicine, College of Medicine, The Catholic changes in regional CPE epidemiology. University of Korea, Seoul, Republic of Korea The Catholic University of Korea, Eunpyeong St. Mary’s Hospital, 93-19 Abbreviations Jingwan-dong, Eunpyeong-gu, Seoul, Republic of Korea ACH acute care hospital CA community-associated Received: 20 March 2023 / Accepted: 23 June 2023 CO-HA community-onset, healthcare-associated CPE Carbapenemase-producing Enterobacterales CRE carbapenem-resistant Enterobacterales HCF healthcare facility HO hospital-onset HO-OHCF healthcar e-onset, outside healthcare facility ICU intensive care unit References IQR interquartile range 1. Park JW, Lee E, Lee SJ, Lee H. 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Joo S, Kim M, Shin E, Kim J, Yoo J. Molecular characteristic analysis and antimicrobial resistance of carbapenem-resistant Enterobacteriaceae (CRE) Ethics approval and consent to participate isolates in the Republic of Korea, 2017–2020. Public Health Weekly Report. This study was approved by the Institutional Review Board at the Catholic 2021;14(53):3790–804. University of Korea, Daejeon St. Mary’s Hospital, and the need for informed consent was waived (DC21ENSI0040). Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 11 of 11 13. Korea Disease Control and Prevention Agency: Statistics of notifiable infec - 26. Salazar-Ospina L, Vanegas JM, Jimenez JN. High intermittent colonization by tious diseases. 2023. https://npt.kdca.go.kr/npt/biz/npp/ist/simple/simplePd- diverse clones of beta-lactam-resistant Gram-negative bacilli suggests an StatsMain.do. Accessed May 28, 2023. excessive antibiotic use and different sources of transmission in haemodialy - 14. 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Active 36. Korean Statistical Information Service: Population by Census. (2021). 2023. screening and interfacility communication of carbapenem-resistant Entero- https://kosis.kr/statHtml/statHtml.do?orgId=101&tblId=DT_1IN1502&c bacteriaceae (CRE) in a tertiary-care hospital. Infect Control Hosp Epidemiol. onn_path=I2. Accessed May 29, 2023. 2018;39(9):1058–62. 24. David S, Reuter S, Harris SR, Glasner C, Feltwell T, Argimon S, et al. Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosoco- Publisher’s Note mial spread. Nat Microbiol. 2019;4(11):1919–29. Springer Nature remains neutral with regard to jurisdictional claims in 25. van Loon K, Voor In ‘t Holt AF, Vos MC. A systematic review and meta-analyses published maps and institutional affiliations. of the clinical epidemiology of carbapenem-resistant Enterobacteriaceae. Antimicrob Agents Chemother 2017;62(1):e01730-17 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Antimicrobial Resistance and Infection Control Springer Journals

The impact of enhanced screening for carbapenemase-producing Enterobacterales in an acute care hospital in South Korea

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Abstract

Background Carbapenemase-producing Enterobacterales (CPE) poses a significant challenge to infection control in healthcare settings. Active screening is recommended to prevent intra-hospital CPE transmission. Methods CPE screening was initiated at a 660-bed hospital in South Korea in September 2018, targeting patients previously colonized/infected or admitted to outside healthcare facilities (HCFs) within 1 month. Universal intensive care unit (ICU) screening was performed at the time of admission. After a hospital-wide CPE outbreak in July- September 2019, the screening program was enhanced by extending the indications (admission to any HCF within 6 months, receipt of hemodialysis) with weekly screening of ICU patients. The initial screening method was changed from screening cultures to the Xpert Carba-R assay. The impact was assessed by comparing the CPE incidence per 1000 admissions before (phase 1, September 2018-August 2019) and after instituting the enhanced screening program (phase 2, September 2019-December 2020). Results A total of 13,962 (2,149 and 11,813 in each phase) were screened as indicated, among 49,490 inpatients, and monthly screening compliance increased from 18.3 to 93.5%. Compared to phase 1, the incidence of screening positive patients increased from 1.2 to 2.3 per 1,000 admissions (P = 0.005) during phase 2. The incidence of newly detected CPE patients was similar (3.1 vs. 3.4, P = 0.613) between two phases, but the incidence of hospital-onset CPE patients decreased (1.9 vs. 1.1, P = 0.018). A significant decrease was observed (0.5 to 0.1, P = 0.014) in the incidence of patients who first confirmed CPE positive through clinical cultures without a preceding positive screening. Compared to phase 1, the median exposure duration and number of CPE contacts were also markedly reduced in phase 2: 10.8 days vs. 1 day (P < 0.001) and 11 contacts vs. 1 contact (P < 0.001), respectively. During phase 2, 42 additional patients were identified by extending the admission screening indications (n = 30) and weekly in-ICU screening (n = 12). Conclusions The enhanced screening program enabled us to identify previously unrecognized CPE patients in a rapid manner and curtailed a hospital-wide CPE outbreak. As CPE prevalence increases, risk factors for CPE *Correspondence: Sun Hee Park sh.park@catholic.ac.kr Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 2 of 11 colonization can broaden, and hospital prevention strategies should be tailored to the changing local CPE epidemiology. Keywords Carbapenemase-producing Enterobacterales, Active screening, Periodic screening, Infection prevention and control Background limited indications, including previous CPE colonization/ Carbapenemase-producing Enterobacterales (CPE) poses infection, previous admission to outside HCFs within the a significant threat to global health, and the prevalence of past month, transfer from outside HCFs, and ICU admis- CPE has increased worldwide. In South Korea, the preva- sion. Screening was performed using two consecutive lence of CPE has steadily increased since 2010, after the rectal swabs sampled on chromogenic agar. Between July first identification of imported case [ 1], and mandatory and September 2019, a CPE outbreak occurred in several notification of carbapenem-resistant Enterobacterales wards. Thus, as of mid-August 2019, an enhanced screen - (CRE) infection/colonization to the Korea Disease Con- ing program was implemented by broadening the screen- trol and Prevention Agency (KDCA) was initiated in June ing indications and updating the screening protocol to 2017. Since then, the number of reported CRE cases has include a rapid polymerase chain reaction (PCR) method, increased substantially from 5,717 to 2017 to 23,311 in the Xpert-Carba-R assay, with culture-based methods. 2021, with CPE accounting for 63.3% of the CRE cases in This study aimed to evaluate the impact of changes in 2021 [1, 2]. CPE screening strategies on the spread of CPE and devel- Early detection and isolation of patients infected or col- opment of clinical infections. We explored the trend of onized with CPE are the main infection control strategies CPE colonization/infection over time and compared to contain the spread of CPE in healthcare settings. For CPE incidence in screening cultures and clinical cul- this purpose, many countries have developed national tures before and after the introduction of the enhanced infection control guidelines based on the active screening screening program. We also investigated the effect of the of patients at high risk of CPE colonization or hospital- enhanced screening program on intra-hospital transmis- ized patients in high-risk units [3–8]. However, it is the sion of CPE. responsibility of individual facilities to make decisions regarding whom to screen and how to screen. This has Methods led to variability in CPE screening strategies among hos- Ethics pitals [9]. The KDCA guidance recommends screening of This study was approved by the Institutional Review patients who are at risk of CPE colonization at the time Board at the Catholic University of Korea, Daejeon St. of admission; suggested risk factors include a history of Mary’s Hospital, and the need for informed consent was contact with a CPE patient or admission to healthcare waived (DC21ENSI0040). facilities (HCFs) where CPE outbreaks have occurred, or previous CPE colonization or infection. However, in the Hospital settings KDCA guidance, the duration of risk is not specified, and This retrospective observational cohort study was con - CPE screening policy primarily depends on the health- ducted at the Catholic University of Korea, Daejeon St. care facilities’ decisions [10]. In South Korea, most hospi- Mary’s Hospital from April 2017 to December 2020. tals have multi-occupancy rooms with shared bathrooms The study population included all hospitalized patients and open-bay design intensive care units (ICUs). In hos- aged ≥ 18 years and those who stayed in the ICU for pital settings, where patient isolation is difficult owing to > 24 h. Our hospital is a 660-bed, university-affiliated sec - the shortage of single rooms, active surveillance is often ondary care hospital in Daejeon, South Korea. Daejeon discouraged. Rapid detection is essential for effectively has a population of 1.5  million people, and this hospital reducing the duration of exposure to CPE when pre- has an average of 24,300 admissions per year. Hospital emptive isolation is difficult. However, conventional and general wards are composed of 95% multi-occupancy commonly-used screening methods, such as culturing rooms with shared bathrooms, 5% en-suite single rooms, samples on selective media, require 24–48 h for growth, and four airborne infection isolation rooms. There are and molecular methods are required for confirmation [ 4]. two ICUs (medical and surgical) that have an open bay Therefore, containment of CPE is a challenge in Korean design and two isolation rooms per ICU. Each ICU healthcare facilities. accommodates 18 patients. In 2017, the first case of CPE was identified at Daejeon St Mary’s Hospital in Daejeon, South Korea. In Septem- Microbiology tests ber 2018, we launched an admission CPE screening pro- For screening cultures, ChromID CARBA agar (bioMéri- gram targeting patients at risk of CPE colonization with eux, France) was used to culture rectal swab specimens. Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 3 of 11 The Xpert Carba-R assay was used to detect carbapen - methods (Table  1). If the Xpert Carba-R test was posi- emases. CPE positivity was defined as both the Xpert tive, the patients were isolated until two consecutives Carba-R assay and screening culture being positive. screening cultures were negative. If CPE colonization Carbapenemase genes were further subtyped using PCR was confirmed, isolation was continued. During phase2, and sequencing as previously described [11]. When the in addition to universal ICU admission screening, ICU Xpert Carba-R assay was negative but the cultures were patients were screened weekly during their stay, using positive, the isolates were considered CRE. Species iden- cultures. Throughout the study period, preemptive isola - tification was performed using matrix-assisted laser tion was performed only for patients with documented desorption/ionization time-of-flight mass spectrom - history of previous CPE colonization/infection. Previous etry (Bruker, Daltonics, Germany), and antimicrobial CPE colonization/infection was verified through flags in susceptibilities were determined according to Clinical electronic medical records and microbiology results at and Laboratory Standards Institute guidelines using the this hospital, and through inter-facility communication. MicroScan WalkAway 96 Plus system and Neg Combo Management of CPE positive patients was as follows. If Panel Type 72 (Beckman Coulter, Brea, California). CPE was confirmed, patients continued to be isolated in a single room until discharge. In case of a shortage of single CPE screening programs and patient management rooms, CPE patients were cohorted in multi-occupancy CPE screening programs and patient management strat- rooms according to carbapenemase gene and organism egies have changed over time, as shown in Table  1. In type. Other infection prevention measures included (1) brief, CPE screening was not performed during phase 0 the signage on isolation room doors and flags in elec - (April 2017-August 2018). During phase 1 (September tronic medical records, (2) the use of personal protective 2018-August 2019), we performed the screening program equipment (PPE) including single-use gloves and gowns with limited indications using only culture-based screen- whenever entering the room, (3) the use of disposable ing. If the screening culture was positive, the patients or dedicated patient care equipment, (4) cohorting of were isolated in a single room. During phase 2 (Septem- nursing and cleaning staff in the event of an outbreak, ber 2019-December 2020), the indications for admis- and (5)  environmental cleaning (twice daily) of isolation sion screening were expanded, the Xpert Carba-R assay rooms and terminal cleaning with hypochlorite solution was used for initial testing, along with culture-based after patient discharge. Table 1 Changes in carbapenemase-producing Enterobacterales control strategy during the entire study period (2017–2020) Phase 0 Phase 1 Phase 2 General ward Ad- None Colonization/infection with CPE within 6 months Colonization/infection with CPE within 6 months prior mission screening prior to admission to admission 1 1 Previous admission to outside healthcare facility Previous admission to any healthcare facility within within the past 1 month the past 6 months Transfer from long-term care facilities or acute care Transfer from long-term care facilities, acute care hos- hospitals pitals, rehabilitation centers or nursing homes Receipt of hemodialysis ICU Admission None Universal screening for all patients admitted to ICU Universal screening for all patients admitted to ICU screening ICU Periodic None None Weekly screening during the ICU stay screening Screening method None Two consecutive rectal swab cultures on chromo- Xpert Carba R assay, followed by two consecutive genic agar with a 24-hour interval, followed by rectal swab cultures on ChromID CARBA agar with a Xpert Carba R assay if cultures are positive 24-hour interval Patient Isolation Patient isolation Patient isolation once cultures reported as positive Patient isolation once Xpert Carba R assay reported as once clinical positive until the following two rectal swab cultures cultures reported reported negative. as positive Isolation continued if cultures reported as positive Patient De-isolation De-isolation De-isolation when 3 consecutive cultures with 1 De-isolation when 3 consecutive cultures with 1 week when 3 con- week interval reported negative interval reported negative and at least 6 months have secutive cultures elapsed since the first negative conversion with 1 week interval reported negative Abbreviation: ICU, intensive care unit 1 2 Footnote: Acute care hospitals, long-term care hospitals, nursing homes and rehabilitation hospitals were included. Preemptive isolation was performed only for patients with previous CPE colonization/infection Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 4 of 11 Contact management was similar during the study (HO): infection detected > 2 days after admission to this period. When any new CPE patients were identified, all hospital. contacts were traced and screened using cultures. The CPE isolates obtained from a single patient were con- Xpert-Carba-R assay was also used for contact screen- sidered duplicates if they were the same species/car- ing of ICU patients during phase  2. CPE contacts were bapenemase combination, regardless of the source of cohorted until they were cleared after obtaining two neg- culture specimens. Otherwise, CPE isolates without such ative swabs > 24 h apart. concordance were considered as non-duplicates. CPE- positive clinical cultures included CPE isolates which Staff education on CPE management were detected in clinical specimens either before or after Since 2017, the hospital’s healthcare workers (HCWs) screening cultures, or in cases where CPE screening was have received regular education and updates on CPE not conducted. management according to the changes in the hospital policies. The CPE screening program was communi - Data collection and analysis cated to the staff before its launch in September 2018. In We collected data on patient demographics and the risk response to the outbreak, comprehensive training was factors described above, the timing of specimen sam- conducted in in-person meetings, with active involve- pling and reporting, exposure duration, number of con- ment of the hospital leadership, to educate all relevant tacts, and CPE screening results. To assess the impact of HCWs in CPE management. Education programs were the enhanced screening program, the incidence of CPE customized to suit the specific requirements and roles colonization/infection per 1,000 admissions was calcu- of each department in containing the outbreak. The lated during phases 1 and 2 and compared using Pois- hospital-wide campaign was initiated and continued to son regression. Given the outbreak period coincided reinforce the enhanced CPE screening program. The per - with parts of both phase 1 and phase2, further analysis formance of hand hygiene, implementation of contact was conducted by dividing the study period into three precaution measures, and adherence to CPE screening periods: pre-outbreak (September 2018-June 2019), out- protocols were monitored and communicated to both break (July-September 2019), and post-outbreak (Octo- HCWs and leadership. ber 2019-December 2020), in order to assess the impact of the enhanced screening program in an endemic set- Definitions ting. The Chi-squared test or Fisher’s exact test was used Compliance with admission screening was calculated by to compare categorical variables. The Student’s t-test dividing the number of patients who were screened ≤ 48 h or Wilcoxon rank-sum test was used to compare con- after admission by the number of patients who were indi- tinuous variables. Risk factors for positive admission cated for screening. Compliance with weekly ICU screen- screening were evaluated using log-binomial regression. ing was calculated by dividing the number of patients Multivariate analyses were conducted, adjusting for age, screened weekly by the number of patients who stayed in sex and patient characteristics which were found signifi - the ICU for ≥ 7 days. cant in the bivariate analysis (P < 0.1). All analyses were The CPE exposure duration was defined as the period performed using Stata (version 17.0; StataCorp, LP, Col- from either the admission date or the date when the most lege Station, TX, US). P < 0.05 was considered statistically recent rectal swab culture was negative during admission significant. to the date of initiation of contact isolation. Patients were considered CPE contacts if they shared a room with a Results CPE patient during the exposure period. Patient demographics and compliance to the enhanced CPE patients were epidemiologically categorized based program on timing of specimen sampled and the presence of risk During the study period, 80,348 patients (30,858, 22,228, factors as follows: (1) community-associated (CA): infec- and 27,262 during phases 0, 1, and 2, respectively) were tion detected ≤ 2 days after admission to this hospital and admitted to this hospital, and 7,413 episodes of ICU with no known exposure to healthcare facilities; (2) com- admission were identified among 6,555 patients. Over munity-onset, healthcare associated (CO-HA): infection time, there was a steady increase in the proportion of detected ≤ 2 days after admission, with a history of hos- patients who had been hospitalized in acute care hos- pitalization, long-term care facility (LTCF) residence, or pitals (ACHs) or resided in LTCFs during the previous hemodialysis within the previous 6 months; (3) Health- 6 months and who were transferred from outside HCFs care-onset, outside healthcare facilities (HO-OHCF): (Table  2). The proportion of patients with comorbidities infection detected ≤ 2 days from admission after transfer such as malignancy, diabetes, dementia, and congestive from outside healthcare facilities; (4) healthcare-onset heart failure increased as well. The mean age of inpa - tients increased from 61.7 to 63.3 years over the study Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 5 of 11 Table 2 Comparisons of patient eligible for screenings, new CPE patients by sample and screen, and the incidence of CPE colonization or infection before (Phase 1) and after (Phase 2) the enhanced screening program Phase 1 Phase 2 P-value Number of patients with risk factors (%) Previous colonization/infection 12 (0.05) 111 (0.4) Previous admission to HCFs within 6 months 6,662 (30.0) 8,889 (32.6) < 0.001 Receipt of hemodialysis 620 (2.8) 798 (2.9) < 0.001 Transfer from outside HCFs 1406 (6.3) 2111 (7.7) < 0.001 Number of ICU patients eligible for screening (%) ICU universal admission screening 2,376 (10.7) 2,652 (9.7) < 0.001 ICU weekly screening NA 765 (2.8) Positive screening per 1,000 screens IRR (95% CI) P-value Admission screening 11.7 5.3 0.45 (0.29–0.71) 0.001 ICU universal admission screening 9.4 4.4 0.47 (0.19–1.14) 0.07 ICU weekly screening 18.8 Positive screening per 1,000 admissions IRR (95% CI) P-value Admission screening 1.2 2.3 1.90 (1.21–2.99) 0.005 ICU universal admission screening 5.5 4.2 0.76 (0.31–1.83) 0.507 ICU weekly screening 15.7 Incidence of CPE colonization/infection per 1,000 admissions IRR (95% CI) P-value Total new CPE patients 3.1 3.4 1.08 (0.79–1.48) 0.613 New CPE from screening samples 2.6 3.3 1.27 (0.91–1.76) 0.162 New CPE from clinical samples 0.5 0.1 0.20 (0.06–0.72) 0.014 Hospital-onset CPE patients 1.9 1.1 0.57 (0.36–0.91) 0.018 Patients with CPE-positive clinical cultures 0.7 0.4 0.65 (0.31–1.39) 0.270 Abbreviations: CI, confidence interval; CPE, carbapenemase-producing Enterobacterales; ICU, intensive care unit; IRR, incidence rate ratio; HCF, healthcare facility; NA, not applicable Footnote: Patients with CPE isolates detected in clinical samples before or after the identification of CPE colonization through screening, or in cases where CPE screening was not conducted, were included period, and those aged ≥ 70 years accounted for 39.6% previously colonized with NDM-1-producing Klebsi- of all inpatients in phase 2 (Supplementary Table  1). The ella oxytoca was found to carry a different CPE isolate mean age of patients who were transferred from out- (KPC-2-producing Klebsiella pneumoniae). A total of 24 side HCFs was higher than those who were not (72.4 CPE cases were identified through universal ICU admis - vs. 62.2 years, P < 0.001). During phase 1 and 2, 13,962 sion screening, and 10 of them (41.7%) had no indica- patients were screened for indications (2,149 in phase tions other than ICU admission. There were 30 patients 1 and 11,813 in phase 2), and 1,851 patients for other with clinical cultures positive for CPE (3 in phase 0, 15 in purposes. The proportion of admitted patients meeting phase 1, and 12 in phase 2), the most common site being screening criteria increased from 14.6% (n = 3,250) in urine (n = 16), followed by sputum (n = 8), wounds (n = 3), Phase 1 to 44.4% (n = 12,100) in Phase 2. Over the study and blood (n = 3). period, the monthly compliance with the CPE screening In terms of epidemiologic categorization, there were program markedly increased from 18.3 to 93.5% (Fig.  1). three HO cases and one CO-HA case during phase 0. On average, compliance with the screening program sig- During phases 1 and 2, there were 47 CO-HA patients nificantly increased between phase 1 and 2, from 59.3 to (42 associated with this hospital and five associated with 86.3% (P < 0.001). Weekly ICU screening was performed other facilities) and 39 HO-OHCF patients, including 21 in 83.7% of the ICU-admitted patients (640/765). from ACHs and 18 from LTCFs or nursing homes. Four CPE cases were considered to be community-associated. Trends in CPE colonization/infection and epidemiological There were 73 HO cases associated with this hospital, characteristics of CPE cases including 29 cases detected during the outbreak period The annual incidence of CPE-colonization/infections (Fig. 1). substantially increased from 0.10 to 4.2 per 1,000 admis- In terms of CPE isolates, there were 175 non-duplicate sions over the 4-year study period. A total of 167 CPE CPE isolates identified, including 8 non-duplicate isolates cases were newly identified during the study period, from 4 patients. Species of CPE isolates and carbapen- including 149 cases from surveillance testing and 18 emase genes were diverse throughout the study period cases from clinical cultures. One patient who was (Fig.  2). Nonetheless, 47.4% (n = 83) of cultures were K. Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 6 of 11 Fig. 1 Trend in newly detected CPE cases according to epidemiological category and compliance to the screening program (2017–2020) Abbreviation: CA, community-associated; CO-HA, community-onset, healthcare-associated; CPE, carbapenemase-producing Enterobacterales; HO, hos- pital-onset; HO-OHCF, hospital-onset at outside healthcare facilities (transferred from outside healthcare facilities). Fig. 2 Trend in non-duplicate CPE isolates by bacterial species and carbapenemase genes (2017–2020) Abbreviations: CPE, carbapenemase-producing Enterobacterales; KPN, Klebsiella pneumoniae; ECO, Escherichia coli; CF, Citrobacter freundii; KO, Klebsiella oxytoca. 1 2 Footnote: Other Enterobacterales are as follows: other includes Citrobacter, E. coli, K. oxytoca, and K. pneumoniae; other includes K. pneumoniae and E. coli; 3 4 5 other includes Citrobacter and K. aerogenes; other includes C. freundii and K. pneumoniae; other includes K. pneumoniae, E. coli, and E. asburiae Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 7 of 11 pneumoniae, and NDM-1 (39.4%, 69/175) and KPC-2 (31.4%, 55/175) were the most commonly identified car - bapenemases. These genes were also frequently detected in patients who were transferred from outside HCFs with NDM-1 accounting for 33.3% (13/39) and KPC-2 accounting for 35.9% (14/39). Impact of the enhanced screening program Compared to phase 1, the incidence of CPE increased from 1.2 to 1,000 admissions to 2.3 per 1,000 admis- sions in phase 2. The total number of patients eligible for admission screening increased from 3,250 in phase 1 to 12,100 in phase 2, and the proportion of positive admis- sion screens decreased during phase 2 (Table 2). Although the incidence of newly detected cases was higher during phase 2, a significant decrease was observed in the inci - dence of newly detected CPE cases from clinical sam- ples without a preceding positive screening, from 0.54 to 1,000 admissions to 0.11 per 1,000 admissions (inci- dence rate ratio [IRR] 0.20; 95% confidence interval [CI] 0.06–0.72; P = 0.014) (Table  2), and CPE-positive clinical cultures per 1000 admissions did not change significantly (IRR 0.65; 95% CI 0.31–1.39; P = 0.27). The incidence of HO cases also decreased during phase 2 (IRR 0.57; 95% CI 0.36–0.91; P = 0.018) (Table 3). Overall, 42 additional patients were identified during phase 2 by extending the admission screening indica- tions (n = 30) and weekly in-ICU screening (n = 12). These accounted for 45.2% (42/93) of the newly detected CPE cases during phase 2. In comparison to phase 1, the median exposure dura- tion to CPE was significantly reduced during phase 2, from 10.8 days (interquartile range [IQR] 2.6–21.0) to 1  day (IQR 0.5–2.6) (P < 0.001). The median number of CPE contacts was also reduced during phase 2, from 11 contacts (IQR 4–19) to 1 contact (IQR 0–5) (P < 0.001). During phase 2, no widespread outbreaks occurred, although there were small clusters or sporadic CPE cases. When analyzing the pre-outbreak, outbreak and post- outbreak periods, similar findings were observed. Com - pared to the pre-outbreak period, a significant reduction was observed in the incidence of newly detected CPE cases from clinical samples (0.5 vs. 0.1 per 1,000 admis- sions, P = 0.033), the exposure duration (7.6 days vs. 1.0 days, P < 0.001), and the number of CPE contacts (9.0 vs. 1.0, P < 0.001) during the post-outbreak period. The incidence of HO cases was similar between the pre-and post-outbreak period (0.8 vs. 0.9; P = 0.528) despite a sub- fi stantial increase in overall CPE incidence (1.4 vs. 3.1 per 1,000 admissions, P < 0.001) (Supplementary Table 2). Risk associated with CPE colonization at admission The risks of CPE-positive admission screening are sum - marized in Table  3. The risk of CPE positive admission Table 3 The relative risk of factors associated with CPE-positive admission screening during the study period after the initiation of screening program (September 2018-December 2020) Proportion of CPE positive screening (%) RR (95% CI, P-value) aRR (95% CI, P-value) Previous colonization/infection No 90 (0.6) Yes 39 (31.7) 53.30 (38.36–74.07, P < 0.001) 37.25 (25.68–54.04, P < 0.001) Transfer from acute care hospitals No 108 (0.9) Yes 21 (1.3) 1.52 (0.95–2.42, P = 0.078) 3.09 (1.93–4.95, P < 0.001) Transfer from long-term care facilities No 107 (0.8) Yes 22 (1.8) 2.15 (1.36–3.39, P = 0.001) 1.66 (1.05–2.61, P = 0.029) Previous hospitalization within 6 months No 29 (0.5) Yes 100 (1.2) 2.53 (1.67–3.82, P < 0.001) 2.30 (1.44–3.68, P = 0.001) Receipt of hemodialysis No 109 (0.8) Yes 20 (2.6) 3.18 (1.98–5.09, P < 0.001) 1.68 (1.09–2.60, P = 0.020) Abbreviations: CI, condence interval; CPE, carbapenemase-producing Enterobacterales; RR, relative risk; aRR, adjusted relative risk Footnote: Adjusted for risk factors above, age and sex Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 8 of 11 screening was the highest in patients with previous increased from 2017 to 2021, as did the number of CPE- CPE colonization/infection with the proportion of posi- colonized patients. In studies conducted before 2017, tive screening upon readmission being 31.7% (39/123) none of the screened patients were positive for CPE [14], (adjusted relative risk [aRR] 37.25, 95% confidence inter - whereas after 2017, 1.4–1.8% of screened patients were val [CI] 25.68–54.04; P < 0.001). Among patients without CPE-positive at the time of admission [15]. In our study, previous CPE colonization/infection, the risk of having the proportion of CPE positivity among the screened a positive CPE screening was highest among patients patients was lower than that reported in previous stud- transferred form ACHs or LTCFs. Also, receipt of hemo- ies because of the extended indications for CPE screen- dialysis was identified as an independent risk factor with ing. However, the incidence of patients positive for CPE the proportion of CPE positive admission screening screening per 1000 admissions increased from 1.2 in being 1.7% (13/784) (Supplementary Table 3). The risk of phase 1 to 2.3 in phase 2, which indicates an increasing CPE screening positivity did not differ between patients risk of carrying CPE among inpatients in South Korea receiving HD at other hospitals compared to those and highlights the importance of active CPE screening. receiving HD at this hospital (RR 1.10, 95%CI 0.36–3.32, In this study, the mean age of inpatients at this hospi- P = 0.869). tal steadily increased over the study period. This aging demographics of the inpatients at this hospital may also Discussion have influenced the high detection rate at admission This study showed that previously unrecognized CPE screening during phase 2. As South Korea is an aging carriers were detected using the enhanced screening society, the number of elderly patients staying at long- program. More than 45% of CPE cases were additionally term care hospitals or nursing homes has increased [16]. detected through the enhanced screening program and The movement of elderly patients between ACHs and increased compliance. Application of the Xpert Carba- LTCFs may increase the risk of acquisition of CPE. In a R assay in combination with screening cultures reduced study examining CPE acquisition rates in LTCFs in South the exposure duration and number of close contacts in Korea, the positivity rate was 22.5% for patients shar- hospital settings. These factors may have prevented wide - ing a room with a CPE-positive patient [17]. In LTCFs, spread CPE outbreaks and reduced the incidence of CPE patients are at an increased risk of persistent coloniza- clinical infections. Universal screening of ICU patients at tion due to frequent admissions and readmissions to admission and weekly thereafter was useful for detecting ACHs, comorbidities, and dependency on nursing care CPE colonization early and potentially reducing the risk [18]. Transfer from ACHs also poses a high risk of CPE of clinical infections in critically ill patients. In particu- colonization [18–20]. The findings of this study provide lar, weekly ICU screening is considered as an important additional evidence that patients transferred from both component of the surveillance program as the positiv- LTCFs and ACHs are at increased risk of CPE carriage ity rate among patients undergoing weekly ICU screen- compared to those from the community. However, not ing was higher than those undergoing ICU admission all healthcare facilities perform CPE screening, and the screening. CPE status of transferred patients is not always commu- In South Korea, the prevalence of CRE has increased nicated. Thus, CPE screening is required to verify CPE rapidly since 2017, and CPE constitutes 73.9% of the CRE colonization status in patients transferred from outside collected from 2017 to 2020 [12]. Among them, KPC-2 HCFs, which possibly poses the risk of covert transmis- was the predominant carbapenemase (KPC-2 73.8%), sion before detection. Interfacility patient transfer plays followed by NDM-1 (12.9%) and OXA-181 (1.8%). KPC- an important role in the spread of CPE [21] and clonal 2-producing K. pneumoniae accounted for 58.7% of CPE spread of CPE within a region and across the country [12]. This increasing trend correlates with the findings has been identified in South Korea [ 12, 22]. Thus, active of this study, and the high prevalence of bacteria with screening is recommended for patients transferred from the KPC-2 and NDM-1 genes in our hospital reflects either LTCFs or ACH, and interfacility communication the nationwide spread of KPC-2- or NDM-1-carrying should be improved for the timely identification of CPE- Enterobacterales in South Korea. However, in this study, colonized patients [23]. the prevalence of NDM-1 (39.4%) was higher than that As CPE endemicity increases and population demo- of KPC-2 (31.4%) despite KPC-2 being more commonly graphics change, the risk factors for CPE colonization identified at the national level. This finding indicates the can broaden. CPE acquisition is more likely to be caused possibility of intra-hospital transmission of NDM-1 car- by within-hospital transmission and interfacility spread rying Enterobacterales in this hospital. within the same country rather than by international Among the CRE cases reported to the KDCA, > 90% travel [21, 24]. Consistent with the evolving risk factors, were colonized cases [13], suggesting that the number this study also showed considerable intra-hospital trans- of healthcare facilities performing active surveillance mission. The CPE positivity among the weekly screened Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 9 of 11 ICU patients was higher than that of patients screened to contain CPE [33]. Even with the implementation of upon ICU admission and that HO CPE colonization/ active screening, it is challenging to preemptively iso- infection continued to occur in the post-outbreak period, late patients in healthcare settings with a shortage of despite the implementation of the enhanced admission single rooms. Therefore, in such healthcare settings, as screening program in Phase 2. In our hospital, the initial an alternative to preemptive isolation, rapid detection CPE screening program with narrow indications failed to with the Xpert-Carba-R assay can reduce the exposure effectively detect CPE-colonized patients, which allowed duration. This study showed that the exposure dura - an undetected influx of CPE patients into the hospital tion and number of patients exposed to CPE cases were and subsequent dissemination of CPE. In this study, the markedly reduced after incorporating the Xpert Carba-R prevalence of newly detected CPE colonization among assay for screening. Furthermore, increased awareness dialysis patients was relatively high at the time of admis- of CPE among leaders and HCWs plays a crucial role in sion (1.7%). Although the prevalence of CPE among the successful implementation of active screening. In our dialysis patients has not been widely studied, hemodialy- hospital, the importance of CPE prevention was widely sis patients are considered at risk of CPE colonization as recognized during the CPE outbreak, and compliance they are repeatedly exposed to healthcare settings [3, 18, with CPE screening increased over time through col- 25]. One study in Korea showed that approximately 8.4% laborative efforts by IPC units, laboratory department, (14/165) carried CRE and 85.7% (12/14) of those iso- HCWs, and leadership. During the CPE outbreak, the lates harbored KPC-type carbapenemase [26]. In South education on CPE management was reinforced among Korea, the number of dialysis patients has increased HCWs, and their compliance with infection prevention annually, reaching 108,873 patients in 2019, more than measures and the screening program was continued to be 50% of whom were over 65 years of age [27]. Therefore, monitored and communicated even after the outbreak. appropriate infection prevention measures should be These concerted efforts led to the significant improve - implemented in hemodialysis units, and the risk of CPE ment in compliance between phase 1 and phase 2, which colonization among dialysis patients should be studied was critical in containing the CPE outbreak. further. This study has a few limitations. Due to the retrospec - The ICU is a high-risk unit for CPE transmission with tive nature of the study, medical histories from other hos- a detrimental impact on clinical outcomes. Thus, most pitals may have been incomplete. Despite this, our study guidelines recommend the active screening of ICU- had high compliance and well-designed screening plans admitted patients. However, screening strategies for ICU during phase 2. Secondly, cost-effectiveness was not con - patients vary, including universal or targeted screening sidered. The enhanced screening program led to more with or without periodic follow-up screening. Also, the testing and higher expenses in terms of contact precau- CPE positivity among ICU patients vary depending on tion measures. However, preventing CPE infections and the screening strategies. Previous studies reported that outbreaks could decrease the costs of additional care the CPE positivity among ICU patients ranged from 0.6% and longer hospital stays. Cost-effectiveness studies in using universal screening to 7.5% using targeted screen- other countries have concluded that screening is more ing for patients transferred from outside facilities [23, economical overall than not screening in CPE-prevalent 28–31]. From the perspective of test efficiency, universal settings with a colonization prevalence of > 0.015% [34, screening may be labor-intensive and less cost effective-, 35]. In South Korea, the estimated prevalence of CPE but many patients would be missed if targeted screening was approximately 0.029% in 2023, based on the number was used [32]. Our study showed a relatively low CPE of CPE cases reported to the KDCA and the estimated positivity (0.48%) among ICU patients who underwent Korean population of 51.4  million in the given year [2, universal screening. However, it is notable that a sub- 36]. Therefore, CPE screening can be cost-effective in stantial proportion of CPE-positive ICU patients (41.7%) South Korea. Thirdly, the impact of the enhanced screen - were solely identified through universal screening. As the ing program itself may be overestimated. The observed acquisition of CPE is frequent during the ICU stay, peri- significant reduction in HO CPE cases during phase 2, odic CPE screening among ICU patients is important for in comparison to phase  1, could have been attributed to detecting patients with CPE colonization and prompt- suboptimal compliance during phase 1. With increased ing timely infection prevention and control (IPC) mea- compliance during phase 1, the incidence of HO CPE sures. In our study, 12 patients with CPE were discovered cases would have decreased, even in the absence of the through weekly screening, which potentially contributed additional CPE screening measures. to preventing widespread CPE dissemination in ICUs. Potential barriers to active CPE screening include a shortage of single rooms, limited availability of screen- ing tests, and a lack of leadership and government efforts Park et al. Antimicrobial Resistance & Infection Control (2023) 12:62 Page 10 of 11 Consent for publication Conclusions Not applicable. This study showed that an enhanced CPE screening pro - Author details gram with high compliance enabled us to identify previ- Infection Prevention and Control Unit, Daejeon St. Mary’s Hospital, The ously unrecognized CPE-colonized patients in a timely Catholic University of Korea, Daejeon, Republic of Korea Division of Infectious Diseases, Department of Internal Medicine, College manner and to rapidly institute contact precaution mea- of Medicine, The Catholic University of Korea, Seoul, Republic of Korea sures that reduced CPE transmission and curtailed a Vaccine Bio Research Institute, College of Medicine, The Catholic widespread CPE outbreak. As CPE endemicity increases, University of Korea, Seoul, Republic of Korea Department of Pediatrics, College of Medicine, The Catholic University of the risk factors for CPE colonization may broaden, and Korea, Seoul, Republic of Korea hospital prevention strategies need to be tailored to Department of Laboratory Medicine, College of Medicine, The Catholic changes in regional CPE epidemiology. University of Korea, Seoul, Republic of Korea The Catholic University of Korea, Eunpyeong St. Mary’s Hospital, 93-19 Abbreviations Jingwan-dong, Eunpyeong-gu, Seoul, Republic of Korea ACH acute care hospital CA community-associated Received: 20 March 2023 / Accepted: 23 June 2023 CO-HA community-onset, healthcare-associated CPE Carbapenemase-producing Enterobacterales CRE carbapenem-resistant Enterobacterales HCF healthcare facility HO hospital-onset HO-OHCF healthcar e-onset, outside healthcare facility ICU intensive care unit References IQR interquartile range 1. Park JW, Lee E, Lee SJ, Lee H. 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Authors’ contributions 2017;22(4):159–86. SHP designed the protocol, performed data analysis and interpretation, 7. World Health Organization: Implementation manual to prevent and control and wrote and revised the manuscript. YY and SKJ reviewed the records the spread of carbapenem-resistant organisms at the national and health and collected data. WS wrote the manuscript and prepared figures. EH and care facility level. 2019. https://apps.who.int/iris/handle/10665/312226. SS identified the species, performed the susceptibility tests, and critically Accessed December 9, 2022. reviewed the manuscript. All the authors have read and approved the final 8. Australian Commission on Safety and Quality in Helathcare Care: Recom- version of the manuscript. mendations for the control of carbapenemase-producing Enterobacterales (CPE). A guide for acute care health service organisations. 2021. https://www. 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Journal

Antimicrobial Resistance and Infection ControlSpringer Journals

Published: Jul 3, 2023

Keywords: Carbapenemase-producing Enterobacterales; Active screening; Periodic screening; Infection prevention and control

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