Investigation of Transmission Rate of Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae (CP-CRE) among Close Contact Patients and Healthcare Workers Using Whole-Genome Sequencing

Abstract

Introduction: To reduce transmission of carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE), screening is recommended for patients who shared a room with a newly detected CP-CRE-infected or -colonized patients and healthcare workers caring for CP-CRE-infected or –colonized patients. The aim of this study was to investigate the rate of positivity in screening tests among patients who shared a room with CP-CRE-infected or –colonized patients and healthcare workers, and to find risk factors for transmission. Methods: This study was conducted in a 1,751-bed tertiary teaching hospital between January 2017 and December 2019. Index patients were defined as those with positive tests for CP-CRE from any infected or colonized site during hospitalization. When an index patient was detected in a shared room, we performed screening tests for patients whose stay overlapped with an index patient for at least one day and healthcare workers who were caring for an index patient. Rectal swabs for screening tests were cultured using MacConkey agar plates supplemented with meropenem. When CRE was isolated on screening test, we checked the presence and type of carbapenemase using PCR. If close contact patients or healthcare workers had CRE, whole-genome sequencing with remeasurement of MIC and multilocus sequence typing were performed to verify genetic relatedness with CRE from their index patients. When CP-CRE from close contact patients or healthcare workers had different types of carbapenemases with their index patients, the pairs were excluded from genetic analysis. Results: During study period, a total of 47 index patients were identified. Among 47 index patients, 32 patients (68.1 %) tested positive for KPC-producing CRE, 15 patients (31.9 %) tested positive for NDM-1-producing CRE, and 2 patients (4.3 %) had OXA-48. Forty-seven index patients were found to have been in close contact with a total of 152 patients in a shared room and 54 healthcare workers. Out of 152 close contact patients, ten had carbapenemase-non-producing carbapenem-resistant Enterobacteriaceae (CNP-CRE) and seven had CP-CRE. None of healthcare works had CRE. Four close contact patients had the same type of carbapenemase with their CP-CRE index patients and all of them were KPC. Whole-genome sequencing with remeasurement of MIC revealed that 3 out of 4 pairs of CP-CRE index/secondary patients showed genotypic and phenotypic accordance between index patients and contacted patients. Consequently, the CP-CRE transmission rate in close contact patients in a shared room was calculated as 2.0% (=3/152). Risk factors for CPE transmission could not be analyzed due to small number of CP-CRE transmitted cases. Conclusion: The CP-CRE transmission rate between CP-CRE index patients and close contact patients in shared rooms was about 2.0%. There was no CP-CRE transmission between CP-CRE index patients and healthcare workers.

서론: 카바페넴분해효소 생성 카바페넴 내성 장내세균속의 (carbapenemase-producing carbapenem-resistant Enterobacteriaceae, CP-CRE) 전파를 줄이기 위해 CP-CRE가 확인된 환자와 동실에 재원했던 환자들과 해당 환자를 돌보았던 의료진들에 대해 CRE 감시 검사를 하는 것이 추천된다. 본 연구의 목적은 CRE 감시 검사에서 CP-CRE 전파로 확인되는 경우의 분율을 파악하고 CP-CRE 전파의 위험인자를 밝히는 것이다. 방법: 본 연구는 2017년 1월부터 2019년 12월까지 1,751 병상의 3차 병원에서 후향적으로 진행됐다. 기준 환자는 입원 기간 동안 감염 부위나 집락 부위에서 CP-CRE 양성으로 확인되는 경우였다. 다인실에서 CP-CRE 기준 환자가 나왔을 경우 최소 1일 이상 동실에 재원했던 환자들과 기준 환자와 최소 1회 이상 접촉했던 의료진들에 대해 CRE 감시 검사를 시행했다. 감시 검사에서 CRE가 검출되면 다중연쇄반응 검사를 이용해 카바페넴분해효소의 유무를 확인했다. 또 염기서열 분석법과 카바페넴 최소억제농도 재측정, 다좌위 형별 분석을 통해 기준 환자와 접촉 환자 사이에 CP-CRE를 비롯한 CRE 전파가 있었는지 살펴보았다. 결과: 총 47명의 CP-CRE 기준 환자가 있었고, 206명의 환자와 의료진이 이 환자들과 접촉했다. 이들 중 14명의 환자들에서 CRE가 검출됐고 여기서 4명만이 CPE 기준 환자와 같은 종류의 카바페넴분해효소를 보유하고 있었다. 염기서열 분석법과 카바페넴 최소억제농도 재측정을 이용해서 이 4명 중 3명에서 CP-CRE 기준 환자와 접촉 환자 사이에 카바페넴분해효소 전파가 있었을 가능성을 보였다. 54명의 의료진에서는 CRE가 검출되지 않았다. 따라서 동실 재원 환자를 대상으로 한 CRE 감시 검사에서의 CP-CRE 전파율은 2.0%로 계산됐다. CP-CRE 전파 사례 수가 적어 CP-CRE 전파의 위험인자는 분석하지 못했다. 결론: 동실 재원 환자를 대상으로 한 CRE 감시 검사에서의 CP-CRE 전파율은 2.0%였다. 의료진에서는 CRE가 검출되지 않았다.