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의료관련감염원론 연세의대진단검사의학교실, 세균내성연구소, 세브란스병원감염관리실 이경원

의료관련감염 (Health care-associated infection, HAI) 원내감염 ( 병원감염, nosocomial 또는 hospital infection) 입원시에는감염도잠복도되지않았으나병원이나의료시설에서감염. 병원에서감염되었으나퇴원후에발병한것도포함. 대부분은입원 48시간후에감염소견을나타냄. WHO definition An infection occurring in a patient during the process of care in a hospital or other health-care facility which was not present or incubating at the time of admission. This includes infections acquired in the hospital but appearing after discharge, and also occupational infections among the staff the facility WHO guide 2002

의료관련감염 세계적으로매년수백만명발생 의료관련감염영향 -중증질환 -입원기간연장 -장애기간연장 - 사망률증가 - 의료비상승 : 환자, 병원, 정부 WHO 2013

의료관련감염 입원 환자 중에 5-10% 감염증 - 요로감염: 30-40% - 수술부위감염 및 호흡기 감염: 15-20% - 균혈증: 5-15% Device 관련 감염이 흔함 - Urinary tract catheter - Endotracheal tube - Central venous catheter

삽입기구관련의료관련감염 감염종류 미국 NHSN (2006-8) 한국 KONIS (2010.6-2011.7) Central line-associated BSI 2.6 3.0 MICU Ventilator-associated pneumonia 2.4 0.9 Urinary catheter-associated UTI 4.7 3.9 Central line-associated BSI 2.3 3.4 SICU Ventilator-associated pneumonia 4.9 1.9 Urinary catheter-associated UTI 4.3 4.1 발생률, 1000 기구명 - 일당병원감염관리 2012;17:28-39 Am J Infect Control 2009;37:783-805

SSI 수술부위감염 KONIS (2010.7 2011.6) NHSN (2006-2008) Gastrectomy 3.5 2.3 CBGB(both) 3.6 2.9 CABG( chest only) 2.6 1.1 Cardiac surgery 2.2 0.8 Craniotomy 3.1 2.6 Colon operation 4.4 7.4 Rectal operation 4.5 5.6 Gallbladder surgery 0.6 0.6 Abdominal hysterectomy 1.3 1.7 Vaginal hysterectomy 0.5 0.9 laminectomy 0.9 1.0 Spinal fusion 1.3 1.5 Hip prosthesis 0.0 1.3 Knee prosthesis 1.0 0.9 수술부위감염건수 / 전체수술건수 X 100 병원감염관리 2012;17:1-12 Am J Infect Control 2009;37:783-805

의료관련감염 의료비상승, 입원기간연장 - 미국 ICU 환자에서 - BSI, 입원기간 24 일연장환자당 $40,000 상승 - SSI, 입원기간 6 일연장, $3,000 상승 감염관리적극적활동 : 의료관련감염, 32% 감소 Not ICP: 18% 증가

감염부위별추가재원일수및추가진료비 병원감염종류 추가재원일수 한국 * ( 미국 ** ) 추가비용 한국 * 미국 ** 요로감염 0.6일 (1.0일) 균혈증 1.0일 (7.0일) 수술창상감염 20.4일 (7.0일) 폐렴 0.25일 (6.0일) 최소 : 650,247원최대 : 2,026,745원최소 : 1,738,613원최대 : 2,930,684원최소 : 3,317,812원최대 : 3,945,829원최소 : 2,964,188원최대 : 6,362,623원 평균 : $593 ( 최고 : $8,286) 평균 : $3,016 ( 최고 : $9,027) 평균 : $2,734 ( 최고 : $26,019) 평균 : $4,947 ( 최고 : $41,628) *Song JH (KJNIC 1999;4:157-66); **Haley RW (JAMA 1987:257:1611-4)

2009 년비용수준추정 : 약 15 억 / 연

의료관련감염, 저소득국가발생률 1.5 배 주요선진국의의료관련감염병유병률 (prevalence), 1995-2010,(WHO) : 3.5-12.0% 중 - 저소득국가의의료관련감염병유병률 1995-2010(WHO) : 5.7-19.1%

주요의료관련감염균 CLA-Bloodstream infection (%) VA-Pneumonia (%) Staphylococcus, coagulase neg. 34 Enterococcus spp. 16 Candida spp. 12 Staphylococcus aureus 10 Klebsiella pneumoniae 5 Staphylococcus aureus 24 Pseudomonas aeruginosa 16 Acinetobacter baumannii 8 Enterobacter spp. 8 Klebsiella pneumoniae 8 CA-Urinary tract infection (%) Surgical site infection (%) Escherichia coli 21 Candida spp. 21 Enterococcus spp 15 Pseudomonas aeruginosa 10 Klebsiella pneumoniae 8 Staphylococcus aureus 30 Staphylococcus, coagulase neg. 14 Enterococcus spp. 11 Escherichia coli 10 Pseudomonas aeruginosa 6 1970-2000: Gram-positive organisms and Candida 2006- : Multiresistant Gram-negative bacilli, CRAB Hidron AI, ICHE 2008

흔한임상분리세균 (KONSAR 2011) Rank Organism No. (%) of isolates Rank (ICU) 1 Escherichia coli 37,308 (22.7) 7 2 Staphylococcus aureus 27,314 (16.6) 1 3 Coagulase neg. staphylococci 19,574 (11.9) 3 4 Klebsiella pneumoniae 16,404 (10.0) 5 5 Pseudomonas aeruginosa 15,032 (9.1) 4 6 Enterococcus faecalis 12,916 (7.8) 8 7 Acinetobacter spp. 11,671 (7.1) 2 8 Enterococcus faecium 9,757 (5.9) 6 9 Enterobacter cloacae 4,499 (2.7) 10 Total 164,686 (100) 34 KONSAR group hospitals

의료관련감염과항균제내성 HAI AMR

Centers for Disease Control and Prevention, 2013

다제내성균의지정전염병고시 2010 년 12 월 30 일긴급고시 다제내성균 1. Vancomycin 내성포도알균 (VRSA, 2000년기고시 ) 2. Methicillin 내성포도알균 (MRSA, 혈액 ) 3. Vancomycin 내성장알균 (VRE, 혈액 ) 4. Carbapenem 내성장내세균 (CRE, NDM-1: 2010/10) 5. 다약제내성녹농균 (MRPA) 6. 다약제내성에시네토박터균 (MRAB) 44개상급종합병원을표본감시기관으로지정 300병상이상병원 56개소추가지정 (2011/7) 2012년 6월의료관련감염병관련웍숍 : 환자, 병원체보유자

다제내성균의추이 80 70 60 50 40 30 20 10 0 MRSA, 66% CRAB, 64% VRE, 23% CRPA, 22% 1960s 1980 1990 1994 1997 1999 2001 2003 2005 2007 2009 2011 KONSAR 1997-2011

Comparison of estimated deaths in the United States in 2005 due to individual infectious agents or other causes (DeLeo FR, JCI 2009).

Clinical impact: VISA and VRE 60 50 40 30 20 10 0 50 33 VISA (n=6) All cause mortality Attributable mortality 23 28 9 8 hvisa MRSA (n=22) (n=215) Khatib R (JAC, 2011) DiazGranados CA (JID 2005)

Mortality: CRAB vs. CSAB, CRKP vs. CSKP 60 50 40 30 20 57% 24% Percent of subjects 60 50 40 30 20 CRKP CSKP 10 10 0 CRAB (n=37) CNRAB (n=42) 0 Overall Mortality Attributable Mortality Esterly JS (AAC, 2011) Patel G (ICHE, 2008)

Jung JY (BMC ID, 2010) Kim SY (JKMS, 2012)

- 2008.1-2009.12: MDR Acinetobacter in ICUs. - 108 (54%): MDR Acinetobacter bacteremia (Jung JY, et al BMC Inf Dis 2010) - 30-day mortality: 79.8% (Kim SY, et al: JKMS 2012)

Imported OXA-232-producing Klebsiella pneumoniae New variant of OXA-48 carbapenemase First report, India to France in 2011 First nosocomial spread of OXA-232 carbapenemase in Korea in 2013 - 인도에서작업중부상, 현지병원치료 3 일후국내 A 병원으로전원치료 국내 B 병원으로전원 - A 병원 3 명, B 병원 23 명에서균배출자확인 - 2013 년 8 월, 총 13 개병원 63 명균배출자확인 - 프랑스분리주와동일한 ST14, PFGE (>90%) 주간건강과질병 (2013)

의료관련감염관리 Strategies Hand hygiene Standard precautions: transmission-based Environmental hygiene Surveillance of infections Antimicrobial stewardship Aseptic technique, HAI bundles for VAP & BSI Strong, supportive leadership - Sufficient, well-trained staff 정부 : 보건복지부질병관리본부보험심사평가원 학회 : 대한병원감염관리학회및관련학회 의료기관 : 대학, 종합및일반병원, 요양병원 개인 : 환자, 보호자 CID 2013; JCI & SHEA 2012

의료법제 47 조 ( 병원감염예방 ) 의료법 1 보건복지부령으로정하는일정규모이상의병원급의료기관의장은병원감염예방을위 하여감염관리위원회와감염관리실을설치 운영하고보건복지부령으로정하는바에따라 감염관리업무를수행하는전담인력을두는등필요한조치를하여야한다. < 개정 2008.2.29, 2010.1.18, 2011.8.4> 의료법시행규칙 제 43 조 ( 감염관리위원회및감염관리실의설치등 ) 1 법제 47 조제 1 항에따라병원 ( 병상이 200 개이상인경우만해당한다 ) 및종합병원으로서중환자실을운영하는의료기관의장은병원감염예방을위하여감염관리위원회 ( 이하 " 위원회 " 라한다 ) 와감염관리실을설치 운영하여야한다. < 개정 2012.8.2> 제 44 조 ( 위원회의구성 ) 제 45 조 ( 위원회의운영 ) 1 위원회는정기회의와임시회의로운영한다. 제 46 조 ( 감염관리실의운영등 ) 1 법제 47 조제 1 항에따라감염관리실에는

2013 년 1-7 월의료관련감염병 ( 내성균 6 종현황 ) ( 단위 : 신고건, 재원일수 1,000 일당분리율 ) 구분총계 VRSA /VISA VRE MRSA MRPA MRAB CRE A 그룹 (27 개 ) 224 (0.11) 0/0 (0.00)/(0.00) 18 (0.01) 168 (0.08) 11 (0.01) 25 (0.01) 2 (0.00) 혈액검체분리율 B그룹 (22개) C그룹 (29개) D그룹 (21개) 699 (0.26) 1,214 (0.29) 1,959 (0.39) 0/0 (0.00)/(0.00) 0/1 (0.00)/(0.00) 0/0 (0.00)/(0.00) 92 (0.03) 150 (0.04) 436 (0.09) 462 (0.17) 746 (0.18) 1,024 (0.20) 21 (0.01) 40 (0.01) 81 (0.02) 121 (0.05) 260 (0.06) 365 (0.07) 3 (0.00) 17 (0.00) 53 (0.01) 계 (99 개 ) 4,096 (0.29) 0/1 (0.00)/(0.00) 696 (0.05) 2,400 (0.17) 153 (0.01) 771 (0.05) 75 (0.01) A 그룹 (27 개 ) 5,570 (2.68) 0/0 (0.00)/(0.00) 578 (0.28) 3,246 (1.56) 485 (0.23) 1,175 (0.57) 86 (0.04) 혈액외검체분리율 B그룹 (22개) C그룹 (29개) D그룹 (21개) 7,391 (2.77) 16,001 (3.76) 14,558 (2.87) 0/0 (0.00)/(0.00) 0/2 (0.00)/(0.00) 0/1 (0.00)/(0.00) 691 (0.26) 1,256 (0.30) 1,822 (0.36) 4,077 (1.53) 8,671 (2.04) 7,016 (1.38) 666 (0.25) 1,106 (0.26) 1,095 (0.22) 1,854 (0.69) 4,724 (1.11) 4,161 (0.82) 103 (0.04) 242 (0.06) 463 (0.09) 계 (99 개 ) 43,520 (3.09) 0/3 (0.00)/(0.00) 4,347 (0.31) 23,010 (1.63) 3,352 (0.24) 11,914 (0.85) 894 (0.06)

대한병원감염관리학회 연도활동 2013, 현재 1995 학회창립및학술대회 1996 감염관리소식, 창간호발행 1996 제1회병원감염관리연수강좌, 연1회 2014년 12월 18차연수강좌 1996 학술지병원감염관리창간호, 연2회 18권 1호 1996 감염관리지침발간 병원감염관리 4판, 2012 2001 홈페이지개설및운영 2012년개편 2002 제 1 회동아시아감염관리학술대회개최 2013 년 11 월중국개최 2014 년 12 월서울개최예정 2006 Korean Noso. Infections Surv. System (KONIS, 전국병원감염감시체계 ) 2006 대한병원감염관리학회영남지회창립 2014년 1월 6차학술대회 2012 대한병원감염관리학회호남지회창립 2014년 4월 3차연수교육 2012 제1차의료관련감염포럼개최 2014년 2월 14일, 5차예정 2013 감염관리실장을위한연수과정 2014년 4월 26일, 2차예정 2014 대한병원감염관리학회학술대회 2014년 5월 29-30일

SAVE LIVES: Clean Your Hands is a major component of Clean Care is Safer Care

Jain R (NEJM 2011)

The US Veterans Administration Experience A MRSA bundle was implemented in 2007 - universal nasal surveillance for MRSA - contact precaution - hand hygiene - institutional culture change Initially implemented in ICUs, then hospital-wide, then added long-term care facilities All US VA hospitals included (n = 150) Intervention from October 2007 through June 2010 Jain R (NEJM 2011)

62% decrease No sign change 45% decrease Jain R (NEJM 2011)

Johnson (JAC 2012)

National Hand Hygiene initiative (NNHI) - WHO 5 moments for hand hygiene - implemented in January 2009 HH compliance rate: 68% (44% 68%) - Nurse 74%; MD 52% Mean annual national rates of MRSAB in 2008, 2009 and 2010 0.4998 > 0.3902 > 0.3497 /10,000 pt-d Grayson ML (MJA 2011)

Keystone ICU project: 108 ICUs in Michigan in 2003 CRBSI Bundle 1. Hand hygiene 2. Full barrier precautions during insertion of central venous catheter 3. Cleaning the skin with chlorhexidine 4. Avoiding femoral site if possible 5. Removing uncessary catheters Pronovost P (NEJM 2006)

Pronovost P et al. N Engl J Med 2006;355:2725-2732 108 ICUs 39 Keystone project Rates of Catheter-Related Bloodstream Infection from Baseline (before I mplementation of the Study Intervention) to 18 Months of Follow-up per 1000 catheter days: 2.7 to 0 ---- median per 1000 catheter days: 7.7 to 1.4 ----- mean *NHSN 50 th percentile: 1.1 Teaching hospitals: 1.7

WHO HH improvement strategy

Flash mob

직원간 - 손위생권하기 캠페인 - 구호외치기 환자가직원에게 Speak up

항생제관리 실행계획 감염내과및감염소아파트협진질과양향상 관리항생제허가체계강화 항생제사용량 feedback 부적절한항생제사용에대한 audit 항생제 de-escalation 관리지표 각중환자실의 carbapenem 사용량 전체항생제사용량 Acinetobacter 내성률 IDSA and SHEA guidelines for developing an institutional program to enhance antimicrobial stewardship (2007)

Antibiotic stewardship & hand hygiene programs were reinforced in a 2,000-bed tertiary hospital in Korea - Computerized prescription restriction was implemented in 2008 - WHO HH program was reinforced in 2008 MRSA BSI (1,000 pt-days) : 0.171 in 2009 0.116 in 2011 (P = 0.009) Antibiotic consumption (DDD/1,000 pt-days): 690 in 2008 652 in 2011 (P =.015) HH performance: 43% in 2008 83% in 2011 (P = 0.043) Kim YC (AJIC 2013)

Source of pathogens causing HAI in ICU More than 20 years ago, - Patients endogenous flora: 40-60% - Hands of personnel: 20-40% - Antibiotic-driven changes in the flora: 20-25% - Other (environment, food, air, unknown): 20% Contamination of environmental surfaces in hospital rooms plays an important role in the transmission of several key healthcare-associated pathogens, including MRSA, VRE, CDIF, ACIB & norovirus Weinstein RA (AJM, 1991); Weber DJ (ICHE 2013)

Weber DJ (ICHE 2013)

병원균의환경오염 Pathogens Contamination rate Contamination dose MRSA Room surface: 1-27% in general ward Hospital surface: < 64% in burn unit VRE Environmental surface: 7-29% Room surface: 60-70% (3-4 body site colonized patient) Chairs and couch: 36-58% < 10 cfu/cm 2 < 100 cfu/25cm 2 (RODAC plate) Acinetobacter spp. Environmental surface: 3-50% (Outbre ak) C. difficile Environmental surface: 2.9-75% 10-100 cfu 1300 cfu (sponge)

Pathogen Contaminated site SAU KPN ABA Air, mattress cover, bathroom floor, bed linen, chairs, table, floor Bed frame, overbed table, bedcovers, drains, sinks Bed rails, sinks, tables, curtains, door handles CDI Bed, sink, toilet, wall, rails, call button, stretcher

Duration of persistence and infective dose of common pathogens of health-care associated infections Pathogens Duration of persistence on hands Duration of persistence on inanimate surfaces Infective dose (CFU) Staphylococcus aureus 150 min 4 wk 7 mo 4 (Methicillin-resistant S. aureus) Unknown 4 wk 7 mo 4 Coagulase-negative Staphylococ cus Normal flora Unknown Enterococcus spp. (VRE) Up to 60 min 5 days 4 mo 10 3 Escherichia coli 6-90 min 2 h 16 mo 10 8 Klebsiella pneumoniae Up to 2 h 2 h 30 mo Enterobacter spp. Unknown Unknown Serratia marcescens 30 min 3 days 2 mo Pseudomonas aeruginosa 30 180 min 6 h 16 mo Acinetobacter spp. 150 min 3 days 5 mo 250 Candida spp. 1 h 1-150 days C. difficile Unknown 24 h (vegetative cells) Up to 5 mo (spores) Clin Microbiol Rev 2004 4

A 1,500-bed teaching hospital in the Miami area in 2012. Crit Care Med 2013

Disinfectants used for environmental disinfection and new room decontamination technology American Journal of Infection Control 41 (2013) S36-S41

Drymist vs Vapor disinfection

항균제내성균증가 중증환자증가 의료관련감염 위험성증가 새로운치료방법 신종감염질환출현

결론 의료관련감염 : 성공적관리가능 성공의필수요인 - 의료인의지속적인교육 - 수행업무점검및평가 - 적극적인행정지원 - 강한지도력, 문화변화및정착