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1 병원감염관리 : 제20권제1호 2015 Korean J Nosocomial Infect Control 2015;20(1):1-6 종설 병원균의병원환경오염과감염관리 김영아 1,4 ㆍ이혁민 2,4 ㆍ이경원 3,4 국민건강보험일산병원진단검사의학과 1, 관동대학교진단검사의학과 2, 연세대학교의과대학진단검사의학교실 3, 세균내성연구소 4 Contamination of the Hospital Environmental by Pathogenic Bacteria and Infection Control Young Ah Kim 1,4, Hyukmin Lee 2,4, Kyungwon Lee 3,4 Department of Laboratory Medicine, National Health Insurance Service Ilsan Hospital 1, Goyang, Department of Laboratory Medicine, Catholic Kwandong University College of Medicine 2, Incheon, Department of Laboratory Medicine 3 and Research Institute of Bacterial Resistance 4, Yonsei University College of Medicine, Seoul, Korea Healthcare-associated infections (HAIs) have increased rapidly, and the wide spread of multidrug resistant (MDR) bacteria has made the control of HAIs a challenging health problem. Transmission of common pathogens from a colonized or infected patient to a susceptible patient has been reported to occur via the hands of healthcare personnel. Therefore, the priority of infection control policy has been allocated in hand hygiene program, contact precautions, and isolation. However, the transmission routes of pathogens are complicated. Furthermore, recent data suggest that the hospital environment could play a role as an important reservoir, and contaminated hospital surfaces, medical equipment, water, and air could be directly or indirectly involved in the transmission pathways. Therefore, we should reconsider the role of hospital environment control in the management of HAIs as well as developing strategies to reduce the contamination of hospital environment. Keywords: Healthcare-associated infection, Hospital environment, Infection control Introduction 의료관련감염 (healthcare-associated infection) 은입원시에존재하지않았고, 잠복기도아닌상태에서의료기관에입원중에발병한감염으로흔히입원 48시간후에감염을말한다 [1]. 기존의병원내에서획득한감염을뜻하는병원감염 (hospital-acquired infection) 에서요양병원이나외래투석등 Received: May 22, 2014 Revised: July 28, 2014 Accepted: July 31, 2014 Correspondence to: Kyungwon Lee, Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul , Korea Tel: , Fax: leekcp@yuhs.ac 의다른의료기관노출로인한감염도포함하는확대된개념이다. 의료관련감염은세계적으로매년수백만명환자에서발생하고, 근래면역억제환자의증가, 침습적시술의보편화등으로증가하는추세에있으며, 이로인해입원기간과장애기간연장, 사망률증가및의료비상승의문제점이있다 [2]. 더욱이최근에는여러계열의항균제에내성을가지는 carbapenem-resistant Enterobacteriaceae (CRE), multidrug-resistant Pseudomonas aeruginosa, multidrug-resistant Acinetobacter, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA), vancomycin-resistant Enterococcus (VRE) 등의다제내성균 (multidrug resistant organisms) 에의한감염이늘어나고있고

2 2 김영아 / 이혁민 / 이경원 관련된비용도급격히증가하여이를줄이기위한적극적인노력이더욱필요한시점이다 [3]. 중환자실에서발생하는의료관련감염은환자가가지고있던정상균무리에의한것이 40-60%, 의료인의손에의한교차감염이 20-40% 정도로대부분을차지한다 [4]. 따라서지금까지의료기관에서의감염관리활동은요로감염, 폐렴, 수술부위감염과혈관카테터관련균혈증등주요의료관련감염의감시, 손위생, 격리, 직원의감염관리, 소독과멸균지침등이주된내용이었다 [5]. 그러나병원균에오염된병원환경과감염전파와연관이있다는보고가많으며 [6], 병원환경의오염도가높을수록의료종사자의가운과장갑의다제내성균의오염이많고 [7], 심지어병원감염과관련이많은 VRE, Acinetobacter spp. 의공기전파도알려져있다 [8,9]. 따라서지금까지간과되어왔던병원환경관리에대해좀더관심이필요하다고생각되며, 본논문에서환경관리의중요성을다시한번검토해보고이를위한전략을살펴보고자한다. 1. 병원환경오염병원환경에는다양한미생물이있고, 기회감염균에부적절하게노출되거나, Aspergillus spp., Legionella spp., Mycobacterium tuberculosis, Varicella-Zoster virus 등공기로전파되는균에의해심각한감염이발생할수있다 [10]. 근래에는병원환경오염이 MRSA, VRE, Clostridium difficile, Acinetobacter 및 P. aeruginosa에의한병원감염에도중요한역할을한다고알려져있으며, 근거는다음과같다 [11]. 즉, 1) 감염된환자의병실이동일한세균에의해자주오염되고, 2) 병원균이의료환경에서장기간생존할수있으며, 3) 의료인의손이나장갑의오염빈도와병실오염빈도가연관성이있고, 4) 사람간전파나의료기기매개로인한집단감염이발생하고, 5) 감염환자가입원한병실의환자가동일한병원균에의한정착이흔하고, 6) 병실을청결하게하면감염률이낮아지며, 7) 소독을잘하면감염률이낮아진다. 병원환경오염으로문제가되었거나환경관리를통하여효과가있었던최근사례는 Table 1과같았다 [8,12-20]. 2. 환경감염관리병원균의원내전파는다양한방법으로이루어진다. 흔하게는환자와의직접적인접촉으로오염된의료인의손을매개로전파되지만, 오염된병원환경이나기구를통해의료인의손이오염되어전파되기도한다 [6]. 따라서손위생수행은가장우선순위에두어야하는감염관리정책 Table 1. Studies investigating the significance of hospital environment control in hospital infection Organisms Key findings Reference MRSA and Molecular typing identified similar strains from the environment, patients and hands 12 (2013) Acinetobacter MRSA and Hydrogen peroxide vapor disinfection and cohorting of colonized or infected patients 13 (2013) Acinetobacter reduced nosocomial MRSA and A. baumannii in burns unit MRSA and In patient rooms and the ward environment, the contamination of specific materials 14 (2013) C. difficile and locations were identified MRSA MRSA was isolated from the environment and hands, indicating the existence of a 15 (2013) secondary reservoir VRE Unrecognized colonization and/or the aerosolization of enterococci with inadequate 8 (2013) cleaning lead to environmental contamination C. difficile Evidence that the contaminated surface environment is important in transmission of 16 (2013) C. difficile Acinetobacter A baumannii infection rate in the renovated ICU significantly decreased 17 (2013) Bacteria resistant Identical strains carrying the same resistance genes were present in both patients 18 (2013) to β-lactams and the hospital environment P. aeruginosa Genotyping of isolates revealed a clonal relationship between patient and water isolates 19 (2014) P. aeruginosa Hospital waste systems act as a reservoir 20 (2012)

3 Contamination and Cleaning of the Hospital Environment 3 이지만, 국내의경우선진외국에비해의료인이담당하고있는환자수가많고, 의료공간이협소하며, 교육이충분하지못한보호자가같이있는현실을감안하면병원환경의관리도간과할수없는부분이다. 환경관리는모든환경요인을관리하는넓은의미이지만, 여기서는미생물에오염된병원환경의감염관리에대해알아보고자한다. 환경감염관리의기본적이고중요한것이환경을물리적으로깨끗하게유지하는것으로환경에존재하는미생물을완전히제거하기는어려우나지속적인관리로감염의위험을최소화하도록노력 하여야한다. 국내의경우 2005년보건복지부의보건의료기술연구개발사업으로개발된환경관리지침이있으며주된내용을 Table 2와 3로정리하였다 [5]. 미국 CDC에서도환경관리지침을제공하고있으며한국과달리미국 CDC에서는 Legionella spp. 의감염예방을위해병원급수시설의주기적감시배양은권고하고있지않다 [10]. 미국 CDC의지침에서는구체적인항목별로권고사항을과학적근거에따라다섯가지범주로구분하여제시하고있지만국내지침에서는세분화된지침과시행방법과횟수등에대한명확한기준이없어 Table 2. Recommendations for environmental infection control-air Item Air-Handling Systems Construction and Repair of Health-Care Facilities Infection-Control for PE Rooms Recommendations Ensure that heating, ventilation, air conditioning (HVAC) filters are properly installed and maintained to prevent air leakages and dust overloads Prevent dust accumulation by cleaning air-duct grilles in accordance with facility specific procedures No use of natural ventilation in protective environment (PE) room Implement infection-control measures relevant to construction and repair Educate both the construction team and the health-care staff in immunocompromised patient-care areas regarding the airborne infection risks associated with construction projects, dispersal of fungal spores during such activities, and methods to control the dissemination of fungal spores Surveillance for airborne environmental disease during construction to ensure the health and safety of immunocompromised patients Minimize exposures of severely immunocompromised patients (solid organ transplant patients or allogeneic neutropenic patients) to activities that might cause aerosolization of fungal spores (vacuuming or disruption of ceiling tiles) Minimize the time that immunocompromised patients in PE are outside their rooms for diagnostic procedures and other activities Incorporate ventilation engineering specifications and dust-controlling processes in construction of new PE units Table 3. Recommendations for environmental infection control-water Items Controlling Legionnaires Disease Control of Hemodialysis centers Recommendations Apply sterile water to breathing therapy and no use of humidifier for the long time to avoid creating infectious aerosols Surveillance to detect health-care associated Legionnaires disease, use of disinfected water for respiratory system and routine culture of water systems Use an effective biocide on a regular basis (2-4/year) and infection-control procedures for operational cooling towers Water treatment: chlorine dioxide, superheat water, UV, ozone, heavy-metal ions (copper or silver) Test regularly water in dialysis settings and repeat the test when chemical or microbiological contamination is observed Disinfect water distribution systems in dialysis settings on a regular schedule Ensure that water does not exceed the limits for microbial counts and endotoxin concentrations Storage tanks should be routinely drained and disinfected

4 4 김영아 / 이혁민 / 이경원 Table 4. Summary of major disinfectants for noncritical items or surfaces Method Level Uses Alcohol Intermediate External surfaces of equipment, such as stethoscopes, ventilators, manual ventilation bags Chlorine and Chlorine Compounds Intermediate 1:10 1:100 dilution of % sodium hypochlorite for decontaminating blood spills Iodophors Intermediate Medical equipment, such as hydrotherapy tanks, thermometers, and endoscopes Phenolics Low Environmental surfaces, such as bedside tables, bedrails, and laboratory surfaces Quaternary Ammonium Compounds Low Ordinary environmental sanitation of noncritical surfaces, such as floors, furniture, and walls. Medical equipment that contacts intact skin, such as blood pressure cuffs Table 5. Methods for monitoring hospital cleanliness Type Method Restriction Visual Inspection Microbiological Screening Fluorescent Marker Adenosine Triphosphate (ATP) Bioluminescence Visually assessed before and after cleaning by checklist. Evidence of visual dirt, rubbish, smears, dust, grease, blood, fingerprints, clinical waste, etc. Culture for microbial hygiene assessment of environment Culture for detecting bacterial pathogens in the environment Invisible fluorescent marker applied to target standardized high-touch surface in hospital rooms before cleaning Measurement of the amount of light generated by ATP, which organic material contains Subjective and only removal of dirty material Impossible to check the presence of bacteria or virus Time and resource consuming Difference with regard to methods and interpretation criteria Inadequate correlation of optimal cleaning when fluorescent marker is over-dried Require Luminometer False positive by Food and drink residues, disinfectant, microfiber, dead bacteria Standardization required 추가보완이필요하겠다. 병원환경에소독제를정기적으로사용할필요성에대해서는여러의견이있지만미국 CDC는청진기나혈액투석기같은의료기구뿐아니라병실바닥같은병원환경에소독제를정기적소독이필요한이유를정리하고, 오염된부분은낮은수준이나중간수준의소독제를사용하여주기적으로청소할것을권고하고있다 [21]. 병원환경에사용할수있는주요소독제는 Table 4에정리하였다 [21]. 환경관리를위해소독제를선택할때에는무조건높은수준의소독제를선택하는것이아니라환경및인체에미치는영향, 세척의빈도와강도, 환자의위생상태, 오염의정도및분변에있는병원균제거등을고려해야한다. 또한의 료관련감염의병원체로최근주목받고있는 C. difficile와 Norovirus처럼일반적인소독제에의해서는제거가어려운세균도있으며, 소독제사용증가에따른소독제내성균의출현및확산등도고려하여소독제를선택해야한다 [22]. 전통적인소독제외에도에어로졸화된과산화수소수, UV radiation 등을이용한방법도있다 [23,24]. 외국에서는적극적감시배양으로무증상의보균자를찾고, 환자피부를 chlorhexidine을이용하여매일소독하는적극적인감염원의관리를시도하고있다 [25]. 3. 병원환경관리에서의미생물검사실의역할미생물검사실은의료관련감염및주요내성세균의감시, 원내집단감염발생시역학조사,

5 Contamination and Cleaning of the Hospital Environment 5 다제내성균의보균자감시등감염관리에중요한역할을수행해왔으며환경관리를위한감시배양도시행하고있다. 원칙적으로공기, 물, 환경표면에대한정기적인미생물검사는시행하지않으며, 유행이발생했을때원인을찾기위해역학조사의한부분으로미생물검사를시행하거나, 오염된표면의오염정도와청결도를평가하기위해미생물검사를시행하여야한다 [5]. 공기, 물, 환경표면의검사는비교할만한표준검사방법이있어야하고, 이에대한충분한기술이있어야하며, 배양방법에따른적절한장비나배지가필요하다. 미생물의공기오염측정을위해서는대용량공기채집기를이용하고, 수질오염을평가하기위해서는적절한증식배지와배양조건을선택해야한다 [5]. 또한경우에따라서는환경에서배양된세균과환자검체에서배양된세균의비교가유용할수있으며, 가능하다면 species 수준까지분석해야한다 [5]. 미국 CDC는환경관리의평가수준을기본 (level I) 과심화 (level II) 로나누었으며, level II에적용하는행위의직접관찰, 미생물배양검사, 형광표지, ATP 측정같은평가방법을 Table 5와같이소개하고있으므로각각의제한점을고려하여평가방법을선택해야하겠다 [26]. 미생물배양검사는환경의청결도를평가하거나환경에존재하는병원균을검출하기위해흔히고려되는방법이나, 표준화된방법과해석에대한합의가부족하고, 시간과자원이많이드는제한점이있다. 따라서 MRSA, VRE, 다제내성그람음성세균, Salmonella spp., C. difficile 같은중증감염이나감염의집단발생의위험이있는표지미생물의존재를확인하는것이좀더효율적이라생각된다. Conclusion 지금까지는병원균에오염된환경이병원감염의어떤역할을하는지에대해간과되어왔고, 환경배양을위한노력은임상미생물검사실과감염관리실의자원낭비이고환자와의료진에게잘못된공포심만일으킬수있다고생각되어온것도사실이다. 하지만이제는환경에존재하는병원균관리의중요성을다시한번검토해보고이 를위한효율적이고실현가능한전략을고민해야하겠다. References 1. CDC. CDC web sites on CDC/NHSN surveillance definitions for specific types of infections. 17pscnosinfdef_current.pdf (Updated on January 2014). 2. WHO. WHO web sites on Health care-associated infections fact sheet. sheet_en.pdf (Updated on 2013). 3. CDC. CDC web sites on Antibiotic resistance threats in the United States, /drugresistance/threat-report-2013/pdf/ar-threats pdf (Updated on 2013). 4. Weinstein RA. Epidemiology and control of nosocomial infections in adult intensive care units. Am J Med 1991;91:179S-84S. 5. Ministry of health and welfare. Hospital infection prevention control guidelines. bokjitimes.com/board-read.do?boardid=official Publications&boardNo= &command=READ&page=10&categoryId= ( ). 6. Otter JA, Yezli S, French GL. The role played by contaminated surfaces in the transmission of nosocomial pathogens. Infect Control Hosp Epidemiol 2011;32: Morgan DJ, Rogawski E, Thom KA, Johnson JK, Perencevich EN, Shardell M, et al. Transfer of multidrug-resistant bacteria to healthcare workers' gloves and gowns after patient contact increases with environmental contamination. Crit Care Med 2012;40: Muzslay M, Moore G, Turton JF, Wilson AP. Dissemination of antibiotic-resistant enterococci within the ward environment: the role of airborne bacteria and the risk posed by unrecognized carriers. Am J Infect Control 2013;41: Munoz-Price LS, Fajardo-Aquino Y, Arheart

6 6 김영아 / 이혁민 / 이경원 KL, Cleary T, DePascale D, Pizano L, et al. Aerosolization of Acinetobacter baumannii in a trauma ICU*. Crit Care Med 2013;41: CDC. CDC web sites on Guidelines for environmental infection control in health-care facilities. in_hcf_03.pdf (Updated on 2003) 11. Weber DJ and Rutala WA. Understanding and preventing transmission of healthcare-associated pathogens due to the contaminated hospital environment. Infect Control Hosp Epidemiol 2013;34: Tan TY, Tan JS, Tay H, Chua GH, Ng LS, Syahidah N. Multidrug-resistant organisms in a routine ward environment: differential propensity for environmental dissemination and implications for infection control. J Med Microbiol 2013;62: Barbut F, Yezli S, Mimoun M, Pham J, Chaouat M, Otter JA. Reducing the spread of Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus on a burns unit through the intervention of an infection control bundle. Burns 2013;39: Faires MC, Pearl DL, Berke O, Reid-Smith RJ, Weese JS. The identification and epidemiology of meticillin-resistant Staphylococcus aureus and Clostridium difficile in patient rooms and the ward environment. BMC Infect Dis 2013;13: Rocha LA, Marques Ribas R, da Costa Darini AL, Gontijo Filho PP. Relationship between nasal colonization and ventilator-associated pneumonia and the role of the environment in transmission of Staphylococcus aureus in intensive care units. Am J Infect Control 2013;41: Rutala WA and Weber DJ. Role of the hospital environment in disease transmission, with a focus on Clostridium difficile. Health Inf 2013; 18: Nah SS, Park YH, Chung JW, Yoo S, Hong SB, Lim CM, et al. Acinetobacter baumannii infection was decreased by the structural renovation of a medical intensive care unit. J Crit Care 2013;28: Betteridge T, Merlino J, Natoli J, Cheong EY, Gottlieb T, Stokes HW. Plasmids and bacterial strains mediating multidrug-resistant hospital- acquired infections are coresidents of the hospital environment. Microb Drug Resist 2013;19: Johansson E, Welinder-Olsson C, Gilljam M. Genotyping of Pseudomonas aeruginosa isolates from lung transplant recipients and aquatic environment-detected in-hospital transmission. AP- MIS 2014;122: Breathnach AS, Cubbon MD, Karunaharan RN, Pope CF, Planche TD. Multidrug-resistant Pseudomonas aeruginosa outbreaks in two hospitals: association with contaminated hospital wastewater systems. J Hosp Infect 2012;82: CDC. CDC web sites on Guideline for Disinfection and Sterilization in Healthcare Facilities. tion_nov_2008.pdf (Updated on December 2008). 22. Tumah HN. Bacterial biocide resistance. J Chemother 2009;21: Andersen BM, Rasch M, Hochlin K, Jensen FH, Wismar P, Fredriksen JE. Decontamination of rooms, medical equipment and ambulances using an aerosol of hydrogen peroxide disinfectant. J Hosp Infect 2006;62: Rutala WA, Gergen MF, Weber DJ. Room decontamination with UV radiation. Infect Control Hosp Epidemiol 2010;31: Vernon MO, Hayden MK, Trick WE, Hayes RA, Blom DW, Weinstein RA; Chicago Antimicrobial Resistance Project (CARP). Chlorhexidine gluconate to cleanse patients in a medical intensive care unit: the effectiveness of source control to reduce the bioburden of vancomycin-resistant enterococci. Arch Intern Med 2006;166: CDC. CDC web sites on Options for evaluating environmental cleaning. /pdfs/toolkits/environ-cleaning-eval-toolkit pdf (Updated on December 2010).

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee University College of Medicine & Hospital E mail : ycell2@yahoo.co.kr Abstract