Hanyang Medical Reviews Vol. 31 No. 3, 2011 141 다제내성균과의료관련감염 Multidrug-resistant Organisms and Healthcare-associated Infections 김미나울산대학교의과대학서울아산병원진단검사의학과 Mi-Na Kim. M.D., Ph.D. Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea 책임저자주소 : 138-736, 서울시송파구올림픽로 43 길 88 서울아산병원진단검사의학과 Tel: 02-3010-4511, Fax: 02-478-0084 E-mail: mnkim@amc.seoul.kr 투고일자 : 2011 년 6 월 6 일, 심사일자 : 2011 년 6 월 7 일, 게재확정일자 : 2011 년 7 월 11 일 Abstract Multidrug-resistant organisms (MDROs), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistnat Staphlyococcus aureus (VRSA), vancomycin-resistant enterococci (VRE), multidrugresistant Acinetobacter baumannii, and multidrug resistant Pseudomonas aeruginosa have been a big challenge in control of healthcare-associated infec tion for a few decades in Korea. Carbapenemresistant Enterobacteriaceae was most recently added to the utmost threatening MDROs. Because of the high and ever increasing level of MDROs and their healthcare-associated infections, prevention and control of MDROs has become a national priority. The above six MDROs have been designated as legislative healthcare-associated infections, which has to be reported to the Korean Center for Disease Control since January 2011 in Korea. This paper is provided to give current perspectives of MDROs and their healthcare-associated infections in Korea. Key Words: Drug Resistance, Multiple, Bacteria; Infection Control; Methicillin-resistant Staphylococcus aureus; Vancomycin; Carbapenems 서론우리나라에병원감염즉의료관련감염 (Healthcare-associated infections; HAIs) 에대한현대적인개념과체계적인관리가도입된것은 1990년초였고, 이때이미 MRSA, 퀴놀론내성 Pseudomonas aeruginosa 는의료관련감염의주요원인균이었다 [1,2]. 이후반코마이신내성장구균 (VRE)[3], 반코마이신내성황색포도알균 (VRSA)[4], 광범위베타락타메제 (ESBL) 생산장내세균, 카바페넴내성 Pseudomonas aeruginosa (CRPA), 카바페넴내성 Acinetobacter baumannii (CRAB) 등이출현하였고 [5], 이들다제내성균에의한의료관련감염을억제하기위한감염관리가지속적으로강화되었음에도현재이들다제내성균은국내의료관련감염의대표적인병원균이되었다 [6]. 최근 2-3년동안세계적으로카바페넴내성장내세균 (CRE) 이확산되면서 CRE가심각한의료관련감염문제를초래할것이라는우려때문에 [7] 국내에서도 2010년 10월 CRE중 New Delhi Metallolactmase (NDM)-1 생산균이가장먼저법정감염병으로지정되었고, 2010년 11월서울의 3차병원에서 NDM-1 K. pneumoniae가출현하였다 [8]. 이후 2011년 1월 MRSA, VRSA, VRE, CRE, 다제내성아시네토박터 (MRAB), 다제내성녹농균 (MRPA) 이지정되어현재총여섯가지다제내성균이질병관리본부에의무적으로신고해야하는법정의료관련감염병이되었다. 이종설에서는여섯가지다제내성균의국내외현황과의료관련감염병으로서의중요성, 감염관리의필요성과전략에대해다루고자한다.
142 Hanyang Medical Reviews Vol. 31, No. 3, 2011 본론 국내에서이들여섯가지주요다제내성균중 MRSA는 1990년대이미현재수준까지증가하였고, VRSA는증례보 Proportion among nosocomial infections 25 20 15 10 5 0 MRSA VRE CRAB CRPA ESBL CRE * 1996 2004 2010 Fig. 1. Last 15 year-trend of multidrug-resistant bacteria as a cause of nosocomial infections in intensive care units in Korea[6,15,16]. The CRE line and data of 1996(*) except MRSA were speculated from general resistant rates of clinical isolates at that time. MRSA, methicillin-resistant Staphylococcus au reus ; VRE, vancomycin-resistant enterococci; CRAB, Acinetobacter baumannii; CRPA, Pseudomonas aeruginosa; ESBL, extended-spectrum beta-lactamase; CRE, cabapenemresistant enterobacteriaceae 고수준에그친것외에지난 20년간지속적으로증가하여대형종합병원뿐아니라중소병원에서도반코마이신과카바페넴항균제치료에심각한제약을주고있다 [9,10]. 이와더불어이들다제내성균은의료관련감염의대표적인원인균으로서그비중이점점커지고있다 (Fig. 1). 1. 메티실린내성황색포도알균 MRSA는 1961년영국에서첫보고되었는데황색포도알균이 meca 유전자가암호화하는 PBP2a 단백을만들어냄으로써베타락타메제에안정한 methicillin, oxacillin, nafcillin 등이결합하지못해서이들항균제에내성을초래한다 [11]. meca유전자는 SCCmec이라는이동성유전자단위안에존재해서수평적전파가이루어진다 [11]. 국내에서는서울지역한대학병원에서 20년간임상분리주의 MRSA비율을조사한연구에서 1976년 5% 정도였던것이 90 년대초부터 60-70% 의비율을유지하였다 [9,12,13]. 1992 년서울지역의다른 3차병원에서 MRSA 비율이원내분리주의 80%, 원외분리주의 22% 로의료관련감염분리주에서 MRSA 비율이현저히높았다 [1]. 이후전국적으로임상분리주의 MRSA 비율은삼차병원이나이차병원모두 70% 전후의결과를보여주고있다 [14]. 1998년전국 15개종합병원의의료관련감염률을조사한연구에서일반병동분리주 Table 1. Percent Distribution of Nosocomial Pathogens in Nationwide Surveillance of Nosocomial Infections in Intensive Care Units in 1996, 2004, and 2010[6,15,16] % isolates Organisms 1996, ICU (n=1,029) 1996, Ward (n=2,743) 2004, ICU (n=534) 2010, ICU (n=4,058) Staphylococcus aureus 20.80 18.00 23.2 13.45 (Methicillin-resistant S. aureus) (19.14) (12.32) (21.5) (12.27) Pseudomonas aeruginosa 17.59 12.32 8.8 6.75 Candida spp. 9.52 3.72 14.8 25.65 Acinetobacter spp. 8.55 6.38 8.7 9.53 Klebsiella pneumonia 7.58 7.77 6.6 4.93 Enterobacter spp. 6.51 5.21 2.6 2.22 Enterococcus spp. 5.83 8.35 12.8 13.30 (E. faecium) NA NA (7.4) (8.35) Escherichia coli 5.25 14.62 5.5 5.94 Serratia marcescens 4.08 1.82 3.7 1.95 Coagulase-negative Staphylococcus 3.69 7.00 3.1 7.34 Others 10.68 15.86 NA 8.94 Total 100.00 100 100 100 ICU, intensive care unit
Multidrug-resistant Organisms and Healthcare-associated Infections 143 의 68.4% 가 MRSA인데비해중환자실분리주의 95.7% 가 MRSA로, 1990년대이미중환자실 MRSA비율은정점에도달해서 2004년, 2010년조사에서비슷한수준을유지하였다 [6,15,16]. 이들연구에서중환자실에서발생한전체의료관련감염중 MRSA감염은빈도 1위의원인균이었다 (Table 1). 국내연구에서는 MRSA균혈증과메티실린감수성황색포도알균 (methicillin-susceptible S. aureus; MSSA) 균혈증일때각사망률이 58.8%, 31.8% 로 MRSA일때높았다는보고가있고 [17], 심내막염만대상으로했을때 MRSA 감염의사망률이 50% 인데비해 MSSA 감염은 9.1% 로더큰차이를보였다 [18]. 의료관련감염에서도 MRSA 균혈증은 MSSA 균혈증보다사망률이유의하게높아서 [19-21] MRSA 감염이사망률을높이는요인으로작용함을알수있다. 세계적으로 2003년 31개의논문을후기분석연구에서 MRSA균혈증의사망률은 MSSA 균혈증의사망률에비해상대비율이 1.0-4.72였고, 이를종합한상대위험도가 1.93 (95% CI, 1.54-2.42) 으로 MRSA 균혈증의사망률이높았다 [22,23]. 사망률뿐아니라재원일수, 비용을더높인다는연구가다수있어서의료관련감염관리의가장중요한목표가되고있다 [24-26]. 2. 반코마이신내성장구균과반코마이신내성황색포도알균 (VRSA) VRE는 1992년국내에서처음분리된후의료관련감염과유행, 고위험군에서집락화율에대해많은보고가이루어졌다 [3,27]. 국내에서보고되는 VRE는 1990년대몇개대학병원에서 vanb 유전형의유행을보고한것 [28,29] 이외에는대부분 vana 유전형의 E. faecium이다 [30,31]. 1997년전국종합병원임상분리 E. faecium의반코마이신내성율이 3.0% 였던데비해 [9] 이후급격히증가해서 2000년전국 23 개병원을대상으로한 Korean Nationwide Surveillance of Antimicrobial Resistance (KONSAR) 자료에서 20% 가된이후계속 20% 를넘는내성율을보이고있다 [10,14,32]. 반코마이신내성장구균이확산되는것은임상검체에서분리되는균종중 E. faecium 이 E. faecalis를넘어설정도로증가하거나 [14,33] 전체의료관련감염에서장구균의빈도가올라가는원인이된다. 국내중환자실의료관련감염에서장구균은 1996년빈도 6위에서 2010년 S. aureus, Candida albicans, Acinetobacter spp. 다음으로 4위가되 었다 [6, 15,16]. 이처럼국내병원에서 VRE 가급속하게확산된것은 VRE의수직전파뿐아니라 vana 유전자를운반하는 Tn1546 트랜스포존이매우효율적으로균주간, 종간수평적전파가이루어진다는점이큰역할을하였다 [34]. Tn1546 트랜스포존은병원환경에서빠르게진화해서다양한변종들이출현하여 VRE를검출하는것이더어려워지고있다 [35,36]. 이에비해반코마이신내성인 S. aureus는 1997년처음 van comycin-intermediate S. aureus가 (VISA) 가보고된이래국내에서 1998년첫증례가발생했지만 [7]. 이후 VRSA 가보고된적은없고, VISA또한산발적으로드물게보고되고있을뿐원내전파나유행을일으킨적이없다 [37-39]. 국내에서는질병관리본부가 2001년부터매년 2개월간전국적으로 VRSA 검사실표본감시를실시하고있다. 2009년까지 61주에서내성을검출하였는데모두 VISA균주였고, MRSA였다 [40]. 국내에서지금까지보고된 VISA균주들은모두 MRSA 였고, 반코마이신치료가실패하였다 [4,38]. 미국의한중환자실에서 1년간 15명의 VISA환자가발생하고 3명의의료진이전비공에 VISA를보균하고있었다고보고하는등 VISA 균이교차오염에의한원내감염의유행이발생할수도있다 [41]. 따라서 VISA 균의출현과확산을감시하고관리하는것이필요하다. vana 유전자가 S. aureus에전파되어반코마이신에고도내성을보이는 VRSA도출현하였다. 미국에서처음보고된 vana 양성 VRSA는 VRE와 MRSA가함께분리되던환자에서출현하여, VRSA 가 VRE 와 MRSA의장기간에걸친접촉과정에서 vana 유전자가전파되어발생한것으로추정된다 [42,43]. 미국에서 2002년에서 2010년까지총 11례가보고된바있지만 44 국내에는아직보고가없다. 국내에서 VRE와 MRSA는의료관련감염으로서높은이환율을보여서때 VRSA가출현할위험은충분하다. 국내한대학병원에서 VRE 보균자의 4% 가같은검체에서 MRSA도분리된다는보고를한바있다 [45]. 지난 30년간반코마이신은 MRSA 가증가하면서 MRSA 감염을치료할수있는마지막항균제로서역할을해왔기에반코마이신내성인그람양성구균이의료관련감염의중요한원인균으로대두되는것은충격적인일이었다. VRE는대표적인기회감염균으로서과거의료관련감염을일으킨다고해도이환률과사망률에미치는영향이크지않다고알고있었지만, VRE 균혈증은반코마이신감수성장구균
144 Hanyang Medical Reviews Vol. 31, No. 3, 2011 감염에비해높은재발율, 사망률, 추가적인비용을초래하는독립적인인자라는보고들이있다 [46]. S. aureus 감염의이환율과사망률을고려하면 VRSA가 VRE와같은확산과정을되풀이하는것은항생제치료에큰위협이아닐수없다. 따라서국내의료현장에서반코마이신내성균을예방하는효과적인전략과실천이반드시필요하다. 3. 다제내성 P. aeruginosa 와 A. baumannii 그람음성간균중 P. aeruginosa, A. baumannii는내인성으로이미다제내성을가지고있고, 획득내성또한가장빈번하게일어나는균종에속해서항균제내성문제가심각한균종이다 [11]. 통상 P. aeruginosa, A. baumannii 에서다제내성은 aminoglycoside, fluoroquinolone, carbapenem 등 3가지계열의약제에모두내성인균주를의미하며, 이경우 colistin 정도가유일하게감수성으로남고, A. baumannii는이에더해서 tigecycline에감수성일수있다 [14]. 의료관련감염의주요원인균인두균종은다제내성때문에카바페넴이거의유일하게유효한항균제였는데, 10여년간카바페넴에도내성인균주가증가하면서항균제치료에큰제한이생겼다는공통점이있다. 1997년 KONSAR자료에서 P. aeruginosa 는이미 imipenem 내성율이 17% 에이르는데 A. baumannii의내성율을 1% 미만이었다. 이후 10년간 P. aeruginosa는약간증가하여 20% 정도가된데비해 A. baumannii 는급속히증가하여 2007년 21% 로 P. aeruginosa의내성율을상회하였고, 최근 3-4년간더빠르게증가하여, 대부분의대형병원에서 50% 를넘 Fig. 2. The trends of carbapenem resistance(%) of Pseudomonas aeruginosa and Acinetobacter baumannii from KONSAR study[14]. KONSAR, Korean Nationwide Surveillance of Antimicrobial Resistance. 었다 (Fig. 2)[5,14,47]. 카바페넴내성율의증가는의료관련감염에서 A. baumannii 의증가로이어져서 2010년전국중환자실의료관련감염율조사에서 P. aeruginosa 를제치고, MRSA, Enterococcus spp. 에이어원인균빈도 3위를차지하였다 (Table 1)[6]. 이때수집한자료에서 P. aeruginosa, A. baumannii의카바페넴내성률은 54.4%, 82.5% 에달했다 [6]. 이들내성의기전은베타락타메제생성과더불어 porin 단백의변이로막투과성이떨어지거나유출펌프가고도로발현되는것이가장흔하다 [48-50]. 이들균종의카바페넴내성이기여하는베타락타메제의종류는 AmpC beta-lactamase, metallo beta-lactamase, OXA type betalactamase 등다양하다 [51-53]. 최근국내에서카바페넴내성 P. aeruginosa, A. baumannii 의급속한증가에 OXA-48, VIM-2형카바페네메제가중요한역할을하고있다 [54-24]. 이런베타락타메제유전자가다른항균제내성유전자들과함께 integron이라는이동성유전자운반체에담겨서균주간, 균종간으로전파되기때문에내성확산이빠르고, 다제내성을유발한다 [55,56]. 카바페넴내성 P. aeruginosa, A. baumannii 의다제내성은결국부적절한항균제치료가이루어질위험을높여서카바페넴내성균균혈증이감수성균에의한균혈증보다높은사망률을보이는원인이될수있다 [57,58]. 4. Fluoroquinolone 내성, ESBL 생성, 카바페넴내성장내세균 Enterobacteriaceae ( 장내세균속 ) 은지역사회획득성이나병원획득성일때모두중요한병원균으로빈도순위가 1-2 위를차지하는중요한균종이다 [1]. Fluoroquinolone은장내세균속에강력한살균작용을나타내는항균제로오랫동안유용하게사용되었지만, 1992년한 3차병원에서지역사회획득 Escherichia coli, Klebsiella pneumoniae는 91.5%, 97.5% 가 ciprofloxacin 감수성이었지만, 병원획득성일때는 84.6%, 88.9% 로현저한차이를보였다 [1], 전국병원임상분리주의감수성자료를수집한데서 fluoroquinolone 내성율이 E. coli는 1997년이미 24% 였고, 2005년 32% 가되었는데, K. pneumoniae에서 1997년 7% 였던것이 2001년 10%, 2003년 19%, 2005년 30% 로증가했다 [10]. 광범위세팔로스포린내성 E. coli, K. pneumoniae 또한 1997년 7% 정도였던 cefotaxime 내성율이 2005년 12%, 25% 로증가하
Multidrug-resistant Organisms and Healthcare-associated Infections 145 였다 [9,10,14,59]. 이에비해카바페넴내성장내세균은최근 10년동안거의변화가없이매우낮은수준으로유지되어왔다. KONSAR의 2005/2007년자료에서장내세균의카바페넴내성율은 E. coli, K. pnumoniae, Enterobacter cloacae, Serratia marscecens 등에서 0.2%/0%, 0.3%/0%, 0.3%/0%, 1%/1% 에불과하였다 [14]. 하지만, 세계적인유행을일으키는KPC, NDM-1 등카바페넴분해효소를생산하는 K. pneumoniae가국내에서도최근 1-2년사이에출현하기시작해서향후확산될우려가있다 [8,60-62]. 중환자실의료관련감염의원인균으로서비율은 1996년조사때 E. coli, K. pneumoniae가각각 5.25%, 7.58% 였던것이 2004년 5.3%, 6.6%, 2010년 5.94%, 4.93% 로두균종을합친비율이약간감소한듯이보이지만, Candida spp., Enterococcus spp. 비율이크게증가한데따른것으로그람음성간균중차지하는비율은비슷하다 (Table 2). 7. 효과적인감염관리전략결과를 관리 하려면원인을찾는것이필수적이다. 다제내성균의온상은병원, 요양원등의료시설이며, 의료관련감염을없앤다면대부분의다제내성균은출현하지도않고, 또사라질것이다. 따라서의료관련병원균의획득과감염이다제내성균이출현하고확산되는일차적인원인이라고할수있다. 반대로, 다제내성균이의료관련감염의주요병원균이라고해도다제내성균을박멸한다고해서의료관련감염을없앨수는없다. 현재다제내성균관리가의료관련감염의가장중요한요소로감염관리의자원이집중되고있지만, 그효과는여전히논란이많다 [63]. 미국 National Healthcare Safety Network 에서 2006-7년에시행한전국적인의료관련감염률조사에 서감염의 16% 는상기의 6가지다제내성균및 ESBL 생산장내세균에의해발생하였다 [64]. 중심정맥관관련균혈증 (Catheter related bloodstream infection; CRBSI) 을줄이기위한묶음식감염관리를적용하여중환자실에서CRBSI를장기간 0% 로유지하였다는보고들이있다 [65,66]. 이경우 MRSA에의한의료관련균혈증은거의사라지게된다. 또한외과병동에서알코올젤손씻기율을올려서의료관련감염을전반적으로감소시키고자하였을때 MRSA 균혈증을 0% 로낮추었다는보고도있다 [67]. 이처럼의료관련감염을박멸하는것이다제내성균을줄이는가장효율적인방법이라는것은증명되어있다. 하지만, 의료관련감염이일어나는데는환자의기저질환과방어기전을떨어뜨리는요인, 항균제사용, 의료기구유치, 침습적시술, 인구밀집도와의료진과밀접한신체적접촉등수많은요인들이복합적으로작용하기때문에모든의료관련감염을예방할수는없고, 다제내성균에의한의료관련감염은적절한항균제치료를하기어렵다. 따라서다제내성균을감소시킴으로써병원균이좀더항균제에잘듣는감수성균으로바뀌기를기대하는것이다. 다제내성균은병원환경에서성공적으로생존하는능력, 다른균주에비해확산하는능력이우월하지만, 병원성이더높다는보고는거의없다. 하지만, MRSA 는다른다제내성균과는달리 MRSA에집락화된경우 MSSA가집락화한경우보다더높은빈도로감염을일으키고 [68,69] 균혈증, 가슴절개술후종격염, 수술부위감염등은더높은사망율을초래한다 [23,24,70,71] 이런 MRSA의임상적특성때문인지병원또는병동에 MRSA가한번도입되고나면전체황색포도알균감염율을증가시킨다는보고들이있다 [72,73]. 반대로 MRSA 를적극적으로감시하고, 탈집락화시키는전략을 Table 2. Comparison of the Mortalities between MRSA and Methicillin-susceptible Staphylococcus aureus Bacteremia in the Previous Korean Publications Reference Study period Hospital setting Total No / nosocomial % MRSA% / nosocomial % Endocarditis, % of cases Mortality MRSA MSSA P value Lee et al[17] 1/1996-12/1997 Tertiary care, Busan 39/NS 43.5/NS NS 58.8 31.8 NS Jung et al.[20] 3/1991-4/1995 Primary care, Seoul 69/53.6 30.4/81.0 NS 42.1 33.3 >0.05 Yoon et al.[18] 3/1986-3/2004 Secondary care, Seoul 32/40.6 31.3/60.0 100 50.5 9.1 0.019 Kim et al.[19] 1999-2003 Secondary care, Seoul 96/100.0 67.7/100.0 NS 57.7 12.9 0.002 Park et al.[21] 1/2003-12/2008 Tertiary care, Seoul 266/65.0 54.3/73.4 NS 21.4 28.9 0.16 MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible Staphylococcus aureus; NS, not stated
146 Hanyang Medical Reviews Vol. 31, No. 3, 2011 Fig. 3. Change of oxacillin susceptibility rate of Staphylococcus aureus for 6 years since opening of the hospital. (*oxacillin susceptibility rate of S. aureus in March 1999 was lower than in previous months (Ref. 75 with permission from Elsevier). 택한유럽국가들중비교적최근이전략을추진한영국에서는 MRSA 뿐아니라전체황색포도알균균혈증이감소하는등 [74] 특정다제내성균의경우다제내성균을감소시켜서의료관련감염을줄일수있을것으로기대된다. 국내에서도황색포도알균은의료관련감염을일으키는병원균중항상수위를점하는가장중요한균종으로, 중환자실의료관련감염의 20% 정도를차지하고, 그중 90% 이상은 MRSA이다. 하지만, 국내 MRSA 비율은 1990년대이미세계적으로가장높은수위에도달해서이후전국병원임상균주들에서 70% 대를유지하고있기때문에 MRSA를줄이려는시도에회의적인시각이있어감염관리를하는데큰장애가되고있다. 하지만, 1999년새로개원한대학병원에서시행한연구에서황색포도알균의초기감수성율이 60% 를상회하다가전국적인자료와비슷한정도로내성율이증가한것으로볼때 (Fig. 3)[78], MRSA가반년정도면원내에서토착화함을보여주었다. 따라서 MRSA가토착화한병원에서원내전파를성공적으로줄인다면메티실린감수성율을 60% 까지높일수있고, 이는 MRSA가토착화된병원이원내전파를성공적으로차단한다면메티실린감수성율을회복할수있음을의미하며, 그이상으로감수성율을회복하려면우리나라전체의료기관들의 MRSA를줄일수있는공동의감염관리전략이필요할것이다. 국내에서도중환자실에서 MRSA를적극적인감시와접촉격리로성공적으로줄였던보고가있고 [76], 신생아중환자실, 단기관연 구, 다기관연구등에서이미 MRSA가토착화된병실에서탈집락화를시도함으로써 MRSA 감염과집락율을성공적으로줄일수있다는보고들이있어서 [77-79], 이미 MRSA 빈도가높은국내현실에서는적극적인감시와탈집락화전략이효과가있을것으로생각된다. VRE과다제내성그람음성간균은장내에집락화되는균종으로서탈집락화시도는지금까지시도에서효과적이라는증거가없다 [80]. 따라서항균제사용을조절해서다제내성균선택압력을줄이거나접촉주의를철저히준수하는것이최선의방법이다 [81]. 다제내성균환자의접촉격리는검사실에서다제내성균보균자를신속하고민감하게검출하고, 보균자를접촉하는모든의료진에게접촉격리대상자임을경고하는시스템, 격리지침, 접촉격리에적절한환경과물품공급, 손씻기의순응도등이중요하다 [82]. 환경소독, 항균제관리 [83,84] 또한내성균관리에주요요소가된다. 이처럼탈집락화가극히어렵거나불가능한다제내성균은집락화에취약한고위험군과유행이발생한병실또는기관에서적극적인감시를해서조기에전파를차단하는것이가장효과적인방법이다.[81] 따라서 VRE[85], VRSA[86], 카바페넴메제생산장내세균 [7] 등은균주가처음출현했을때철저한감염관리조치를취하는것이권장된다. 국내많은병원들은최근 10년간 VRE, CRAB, CRPA 의확산방지에실패하여이미토착화단계가되어버렸다. 하지만, MRSA, VRE, 다제내성아시네토박터등이토착화된경우에도적극적인감시와철저한접촉주의로다제내성균을박멸할수있다 [81]. 수학적모델링에서도임상검체배양만으로는 MRSA관리를할수없고, 보균자까지감시배양하는적극적인감시가필요함을보여준다 [87]. 하지만, 모든의료환경에서적극적인감시배양이필수적인지는미국의 Society for Healthcare Epidemiology of America (SHEA) 와 Healthcare Infection Control Practices Advisory Committee (HICPAC) 의지침이이견을보일정도로아직은정립되어있지않다 [88,89]. 미국의 Healthcare Infection Control Practices Advisory Committee HICPAC과 CDC는의료환경에서다제내성균을줄이는감염관리를위한 7가지요소가제시한다 [81]. 그 7가지요소들은감염관리전문가가리더쉽을가지고감염관리지침을적용하고평가하는것, 다제내성균에대한교육, 적절한항균제사용, 다제내성균의감시, 다제내성균전파를예방하는접촉주의준수, 환
Multidrug-resistant Organisms and Healthcare-associated Infections 147 경관리, 탈집락화등이다. 이요소들은우리나라처럼다제내성균이높거나증가하는환경에도효과적으로적용할수있음이입증되어있다. 결론우리나라는의료환경에서이미다제내성균비율이아주높거나증가하고있다. 다제내성균문제를해결하는것은국가보건의중요한문제로대두되고있다. 감염관리전문가가리더쉽을가지고감염관리지침을적용하고평가하는것, 다제내성균에대한교육, 적절한항균제사용, 다제내성균의감시, 다제내성균전파를예방하는접촉주의준수, 환경관리, 탈집락화등의요소를의료기관들이자체적으로적용하는것외에국가적인차원의적용과지원이필요하다. References 1. Kim MN, Jeong JS, Kim BC, Song JH, Pai JH. Comparison of antimicrobial susceptibility of nosocomial and community-acquired pathogens. Korean J Infect Dis 1993;25:333-42. 2. Kim JS, Kim EC, Ki CS, Lee NY. Nosocomial outbreak of methicillin-resistant Staphylococcus aureus analyzed by molecular epidemiology. Korean J Nosocomial Infect Control 1996;1:63-72. 3. Park J, Kim Y, Shin W, Kang M, Han K, Shim S. Susceptibility tests of vancomycin-resistant enterococci. Korean J Infect Dis 1992;24:133-7. 4. Kim MN, Pai CH, Woo JH, Ryu JS, Hiramatsu K. Vancomycin-intermediate Staphylococcus aureus in Korea. J Clin Microbiol 2000;38:3879-81. 5. Lee K, Chang CL, Lee NY, Kim HS, Hong KS, Cho HC. Korean nationwide surveillance of antimicrobial resistance of bacteria in 1998. Yonsei Med J 2000;41:497-506. 6. Cho YK. The nationawide surveillance system of no socomial infection in Intensive care units. Korean J Nosocomial Infect Control 2011;16:S7-13. 7. Centers for Disease Control and Prevention. Guidance for control of infections with carbapenem-resistant or carbapenemase-producing Enterobacteriaceae in acute care facilities. MMWR 2009;56:256-60. 8. Kim MN, Park SH, Ahn D, Lee M. Emergence and epidemiology of new delhi metallo-β-lactamase 1-pro ducing Klebsiella pneumonae in a Korean tertiary care hospital. Clinical Microbiology and Infection 2011;17:S138. 9. Chong Y, Lee K, Park YJ, Jeon DS, Lee MH, Kim MY, et al. Korean nationwide surveillance of antimicrobial resistance of bacteria in 1997. Yonsei Med J 1998;39:569-77. 10. Lee K, Kim YA, Park YJ, Lee HS, Kim MY, Kim EC, et al. Increasing prevalence of vancomycin-resis tant enterococci, and cefoxitin-, imipenem- and fluoro quinolone-resistant gram-negative bacilli: a KONSAR study in 2002. Yonsei Med J 2004;45:598-608. 11. Rice LB, Bonomo PA. Mechanisms of resistance to antibacterial agents. In Murray PR, Baron EJ, Jorgensen JH, Landry ML, Pfaller MA, eds. Manual of Clinical Microbiology. 9th ed. Washington DC: ASM Press; 2007:1114-45. 12. Chong Y. Antimicrobial susceptibilities of recent clinical isolates of bacteria. J Korean Soc Chemother 1991;9:5-11. 13. Chong. Y, Lee K, Shin JW, Shin HB, Lim JB. Activities of arbekacin against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. J Korean Soc Chemother 1997;15:391-27. 14. Lee K, Lee MA, Lee CH, Lee J, Roh KH, Kim S, et al. Increase of ceftazidime- and fluoroquinolone-resistant Klebsiella pneumoniae and imipenem-resistant Acinetobacter spp. in Korea: analysis of KONSAR study data from 2005 and 2007. Yonsei Med J 2010;51:901-11. 15. Kim JM, Park ES, Jeong JS, Kim KM, KIm JM, Oh HS, et al. 1996 National nosocomial infection surveillance in Korea. Korean J Nosocomial Infect Control 1997;2:157-76. 16. Kim KM, Yoo JH, Choi JH, Park ES, Kim KS, Kim KS, et al. The nationwide surveillance results of nosocomial infections along with antimicrobial resistance in intensive care units of sixteen university hospitals in Korea 2004.
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