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1 대한내과학회지 : 제 77 권제 2 호 2009 특집 (Special Review) - 신종감염병의최신지견 항생제내성의국내현황및대책 성균관대학교의과대학삼성서울병원감염내과, 아시아태평양감염연구재단 송재훈 Current status and future strategies of antimicrobial resistance in Korea Jae-Hoon Song, M.D., Ph.D. Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Asian-Pacific Research Foundation for Infectious Diseases (ARFID) Antimicrobial resistance in major bacterial pathogens became a serious problem in the clinical practice. In Korean hospitals, prevalence rates of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and multidrug-resistant gram-negative bacilli are very high. In the community, macrolide-resistant Streptococcus pneumoniae and community-associated MRSA are major resistant pathogens. Infections caused by antimicrobial-resistant bacteria are associated with a greater likelihood of inappropriate antimicrobial therapy and poor clinical outcome. Physicians should have updated information and knowledge about current epidemiological status of resistance and appropriate use of antimicrobial agents. Appropriate use of antimicrobial agents, strict infection control, and development of new antibiotics and vaccines are important future strategies for the control of antimicrobial resistance. This review focuses on the current epidemiology and clinical implications of antimicrobial-resistant bacterial infections in Korea based on the published data for the past 10 years. (Korean J Med 77: , 2009) Key Words: Antimicrobial Resistance; Bacterial infections; Epidemiology; Korea 서론항생제의개발은현대의학이이룩한가장위대한업적중의하나로서페니실린이도입된 1940년이후수많은감염질환의완치가가능해졌다. 그러나항생제가임상의학에도입된지불과 60여년만에항생제내성의광범위한출현은각종감염질환의치료실패와치명적인결과를일으키고있다. 항생제내성은항박테리아제제뿐아니라항바이러스제, 항진균제, 항결핵제의공통된문제점이다. 그중에질병의빈도가가장높은세균감염질환의치료제에대한내성은의학적으로나사회적으로심각한문제가되고있다. 항생제내성은 WHO에서세계공공보건의심각한위협으로규정할정도로선진국이나후진국모두의공통된문제이기는하나, 특히한국을포함한아시아국가들이주요세균의내성률이서구국가들에비하여전반적으로높은양상을보이고있다. 항생제내성이특히문제가되고있는주요세균으로 * This study was partly supported by a grant from the Korea Health 21 R & D Project, Ministry of Health, Welfare & Family affairs, Republic of Korea (Grant No. A084063)

2 - The Korean Journal of Medicine: Vol. 77, No. 2, 소위 ESKAPE 균주들이있는데, 이는 Enterococci, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species를지칭한다. 또한, 지역사회감염을흔하게일으키는 Streptococcus pneumoniae나 Staphylococcus aureus에서도항생제내성문제는심각한상태이다. 저자는가장문제가되고있는병원성및지역사회 MRSA, Vancomycin 내성 enterococci (VRE), macrolide 내성 Streptococcus pneumoniae, ESBL-producing gramnegative bacilli, 다제내성 Pseudomonas aeruginosa와 Acinetobacter species의국내현황을최근 10년간국내외학술지에발표된자료를토대로하여정리해보고자한다. 주요병원균의항생제내성현황 1. 메티실린내성황색포도알균 (methicillin-resistant Staphylococcus aureus, MRSA) 황색포도알균은폐렴, 균혈증, 심내막염, 수술창상감염등지역사회와병원에서발생하는감염증의중요한원인균으로써, 항생제내성은페니실린내성, 메티실린내성및반코마이신내성으로대별할수있다. 이중임상적으로가장중요한문제는 methicillin-resistant Staphylococcus aureus (MRSA) 이다. MRSA 는 1970년대말부터영국과호주등지에서새로운유행균주가등장한이후전세계적으로빈도가급격히증가하였다. 우리나라의경우 1997년의보고에따르면병원감염의가장흔한원인균은황색포도알균 (17.2%) 이었으며, 이중약 80% 가 MRSA 였다 1). 다른국내연구보고들에서도 MRSA 는황색포도알균중대개 70~80% 의빈도로나타나고있어, 세계에서가장높은비율을보이고있다. 이처럼 MRSA 는병원에서발생하는황색포도알균감염증의주원인이었지만 1990년대후반부터는지역사회에서자연발생한 MRSA (community-associated MRSA, CA-MRSA) 가전세계적으로출현하고있다. 특히미국의경우에 CA-MRSA는지역사회에서발생한피부연조직감염원인균의 75~77% 를차지한다 2). 우리나라의경우는저자가시행한아시아지역에서의다국가공동연구 (ANSORP) 결과에서는국내지역사회에서발생한황색포도알균감염의 20% 가 CA-MRSA에의한것이며, 다른연구를보면 CA-MRSA가 MRSA 의 5.9% 를차지하고, CA-MRSA 균주의 47% 가다제내성을나타내었다 3). 최근 CA-MRSA가역으로병원으로전파되어병원감염을일으키는예들이늘어나병원내에서의 MRSA 감염증의빈도를높이는데기여하고있다. MRSA 감염증은감수성균주감염에비하여이환율과사망률을증가시킨다. MRSA 균혈증환자가급성신부전과혈역학적불안정, 중환자실의장기입원이증가하고 30일병원내사망률이 64% 로 24% 인감수성균주 (MSSA) 균혈증환자에비해서의미있게높다 (p<0.005) 4). 메타분석에서도 MRSA 감염이있는경우는 MSSA 감염이있는경우보다사망률이더높은것으로보고되었다 5). 또황색포도알균균혈증이있는환자에서시행된전향적연구를보면, MRSA 균혈증의경우 MSSA 균혈증이있는환자에비해서심내막염과같은합병증의빈도와부작용이의미있게높았다 6). MRSA 감염증의치료제로써 vancomycin (1 g 2회 / 일 ) 이나 teicoplanin (400 mg 1회 / 일 ) 등의 glycopeptides가지난 20년이상많이쓰였으나, 최근내성균주가출현하고심내막염이나폐렴에서의치료실패율이높다는보고가있어임상적유용성에의문이제기되고있다. 새로운치료제로는 linezolid (600 mg 2회 / 일 ), daptomycin (4 mg/kg 또는 6 mg/kg 1회 / 일 ), tigecycline (100 mg투여후에 50 mg 2회 / 일 ) 등이있다 7). 치료기간은전이감염이없는균혈증인경우는 10~14일정도치료가필요하고피부연조직감염은 2주, 폐렴이동반된경우는 3주, 심내막염이나골수염이동반된경우는 4~6주의치료가필요하다. MRSA 감염을예방하기위해서는항생제 ( 특히광범위 cephalosporin이나 fluoroquinolone 제제 ) 의오남용을방지하여 MRSA 의출현을최소화하고, 병원감염관리를철저히하여추가확산을막는것이가장중요하다. 그이외에보균을없애기위해서 mupirocin (1일 2회 5일간비강에바름 ) 을사용할수있으나재발률이높고실제로황색포도알균에의한수술창상감염의예방효과가분명치않으며, 내성의출현등으로문제가있는상황이다 8). 최근에황생포도알균감염을예방하는단백접합항포도알균백신이개발되어임상연구가진행중이거나계획중이다 9). MRSA 균주중에서반코마이신에내성을보이는 vancomycin-intermediate S. aureus (VISA) 혹은 vancomycin-resistant S. aureus (VRSA) 의문제가이미시작되었다. VISA 는 1996 년일본의 Hiramatsu 가처음보고하였으며이후점차그수가증가하여전세계적으로 30예이상이보고되고있다 10,11). VISA 균주는황색포도알균의세포벽이두꺼워지면서내성이발현한다. 2002년에는반코마이신내성장알균 (VRE) 으로부터전파된 vana 유전자를보유하여 vancomycin에고도내성을보이는 VRSA가미국에서처음보고되었고, 이후미국에서만총 9균주가보고되었다 11,12). 2000년에우리나라에서도 VISA가보고된이래로 13) 총 4건의 VISA에의한감염증

3 - Jae-Hoon Song. Current status and future strategies of antimicrobial resistance in Korea - 이보고되었으나 14) VRSA는아직까지보고되지않았다. 2. 반코마이신내성장알균 (Vancomycin-resistant Enterococci, VRE) 장알균은피부, 점막, 위장관등에흔한상재균이기때문에장알균이동정된경우감염과단순집락화 (colonization) 된경우를구분해야한다. 장알균중실제주요감염을일으키는균종은 Enterococcus faecalis와 Enterococcus faecium이다. 과거에는 E. faecalis에의한감염이그외장알균감염에비하여약 10배정도흔하다고알려졌으나최근 E. faecium에의한감염이상대적으로늘고있다 15). 최근장알균이병원감염을일으키는빈도가증가하고있으며, 다제내성의증가로그임상적중요성이증대되고있다. 국내에서 E. faecium 중반코마이신내성장알균 (VRE) 의빈도는점점증가하여 2006 년에 24% 에달하였다 16-20). 또한 VRE 균혈증이있는환자에서는적절한항생제치료에도사망률이더높게보고되고있다 21). 그러나모든 VRE 감염증의치료에항균제를필요로하지는않는다. 심각하지않은 VRE 감염증즉, 도관과연관된요로감염, 표재성창상감염혹은복강내농양등은도관을제거하거나, 적절한배농, 배액, 조직제거술등에의하여호전될수있다 22). 또한하부요로감염에서는 fosfomycin (3 g 1회 / 일 ) 이나 nitrofurantoin (2 mg/kg 1회 / 일 ) 등도사용될수있다 23). 그러나보다심각한 VRE 감염증의치료에는새로운항생제의치료를필요로하게된다. Linezolid는 oxazolidinone 계열의항생제로 VRE 감염증의 1차치료제로사용되고있으며, E. faecium과 E. faecalis 모두에정균효과를가진다. 반면에 quinupristin-dalfopristin (7.5 mg/kg 3회 / 일 ) 은 E. faecium에만효과가있다 23). Daptomycin은중증피부및연조직감염에서사용할수있는항생제로, 살균효과가있어앞으로의활용이기대되나, 폐농도가낮아폐렴의치료에는사용할수없다. Tigecycline도 VRE에감수성이있어새로운치료제로가능성이있으나, 향후보다많은임상자료가필요하다 24). 최근에새로이개발되고있는약제로는 dalbavancin, telavancin, oritavancin 등이있다. 그러나중증 VRE 감염증의치료를위하여사용할수있는항생제가제한되어있기때문에이를예방하는것이중요하다 24). VRE 감염증을예방하기위하여장관내 VRE 보균을없애는치료에대한연구가있었으나, 아직까지는연구결과가부족하여이를위한항생제사용은그근거가불충분하다. 병원내에서 VRE 의전파확산을방지하기위해서는 VRE 보균환자의접촉격리 (contact precaution) 를시행하여야한다. 이는격리병실 사용, 일회용장갑과덧가운의사용및철저한손씻기가포함된다 23). 3. 마크로라이드내성폐렴알균 (macrolide-resistant Streptococcus pneumoniae) 폐렴알균은지역사회에서폐렴, 중이염, 부비동염및세균성수막염의가장흔하고중요한원인균이다. 페렴알균의항생제내성은페니실린내성, 마크로라이드내성, 퀴놀론내성및다제내성으로대별할수있다. 1967년이래폐렴알균의가장대표적인내성은페니실린내성이었으나, 2008년에미국의 CLSI (Clinical and Laboratory Standards Institute) 에서비중추신경계감염증에서분리된폐렴알균의페니실린내성을정의하는최소억제농도 (MIC) 의기준을 2 μg/ml에서 8 μg/ml 로상향조정한이후전세계적으로폐렴알균의페니실린내성은 5% 미만으로바뀌었다. 이렇게내성기준을변경한이유는기존의내성기준이폐렴과같은비중추신경계감염증의항생제치료반응과일치하지않기때문이었다. 따라서, 페니실린내성은수막염치료에서는여전히의미있으나, 그외의감염증인폐렴이나중이염등에서는임상적의미가별로없다고볼수있다. 역학적으로볼때가장문제가되는폐렴알균내성은마크로라이드내성이다. 폐렴알균의마크로라이드내성은 1990년대이후부터전세계적으로크게증가했으며, 아시아지역에서시행된 ANSORP 연구에따르면국내폐렴알균의마크로라이드내성은 80.6% 이고, 중국, 대만, 홍콩등에서도 70~80% 내외의내성률이보고되었다. 아시아지역국가에서의마크로라이드내성은 MIC가 64~128 μg/ml 이상인고도내성으로임상에서마크로라이드제제의용량을올려도도달할수없는수준이므로임상적인의미가있다. 마크로라이드내성은실제로폐렴알균에의한뇌수막염, 중이염및지역사회폐렴에서마크로라이드치료실패가종종보고되고는있지만, 시험관내감수성데이터와일치하지않는경우가많으며, 여러역학연구에따르면내성균주와감수성균주사이에유의한사망률의차이를밝히지못했다. 또한마크로라이드치료에실패한환자대부분이다른계열의항생제로호전을보이거나, 지역사회획득성폐렴의경우베타락탐항생제와마크로라이드병합요법이기본치료방침으로되어있어마크로라이드내성폐렴알균의임상적영향은평가하기가쉽지않으나 25), 내성균주감염증이있는환자에서의치료실패율이높고사망예가보고되고있어, 아시아국가들과같이고도내성률이높은지역에서는특히항생제감수성결과가확인되기전까지는폐

4 - 대한내과학회지 : 제 77 권제 2 호통권제 588 호 렴의단독치료제로마크로라이드를사용하는것은위험할수있다. 침습적폐렴알균감염예방을위한백신은 23가피막다당류백신 (23-valent pneumococcal polysaccharide vaccine, PPV-23) 과 7가결합백신 (7-valent protein-conjugate pneumococcal vaccine, PCV-7) 이있다. 피막다당류백신 (PPV-23) 은지난 30년이상사용되어왔던백신으로, 침습성폐렴알균감염의발생을낮추는데크게기여해왔지만, 백신을투여받은노인군에서폐렴자체의발생률을감소시키지는못했고, 2세미만의영아에서면역반응유발이안되는문제점이있다 26). PPV-23 은침습적폐렴알균감염의위험이높은성인환자에서의접종이권고된다. 단백결합백신 (PCV-7) 은 7가지혈청형에대한백신으로써, 2000년도이후부터미국내에서사용되어왔으며, PCV-7 의도입이후소아환자에서침습성폐렴알균감염의발생률뿐아니라항생제내성률을현저히낮추는데기여했다 27). PCV-7 백신은현재까지소아예방접종을위해서만권고되고있지만 28,29), 성인환자및장기이식환자를대상으로 PCV-7 의유효성에대해활발한연구가진행중이다 30-33). 향후 10가결합백신과 13가결합백신이임상에서사용될예정이다. 4. ESBL 생성폐렴간균과대장균 (ESBL-producing Klebsiella pneumoniae, Escherichia coli) 최근폐렴간균과대장균에서가장문제가되고있는항생제내성은광범위 cephalosporin 계열항생제에내성을나타내는 extended-spectrum β-lactamase (ESBL) 의생성이다. ESBL을생성하는균주의경우실험실적으로 cephalosporin 에감수성을나타낸다고하더라도임상적으로치료실패를나타낼가능성이높으므로모든 cephalosporin 계열항생제에내성인것으로간주한다. 최근발표된국내자료에따르면폐렴간균의 ceftazidime 내성률은 25~35% 에이르고있고, quinolone 내성률은 2004년에는 30% 에이르렀다 34). ESBL 생성균주에의한균혈증의위험인자로는담즙배액관거치, 이전항균제사용력, 배뇨관거치, 이전에침습적처치를받은경우등이알려져있다 35,36). 국내에서시행된 ESBL 생성폐렴간균에의한균혈증에대한연구에서 ESBL 생성균감염의경우 23.3% 의사망률을보였고, non-esbl 균주감염의경우 20.0% 의사망률을보여서유의한차이를보이지는않았다 36). 하지만재원기간이각각 39.6일과 23.9일로서 ESBL 생성균주감염에서유의하게길었다. 소아환자를대상으로한연구에서는 ESBL 생성균주감염의사망률은 26.7%, non-esbl 생성균주감염의사망률은 5.7% 로서유의한차이를나타내었다 37). ESBL 생성균주에의한중증감염의경우 cephalosporin에감수성을보이는경우라고하더라도 cephalosporin 치료에실패할가능성이높으므로 carbapenem (meropenem 1 g 3회 / 일, imipenem/cilastatin 500 mg 4회 / 일, ertapenem 1 g 1회 / 일 ) 이선택약제로권고된다. ESBL 생성균에의한경증및중등증감염의경우감수성결과에따라 β- lactam/β-lactamase inhibitor, fluoroquinolone을사용해볼수있다 38-42). 국내에서는 ciprofloxacin 내성대장균의빈도가 20~30% 수준으로증가하였으므로요로감염에서항생제치료반응이좋지않은경우 ciprofloxacin 내성균에의한감염을고려하여야한다 43). 최근새롭게개발된항생제인 tigecycline은 ESBL 생성균주에의한감염의치료에사용할수있을것으로생각된다 44). 5. 다제내성녹농균 (multidrug-resistant Pseudomonas aeruginosa) 원내감염의주요원인균중의하나인녹농균은폐렴, 균혈증, 요로감염등을주로일으킨다. 최근세가지이상계열의항생제에내성을나타내는다제내성녹농균에의한감염이문제가되고있다. 녹농균내성의최근문제점은 carbapenem 내성균주의비율이증가하고있는것이며, 2006년자료에따르면중환자실에서분리된녹농균의 imipenem 과 meropenem의내성률은각각 37%, 28% 에이른다 45-50). 국내에서 carbapenem 내성녹농균의치료제로는 colistin이최선이며 2004년일개대학병원과 2005년에국내 5개의대학병원에서분리된 imipenem 내성녹농균중 colistin에대한내성균주는없었다 51,52). 그러나 colistin에도내성인균주들이출현하고있어향후치료상의문제가될것으로예상된다 53). 1, 2차의료기관에서의분리균들은 3차병원과비교하여 carbapenem과 ceftazidime 에대한내성률은낮지만 aminoglycoside 와 fluoroquinolone에대한내성률은 30% 이상으로비슷한내성률을보이고있다. 2002년에서 2006년까지의조사에따르면내성률은 2005년부터조금씩감소하였고, 다제내성균의발생률도감소하였는데, 그이유는 2000년이후의약분업으로항생제가전문약품으로분류되면서사용량이줄었기때문으로추정하고있다 54). 다제내성녹농균에의한혈류감염환자에서의 30일사망률은 44% 로감수성있는균주에의한사망률이 33.9% 인것에비해높았으나통계적으로유의하지는않았다 55). 녹농균감염증에대한경험적항생제의선정은그지역또는병원에서분리된균주들의감수성에따라결

5 - 송재훈. 항생제내성의국내현황및대책 - Figure 1. Antibiotics prescription rates according to the type of hospital (modified from reference No.64 & 65) 정되어야한다. 전통적으로녹농균감염에병합요법이추천되는데그이유는서로다른기전을가진항균제사이에상승작용을기대할수있고, 항균범위를넓혀초기부적절한항균치료를예방하며내성의발생을예방하기위함이다. 그러나이런근거들은대부분실험실내의연구 (in vitro) 결과에서나온것으로실제임상에서병합요법이환자들의예후를호전시킬수있는지에대해서는증명된바가없다 56). Carbapenem 내성균주에의한감염의치료는 colistin (150 mg 2회 / 일 ) 이며임상적반응률은 60~80% 이나다른항균제와의병합요법은아직치료근거가부족하다 52,57). 6. 다제내성 Acinetobacter species Acinetobacter species (spp.) 는녹농균과더불어병원감염에서문제가되고있는원인균중하나이다. 2008년의국내보고에따르면 Acinetobacter spp. 는중환자실에서발생한혈류감염의원인균중 11.6% 를차지하여황색포도알균과 coagulase-negative Staphylococcus 다음으로흔하였으며그람음성균중에서는 1위를차지하였다. Ceftazidime 과 fluoroquinolone에대한내성률은 10년전부터이미 50% 이상이며, imipenem에대한내성률은 2008년에 36.3% 에이르고있어녹농균과비교하여매우빠른내성률의증가속도를보이고있다 45-50,58). Acinetobacter spp. 의 colistin에대한내성률은 2002 년에서 2006년까지분리된 Acinetobacter spp. 중에서는 18.2% 가 colistin에내성을보였다 51). Imipenem 내성 A. baumannii에의한균혈증의사망률은 57.5% 로 imipenem 감수성 A. baumannii에 의한균혈증의 20% 에비하여높으며, 이는균혈증초기에부적절한항생제치료로인한결과일것으로설명하고있다 59). 녹농균과마찬가지로 A. baumannii 감염증에대한경험적항생제의선정은대상기관의항균제내성분포에따라결정되어야한다. 감수성균주의경우 ceftazidime, piperacillin/tazobactam, carbapenem 등을사용할수있다. Carbapenem 내성균주의치료에사용할수있는항생제는 colistin 이지만 colistin 감수성인균주임에도불구하고단독치료의임상적성공률은 57~78% 정도이다 60). Colistin에내성인 A. baumannii에대한치료는현재까지정립된것이없으나아직국내에서는많이사용되고있지않은 tigecycline이효과가있을것으로기대되고있다 61). 항생제내성의증가원인 1. 항생제의사용항생제내성은항생제사용량과밀접한관계를보이고있기때문에국내항생제내성증가의원인을파악하기위해서는국내항생제사용량의변화를살펴보는것이중요하다. 국내의항생제처방및사용량은의약분업이시작된 2000 년 7월을기점으로변화를보여왔다 ( 그림 1). 서울소재한대학병원에서의약분업시작전인 2000년 3월과시작후인 2001년 3월의한달간의외래항생제처방순위및발생건수를비교한결과, 2001년 3월이후항생제처방과사용량이감소한것이관찰되었고, 심사평가원자료에따르면 2002년

6 - The Korean Journal of Medicine: Vol. 77, No. 2, 이후전체약품처방품목중항생제처방비율은연간감소추세를보이고있다 62,63). 현재까지국내전체항생제사용량을조사한자료는없으며, 항생제사용량의변화와이와관련된내성의변화를다룬국내역학자료는부재한상태이다. 2007년국내의 5개 3 차병원에서 β-lactam계항생제사용실태및항생제내성과의상관관계를분석한자료에따르면, β-lactam계항생제사용이폐렴간균의 ESBL 생성과관계가있는것으로나타났다 64). 2004년부터 2007년까지 39개월에걸쳐일개대학병원에서항생제사용량과내성과의추이를살펴보면, 3세대 cephalosporin의사용량과폐렴간균에서의내성률및 imipenem의사용량과녹농균에서의내성률간의유의한상관관계를보여주었고, oxacillin의사용량과 MRSA 그리고 ciprofloxacin의사용량과 ciprofloxacin 내성대장균과관계에서시계열적합성이확인되었다 65). 이러한자료들은항생제내성의출현에항생제의사용, 특히오남용이가장중요한영향요소임을확인하는것으로내성에대한대책의첫걸음역시항생제의올바른사용임을강조하는것이다. 2. 내성균의전파일단항생제내성균주가출현하면이를단기간에급증시키는주요원인은내성균주의전파확산이다. MRSA 나 VRE의병원내전파확산이대표적인예이며, 병원감염관리가효과적이지못한경우내성균주의급속한전파가이루어지게된다. 이외에특정내성유전자, 세균의혈청형, 내성에대한대책의부재등여러요인들이복합적으로작용하여항생제내성의문제를악화시키고있다. 항생제내성의대책항생제내성률을감소시키기위한대책은적절한항생제사용, 철저한병원감염관리, 새로운항생제의개발및백신의보급등으로나누어진다. 항생제의사용, 특히항생제의오남용은항생제내성발생의가장중요한위험인자로알려져있고, 항생제사용량과내성률의상관관계가밝혀져있다. 따라서항생제를적절하게사용하여항생제오남용을줄이는것이항생제내성감소대책의첫걸음이다. 항생제의적절한사용이란항생제를꼭필요한세균감염증의경우에만사용하는것을필두로하여, 항균력, 내성유도력, 약물동력학적측면, 가격등으로보아가장적당한항생제를선택 하여적절한용량과치료기간을지키는것을모두포함한다. 초기에광범위항생제를사용하더라도미생물검사결과가나온후에는항균범위를좁히는 de-escalation therapy를하여야한다. 그러나항생제사용을관리하는것만으로는내성을효과적으로감소시킬수없다. 일단출현한항생제내성균은병원내에서환자들사이또는환자와의료인사이에서전파확산이이루어지며병원간, 지역간, 국가간에전파확산된다. 내성의전파는항생제내성률을단기간에급증시키는역할을한다. 따라서병원감염관리를철저히하여내성균전파를방지하는것이중요하다. 특히 MRSA, VRE 같은항생제다제내성균이분리된환자들은접촉격리 (contact precaution) 를하는것이필요하며, 손씻기를철저히하는것이필수적이다. 항생제내성균에효과적인새로운항생제를개발하는것또한시급한과제이지만항생제개발에오랜시간과비용이들어가고새롭게개발되었다고하더라도다시내성을획득하는문제로인하여많은제약회사들이항생제개발을포기하고있다. 그결과현재까지다제내성세균에효과적인새로운항생제는매우드문실정이며특히그람음성다제내성균에대한새로운항생제는전무한실정이다. 세균에대한백신은감염증발생자체를방지하기때문에내성관리의근본적인해결책이될수도있으나, 폐렴알균백신, 헤모필루스백신이외에는임상에서사용할수있는백신이없어문제가된다. 폐렴알균백신은항생제내성률도성공적으로감소시키는효과가있음이입증되었다. 현재포도알균백신이개발중이며, 녹농균을포함한주요세균에대한백신개발연구도진행중이다. 항생제내성의감소는의료인개개인의노력만으로이루어지는것은아니다. 의료인, 의료기관, 의료인단체, 보건관련단체, 보건의료정책부서모두의포괄적이고적극적인노력이뒷받침되어야한국가의항생제내성률을감소시키고아울러항생제내성균에의한병원감염을줄일수있을것이다. 결론국내병원에서분리되는임상적으로중요한세균들에서항생제내성률은세계적으로최고수준을보이고있다. 특히 MRSA, VRE, ESBL 생성그람음성균, 다제내성녹농균및 Acinetobacter species 등은임상에서심각한문제가되고있다. 항생제내성균에의한감염증을치료할때에는각병원의역학적상황을잘이해하는것이첫번째이고, 이에맞추

7 - Jae-Hoon Song. Current status and future strategies of antimicrobial resistance in Korea - 어적절한항생제를사용하여야한다. 항생제내성의문제는향후더욱심화될것이므로이에대한다각적인대책을마련하는것이필요하다. 감사의글 이논문의작성에큰도움을주신강철인교수와자료수집을한정미경, 이정아, 손경목, 하영은, 주은정, 정호중선생님께감사를드립니다. REFERENCES 1) Kim JM, Park ES, Jeong JS, Kim KM, Kim JM, Oh HS, Yoon SW, Chang HS, Chang KH, Lee SI, Lee MS, Song JH, Kang MW, Park SC, Choe KW, Pai CH. Multicenter surveillance study for nosocomial infections in major hospitals in Korea. Nosocomial Infection Surveillance Committee of the Korean Society for Nosocomial Infection Control. Am J Infect Control 28: , ) Fridkin SK, Hageman JC, Morrison M, Sanza LT, Como-Sabetti K, Jernigan JA, Harriman K, Harrison LH, Lynfield R, Farley MM. Methicillin-resistant Staphylococcus aureus disease in three communities. N Engl J Med 352: , ) Kim ES, Song JS, Lee HJ, Choe PG, Park KH, Cho JH, Park WB, Kim SH, Bang JH, Kim DM, Park KU, Shin S, Lee MS, Choi HJ, Kim NJ, Kim EC, Oh MD, Kim HB, Choe KW. A survey of community-associated methicillin-resistant Staphylococcus aureus in Korea. J Antimicrob Chemother 60: , ) Blot SI, Vandewoude KH, Hoste EA, Colardyn FA. Outcome and attributable mortality in critically III patients with bacteremia involving methicillin-susceptible and methicillin-resistant Staphylococcus aureus. Arch Intern Med 162: , ) Cosgrove SE, Sakoulas G, Perencevich EN, Schwaber MJ, Karchmer AW, Carmeli Y. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis 36:53-59, ) Chang FY, MacDonald BB, Peacock JE Jr, Musher DM, Triplett P, Mylotte JM, O'Donnell A, Wagener MM, Yu VL. A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance. Medicine (Baltimore) 82: , ) Kluytmans J, Struelens M. Meticillin resistant Staphylococcus aureus in the hospital. BMJ 338:b364, ) Loeb M, Main C, Walker-Dilks C, Eady A. Antimicrobial drugs for treating methicillin-resistant Staphylococcus aureus colonization. Cochrane Database Syst Rev:CD003340, ) Schaffer AC, Lee JC. Vaccination and passive immunisation against Staphylococcus aureus. Int J Antimicrob Agents 32(Suppl 1):S71-S78, ) Center for Disease Control and Prevention (CDC). Reduced susceptibility of Staphylococcus aureus to vancomycin: Japan, MMWR Morb Mortal Wkly Rep 46: , ) Appelbaum PC. The emergence of vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus. Clin Microbiol Infect 12(Suppl 1):16-23, ) Sievert DM, Rudrik JT, Patel JB, McDonald LC, Wilkins MJ, Hageman JC. Vancomycin-resistant Staphylococcus aureus in the United States, Clin Infect Dis 46: , ) Kim MN, Pai CH, Woo JH, Ryu JS, Hiramatsu K. Vancomycin-intermediate Staphylococcus aureus in Korea. J Clin Microbiol 38: , ) Hong KH, Park JS, Kim EC. Two cases of vancomycin-intermediate Staphylococcus aureus isolated from joint tissue or wound. Korean J Lab Med 28: , ) Sood S, Malhotra M, Das BK, Kapil A. Enterococcal infections & antimicrobial resistance. Indian J Med Res 128: , ) Koh EM, Lee SG, Kim CK, Kim M, Yong D, Lee K, Kim JM, Kim DS, Chong Y. Microorganisms isolated from blood cultures and their antimicrobial susceptibility patterns at a university hospital during Korean J Lab Med 27: , ) Hong SG, Yong D, Lee K, Kim EC, Lee WK, Jeong SH, Song WK, Park YJ, Kim MN, Uh Y, Shin JH, Lee J, Ahn JY, Lee SW, Kim JS, Shin HB. Antimicrobial resistance of clinically important bacteria isolated from hospitals located in representative provinces of Korea. Korean J Clin Microbiol 6:29-36, ) Hong SG, Lee J, Yong D, Kim EC, Jeong SH, Park YJ, Choi TY, Uh Y, Shin JH, Lee WK, Ahn JY, Lee SH, Woo GJ, Lee K. Antimicrobial resistance of clinically important bacteria isolated from 12 hospitals in Korea. Korean J Clin Microbiol 7: , ) Lee H, Kim CK, Lee J, Lee SH, Ahn JY, Hong SG, Park YJ, Jeong SH, Kim EC, Lee WK, Uh Y, Shin JH, Choi TY, Kwak H-S, Lee K. Antimicrobial resistance of clinically important bacteria isolated from 12 hospitals in Korea in 2005 and Korean J Clin Microbiol 10:59-67, ) Lee K, Kim MY, Kang SH, Kang JO, Kim EC, Choi TY, Chong Y. Korean nationwide surveilance of antimicrobial resistance in 2000 with special reference to vancomycin resistance in enterococci, and expanded-spectrum cephalosporin and imipenem resistance in gram-negative bacilli. Yonsei Med J 44: , ) Han SH, Chin BS, Lee HS, Jeong SJ, Choi HK, Kim CO, Yong D, Choi JY, Song YG, Lee K, Kim JM. Vancomycin-resistant enterococci bacteremia: risk factors for mortality and influence of antimicrobial therapy on clinical outcome. J Infect 58: , ) Linden PK. Optimizing therapy for vancomycin-resistant enterococci (VRE). Semin Respir Crit Care Med 28: ,

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