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1 Korean J Clin Microbiol Vol. 14, No. 1, March, 2011 DOI: /KJCM Prevalence and Clinical Characteristics of Mupirocin-Resistant Staphylococcus aureus A-jin Lee, Hun-Suk Suh, Chang-Ho Jeon, Sang-Gyung Kim Department of Laboratory Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea Background: Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) is a known risk factor for nosocomialtransmission and infection. In an effort to mitigate this problem, topical mupirocin has been widely used for clearing nasal carriage of MRSA. However, mupirocin resistance has become a worldwide concern due to increased use of the antibiotic. The aims of this study were to evaluate the clinical characteristics and prevalence of mupirocin resistance among clinical isolates of staphylococci and to investigate antimicrobial susceptibility. Methods: A total of 175 S. aureus specimens recovered over a 4-month period from various body sites were tested for resistance to mupirocin and other antibiotics using the Vitek2 automated system. The presence of the mupa gene was assessed in isolates exhibiting resistance to mupirocin and in other selected organisms. The clinical characteristics of the isolates were also reviewed. Results: Of the 175 S. aureus isolates, 9.1% (16/175) were resistant to mupirocin, with 1.7% (3/175) having high-level resistance (HR) and 7.4% (13/175) having low-level resistance (LR). Patients with HR-mupirocinresistant S. aureus had a longer duration of hospitalization (P=0.026). Of the 13 LR-mupirocin-resistant S. aureus strains, 11 had identical antibiogram patterns. The mupa gene was detected only among HR isolates. Conclusion: The rate of mupirocin resistance in the S. aureus isolates was high. The spread of mupirocinresistant S. aureus may be due to nosocomial infection. (Korean J Clin Microbiol 2011;14:18-23) Key Words: Mupirocin, Staphylococcus aureus, Drug resistance 서 메티실린내성황색포도알균 (methicillin-resistant Staphylococcus aureus, MRSA) 은병원감염의중요한원인균으로 [1,2] 현재국내에서분리되는 Staphylococcus aureus의약 70% 정도를차지하고있다 [3]. MRSA 의전파경로는오염원과의직접접촉, 의료인의손등을통한간접전달, 공기등으로알려져있고 [4], MRSA 감염관리와전파방지를위해서원내에서의 MRSA 오염원과전파경로를파악하여제거및차단하는것이중요하다. MRSA 감염및원내전파경로중의하나가 MRSA의비강정착이다 [5]. MRSA 의비강정착을제거하기위하여국소항생제인뮤피로신 (mupirocin) 이사용된다 [6]. 뮤피로신은세균의 isoleucyl-trna synthetase를경쟁적으로억제하여세균의단백합성을방해함으로써약리학적작용을하게된다 [7]. 최근에뮤 Received 4 May, 2010, Revised 28 June, 2010 Accepted 20 July, 2010 Correspondence: Hun-Suk Suh, Department of Laboratory Medicine, Catholic University of Daegu School of Medicine, Daemyeong 4-dong, Nam-gu, Daegu , Korea. (Tel) , (Fax) , ( ) hssuh@cu.ac.kr 론 피로신의사용이증가됨에따라, 뮤피로신내성이여러나라에서보고되고있으며 [8-10], 국내에서는 2003년도에처음으로보고되었다 [11]. 뮤피로신내성은전세계적인문제로뮤피로신내성이생길경우 MRSA를박멸하는데실패하여병원감염및전파를관리하는데어려움이생길수있다. 뮤피로신내성에는고농도내성 (high-level resistance, HR) 과저농도내성 (low-level resistance, LR) 의두가지군이있다. 고농도내성은최소억제농도 (minimal inhibitory concentration, MIC) 가 512 μg/ml 이상되는군으로플라스미드에존재하는 mupa 유전자 (mupa gene) 가전파될수있어임상적으로중요한것이다 [12,13]. 저농도내성은 MIC가 8에서 256μg/mL 사이에속하는것으로 t-rna synthetase를코딩하는유전자의염색체성돌연변이때문인것으로여겨지나, 임상적유용성은밝혀지지않은상태이다 [12,13]. 뮤피로신내성의빈도는여러차례보고되고있으나, 임상적특성은정확하게밝혀지지않은상태이다. 본연구는임상검체에서분리된황색포도알균에서뮤피로신내성률을측정하고 MIC에따른내성균주의특징을 mupa 유전자를이용하여분석하였다. 또한, 뮤피로신내성과연관된임상적지표도분석하여임상적특성을밝히고자하였다. 뮤피 18

2 A-jin Lee, et al. : Mupirocin-Resistant S. aureus 19 로신외의항생제에대한감수성검사를시행하여균주별특징을비교하였다. 대상및방법 1. 연구대상 2009년 12월부터 2010년 3월까지본원의일반병동, 중환자실, 외래, 응급실에서본원미생물검사실로의뢰된임상검체중황색포도알균으로동정된 175균주를대상으로하였다. 동일한환자의검체가같은부위에서반복하여의뢰된경우처음의균주만을포함하였고, 동일한환자라도검체가다른부위에서채취된경우대상에포함하였다. 균주는균혈증 (30/175, 17.1%), 상처감염 (38/175, 21.7%), 관삽입부감염 (6/175, 3.4%), 요로감염 (17/175, 9.7%), 병원성폐렴 (69/175, 39.4%), 기타감염 (15/175, 8.6%) 과관련이있었다. 분리된균주는 brain-heart infusion broth (Becton Dickinson, San Diego, CA, USA) 에 20% glycerol (Amrescro, Solon, OH, USA) 을첨가하여 70 o C에서냉동보관하였다. 2. 연구방법 1) 항생제감수성검사 : Vitek2 (biomerieux, Marcy I Etoile, France) 자동화장비패널의 GP601 카드 (biomerieux, Marcy I Etoile, France) 를이용하여 mupirocin, ciprofloxacin, clindamycin, erythromycin, fusidic acid, nitrofurantoin, gentamicin, oxacillin, arbekacin, linezolid, penicillin G, quinupristin-dalfopristin, rifampin, teicoplanin, tetracycline, trimethoprim-sulfamethoxazole, telithromycin, tigecycline, vancomycin 등 19개의항생제에대한감수성검사를시행하였다. 뮤피로신내성군은 MIC에따라다시저농도내성군 (LR, 8 256μg/mL) 과고농도내성군 (HR, 512 μg/ml) 으로구분하였다. 뮤피로신을제외한 18개의항생제에대해서는감수성인지, 내성인지만을확인하였다. 2) 뮤피로신내성과연관된임상적지표조사 : 의무기록을열람하여대상균주가분리된검체, 주진단명, 입원기간, 입원장소등을분석하여뮤피로신감수성군과뮤피로신내성군을비교하였다. 환자의연령, 성별비교시, 다른부위에서검체가분리되어동일한환자가여러번포함된경우한번만인정하여비교하였다. 3) PCR 을통한 mupa 유전자검출 : 분리된 MRSA 중뮤피로신내성을보이는모든균주 (MIC 8 μg/ml) 와뮤피로신감수성을보이는균주중 7개를무작위로선별하여 PCR을시행하였다. 70 o C 냉동고에보관중인대상균주를녹여하룻밤배양한후, Qiagen kit DNeasy Blood & Tissue (Qiagen, GmbH, Germany) 를이용하여제조사의설명서에따라염색체성 DNA를분리하여주형으로사용하였다. 한쌍의시발체 (5 -TGA CAA TAG AAA AGG ACA GG-3 및 5 -CTA ATT CAA CTG GTA AGC C-3 ) 를사용해 190 bp 크기의산물을증폭하여 mupa 유전자 (GenBank accession no. X75439) 를검출하였다 [14]. PCR 반응을위해서 PCR Premix (Bioneer, Chongwon, Korea) 20μL 시험관을사용하였는데, DNA 추출액 1 μl와각시발체를 1 μl (20 pmole) 씩및멸균증류수 17 μl를혼합하여시험에사용하였다. 먼저 94 o C에서 5분간처리한후, 94 o C 30초, 52 o C 40초, 72 o C 1분의조건으로 35회반응시켰다. 반응액 10 μl를 1 μg/ml의 ethidium bromide가포함된 1.5% 아가로즈겔에서전기영동후 190 bp의밴드가있는지를확인하였다. 4) 통계처리 : SPSS 소프트웨어, 버전 (SPSS Inc., Chicago, IL, USA) 를사용하였다. 뮤피로신감수성군과뮤피로신 LR 및뮤피로신 HR의비교를위하여 Kruskal-Wallis 검정을시행하고, 그룹간차이가나는경우사후검정으로 Mann- Whitney U 검정, Scheffe, Duncan을사용하였다. P값이 0.05 미만인경우를통계적으로의의가있는것으로보았다. 결 Table 1. Distribution of mupirocin MICs among 175 strains of Staphylococcus aureus Mupirocin resistance MIC (μg/ml) No. of isolate (%) 과 1. 뮤피로신및메티실린내성균검출률 연구기간 4개월중 175개의균주에서황색포도알균이검출되었다. 그중 MRSA 는 108균주 (61.7%) 에서검출되었다. Vitek2 자동화장비를이용하여뮤피로신에대한 MIC를측정한결과 64 μg/ml를보이는 LR이 13균주로 7.4% 를차지하였고, 512 μg/ml를보이는 HR이 3균주로 1.7% 를차지하였다 (Table 1). 뮤피로신에내성을보이는균주는모두 MRSA였고, 메티실린감수성황색포도알균에서는뮤피로신내성이관찰되지않았다. MRSA 중에서뮤피로신내성빈도는 LR 12.0%, HR 2.8% 였다. 뮤피로신내성균주가동일환자에서분리된경우는 1명으로, LR, HR 각각한번씩분리되었다. 2. 뮤피로신감수성및내성을보이는균주의임상적특성 대상균주 175개는총 141명으로터분리되었다. 연령은그룹별로뮤피로신감수성군은 59세 (0 89), 뮤피로신 LR은 56세 (17 73), 뮤피로신 HR은 56세 (21 69) 로연령별통계학적인차이는없었다 (P=0.719). 성별은남자 85명 (60.3%), 여자 56명 (39.7%) 으로모든그룹에서남성이많은비율을차지하고있었다. 입원기간은뮤피로신감수성군에서는 6일 (1 1670), 뮤피 Susceptible <2 150 (85.7) 4 9 (5.1) Low-level resistant (7.4) High-level resistant (1.7) Total 175 (100) Abbreviation: MIC, minimal inhibitory concentration.

3 20 Korean J Clin Microbiol 2011;14(1):18-23 로신 LR에서는 6일 (2 60), 뮤피로신 HR에서는 55일 (24 222) 로뮤피로신 HR에서입원기간이길었다 (P=0.026). 분리된검체는객담이가장흔하였고, 뮤피로신 HR은객담 1건, 혈액 1건, 상처 1건에서분리되었다. 일반병동에서황색포도알균이가장많이분리되었고, 뮤피로신내성군이분리된빈도는중환자실보다는일반병동에서더많았다 (Table 2). 3. 항생제감수성결과 뮤피로신에내성을보이는균주모두 MRSA 였고, MRSA 의 Table 2. Clinical characteristics of 175 strains of Staphylococcus aureus Hospital stay, median days (range) Mupirocin susceptible (N=159) 6 (1 1,670) Mupirocin LR (N=13) 6 (2 60) Mupirocin HR (N=3) 55 (24 222) Specimens, N (%) Sputum 69 (39.4) 59 (85.5) 9 (13.0) 1 (1.4) Urine 17 (9.7) 17 (100.0) 0 (0.0) 0 (0.0) Blood 30 (17.1) 28 (93.3) 1 (3.3) 1 (3.3) Wound 38 (21.7) 35 (92.1) 2 (5.3) 1 (2.6) Others 21 (12.0) 20 (95.2) 1 (4.8) 0 (0.0) Total 175 (100.0) 159 (90.9) 13 (7.4) 3 (1.7) Place, N (%) ICU 48 (27.4) 44 (91.7) 3 (6.2) 1 (2.1) GW 95 (54.3) 84 (88.4) 9 (9.5) 2 (2.1) OPD 11 (6.3) 11 (100.0) 0 (0.0) 0 (0.0) ED 21 (12.0) 20 (95.2) 1 (7.7) 0 (0.0) Total 175 (100.0) 159 (90.9) 13 (7.4) 3 (1.7) Abbreviations: LR, low-level resistant; HR, high-level resistant; ICU, intensive care unit; GW, general ward; OPD, outpatient department; ED, emergency department. Table 3. Antimicrobial resistance profile of 108 MRSA strains Antimicrobial No. (%) Ciprofloxacin 88 (81.5) Clindamycin 95 (87.9) Erythromycin 96 (88.9) Fusidic acid 74 (68.5) Nitrofurantoin 6 (5.6) Gentamicin 89 (82.4) Arbekacin 0 (0.0) Linezolid 0 (0.0) Penicillin G 108 (100) Quinupristin-Dafopristin 0 (0.0) Rifampin 7 (6.5) Teicoplanin 0 (0.0) Tetracycline 92 (85.2) Trimethoprim-sulfamethoxazole 9 (8.3) Telithromycin 87 (80.6) Tigecycline 0 (0.0) Vancomycin 0 (0.0) 경우다약제내성을보일수있어분리된 MRSA에대한항생제감수성을조사하였다. Ciprofloxacin에 81.5%, clindamycin 에 87.9%, erythromycin에 88.9%, fusidic acid에는 68.5% 의내성을보였다. Gentamicin에는 82.4%, tetracycline에는 85.2% 의내성을보였으며, rifampin에는 6.5%, trimethoprim-sulfamethoxazole에는 8.3% 의내성을보였다. Arbekacin, linezolid, quinupristin-dafopristin, tigecycline, teicoplanin, vancomycin에는 100% 감수성을보였으며, 그외의항생제에대해서도 Table 3 에요약하였다. 뮤피로신에대해서내성을가지는경우의항균제감수성양상 (antibiogram) 을분석한결과 13개의 LR 중 11개의 LR 균주가같은양상을보였는데, 일반병동에서분리된 8개의균주와응급실에서분리된 1개의균주, 중환자실에서분리된 2개의균주가 linezolid, quinupristin-dafopristin, rifampin, trimethoprimsulfamethoxazole, vancomycin, teicoplanin에감수성을보이는 Table 4. Epidemiologic and clinical features of the sixteen mupirocinresistant Staphylococcus aureus No. MR Antibiogram* Specimen Place Hospital stay (days) Primary diagnosis 4 HR LQVT Blood ICU 222 COPD 8 LR LQRTsVT Sputum GW 6 COPD 10 LR LQRTsVT Ascitic GW 24 Duodenal ulcer fluid 15 LR GLQRTsVT Sputum ICU 5 SAH 55 LR LQRTsVT Sputum ED 2 COPD 65 LR LQRTsVT Sputum GW 30 Gangrene of toe 66 LR LQRTsVT Wound GW 2 Sacral sore 79 LR LQRTsVT Sputum GW 4 ESRD 92 LR LQVT Sputum GW 9 Pneumothorax 99 LR LQRTsVT Sputum GW 60 Aplastic anemia 100 LR LQRTsVT Sputum ICU 4 Septic shock 106 LR LQRTsVT Blood GW 4 ESRD 107 HR CLQRTsVT Wound GW 24 Sacral sore 109 HR CiCELQRTs Sputum GW 55 SAH TeVT 153 LR LQRTsVT Wound GW 35 Open wound of ankle and foot 169 LR LQRTsVT Sputum ICU 23 Spine fracture *Type of antibiogram: LQVT (susceptible to linezolid, quinupristindafopristin, vancomycin, teicoplanin), LQRTsVT (susceptible to linezolid, quinupristin-dafopristin, rifampin, trimethoprim-sulfamethoxazole, vancomycin, teicoplanin), GLQRTsVT (susceptible to gentamicin, linezolid, quinupristin-dafopristin, rifampin, trimethoprim-sulfamethoxazole, vancomycin, teicoplanin), CiCELQRTsTeVT (susceptible to ciprofloxacin, clindamycin, erythromycin, linezolid, quinupristin-dafopristin, rifampin, trimethoprim-sulfamethoxazole, tetracycline, vancomycin, teicoplanin). Abbreviations: MR, mupirocin resistance; LR, low-level resistant, HR, high-level resistant; ICU, intensive care unit; GW, general word; ED, emergency department; COPD, chronic obstructive pulmonary disease; SAH, subarachnoidal hemorrhage; ESRD, end-stage renal disease.

A-jin Lee, et al. : Mupirocin-Resistant S. aureus 21 Fig. 1. Bands of mupa gene in 3 high-level resistance of mupirocin. Lane 1, patient No. 162; Lane 2, patient No. 192; Lane 3, patient No.

4 A-jin Lee, et al. : Mupirocin-Resistant S. aureus 21 Fig. 1. Bands of mupa gene in 3 high-level resistance of mupirocin. Lane 1, patient No. 162; Lane 2, patient No. 192; Lane 3, patient No. 195; Lane 4, PCR size marker. 양상 (LQRTsVT) 을보였다. 일반병동에서분리된 1개의 LR 균주는 rifampin과 trimethoprim-sulfamethoxazole 내성을나타내는것만이다른양상 (LQVT, linezolid, quinupristin-dafopristin, vancomycin, teicoplanin에감수성 ) 을보였다. 중환자실에서분리된나머지 1개의 LR 균주는 gentamicin에감수성을보여 GLQRTsVT (gentamicin, linezolid, quinupristin-dafopristin, rifampin, trimethoprim-sulfamethoxazole, vancomycin, teicoplanin에감수성 ) 양상을보였다 (Table 4). 3개의 HR 균주는모두다른양상을보였는데중환자실에서분리된 1개의균주는 LQVT 양상을보였고, 일반병동에서분리된 1개의균주는 clindamycin에추가로감수성을보이는 CLQRTsVT 양상을보였다. 일반병동에서분리된나머지 1개의균주는 ciprofloxacin, clindamycin, erythromycin, tetracyclin에추가로감수성을보여 CiCELQRTsTeVT 양상을보였다 (Table 4). 4. mupa 유전자검출과 MIC 로분류된뮤피로신내성군분류비교 뮤피로신 HR 을보이는 3 개의균에서 190 bp 크기의 mupa 유전자가검출되었다 (Fig. 1). 뮤피로신 LR을보이는 13개의균과뮤피로신에감수성을보이는균에서는 mupa 유전자가검출되지않았다. 고 MRSA는병원감염을일으키는중요한원인균중의하나이며특히원내집단감염발생이의심되는경우는발생원, 감염원확인및감염경로조사를하고, 이를차단하여야한다. MRSA 에의한병원감염경로는 MRSA에감염되었거나비강의정착, 드물게는오염된주변환경으로부터의료진의손을통하여감염된다고알려져있다 [1,2,4]. MRSA 비강정착자의경우비정착자에비하여원내감염, 수술후감염률이높아비강정착을제거하여야하는데이때효과적인약제가뮤피로신이다 [15]. 찰 그러나, 뮤피로신이처음으로도입된지 2년만에뮤피로신내성이보고되었다 [8]. 국내에서는 1994년부터 MRSA의비강보균자를박멸하기위하여국소적항생제인뮤피로신을사용하였고, 도입된지얼마지나지않아뮤피로신내성이나타나기시작하였다 [16-18]. 뮤피로신내성중에서도뮤피로신 HR은비강보균자를박멸하는치료의실패로이어질확률이높아임상적으로문제이다 [19]. 뮤피로신 LR 또한임상적인의미가명확히밝혀지지는않았지만, 뮤피로신에감수성인경우보다는박멸실패의위험이높다고보고되고있다 [19,20]. 본연구에서는임상검체에서분리된황색포도알균중뮤피로신내성률을알아보고, 뮤피로신내성과연관된임상적지표를찾고자하였다. 또한항생제감수성양상을비교하여균간의특징을비교하고, MRSA의병원전파경로를추정해보고자하였다. 연구기간동안분리된 175개의황색포도알균중뮤피로신내성은전체내성률이 9.1% 로 LR 7.4%, HR 1.7% 였다. Bradley 등 [9] 은 1,309명의황색포도알균비강보균자중 1% 에서뮤피로신내성균이분리되었다고보고하였고, Wise와 Johnson [21] 은 228개의분리균중 8.3% 에서뮤피로신내성을보인다고하였다. 본연구에서, 175개의황색포도알균중 61.7% 로분리된 108개의 MRSA 중에서는뮤피로신내성이 LR 12.0%, HR 2.8% 로전체 14.8% 를차지하였다. 이는 MRSA를대상으로뮤피로신내성을보고한 Australia에서의 18% 의내성률과비슷하다 [10]. 그러나 Orrett [22] 의연구에서는분리된 MRSA 중 LR 44.1%, HR 26.1% 라고내성률을보고하였는데이는중환자실환자만을대상으로조사한것이어서본연구와차이점이있다고생각된다. 국내에서는 2003년도에처음뮤피로신내성이보고되었는데 3차병원에서분리된 319개의황색포도알구균중 16개의균, 즉 5% 에서 HR이검출되었다고하였다 [11]. 이중 15개가 MRSA, 1개가 MSSA로본연구에서 MRSA에서만뮤피로신내성이나타난것과는차이가난다 [11]. 2006년도에는중환자실환자들만을대상으로하여검출된 407개의황색포도알구균중 21개 (5.2%) 가 LR, 25개 (6.1%) 가 HR로본연구보다 LR은낮게, HR은높게검출되었다. 중환자실환자들만을대상으로한연구와는달리, 본연구에서는중환자실은물론, 일반병동, 응급실, 외래의환자까지대상환자로포함시켜대상의차이로인한빈도차이라고여겨진다 [16,23]. 본연구에서는임상적특성을규명하기위하여뮤피로신감수성군과뮤피로신 LR, HR을비교하였는데뮤피로신 HR에서입원기간이좀더긴것으로나타났다. 이는뮤피로신내성균감염이원내전파에기인하여입원기간이오래될수록감염의기회가높아졌기때문이라고생각된다 [11,16,22,23]. 국내에서 MRSA의빈도는 77 80% 이상이고중환자실에서의 MRSA의빈도는약 90% 이상으로보고되었다 [3,22]. 특히중환자실의

5 22 Korean J Clin Microbiol 2011;14(1):18-23 료진에서비강의 MRSA 보균율은 % 로비강정착자의경우수술후창상감염이비정착자에비해 17배나높게생기는것으로보고되어, 중환자실에서 MRSA에감염될확률이높을것으로생각된다 [15]. 본연구에서는장소별로 MRSA의검출률을비교했을때, 일반병동에서 63.2% (60/95), 중환자실에서 75.0% (36/48) 로관찰되었고, MRSA 중뮤피로신내성검출률을비교해보았을때, 일반병동에서 18.3% (11/60), 중환자실에서 11.1% (4/36) 으로일반병동에서뮤피로신내성의빈도가높은것으로나타나기존의보고와차이가난다 [16,22,23]. 뮤피로신내성을가지는경우의항생제감수성양상을분석한결과, LR을보이는 11개의균주가같은양상을보여 (LQRTsVT) 같은종류로추정할수있고, 나머지 2개의 LR 균주와 3개의 HR 균주는차이가나다른종류로추정하여뮤피로신내성 MRSA의집단발생을의심해볼수있었다. 그러나항생제감수성양상이동일한균주간이라도유전형에차이가날수있기때문에항균제감수성양상으로같은클론으로판단하더라도분자역학적인방법으로타이핑을하면더세분화될수있지만 [24], 이전의국내외여러연구에서황색포도알균에항균력이있는다수의항균제들에대한감수성양상으로구분한형별은분자역학적인타이핑과높은상관성을보인다 [25,26]. 따라서이연구에서뮤피로신 LR 황색포도알균대부분이동일한항균제감수성양상을보이는것은원내에서교차오염에의한클론성전파가이루어졌음을시사한다. 뮤피로신내성황색포도알균발생은원내전파로인한것으로생각된다. mupa 유전자를 PCR 을통하여검출하였는데 MIC 로분류된 HR ( 512 μg/ml) 에서 mupa 유전자가검출되었다. 이전의연구에서, Vitek2 자동화장비와 MIC를결정하는데표준검사법인디스크확산법을이용하여뮤피로신감수성시험결과를비교한결과, 100% 일치율을보이고 HR에서는 mupa 유전자가검출된반면, LR 및감수성군에서는유전자가검출되지않았다고보고한것과일치한다 [27]. 본연구에서는전체균수가 175개로다소적은단점이있어, 향후충분한기간동안더많은검체를대상으로뮤피로신내성을가지는황색포도알균을수집하여이균들의유전형연구를하는것이필요하겠다. 뮤피로신내성황색포도알균은높은빈도를나타내었다. 뮤피로신 HR일수록입원기간이길었으며, 뮤피로신 LR 13개중 11개가동일한항생제감수성양상을보여뮤피로신내성황색포도알균발생은원내전파로인한것으로생각된다. 참고문헌 1. Muder RR, Brennen C, Wagener MM, Vickers RM, Rihs JD, Hancock GA, et al. Methicillin-resistant staphylococcal colonization and infection in a long-term care facility. Ann Intern Med 1991;114: Klevens RM, Edwards JR, Tenover FC, McDonald LC, Horan T, Gaynes R; National Nosocomial Infections Surveillance System. Changes in the epidemiology of methicillin-resistant Staphylococcus aureus in intensive care units in US hospitals, Clin Infect Dis 2006;42: Lee K, Chang CL, Lee NY, Kim HS, Hong SK, Cho HC. Korean nationwide surveillance of antimicrobial. resistance group. Korean nationwide surveillance of antimicrobial resistance of bacteria in Yonsei Med J 2000;41: Boyce JM. Methicillin-resistant Staphylococcus aureus. Detection, epidemiology, and control measures. Infect Dis Clin North Am 1989;3: Huang SS and Platt R. Risk of methicillin-resistant Staphylococcus aureus infection after previous infection or colonization. Clin Infect Dis 2003;36: Yang JA, Park DW, Sohn JW, Yang IS, Kim KH, Kim MJ. Molecular analysis of isoleucyl-trna synthetase mutations in clinical isolates of methicillin-resistant Staphylococcus aureus with low-level mupirocin resistance. J Korean Med Sci 2006;21: Yanagisawa T, Lee JT, Wu HC, Kawakami M. Relationship of protein structure of isoleucyl-trna synthetase with pseudomonic acid resistance of Escherichia coli. A proposed mode of action of pseudomonic acid as an inhibitor of isoleucyl-trna synthetase. J Biol Chem 1994;269: Rahman M, Noble WC, Cookson B, Baird D, Coia J. Mupirocinresistant Staphylococcus aureus. Lancet 1987;2(8555): Bradley SF, Ramsey MA, Morton TM, Kauffman CA. Mupirocin resistance: clinical and molecular epidemiology. Infect Control Hosp Epidemiol 1995;16: Riley TV, Carson CF, Bowman RA, Mulgrave L, Golledge CL, Pearman JW, et al. Mupirocin-resistant methicillin-resistant Staphylococcus aureus in Western Australia. Med J Aust 1994;161: Yun HJ, Lee SW, Yoon GM, Kim SY, Choi S, Lee YS, et al. Prevalence and mechanisms of low- and high-level mupirocin resistance in staphylococci isolated from a Korean hospital. J Antimicrob Chemother 2003;51: Gilbart J, Perry CR, Slocombe B. High-level mupirocin resistance in Staphylococcus aureus: evidence for two distinct isoleucyl-trna synthetases. Antimicrob Agents Chemother 1993;37: Pérez-Roth E, López-Aguilar C, Alcoba-Florez J, Méndez-Alvarez S. High-level mupirocin resistance within methicillin-resistant Staphylococcus aureus pandemic lineages. Antimicrob Agents Chemother 2006;50: Hodgson JE, Curnock SP, Dyke KG, Morris R, Sylvester DR, Gross MS. Molecular characterization of the gene encoding highlevel mupirocin resistance in Staphylococcus aureus J2870. Antimicrob Agents Chemother 1994;38: Kim EC, Jung HJ, Oh MD, Lee HJ, Oh HS, Choe KW. Epidemiological typing of methicillin-resistant Staphylococcus aureus outbreak isolates by pulsed-field gel electrophoresis and antibiogram. Yonsei Med J 1998;39: Yoo JI, Shin ES, Cha JO, Lee JK, Jung YH, Lee KM, et al. Clonal dissemination and mupa gene polymorphism of mupirocin-resistant Staphylococcus aureus isolates from long-term-care facilities in South Korea. Antimicrob Agents Chemother 2006;50: Boyce JM. Preventing staphylococcal infections by eradicating nasal carriage of Staphylococcus aureus: proceeding with caution. Infect Control Hosp Epidemiol 1996;17: Baird D and Coia J. Mupirocin-resistant. staphylococcus aureus. Lancet 1987;2: Walker ES, Vasquez JE, Dula R, Bullock H, Sarubbi FA. Mu-

6 A-jin Lee, et al. : Mupirocin-Resistant S. aureus 23 pirocin-resistant, methicillin-resistant Staphylococcus aureus: does mupirocin remain effective? Infect Control Hosp Epidemiol 2003;24: Harbarth S, Dharan S, Liassine N, Herrault P, Auckenthaler R, Pittet D. Randomized, placebo-controlled, double-blind trial to evaluate the efficacy of mupirocin for eradicating carriage of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 1999;43: Wise R and Johnson J. Mupirocin resistance. Lancet 1991;338 (8766): Orrett FA. The emergence of mupirocin resistance among clinical isolates of methicillin-resistant Staphylococcus aureus in Trinidad: a first report. Jpn J Infect Dis 2008;61: Jones JC, Rogers TJ, Brookmeyer P, Dunne WM Jr, Storch GA, Coopersmith CM, et al. Mupirocin resistance in patients colonized with methicillin-resistant Staphylococcus aureus in a surgical intensive care unit. Clin Infect Dis 2007;45: Song W, Lee TJ, Kim SJ, Park MJ, Lee KM. Methicillin-resistant staphylococcus aureus infections in intensive care unit (ICU) patients: relation to nasal carriage of patients or ICU personnels. Korean J Clin Microbiol 2001;4: Ko KS, Park S, Peck KR, Shin EJ, Oh WS, Lee NY, et al. Molecular characterization of methicillin-resistant Staphylococcus aureus spread by neonates transferred from primary obstetrics clinics to a tertiary care hospital in Korea. Infect Control Hosp Epidemiol 2006;27: Okuma K, Iwakawa K, Turnidge JD, Grubb WB, Bell JM, O'Brien FG, et al. Dissemination of new methicillin-resistant Staphylococcus aureus clones in the community. J Clin Microbiol 2002;40: Malaviolle X, Nonhoff C, Denis O, Rottiers S, Struelens MJ. Evaluation of disc diffusion methods and Vitek 2 automated system for testing susceptibility to mupirocin in Staphylococcus aureus. J Antimicrob Chemother 2008;62: = 국문초록 = 뮤피로신내성황색포도알균의빈도및임상적특성 대구가톨릭대학교의과대학진단검사의학교실이아진, 서헌석, 전창호, 김상경 배경 : 메티실린내성황색포도알균 (MRSA) 의비강정착은원내전파및감염의위험인자로알려져있다. MRSA의비강정착을제거하기위하여국소항생제인뮤피로신이사용된다. 하지만뮤피로신의사용이증가됨에따라뮤피로신내성이전세계적인문제로대두되고있다. 본연구는임상검체에서분리된황색포도알균에서뮤피로신내성의빈도와연관된임상적지표를분석하고자하였고항생제감수성양상을조사하였다. 방법 : 4개월동안의뢰된임상검체중황색포도알균이분리된 175개의균주를대상으로 Vitek2 자동화장비를이용하여뮤피로신내성및그외의항생제감수성검사를시행하였다. 뮤피로신내성을보이는균주모두와뮤피로신감수성을보이는균주를선택하여 mupa 유전자를분석하였다. 균주의임상지표또한조사하였다. 결과 : 175개의황색포도알균중 9.1% (16/175) 가뮤피로신에내성을보였는데 1.7% (3/175) 가고농도내성이었고, 7.4% (13/175) 가저농도내성이었다. 뮤피로신내성을가지는황색포도알균의경우입원기간이길었다 (P=0.026). 뮤피로신에저농도내성을보이는 13개의균주중 11균주가동일한항생제감수성양상을보였다. mupa 유전자는뮤피로신에고농도내성을보이는균주에서만검출되었다. 결론 : 황색포도알균에서뮤피로신내성률이높았다. 뮤피로신내성황색포도알균의전파는원내감염에의한것으로생각된다. [ 대한임상미생물학회지 2011;14:18-23] 교신저자 : 서헌석, , 대구시남구대명 4 동 번지대구가톨릭대학교의과대학진단검사의학교실 Tel: , Fax: hssuh@cu.ac.kr

Lumbar spine

Lumbar spine CT 32 111 DOI : 10.3831/KPI.2010.13.2.111 Lumbar Spine CT 32 Received : 10. 05. 23 Revised : 10. 06. 04 Accepted : 10. 06. 11 Key Words: Disc herniation, CT scan, Clinical analysis The Clinical