주외막단백 유전자 분석을 이용한 Brucella abortus의 동정

이유지 ( Yu Ji Lee ),고관수 ( Kwan Soo Ko ),박미연 ( Mi Yeoun Park ),오원섭 ( Won Sup Oh ),권기태 ( Ki Tae Kwon ),류성열 ( Seong Yeol Ryu ),허상택 ( Sang Taek Heo ),백경란 ( Kyong Ran Peck ),이남용 ( Nam Yong Lee ),송재훈 ( Jae Ho 대한내과학회 2006 대한내과학회지 Vol.71 No.1

Background: As the incidence of bovine brucellosis increases in Korea, the incidence of human brucellosis is also increasing since 2002. However, it is difficult to identify Brucella species by using the conventional methods. Methods: Three strains of gram-negative coccobacilli were isolated from blood specimens of three patients with prolonged fever, which were not identified by using the conventional methods. After extracting total DNA from these isolates, PCR amplification of 16S rRNA and omp2 genes was performed. These sequences secured by PCR assay were compared with known sequences by using GenBank BLAST. Results: DNA sequences were obtained from 3 isolates by using PCR amplification of 16S rRNA. These sequences had more than 99.9% similarities with Brucella species by using GenBank BLAST. In the second place, after comparing DNA sequences secured by PCR amplification of omp2a and omp2b by using GenBank BLAST, these isolates were confirmed as B. abortus. Conclusions: DNA sequence analysis is a rapid and accurate method for identification of uncommon microorganisms, such as Brucella species.(Korean J Med 71:10-16, 2006)

감염성 심내막염 환자에서 16S rRNA 유전자 염기서열 분석을 통한 Gemella 동정 2예

손경목 ( Kyung Mok Sohn ),고관수 ( Kwan Soo Ko ),김정 ( Jeong Kim ),이지영 ( Ji Young Rhee ),오원섭 ( Won Sup Oh ),백경란 ( Kyong Ran Peck ),송재훈 ( Jae Hoon Song ) 대한내과학회 2006 대한내과학회지 Vol.70 No.5

Q열로 진단된 불명열 3예

허상택 ( Sang Taek Heo ),박미연 ( Mi Yeoun Park ),최영실 ( Young Sill Choi ),오원섭 ( Won Sup Oh ),고관수 ( Kwan Soo Ko ),백경란 ( Kyong Ran Peck ),송재훈 ( Jae Hoon Song ) 대한내과학회 2008 대한내과학회지 Vol.74 No.1

Q열은 국내에서도 드물지 않은 질환으로 생각되며, 조기에 진단하지 못하는 경우에 심내막염이나 혈관염 등의 만성 Q열로 진행하여 사망에 이를 수 있다. 물론 급성 Q열은 비특이적 증상에서 폐렴이나 간염 소견으로 내원하는 환자가 대부분이나 발열의 원인이 확실한 경우 원인균이 밝혀지지 않아도 Q열의 혈청학적 의뢰를 요하는 경우는 흔하지 않다. 하지만 발열을 주소로 내원한 환자들에 대하여 상기 증례들처럼 불명열의 경우 가축이나 이들의 부산물에 접촉력이 있는 경우 뿐만 아니라 특별한 접촉력이나 직업력이 없더라도 불명열로 내원한 환자들의 감별진단에서 Q열의 가능성을 고려하여 혈청학적 검사 및 핵형 분석을 시행해야 하겠다. 향후 국내에서도 사람뿐만 아니라 가축에서의 대규모의 역학적 조사가 추가적으로 필요할 것으로 생각된다. Q fever is an orthozoonotic infection caused by Coxiella burnetii, which was recently reclassified from the order Rickettsials to the order Legionellales. Although Q fever is usually mild and self-limiting, it may be manifested as a serious disease, such as pneumonia, endocarditis, or meningoencephalitis. We describe three separate cases of acute Q fever, which were diagnosed by an indirect micro-immunofluorescence assay (MIFA) test and DNA amplification (PCR). Three adult patients were admitted between December 2004 and August 2006 because of a fever of greater than three weeks duration. Only one patient had contact history with a dog. Of the three patients, two patients had myalgia, headache, skin rash, lymphadenopathy, and hepatosplenomegaly. Although all sets of blood cultures were negative, anti-phase II antibody titers by using an indirect MIFA (IgG 1:512-1,024 and IgM 1:320) were markedly increased in sera from all of three patients. Concomitant PCR assays also demonstrated the presence of OMP com1 for C. burnetii in blood from all of the three patients. Two patients had complete resolution of symptoms and signs with a two-week course of doxycycline, while one patient had spontaneous defervescence. Although the incidence of Q fever is not well known yet in Korea, it should be considered in the differential diagnosis of patients with fever of unknown origin. (Korean J Med 74:100-105, 2008)

다발성 골수종 환자에서 척추염을 동반한 브루셀라 심내막염

강용운 ( Yung Un Kang ),정영선 ( Young Sun Jung ),박경화 ( Kyung Hwa Park ),정숙인 ( Sook In Jung ),신종희 ( Jong Hee Shin ),안병희 ( Byung Hee Anh ),고관수 ( Kwan Soo Ko ) 대한내과학회 2008 대한내과학회지 Vol.74 No.5

Brucella endocarditis is a rare complication, but it is responsible for the majority of deaths related to this illness. A 67 year-old man presented with complaints of fever and lower back pain that he had experienced during the previous four weeks. The laboratory finding showed pancytopenia and an inverted total protein/globulin ratio. Multiple myeloma was diagnosed by bone marrow biopsy and serum electrophorosis. The spine MRI scan demonstrated spondylitis with epidural abscess (L5-S1). On the echocardiographic examination, there was vegetation on the right coronary cusp of the aortic valve and perivalvular abscess. The blood isolate was confirmed as Brucella abortus by using DNA sequencing of the 16S rRNA and the omp2a and omp2b genes. The clinical manifestations improved after appropriate antibiotics and aortic valve replacement. We describe here the first Korean case of human brucella endocarditis that was treated by valve replacement.(Korean J Med 74:561-565, 2008)

Clostridium difficile 연관 설사에 대한 metronidazole의 치료효과

정혜숙 ( Hae Suk Cheong ),김종규 ( Jong Kyu Kim ),임태규 ( Tae Kyu Lim ),권기태 ( Ki Tae Kwon ),류성열 ( Seong Yeol Ryu ),허상택 ( Sang Taek Heo ),고관수 ( Kwan Soo Ko ),오원섭 ( Won Sup Oh ),백경란 ( Kyong Ran Peck ),이남용 ( Nam 대한내과학회 2007 대한내과학회지 Vol.72 No.6

Background: The rate of treatment failure with metronidazole for C. difficile-associated diarrhea (CDAD) has been recently increasing in Western countries. A retrospective study was performed to evaluate the clinical outcome of metronidazole treatment and determine the risk factors for treatment failure for patients with CDAD in Korea. Methods: From January 2000 to May 2005, patients who had shown a positive result for C. difficile toxin A assay in feces were considered for the study. Patients who had diarrhea and one or more symptoms of fever, abdominal pain or leukocytosis after 48 hours of hospitalization were included. The medical records of the patients and laboratory data were reviewed. Results: A total of 476 patients (mean age, 56.7 years old) were enrolled in the study. Of these, 382 patients (80.3%) were treated with metronidazole as an initial regimen for CDAD; 316 patients (82.7%) received successful treatment within 14 days, 29 patients (6.3%) had persistent symptoms and signs of colitis and 37 patients (9.7%) had a recurrence of symptoms and signs within 4 weeks after completion of treatment. There were no significant differences in the rates of treatment success for each 5-year period (p>0.05). Among 66 patients who failed to respond to an initial course of metronidazole, 48 patients underwent prolonged or additional courses of metronidazole treatment. Of these, 34 patients (70.8%) were successfully treated. By multivariate analysis, severe diarrhea (p=0.02), prior use of fluroquinolones (p=0.02) and enteral tube feeding (p=0.02) were the risk factors for treatment failure of CDAD with metronidazole. Conclusions: Contrary to a recent survey in Western countries, metronidazole is still useful as a primary regimen for the treatment of patients with CDAD in our institution. In CDAD patients with tube feeding, severe diarrhea or the prior use of quinolones, precautions for treatment failure should be taken. (Korean J Med 72:639-646, 2007)

증례 : 감염 ; 건강한 사람에서 메티실린 내성 황색포도알균에 의한 삼첨판 심내막염

박평균 ( Pyoeng Gyun Park ),강승지 ( Seung Ji Kang ),박경화 ( Kyung Hwa Park ),정영선 ( Young Sun Jung ),정숙인 ( Sook In Jung ),신종희 ( Jong Hee Shin ),고관수 ( Kwan Soo Ko ) 대한내과학회 2009 대한내과학회지 Vol.76 No.1S

다이어트 약물 치료 후 Candida guilliermondii에 의한 칸디다 혈증

임민희 ( Min Hee Lim ),허상택 ( Sang Taek Heo ),배인규 ( In Gyu Bae ),정용근 ( Yong Geun Jeong ),김현옥 ( Hyun Ok Kim ),고관수 ( Kwan Soo Ko ),김선주 ( Sun Joo Kim ) 대한내과학회 2009 대한내과학회지 Vol.77 No.2

Candida guilliermondii is found in sea water, animal feces, buttermilk, and beer and has been isolated from human infections, mostly of cutaneous origin. It usually causes skin and soft tissue infections and has decreased susceptibility to fluconazole. Systemic infections occur mostly in immunocompromised patients. A 38-year-old female was admitted with a 4-day fever. Her cal and family histories were unremarkable, except for obesity. She had been taking diet pills for 3 months and had undergone injection therapy into her abdomen for lipolysis for 1 month. She did not respond to empirical antibiotics. A Candida species was isolated from blood cultures and identified as C. guilliermondii based on partial LSU rRNA gene sequence analyses. She was treated with amphotericin B, and recovered completely. (Korean J 77:251-254, 2009)

건강한 사람에서 메티실린 내성 황색포도알균에 의한 삼첨판 심내막염

박평균 ( Pyoeng Gyun Park ),강승지 ( Seung Ji Kang ),박경화 ( Kyung Hwa Park ),정영선 ( Young Sun Jung ),정숙인 ( Sook In Jung ),신종희 ( Jong Hee Shin ),고관수 ( Kwan Soo Ko ) 대한내과학회 2009 대한내과학회지 Vol.76 No.8

아시아 지역 폐렴 구균의 항균제 내성 현황 및 변화 양상 : Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study

정숙인,김나영,손준성,기현균,고관수,서지연,장현하,김연숙,오원섭,백경란,이남용,송재훈,항생제 내성 감시를 위한 아시아 연합 (ANSORP) 대한감염학회 2004 감염과 화학요법 Vol.36 No.1

목적 : 1980년대부터 페니실린을 비롯한 β-lactam 계열과 비 β-lactam 계열 항균제에 대한 폐렴구균의 항생제 내성이 급격하게 증가하여 국내 뿐 아니라 세계적인 문제로 대두되고 있다. ANSORP 에서는 아시아 지역에서 폐렴구균의 항균제 내성과 그 변화 추이, 내성의 기전 및 위험인자를 분석하고자 본 국제 공동 연구를 시행하였다. 재료 및 방법 : 1999년 11월부터 2001년 8월까지 아시아 지역 12개국의 14개 기관에서 폐렴구균 감염증 환자의 임상 검체로 분리된 침습성 폐렴구균을 대상으로 액체배지 미량희석법을 이용하여 16개 항생제의 MIC를 구하였다. 위험인자의 분석을 위하여 폐렴구균 감염증 환자를 대상으로 의무기록지를 조사하였다. Quellung 반응을 통해 혈청형을 결정하였다. 결과 : 총 685균주 중 52.4%가 페니실린에 대하여 비감수성(중등도 내성 22.9%, 내성 29.5%)을 보였고, 그 빈도는 베트남(92.1%), 스리랑카(85.7%), 홍콩(67.9%), 한국(64.5%)의 순이었다. Erythromycin에 대한 비감수성 비율은 베트남(92.1%), 대만(87.7%), 한국(80.6%), 홍콩(76.8%) 등에서 높게 나타났고, 베트남, 대만, 한국, 홍콩 등의 erythromycin의 MIC_(90)이 32㎍/mL를 넘는 고도내성을 보였다. 홍콩, 싱가포르, 대만, 인도에서는 fluoroquinolone에 대한 내성 균주가 출현하였다. 전체 균주 중 다제내성 균주의 비율은 47.7%였다. 혈청형은 19형과 23형이 가장 많았고, 그 외 6형, 14형 등이 있었다. 페니실린 비감수성 감염증의 위험인자로는 5세 미만(OR=1.7; 95%, CI, 1.2-2.4; P=0.002), 기관지폐질환(OR=2.0; 95%, CI, 1.3-3.1; P=0.003), 악성종양(OR=2.3; 95%, CI, 1.2-4.6; P=0.015), 스테로이드의 사용(OR=2.8; 95%, CI, 1.1-7.4; P=0.032)이 확인되었다. 결론 : 침습성 폐렴구균 균주를 대상으로 한 본 연구의 결과 아시아 국가들에서 페니실린, β-lactam 및 macrolide에 대한 폐렴구균의 내성률 및 내성 정도가 급증하고 있음을 확인하였다. Background : Emergence of pneumococcal resistance became a global issue since 1990s. According to the ANSORP studies with clinical isolates and carriage isolates between 1996 and 1999, some Asian countries showed alarmingly high prevalence of resistance to penicillin and other antimicrobial agents. To investigate the changing trends of pneumococcal resistance, ANSORP study group has performed a multinational surveillance study with invasive pneumococcal isolates from Asian countries. Methods : All isolates from various invasive pneumococcal diseases were prospectively collected from 14 centers in 12 countries between November 1999 to August 2001. Broth microdilution tests with 16 antimicrobial agents were performed according to the NCCLS procedures. Serotyping was performed by means of Quelling reaction with use of group-specific antisera. Results : A total of 685 isolates were collected. Overall, 52.4% of invasive isolates from Asian countries were not susceptible to penicillin (intermediate (1), 22.9%, Resistant (R), 29.5%). Vietnam showed the highest prevalence of penicillin non-susceptibility (1 20.6%, R 71.4%) followed by Sri Lanka (1 71.4%, R 14.3%), Hong Kong (1 24.1%, R 76%) and Korea (1 9.7%, R 54.8%). China (I 19.8%, R 23.4%) and Malaysia (1 9.1%, R 29.5%) also showed remarkable increase in penicillin resistance compared with previous ANSORP data, which were less than 10%. Vietnam (92.1%), Taiwan (87.7%), Korea (80.6%), and Hong Kong (76.8%) showed high prevalence of erythromycin resistance. MIG_(90)S for ciprofloxacin were 4 ㎍/mL (Hong Kong) and 2 ㎍/mL (11 Asian countries except Hong Kong), respectively. Conclusion : Compared with previous data from ANSORP studies, antimicrobial resistance among invasive pneumococcal isolates has markedly increased in Vietnam, Sri Lanka, Taiwan, China, and Malaysia. Continuous surveillance of pneumococcal resistance in Asia is strongly warranted.

국내 5개 3차 병원의 β-lactam계 항생제 사용 실태 및 Klebsiella pneumoniae의 항생제 내성과의 상관 관계

정숙인,박경화,권기태,고관수,오원섭,정두련,백경란,염준섭,장현하,김신우,손준성,송재훈 대한감염학회 2007 감염과 화학요법 Vol.39 No.4

Background : This study was performed to evaluate the prescribing pattern of β-lactam antibiotics and the relationship between antimicrobial resistance and antimicrobial use in 5 tertiary care hospitals in Korea. Materials and Methods : Data on annual patient-days and annual consumption (defined daily dose (DDD) per 100 patient-days) of β-lactam antibiotics from 2003 to 2005 in 5 tertiary hospitals were analyzed. To determine the antimicrobial resistance in K. pneumoniae, broth microdilution test and double disk synergy were performed according to the CLSI performance standards. Spearman's correlation coeffient was used to determine the relationship between antibiotic consumption and resistance. Results : The prescription of β-lactam antibiotics in 5 tertiary hospitals markedly varied. In two hospitals, increase in consumption of β-lactam antibiotics was more than 30% during recent 3 years. The higher consumption of β-lactam antibiotics significantly correlated with the higher rate of antibiotic-resistant K. pneumoniae in 5 tertiary care hospitals. Conclusion : Continuous surveillance of antibiotic use is needed to encourage appropriate prescribing of antibiotics and to reduce antibiotic resistance. 목적 : 항생제의 오남용으로 인한 내성균의 발현 및 급속한 확산이 전세계적으로 문제시 되고 있다. 특히 병원은 항생제 내성의 중심점에 있는 것으로 여겨진다. 본 연구에서는 최근 3년간 국내 5개 3차 병원의 β-lactam계 항생제의 사용량을 조사하고, 각 병원별 항생제 사용량과 K. pneumoniae의 항생제 내성률과의 상관관계를 알아보고자 하였다. 재료 및 방법 : 국내 5개 3차 병원에서 2003년 1월부터 2005년 12월까지 병원 입원 환자를 대상으로 연도별 재원연인원수와 각 β-lactam계 항생제의 총사용량을 수집하여 DDD (defined daily dose) per 100 patient-days로 환산하여 비교하였다. 2005년 6월부터 8월까지 각 병원의 임상검체에서 동정된 K. pneumoniae를 수집하여 액체배지미량희석법으로 항생제 감수성 검사를 시행하였고 ESBL(extended-spectrum β-lactamase) 생성 여부는 double disk synergy test를 시행하였다. 항생제 사용량과 내성의 상관관계는 Spearman 상관관계 분석을 시행하였다. 결과 : 5개 병원 중 3개 병원에서는 연도별 β-lactam계 항생제 사용량이 비슷하게 유지되었으나, 2개 병원에서는 2003년에 비해 2005년에 항생제 사용량이 30% 이상 증가하였다. β-lactam계 항생제 중 제제별 비율은 각 병원마다 차이가 있었으나, 3세대 cephaosporin의 사용이 가장 많았고 2세대 ceaphlosporin, β-lactam/β-lactamase inhibitor, 1세대 cephalosporin 순이었다. 경구용 β-1actam계 항생제의 사용량(r=0.900, P<0.037)과 2세대 cephalosporin의 사용량(r=0.900, P<0.037)은 각각 K. pneumoniae의 ESBL 생성과 양의 상관관계가 있었다. Ceftazidime의 사용량은 K. pneumoniae의 ceftazidime 내성률과 양의 상관관계가 있었다(r=0.900, P<0.037). 반면 imipenem의 사용량은 piperacillin/tazobactam 내성과 음의 상관관계가 있었다(r=-0.900, P<0.037). 결론 : 최근 3개년간 항생제 사용량은 병원별로 차이가 있으나 일부 병원에서는 증가하였다. β-lactam계 항생제의 사용량은 K. pneumoniae의 항생제 내성과 상관관계가 있었다. 항생제 사용을 줄임으로써 항생제 내성을 감소시킬 수 있을 것으로 기대되며, 병원별로 항생제 사용에 대한 지속적인 감시가 필요할 것이다.