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1 KMJ Case Report A Case of Infective Endocarditis Occurred during Treatment for Infectious Spondylitis Accompanied by Peptostreptococcus Anaerobius Bacteremia Byung Hee Lee 1, Myung Hee Lee 1, Sook Kyung Oh 1, Ji Young Seo 1, Joon Hoon Jeong 1, Jae Woo Lee 2 1 Department of Internal Medicine, Wallace Memorial Baptist Hospital, Busan, Korea 2 Department of Cardiology, College of Medicine, Kosin University, Busan, Korea Peptostreptococcus Anaerobius 균혈증을동반한감염성척추염치료중발생한감염성심내막염 1 예 이병희 1 이명희 1 오숙경 1 서지영 1 정준훈 1 이재우 2 왈레스기념침례병원내과 1, 고신대학교의과대학순환기내과 2 It is necessary to distinguish between pyogenic and tuberculous spondylitis of infectious spondylitis, if it is pyogenic spondylitis, antimicrobial therapy should be directed against an identified microorganism and clinical assessment should be done at 4 weeks. But if microorganism is a anaerobic bacteria, especially Peptostreptococcus anaerobius, combination antibiotic therapy should be considered bacause it may be a component of mixed infections as a passenger and have abilities to induce abscesses, other bacterial growth as a synergy effect. In addition, echocardiography may be necessary because pyogenic spondylitis is associated with infective endocarditis about 12%. We report a 64-year-old man who was treated for infectious spondylitis accompanied by Peptostreptococcus anaerobius bacteremia, but had to undergo heart surgery because an attack of infective endocarditis with systemic embolism during hospitalization. Key Words: Endocarditis, Peptostreptococcus, Spondylitis 감염성척추염은인구 10만명당 2.4 명정도로드물게발생하는질환으로서병인에기준하여화농성, 육아종성 ( 결핵, 브루셀라, 진균 ), 기생충으로분류하며이중화농성과결핵성이가장흔하다. 1-3 화농성척추염은혈액을통한균의전파가주요한원인으로서빈도별로 Staphylococcus aureus, Enterobacteriaceae, Coagulase negative staphylococci, Streptococci, Enterococci가있고 4% 이내로혐기성세균이있다. 3 혐기성세균중하나인 Peptostreptococcus anaerobius 는그람양성구균으로소 화기관, 구강, 비뇨생식기관에존재하는정상세균총이며뇌, 흉강, 복강부위의농양과혈액, 척수, 관절액, 골수염, 감염성심내막염에서동정되고혼합감염이흔하다. 병원성은명확하게밝혀지지않았지만, 혼합감염의일부로서동반균주의운반체역할을하면서이들균의성장과농양형성을돕는것으로추정하고있다. 이러한혼합감염과함께균주자체의항생제내성문제가있어치료에어려움이있을수있다. 4 저자들은혈액배양에서혐기성세균인 Peptostrepto- Corresponding Author: Joon Hoon Jeong, Department of Internal Medicine, Wallace Memorial Baptist Hospital, Namsan-dong, Geumjeong-gu, Busan , Korea TEL: FAX: jjhoon69@yahoo.co.kr Received: July 10, 2012 Revised: September 14, 2012 Accepted: October 17,

2 coccus anaerobius 가동정되었던감염성척추염환자에서치료과정중전신성색전증을동반한감염성심내막염이발생하여수술적치료를병행하였던 1예를문헌고찰과함께보고하는바이다. 증례 환자 : 박00, 남자, 64세. 주소 : 요통, 하지저림, 발열. 현병력 : 1개월전부터요통이지속되어인근의원에서약물복용과물리치료및한의원에서침술을받았으나호전이없고약 2주전부터발열증상이나타나본원신경외과에입원하였다. 과거력 : 특이소견없었다. 가족력및사회력 : 특이소견없었다. 이학적소견 : 입원당시의식은명료한상태로급성병색을보였으며활력징후는혈압 120/80 mmhg, 맥박 72회 / 분, 호흡수 20회 / 분, 체온 38.0 였다. 양하지로감각및운동기능상특이소견없었으나하지직거상검사상 60도에서양성소견을보였다. 검사소견 : 입원당시일반혈액검사에서혈색소 11.8 g/dl, 백혈구 16,000/mm 3 ( 중성구 : 85%), 혈소판 433,000 /mm 3 였다. 적혈구침강속도 110 mm/hr, C-반응단백 mg/dl 로증가되어있었다. 이외검사에서는특이소견이없었다. 미생물소견 : 입원즉시두쌍의혈액을각각호기성, 혐기성액체배지에담아 BacT/ALERT 3D 자동화혈액배양기에서배양하였다. 호기성배지에서는자라는균이없었고혐기성배지에서균이자라는것이확인되어이를면양혈액한천배지 (sheep blood agar), 초콜릿한천배지 (chocolate agar) 에접종하여 BD GasPak TM EZ Pouch 에담아혐기성조건을만든후 Precision 배양기로배양하였다. 이를통해그람양성구균이확인되었고 Rapid ID 32A (biomerieux, Durham, USA) 로동정하였을때 Peptostreptococcus anaerobius 가확인되었으며 Chromogenic cephalosporin 방법으로 (Cefinase discs, BBL) 감 수성검사를하였을때 beta-lactamase 음성이었다. 방사선소견 : 요추부자기공명영상에서요추 5번, 천추 1번부위로척추염이확인되었다 (Fig. 1). 흉부및복부전산화단층촬영에서심장비대와비장경색이확인되었다 (Fig. 2A). 치료및임상경과 : 감염성척추염을의심하고경험적으로 Cefotaxime (4 g/day), (500 mg/day) 을투여하였고입원 1주째 Peptostreptococcus anaerobius 가확인되어표준치료로권고하고있는 Penicillin G (1,500 만단위 /1일 ) 를처방하고혼합감염가능성이있어 Cefotaxime 을유지하고 은중단하였다. 4주간처방을유지한이후발열은없었고혈액검사에서백혈구 3,600/mm 3 ( 중성구 : 40%), 적혈구침강속도 48 mm/hr, C-반응단백 3.71 mg/dl 로호전되어있었으며혈액배양에서균음전된상태였다. 하지만요통이지속되고자기공명영상을추적확인한결과에서해당병변의호전이없어감별을위해요추 5번부위골편체취후조직검사와함께그람염색, 배양, 항산균염색과배양을시행하였다. 검사 Fig. 1. Spine MRI shows diffuse contrast enhancement of prevertebral soft tissue and endplate at L5-S1 (arrow). 186

Infectious Spondylitis Accompanied by Peptostreptococcus Anaerobius Bacteremia Fig. 2. Septic emboli identified according to imaging modalities (arrow).

(D) CT angiography of femoral artery shows focal segmental occlusion at distal portion of right popliteal artery. Fig. 3. Vegetation on the posterior leaflet of mitral valve (arrow).

3 Infectious Spondylitis Accompanied by Peptostreptococcus Anaerobius Bacteremia Fig. 2. Septic emboli identified according to imaging modalities (arrow). (A) Contrast-enhanced abdominal CT shows wedge shaped low attenuated lesion at spleen. (B) Aggravated state of spleen after 8 weeks. (C) Brain MRI shows acute ischemic infarct in both occipital lobe. (D) CT angiography of femoral artery shows focal segmental occlusion at distal portion of right popliteal artery. Fig. 3. Vegetation on the posterior leaflet of mitral valve (arrow). (A) Transthoracic echocardiographic finding. (B) Transesophageal echocardiographic finding after 4 weeks. 결과에서이상소견이발견되지않았지만결핵성척추염을배제하기힘들다고판단하여입원 5주째부터 4제요법으로항결핵제를복용하고기존 Penicillin G를다시 으로변경하였다. 하지만약물변경 3주후재차발열이나타났고혈액검사에서백혈구 16,300/mm 3 ( 중성구 : 79.4%), 적혈구침강속도 65 mm/hr, C-반응단백 187

4 14.29 mg/dl 로악화되어있었다. 발열이외에구음장애, 시야장애, 복통이동반되었다. 뇌자기공명영상에서양측후두엽과좌측소뇌부위로다발성의급성뇌경색소견이관찰되어혈전용해제 (TPA, tissue plasminogen activator) 를투여하고본원순환기내과에의뢰되었다 (Fig. 2C). 의뢰당시흉부청진상심잡음이들렸고경흉부심초음파검사에서승모판에 10*10 mm 가량의움직임이있는우종과중등도의승모판역류가나타났다 (Fig. 3A). 복부전산화단층촬영에서비장경색이입원당시에비해악화 되어있었고발목-상완지수가우측이 0.58로감소되어있으며대퇴동맥전산화단층촬영에서우측슬와동맥의폐쇄가확인되었다 (Fig. 2B, 2D). 시야장애는색전에의한것이아닌후두부뇌경색에따른신경학적결손에의한것임을확인하였다. 감염성심내막염진단하에세쌍의혈액배양검사를시행하였으나확인되는균주는없었다. 혼합감염, 원내감염, Penicillin G 투여중단에따른 Peptostreptococcus anaerobius 의재활성화와내성균주출현등여러가지가능성이있지만명확하지않아혈액배양음성자연판막 Table 1. Laboratory findings, events and antibiotics administered during hospitalization Date Laboratory findings Antibiotics Events 1 day WBC: 16,000/mm 3 Cefotaxime Neutrophil: 85% ESR: 110 mm/hr CRP: mg/dl 1 week WBC: 11,100/mm 3 Neutrophil: 81.0% ESR: 120 mm/hr CRP: 7.54 mg/dl 5 weeks WBC: 3,600/mm 3 Neutrophil: 40% ESR: 48 mm/hr CRP: 3.71 mg/dl WBC: 16,300/mm 3 8 weeks Neutrophil: 79.4% ESR: 65 mm/hr CRP: mg/dl 12 weeks WBC: 6,300/mm 3 Neutrophil: 54% ESR: 47 mm/hr CRP: 1.75 mg/dl 13 weeks WBC: 9,400/mm 3 Neutrophil: 58% ESR: 65 mm/hr CRP: 1.19 mg/dl 14 weeks WBC: 6,100/mm 3 Neutrophil: 42% ESR: 46 mm/hr CRP: 0.28 mg/dl 15 weeks WBC: 6,100/mm Neutrophil: 56% ESR: 33 mm/hr CRP: 0.14 mg/dl Cefotaxime Penicillin G Cefotaxime HREZ Vancomycin Ciprofloxacin HREZ Vancomycin Ciprofloxacin HREZ Ciprofloxacin HRE Cefixime HRE Cefixime HRE Blood culture (Peptostreptococcus anaerobius) Bone biopsy and culture Infective endocarditis Cerebral hemorrhage Operation (Mitral valve replacement) Discharge WBC, white blood cell; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; H, isoniazid; R, rifampin; E, ethambutol; Z, pyrazinamide

5 Infectious Spondylitis Accompanied by Peptostreptococcus Anaerobius Bacteremia 감염성심내막염과원내감염에중점을두고 Vancomycin (2 g/day), Ciprofloxacin (400 mg/day), (500 mg/day) 로처방을변경하였다. 이와함께수술을계획하였으나혈전용해제투여 2일경과후뇌전산화단층촬영에서좌측전두엽부위로급성뇌출혈소견이관찰되어보류하였고 4주간처방을유지하고추적한뇌전산화단층촬영에서병변은호전되어있었으며혈액검사에서백혈구 6,300/mm 3 ( 중성구 : 54.0%), 적혈구침강속도 47 mm/hr, C- 반응단백 1.75 mg/dl 로호전되고발열은없었다. 하지만경식도심초음파검사에서움직임이있는우종과중등도의승모판역류가남아있어색전재발및심부전진행가능성이높다고판단하고수술적치료를하였다 (Fig. 3B). 절제한우종의조직소견에서급성염증세포침윤이있었으나그람염색및배양에서확인되는바는없었다. 환자는수술후상태호전보여경구용항생제인 Cefixime (200 mg/day) 로유지하고퇴원하였다. 한편, 골편조직의항산균배양검사에서특이소견이없었으나신경외과협진상결핵성척추염가능성을배제하기힘들다고하여총 6개월간복용하였고우측슬와동맥의폐쇄는연관증상이없고시술에대한부담감을호소하여특별한처치없이외래에서경과관찰중이다. 입원기간별항생제처방내역과혈액검사결과는 Table 1에정리하였다. 고찰 감염성척추염중화농성과결핵성은서로다른부문이있다. 먼저화농성척추염은이환기간이평균 1.8 개월이고발열이흔하며검사실소견에서백혈구, 중성구비율, C- 반응단백및적혈구침강속도와같은염증수치가유의하게높고요추부에병변이주로나타나며치료기간은평균 14.7 주이다. 반면결핵성척추염은이환기간이평균 4.3 개월로서발열과염증수치상승이저명하지않고병변이흉추부에호발하며추체의파괴정도가심하고치료기간이 6개월이내일경우재발가능성이있어 12개월을권고한다. 1-3,5,6 이를바탕으로할때, 본증례는화농성일 가능성이높다. 화농성척추염에서혈액배양양성률은평균 58% 이고혼합감염이의심될경우혈액배양양성소견에관계없이골편조직을통한배양검사를시행하며양성률은평균 77% 이다. 5 항생제는동정된균주를바탕으로선택하며배양음성일경우 Staphylococcus aureus 를포함할수있도록선택한다. 5,6 투여 4주째질환평가를하고자기공명영상검사는초기유용성이낮아증상이나염증수치의호전이없는경우에한정해서시행한다. 이는자기공명영상검사의호전소견이치료후반부에나타나기때문으로, 4-8 주째해당검사에서변화가없거나악화가있더라도이들환자의약 85% 에서실제임상증상은호전을보일수있어시술이나약물변경에주의가필요하다. 3,5 또한화농성척추염의약 12% 에서감염성심내막염이동반될수있어위험인자가있거나배양에서이와연관된균주가발견되면심초음파검사로배제가필요하고반대로감염성심내막염환자에서요통을호소할경우화농성척추염동반여부를확인해야한다. 6 본증례에서확인된 Peptostreptococcus anaerobius 는 Penicillin 이적합한항생제로알려져있지만이에대한내성이일부보고되어있고문헌에따라각종항생제에대한효과와내성에편차가있어추가적인연구가필요하다. 4,7-9 환자에서균혈증의요인은치아와잇몸상태가좋지않았던점과한의원에서침술을받은점을들수있으며 Penicillin G 투여에따른반응을볼때질환과연관성이있다고추정된다. 본증례에서입원당시비장경색소견과입원 8주후발생한전신성색전증소견은폐혈성색전 (septic emboli) 에의한것으로판단된다. 8주후소견은심장이기원으로밝혀졌지만입원당시소견은심장초음파검사를하지않아기원이불분명하다. 이러한색전은 Peptostreptococcus anaerobius 가아닌농양형성을유발하는동반균주에의한것일가능성이높다. 하지만초기에골편배양검사가시행되지않았고다른배양검사에서도음성으로나타나밝혀내지못하였다. 치료 8주에발생한 189

6 감염성심내막염의경우도밝혀내지못하였지만혈액배양결과동정된균이없는자연판막심내막염은이전항생제사용이가장흔한요인으로급성경과이면 Staphylococcus aureus, 아급성경과이면 Staphylococcus aureus, Streptococcus, Enterococcus, HACEK (Haemophilus parainfluenzae, H. aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae) 가주요원인균이라는점, Penicillin G, Cefotaxime,, 항결핵제에반응이좋지않았던점, Vancomycin, Ciprofloxacin, 에반응이있었던점, 그리고절제한우종에서균주가발견되지않은점등을고려할때 Staphylococcus aureus 였을가능성이있고 Rifampin 이도움이되었을것으로보인다. 10 이를볼때화농성척추염에서혐기성세균이동정된다면혼합감염가능성을고려하여이에대한추가적인검사와복합적인항생제투여가필요할수있고투여 4주후치료반응평가를할때추가적인검사, 시술그리고약제변경에주의가필요하며감염성심내막염동반여부를확인하기위해심초음파검사를고려해볼수있겠다. 참고문헌 1. Kim YI, Kim SE, Jang HC, Jung SI, Song SK, Park KH. Analysis of the Clinical Characteristics and Prognostic Factors of Infectious Spondylitis. Infect Chemother 2011;43: Koo KH, Lee HJ, Chang BS, Yeom JS, Park KW, Lee CK. Differential Diagnosis between Tuberculous Spondylitis and Pyogenic Spondylitis. J Korean Soc Spine Surg 2009;16: Gouliouris T, Aliyu SH, Brown NM. Spondylodiscitis: update on diagnosis and management. J Antimicrob Chemother 2010;65:iii Murdoch DA. Gram-positive anaerobic cocci. Clin Microbiol Rev 1998;11: Zimmerli W. Clinical practice. Vertebral osteomyelitis. N Engl J Med 2010;362: Cottle L, Riordan T. Infectious spondylodiscitis. J Infect. 2008; 56: Minces LR, Shields RK, Sheridan K, Ho KS, Silveira FP. Peptostreptococcus infective endocarditis and bacteremia. Analysis of cases at tertiary medical center and review of the literature. Anaerobe 2010;16: Könönen E, Bryk A, Niemi P, Kanervo-Nordström A. Antimicrobial susceptibilities of peptostreptococcus anaerobius and the newly described peptostreptococcus stomatis isolated from various human sources. Antimicrob Agents Chemother 2007;51: Lee KY, Chong YS, Jeong SH, Xu XS, Kwon OH. Emerging Resistance of Anaerobic Bacteria to Antimicrobial Agents in South Korea. Clin Infect Dis 1996;23:S The Korean Society of Infectious Diseases, Korean Society for Chemotherapy, The Korean Society of Clinical Microbiology, The Korean Society of Cardiology, The Korean Society for Thoracic and Cardiovascular Surgery. Clinical Guideline for the Diagnosis and Treatment of Cardiovascular Infection. Infect Chemother 2011;43:

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( )Kju269.hwp 만성세균성전립선염모델흰쥐에서 의항염효과 Anti-inflammatory Effect of Lycopene on Chronic Bacterial Prostatitis Rat Model Cho Hwan Yang, Dong Wan Sohn, Yong-Hyun Cho From the Department of Urology, The Catholic University