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1 Korean J Clin Microbiol Vol. 12, No. 2, June, 2009 A Case of Streptococcus salivarius Meningitis in a Patient with Cerebrospinal Fluid Rhinorrhea after Skull Base Fracture Kyeong Seob Shin 1, Dong Ik Shin 2, Woo Sub Shim 3, Byeong Cheol Rim 4, Il Hun Bae 5, Seung Young Lee 5, Dong Hee Ryu 6, Eun Jung Kim 7, Bo Ra Son 1 Departments of 1 Laboratory Medicine, 2 Neurology, 3 Otorhinolaryngology-Head and Neck Surgery, 4 Neurosurgery, 5 Radiology and 6 Surgery, Chungbuk National University College of Medicine, 7 Department of Pathology, Chungbuk National University Hospital, Cheongju, Korea Streptococcus salivarius meningitis is very uncommon, and most cases are iatrogenic, occurring after invasive procedures such as spinal anesthesia or lumbar puncture etc.. Post-traumatic occurrence of this infection is especially rare. A 20-year-old man with a previous history of skull base fracture was seen at the emergency department with signs of acute bacterial meningitis. The CSF had a few gram positive cocci with neutrophilic pleocytosis, which were identified as S. salivarius by the Vitek system (biomerioux, Inc., Hazelwood, MO, USA), rapid ID 32 Strep (biomerieux, Marcy-l Etoile, France) and 16S rrna sequencing. The microorganism showed intermediate resistance to penicillin (MIC=0.25μg/mL) but was susceptible to cefotaxime (MIC=0.25μg/mL) and vancomycin (MIC= 0.75μg/mL). The patient was treated with ceftriaxone and vancomycin. He also had his CSF leakage repaired by an endoscopic approach. To our knowledge, this is the first case of S. salivarius meningitis reported in Korea. (Korean J Clin Microbiol 2009;12: 92-96) Key Words: Streptococcus salivarius, Meningitis, Skull fracture, Basilar 서 론 증 례 Viridans군연쇄구균인 Streptococcus salivarius는인체의피부, 구강, 상기도, 장관및여성비뇨생식기의상재균으로알려져있다 [1]. S. salivarius를포함하는 viridans군연쇄상구균은흔히균혈증및심내막염을일으킬수있으나, 낮은병원성및뇌척수막에대한낮은친화성등으로인해이들균에의한수막염은드물게발생된다 [2]. S. salivarius 수막염의대부분원인은환자신체내의상재균이며, 다양한침습적시술을통하여감염이발생되나 [3-5], 외상에의한 S. salivarius 수막염은매우드물고 [6,7] 국내에서는아직까지이균에의해발생한어떠한형태의수막염도보고되지않았다. 최근에저자들은두개골기저부골절후 5개월동안지속적인뇌척수액비루가있던 20세남자환자에서 S. salivarius에의한수막염 1예를경험하였기에간단한문헌고찰과함께보고하는바이다. Received 13 January, 2009, Revised 20 February, 2009 Accepted 15 March, 2009 Correspondence: Kyeong Seob Shin, Department of Laboratory Medicine, College of Medicine, Chungbuk National University, San 62, Gaeshindong, Heungduk-gu, Cheongju , Korea. (Tel) , (Fax) , ( ) ksshin@chungbuk.ac.kr 20세남자환자가하루전부터발생한심한두통과수회의반복되는분출구토를주소로응급의학과를방문하였다. 환자는 5개월전에교통사고에의해두개골기저부골절을경험하였으며, 당시에기저부골절은전두동의상부벽, 양쪽안와및양쪽접형동 (sphenoidal sinus) 부위가포함되어있었다. 내원당시체온은 39.5 o C, 혈압 100/60 mmhg, 맥박 98/ 분, 호흡수 22/ 분이었다. 신경학적검사에서의식은명료하였으나경부경직및 Brudzinski s sign 등이관찰되었다. 환자는세균성뇌수막염의의심하에신경과로입원하였다. 입원당시시행한요추천자에서화농성뇌척수액을보였으며, 뇌척수액은백혈구수 23,600/uL ( 호중구 95%), 총단백 4.66 g/l, 그리고포도당 0.01 g/l이었다. 초기에비원침뇌척수액의그람염색과세균항원검사는음성이었으나, 원침뇌척수액의 Wright 염색및그람염색에서호중구의세포질내에서그람양성구균이관찰되었다 (Fig. 1). 24시간배양후혈액한천배지에서회백색의작은균집락이관찰되었으며이들균은 catalase 음성이었고, Vitek 미생물자동동정기 (biomerieux, Inc., Hazelwood, MO, USA) 및 rapid ID 32 Strep (biomerieux, Marcy l Eltoile, Fance) 에서각각 71% (bionumber: ) 및 99.9% 의확률로 S. salivarius로 92

Kyeong Seob Shin, et al. : Post-traumatic S. salivarius Meningitis 93 동정되었으며, 생화학적성상은 Table 1과같았다. 그리고 마크로젠에의뢰한 16S rrna 염기서열분석에서 S. salivarius GenBank AB355616와 99.58% 일치하였다.

응급으로시행한 3 차원안면컴퓨터단층촬영에서전두동상부벽, 양쪽안와및양쪽접형동의천정부위에골절이관찰되었다 (Fig. 2). 세프트리악손과반코마이신을 2주동안투여하였으며, 이어서시행한뇌척수액배양은음성이었다. 이후환자는뇌척수액누출의수술적교정을위해이비인후과로전과되었다.

3 5% 정도로매우드물다 [8]. 또한이들군가운데뇌수막염을일으키는것은 S. salivarius가가장흔한균이나, S. salivarius 수막염의대부분은척수또는경막외마취 [5], 요추부천자그 Table 1.

2 Kyeong Seob Shin, et al. : Post-traumatic S. salivarius Meningitis 93 동정되었으며, 생화학적성상은 Table 1과같았다. 그리고 마크로젠에의뢰한 16S rrna 염기서열분석에서 S. salivarius GenBank AB355616와 99.58% 일치하였다. 이균은 E-test (AB BIODISK, Solna, Sweden) 에의해페니실린에중간내성 (MIC, 0.25μg/mL), 세포탁심 (MIC, 0.25μg/mL) 및반코마이신 (MIC, 0.75μg/mL) 에감수성을보였다. 혈액배양및소변배양에서균은분리되지않았다. 응급으로시행한 3 차원안면컴퓨터단층촬영에서전두동상부벽, 양쪽안와및양쪽접형동의천정부위에골절이관찰되었다 (Fig. 2). 세프트리악손과반코마이신을 2주동안투여하였으며, 이어서시행한뇌척수액배양은음성이었다. 이후환자는뇌척수액누출의수술적교정을위해이비인후과로전과되었다. 수술중두개골기저부골절및뇌척수액누출이좌측전안장부위 (presella area) 에서관찰되었고결손부위는내시경적방법으로 복구되었다. 환자는신경학적이상소견이나증상이없이퇴원하였으며 1년이상재방문기간동안뇌수막염증상이나뇌척수액누출의증거는관찰되지않았다. 고 Viridans 군연쇄구균은흔한패혈증및심내막염의원인균이지만뇌수막염의원인으로는배양으로증명된경우의 0.3 5% 정도로매우드물다 [8]. 또한이들군가운데뇌수막염을일으키는것은 S. salivarius가가장흔한균이나, S. salivarius 수막염의대부분은척수또는경막외마취 [5], 요추부천자그 Table 1. Biochemical reactions of Streptococcus salivarius isolated from this case compared with those reported in literature 찰 Biochemical This Reference[16] reaction case Fig. 1. The findings of Gram stain of cytocentrifuged cerebrospinal fluid. Many neutrophils with gram positive cocci in their cytoplasm were seen ( 1,000). Hemolysis Alpha or none Alpha Catalase Voges-Proskauer + + test Hydrolysis of Esculin + + Arginine Urea V + Production of Alkaline phosphatase V β-glucuronidase H 2O 2 NT Acid from Mannitol Sorbitol + Raffinose + + Inulin V NT Trehalose + (80) + Salicin + NT Starch + (70) NT Glycogen Abbreviations: V, variable; NT, not tested. Fig. 2. Coronal computed tomography scan at the time of head trauma (A) and 5 months later (B). The bony defect in the roof of the sphenoid sinus (vertical arrow) was fairly enlarged compared to the fracture line across the roof of the sphenoid sinus at the time of the head trauma (A).

3 94 Korean J Clin Microbiol 2009;12(2):92-96 리고척수조영술등 [3,4] 과같은의원성에기인한다. 그러나외상후이균에의한뇌수막염의예는극히드문데, 문헌조사에의하면아직까지전세계에서 2예정도가보고되었을뿐이다 [6,7]. 게다가보고된예모두두부-안면부외상후즉시발생한예였으며, 본증례와같이두개골골절후상당히오랜기간후발생한뇌수막염의예는없었다. 국내에서는 S. salivarius에의한뇌수막염의보고자체가아직까지없었는데, 이는 S. salivarius가피부의상재균또는검사실내오염균으로간주되었을가능성을배제할수없다. 두개안면부외상은뇌수막염의주요위험인자중하나이며, Streptococcus pneumoniae가외상에의한뇌수막염의 90% 이상을차지한다 [9]. 국내에서도 S. pneumoniae가외상후뇌수막염의가장흔한예였으며 (6예중 4예 ), 감염된대부분의환자는두개기저부의골절을가지고있었다 (Table 2)[10-14]. 본증례의경우환자는 5개월전에전두동의상부벽, 양측안와및양측접형동부위의골절을포함하는두부안면부외상을경험하였으며사고당시에항경련제및보전적치료만받았다. 사고 5개월후뇌수막염이발생하였고, 즉시촬영한안면부컴퓨터단층촬영에서는접형동의천정부위의골결손이 5개월전사고당시보다커져있어이부위를통하여환자의내인성세균에의한감염으로추정되었다 (Fig. 2). 미생물검사실에서뇌척수액의배양을위한검체량이적어 (1 ml 이하 ) 원심분리하기에부적절한경우가종종있을수있다. 본예에서도배양을위한뇌척수액의검체량이적어 (1 ml 이하 ) 원심분리를하지않고시행한그람염색에서균이관찰되지않았다. 그러나뇌척수액의세포수를세기위한 cytospin 슬라이드의그람염색에서호중구가증가되어있었으며호중구의세포질내에서그람양성구균이관찰되었다 (Fig. 1). 따라서배양을위한검체량이충분하지않을경우 cytospin에의한슬라이드제작방법이유용할수있으며, 호중구가증가되어있을경우에는미생물에대한좀더주의깊은관찰이필요할것으로생각한다. 초기에뇌척수액의 S. pneumoniae에대한라텍스응집검사에서음성을보여 S. pneumoniae 이외의 streptococci 또는 enterococci로추정되었으며, 24시간배양후회백색의균집락은 catalase 음성, bile esculin 음성이었다. 인체에서분리되는 S. salivarius group에는 S. salivarius 및 S. vestibularis가있 으며이들균은서로유사한생화학적성상을보이는데 1) glucose로부터 acetoin의생성 (VP 양성 ), 2) urea의가수분해, 3) mannitol 및 sorbitol에서산의생성, 4) arginine의가수분해등으로이들균이외의 viridans 군연쇄구균과감별할수있다 [15]. 또한 S. salivarius는 H 2O 2 를생성하지못하나 raffinose로부터산을생성하는것으로 S. vestibularis와감별될수있다 [16]. S. salivarius는 sorbitol를발효하는못하는데이증례에서는 sorbitol을발효한다는점에서차이를보였고그외검사결과는일치하였다 (Table 1). Rapid ID 32 Strep은 viridans군연쇄구균의동정에일부균종 (S. mitis 및 S. oralis) 을제외하면종 (species) 수준까지동정이가능하다고알려져있으며 [17], 본예에서도 Vitek system에서 71% 로동정되었으나 rapid ID 32 Strep에서 99.9% 로동정되었다. Viridans 군연쇄구균에서종수준까지의동정은표현학적동정방법으로신뢰할수없는경우가종종있을수있는데이런경우 16S rrna 염기서열분석은이들균의동정에보조적인수단으로유용하게이용될수있다 [15]. 본증례의경우 16S rrna 염기서열분석결과는 S. salivarius GenBank AB355616과 99.58% 일치하였다. Clinical and Laboratory Standards Institute는페니실린에중간내성인 viridans streptococci에의한뇌수막염의경우적절한살균성작용을위하여아미노글라이코사이드제제와혼합치료를권고하고있다 [18]. 본예에서분리된균은페니실린에중간내성이었으나세포탁심과반코마이신에감수성을보였으며, 아미노글라이코사이드제제의투여없이최초경험적으로투여한항균제 ( 세포트리악손과반코마이신 ) 를 2주간투여하였으며, 이후시행한뇌척수액배양은음성이었다. 이어서침습적내시경검사를통하여뇌척수액누출부위가발견되었고내시경적방법으로결손부위가복구되었으며환자는신경학적증상이호전되어퇴원하였다. 결론적으로저자들은흔히오염균으로간주되기도하는 S. salivarius에의해발생한뇌수막염 1예를보고하는바이다. 본예는특이하게도두개기저부골절후에 5개월동안뇌수막염의증상없이지속적인뇌척수액누출을보였을뿐만아니라, 국내에서 S. salivarius에의한뇌수막염의첫보고로여겨진다. 마지막으로뇌척수액에서 S. salivarius가분리된다면임상의는뇌척수강을포함하는침습적시술또는외상과같은선행요인 Table 2. The causative organisms and findings of skull radiology in the cases of posttraumatic bacterial meningitis reported in Korea Patient (age/sex) Causative trauma Radiologic findings Causative agents Reference 9/M Posttraumatic by traffic accident Fracture of basal skull and temporal bone Streptococcus pneumoniae [10] 6/M Posttraumatic by traffic accident Fracture of skull Gram negative bacteria [11] 6/M Posttraumatic by traffic accident Fracture of frontal skull base Streptococcus pneumoniae [12] 43/M Cranial trauma by person Fracture of temporal bone Streptococcus pneumoniae [13] 14/F Cranial trauma by fall down Facture of ethmoid and sphenoid bone Streptococcus pneumoniae [14] 20/M Posttraumatic by traffic accident Fracture of basal skull Streptococcus salivarius This study

4 Kyeong Seob Shin, et al. : Post-traumatic S. salivarius Meningitis 95 을반드시조사할필요가있을것이다. 감사의글 이논문은 2008학년도충북대학교학술지원사업의연구비에의하여연구되었음. 참고문헌 1. Jonhson CC, Tunkel AR. Viridans Streptococci and Group B and G Streptococci. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett s Principles and Practices of Infectious Diseases. 5th ed, London; Churchill Livingstone, 2000: Conte A, Chinello P, Civljak R, Bellussi A, Noto P, Petrosillo N. Streptococcus salivarius meningitis and sphenoid sinus mucocele. Case report and literature review. J Infect 2006;52:e27-e Veringa E, van Bekum A, Schellekens H. Iatrogenic meningitis by Streptococcus salivarius following lumbar puncture. J Hosp Infect 1995;29: Watanakunakorn C and Stahl C. Streptococcus salivarius meningitis following myelography. Infect Control Hosp Epidemiol 1992;13: Trautmann M, Lepper PM, Schmitz FJ. Three cases of bacterial meningitis after spinal and epidural anesthesia. Eur J Clin Microbiol Infect Dis 2002;21: Maeda H, Shinoda G, Kuroki S, Tsutsui T, Kubota M, Haruta T. Streptococcus salivarius meningitis after oral trauma by a skewer: a case report. Kansenshogaku Zasshi 2002;76: Aladag MA, Refik M, Ozerol IH, Tarim O. Post-traumatic Streptococcus salivarius meningitis in a child. Pediatr Int 2007;49: Enting RH, degans J, Blankevoort JP, Spanjaard L. Meningitis due to viridans streptococci in adults. J Neurol 1997;244: Holeckova K, Kolenova A, Lesnakova A, Steno J, Streharova A, Kisa P, et al. Bacterial meningitis after craniocerebral trauma in the community. Neuro Endocrinol Lett 2007;28(Suppl 3): Lim YS, Han CH, Hwang SS, Lee KY, Park LS. A case of recurrent bacterial meningitis with posttraumatic CSF otorrhea. Infect 1994;26: Chang SH, Kim SJ, Kim JS. Recurrent bacterial meningitis secondary to cochlear aplasia, right and acquired cribriform plate defect due to trauma. Korean J Pediatr Inefct Dis 1998;5: Lee KS, Ko Y, Paek KH, Kim JM, Kim YS, Kim CH, et al. Recurrent meningitis due to growing basal skull fracture of orbital roof: a case report. J Korean Neurosurg Soc 1998;27: Yu SW, Kim DR, Kim BJ, Park MK, Kim MJ, Lee DH. A case of recurrent bacterial meningitis associated with traumatic cerebrospinal fluid fistula. Infect 1999;31: Kim EJ, Song MH, Sung TH, Shin SH, Kim SK, Kim HD, et al. A case of pneumococcal meningitis associated with posttraumatic cerebrospinal fluid rhinorrhea. Korean J Pediatr Neurol 2006;14: Murray PR, Baron EJ, et al. eds. Manual of Clinical Microbiology. 9th ed. Washington; American Society for Microbiology; 2007: Coykendall AL. Classification and identification of the viridans streptococci. Clin Microbiol Rev 1989;2: Kikuchi K, Enari T, Totsuka KI, Shimizu K. Comparison of phenotypic characteristics, DNA-DNA hybridization results, and results with commercial rapid biochemical and enzymatic reaction system for identification of viridans group Streptococci. J Clin Microbiol 1995;33: Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; Eighteenth informational supplement. M100-S18. Wayne, PA: Clinical and Laboratory Standards Institute, 2008.

5 96 Korean J Clin Microbiol 2009;12(2):92-96 = 국문초록 = 두개골기저부골절후뇌척수액비루가있던환자에서발생한 Streptococcus salivarius 수막염 1 예 충북대학교의과대학 1 진단검사의학교실, 2 신경과학교실, 3 이비인후과학교실, 4 신경외과학교실, 5 영상의학과학교실, 6 외과학교실, 7 충북대학교병원병리과신경섭 1, 신동익 2, 심우섭 3, 임병철 4, 배일헌 5, 이승영 5, 류동희 6, 김은중 7, 손보라 1 Streptococcus salivarius 수막염은매우드물며보고된대부분의예는척추마취또는요추천자술과같은의인성에기인한다. 외상후이균에의한뇌수막염은특히드물다. 이전에두개골기저골절을당한 20세남자가세균성수막염증상으로내원하였다. 뇌척수액에서호중구가증가되어있었으며그람양성구균이관찰되었다. Vitek 미생물자동동정기, rapid ID 32 Strep 및 16S rrna 염기서열분석에의해 S. salivarius로동정되었으며, 페니실린에중간내성 (MIC=0.25μg/mL), 세포탁심 (MIC=0.25μg/mL) 과반코마이신 (MIC=0.75μg/mL) 에감수성을보였다. 환자는세프트리악손과반코마이신으로치료받았으며, 내시경적수술로뇌척수액누출부위가복구되었다. 이증례는국내에서 S. salivarius에의해발생한뇌수막염의최초보고로여겨진다. [ 대한임상미생물학회지 2009;12:92-96] 교신저자 : 신경섭, , 충북청주시흥덕구개신동산 62 충북대학교의과대학진단검사의학교실 Tel: , Fax: ksshin@chungbuk.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