대한안과학회지 2019 년제 60 권제 6 호 J Korean Ophthalmol Soc 2019;60(6):582-586 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) https://doi.org/10.3341/jkos.2019.60.6.582 Case Report 코리네박테리움맥긴레이각막궤양 Corneal Ulcer Caused by Corynebacterium macginleyi 방소라 1 안민 1,2,3 조남천 1,2,3 유인천 1,2,3 So Ra ang, MD 1, Min hn, MD, PhD 1,2,3, Nam Chun Cho, MD, PhD 1,2,3, In Cheon You, MD, PhD 1,2,3 전북대학교의학전문대학원안과학교실 1, 전북대학교임상의학연구소 2, 전북대학교병원의생명연구원 3 Department of Ophthalmology, Chonbuk National University Medical School 1, Jeonju, Korea Research Institute of Clinical Medicine, Chonbuk National University 2, Jeonju, Korea iomedical Research Institute, Chonbuk National University Hospital 3, Jeonju, Korea Purpose: To report a case of a Corynebacterium macginleyi-infected corneal ulcer of a patient who had been treated for conjunctivitis for more than 3 months. Case summary: 72-year-old female was transferred from a private ophthalmic clinic for evaluation of herpetic keratitis with progressive corneal edema and infiltration in the left eye. She had a history of conjunctival hyperemia and eyeball pain in her left eye 3 months prior to her visit. She was treated with levofloxacin eye drops and acyclovir ointment (Herpesid, Samil, Co., Ltd. Seoul, Korea). On slit lamp examination, 5.4 4.0 mm corneal epithelial defects and stromal infiltrations were observed in the upper to central cornea, and endothelial keratic precipitates were found. Gram positive bacteria were detected on Gram staining and Corynebacterium macginleyi was identified on bacterial cultures from the conjunctiva and cornea. She was treated with topical vancomycin eye drops. fter 3 months of treatment, the corneal ulcer was completely resolved, leaving mild superficial opacity on the cornea. Conclusions: While Corynebacterium macginleyi, normal flora of the conjunctiva, is considered a major causative agent for conjunctivitis and blepharitis, Corynebacterium macginleyi should also be considered a possible cause of slowly progressive keratitis in patients with chronic conjunctivitis. J Korean Ophthalmol Soc 2019;60(6):582-586 Keywords: Corynebacterium macginleyi, Conjunctivitis, Corneal ulcer, Normal flora of conjunctiva 각막궤양은현재까지도주요한실명의원인중하나로바이러스및세균에의해발생할수있으며특히안구의표 Received: 2018. 9. 6. Revised: 2018. 10. 25. ccepted: 2019. 5. 17. ddress reprint requests to In Cheon You, MD, PhD Department of Ophthalmology, Chonbuk National University Hospital, #20 Geonji-ro, Deokjin-gu, Jeonju 54907, Korea Tel: 82-63-250-1965, Fax: 82-63-250-1960 E-mail: you2ic@daum.net * This study was presented as a poster at the 119th nnual Meeting of the Korean Ophthalmological Society 2018. * Conflicts of Interest: The authors have no conflicts to disclose. 면을손상시키는기존의안질환이있을때흔히발생할수있다. 1 초기의적절한진단과치료가중요한데, 세균각막궤양의경우균주의확인과항생제감수성결과가치료에필수적이며원인균에따라감수성있는항생제의적절한사용이중요하다. 코리네박테리움맥긴레이 (Corynebacterium macginleyi) 는 1995년 Riegel et al 2 이처음보고하였으며, 모두결막에서검출된결막상주균으로결막염의원인이되거나다른안구표면질환에서기회감염을일으킨다. 드물게각막염, 안내염이발생한경우가보고되어있으나 3,4 임상적으로현성감염은드물다고알려져있다. 5 또한이균주는페니실린, 퀴놀론, 아미노글리코시드항생제등많은종류의항생제 c2019 The Korean Ophthalmological Society This is an Open ccess article distributed under the terms of the Creative Commons ttribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 582
- 방소라외 : 코리네박테리움맥긴레이각막궤양 1 예 - 에감수성을가지기때문에치료가상대적으로어렵지않지만, 배양검사에서늦게자라며집락이작아흔히보고되지않고있다. 6 과거에도 Corynebacterium macginleyi가안구표면질환이있는환자에서현성감염을일으킬수있다는가능성이제시되어적절한항생제사용에대한논의가이루어진바있다. 5 국내에서는아직까지각막궤양의단독원인균으로 Corynebacterium macginleyi가분리배양된보고가없다. 이에저자들은오랜시간결막염으로치료받은환자에서발생한 Corynebacterium macginleyi 각막궤양 1예가있어이를보고하고자한다. 증례보고 72세여자환자가개인안과에서 3개월전부터양안의잦은충혈과통증으로결막염치료를지속하였으나호전되지않고, 본원내원전부터는좌안의각막부종과각막침윤이생기고악화되어헤르페스각막염의심하에내원하였다. 개인의원에서 levofloxacin 성분의안약을하루 4회씩약 1달가량사용하였으며, 호전이보이지않아 levofloxacin을하루 6회로증량함과동시에 acyclovir 연고 (Herpesid, Samil, Co., Ltd., Seoul, Korea) 를하루 5회씩추가하여 1달을더사용한후전원되었으며, 경구약제복용없이좌안에치료용콘택트렌즈를착용중이었다. 본원내원당시시력은우안 0.6, 좌안 0.02 ( 교정불가 ) 였고, 기저질환으로당뇨와고혈압외특이병력은없었으며, 문진시외상이나이물질이들어간기왕력은없었다. 세극등현미경검사에서좌안결막에심한충혈이있었고각막상부에서중앙부위에걸쳐약 5.4 4.0 mm 크기의상피결손이있었다. 각막상피결손부위를중심으로불규칙한 모양의깊은각막기질의침윤, 경도의전체적인각막부종및데스메막주름을보였으며현저한전방축농은없었으나각막후면의침착물을보였다 (Fig. 1). 반대편눈의각막에도전반적으로경한표층점모양상피병증및실모양체가닥을보였다 (Fig. 2). 이에좌안에대하여그람염색및균도말배양검사를시행하였고, 배양검사결과가나오기전까지헤르페스각막염및세균각막궤양의심하에입원하여 moxifloxacin 점안액 (Vigamox, lcon, Fort Worth, TX, US) 을 1시간간격으로, acyclovir 연고 (Herpesid, Samil, Co., Ltd.) 를하루 5회점안하도록하였으며, 경구복용 acyclovir (clova, KyungDong pharm. Co., Ltd., Seoul, Korea) 를병행하여치료를시작하였다. Moxifloxacin (Vigamox, lcon) 과 acyclovir 연고 (Herpesid, Samil, Co., Ltd.) 를점안하며수일간각막상피결손이호전되는소견을보였으나, 입원 4일째에호전되었던각막상피결손의갑작스러운증가와함께전반적인각막미란과각막혼탁이진행되었다 (Fig. 3). 입원시시행한도말검사에서그람양성균이검출되었으며세균배양검사에서각막및결막검체, 환자가착용하고있던콘택트렌즈, 3곳모두 Corynebacterium macginleyi가배양되어 vancomycin 2.5% 안약을 1시간마다점안하도록하였다. 각막상피결손은점차다시호전되는양상을보여 vancomycin 안약의점안간격을 2시간으로늘리도록하였다. 입원후 8일째에거의완전히각막상피가회복되었다. 상피재생후에도각막의혼탁이지속되어 0.1% fluorometholone (Flumethorone, Santen Pharmaceutical Co., Ltd., Osaka, Japan) 점안액을 4회추가하였으며퇴원시 acyclovir 연고 (Herpesid, Samil, Co., Ltd.) 는중단하고 moxifloxacin (Vigamox, lcon) 은 3시간간격, vancomycin 안약은 4시간간격으로조정후외래경과관찰하였다. 약 10일 Figure 1. Slit-lamp photograph of the left eye at the first visit. () Deep corneal stromal infiltration and diffuse corneal edema were seen. () Corneal epithelial defects in the fluorescein staining were observed. 583
- 대한안과학회지 2019 년제 60 권제 6 호 - 후각막의상태가안정적임을확인하여 vancomycin 안약을중단하고 moxifloxacin (Vigamox, lcon) 과 fluorometholone (Flumethorone, Santen Pharmaceutical Co., Ltd.) 만을각 4회씩유지점안하도록하였다. 치료 2달째, 좌안각막의굴절력은 SPH +1.50 diopter, CYL -3.50 diopter로최대교정시력은 0.4까지회복하였으며, 좌안각막은경한혼탁과 Figure 2. Slit-lamp photograph of the right eye at the first visit. () Mild focal corneal opacity was seen. () Some filaments and mild corneal punctate erosions were seen. Figure 3. Slit-lamp photograph of the left eye at hospital day 4. () Diffuse corneal opacity and keratoprecipitates. () Increased corneal epithelial defects in the fluorescein staining were seen. Figure 4. Slit-lamp photograph of the left eye after 2 months of treatment. (, ) Fully healed corneal epithelium with remained mild corneal opacity were observed. 584
- 방소라외 : 코리네박테리움맥긴레이각막궤양 1 예 - 난시를남기고완전히치료되었다 (Fig. 4). 고찰 본증례의원인균인코리네박테리움맥긴레이 (Corynebacterium macginleyi) 는그람양성간균으로, 지질친화적이고자연환경에흔하게존재하며인체에서는주로피부나점막에정상상재균으로분포하고있다. 7 1995년 Riegel et al 2 이처음보고하였으며, 안구에서는주로결막의표면에분포하고있음이알려져있다. 1 Corynebacterium macginleyi의지질친화적인특성은배양검사에서도나타나는데혈액배지에서는잘자라고초콜릿배지에서는잘자라지않는양상을보인다. 그동안보고된 Corynebacterium macginleyi에의한현성감염은대개정상적인면역체계를가진사람에서는발병력이낮아결막에국한된결막염정도를일으키는것으로알려져있다. 1,3 그러나면역저하자에서는결막염을비롯하여여러기회감염을일으킬수있으며, 인공호흡기의사용및기관절개부위와관련하여전신적인중복감염 (superinfection) 의여러증례들이보고되어있다. 8-10 안과영역에서는 Joussen et al 7 이 10명의결막염환자를대상으로균배양을실시한결과 10명의환자모두에서 Corynebacterium macginleyi를분리배양한바있으며, lsuwaidi et al 11 은특별한외상이나기존의안과적병력없이발생한양안결막염환자에서배양검사상 Corynebacterium macginleyi를보고하였다. 또한최근에는눈꺼풀테염환자에서가장흔히검출되는균주의하나로보고되고있으며, Streptococcus epidermidis, Staphylococcus aureus와함께눈꺼풀테염의발생및병태생리기전에관여한다고하였다. 12 본증례는고령이외의특별한면역저하의병력이없는환자에서 Corynebacterium macginleyi에의한만성적인결막염에의해야기된지속적인안구표면의손상으로정상적인각막의방어기전이파괴되어세균이침투하기쉬운민감한환경에서각막궤양이발생하였을것으로생각된다. 또한항바이러스연고의장기적인사용으로안구표면손상및 toxic medicamentosa로인해상재균인 Corynebacterium macginleyi의각막및결막의기회감염가능성도있다. Corynebacterium macginleyi는대부분의항생제에좋은감수성을보이는데, Espínola et al 6 은결막에서분리한총 33개의 Corynebacterium macginleyi 균주 (strain) 중한개의균주에서는 ciprofloxacin에저항성을보였고두개의균주에서는 tetracyclin에저항성을보였으나, 나머지 30개의균주는검사한모든항생제에감수성을보인다고보고하였다. 반면몇몇보고에서는 erythromycin과 clindamycin에 저항성을보인다고하였고, 7,11 일부보고에서는퀴놀론계항생제에도저항성을보이는경우가많다고하였다. 13 본증례에서는 3개월이상장기간 levofloxacin과 moxifloxacin (Vigamox, lcon) 의사용에도결막병변이호전되지않고각막궤양으로진행하는양상을보였으며, 이후배양검사의결과에따라그람양성균에대한강력한효과를보이는항생제인 vancomycin으로변경후호전되는경과를보였다. 따라서대부분의항생제에감수성을보인다고알려진병원체라하더라도항생제의경험적사용과더불어반드시도말검사와함께배양검사및항생제감수성검사를시행하여치료에이용해야하겠다. 또한배양검사상혈액배지에서서서히자라는그람양성균의경우에는이세균을반드시염두에두어야한다. 결막의정상상재균인 Corynebacterium macginleyi가최근결막염과안검염등의주요원인으로대두되고있는데, 본증례와같이장기간결막염을앓은환자에서안구표면의손상과함께서서히진행하는각막궤양의경우에는원인균으로 Corynebacterium macginleyi 를고려해보는것이치료에도움이되겠다. REFERENCES 1) Ruoff KL, Toutain-Kidd CM, Srinivasan M, et al. Corynebacterium macginleyi isolated from a corneal ulcer. Infect Dis Rep 2010;2:1568. 2) Riegel P, Ruimy R, de riel D, et al. Genomic diversity and phylogenetic relationships among lipid-requiring diphtheroids from humans and characterization of Corynebacterium macginleyi sp. nov. Int J Syst acteriol 1995;45:128-33. 3) Suzuki T, lihara H, Uno T, et al. Suture-related keratitis caused by Corynebacterium macginleyi. J Clin Microbiol 2007;45:3833-6. 4) Ferrer C, Ruiz-Moreno JM, Rodríguez, et al. Postoperative Corynebacterium macginleyi endophthalmitis. J Cataract Refract Surg 2004;30:2441-4. 5) Funke G, Pagano-Niederer M, ernauer W. Corynebacterium macginleyi has to date been isolated exclusively from conjunctival swabs. J Clin Microbiol 1998;36:3670-3. 6) Espínola M, Somodevilla, Domingo D, et al. ntibiotic susceptibility of Corynebacterium macginleyi strains causing conjunctivitis. Rev Esp Quimioter 2010;23:196-200. 7) Joussen M, Funke G, Joussen F, Herbertz G. Corynebacterium macginleyi: a conjunctiva specific pathogen. r J Ophthalmol 2000;84:1420-2. 8) Dias M, Shreevidya K, Rao SD, Shet D. Corynebacterium macginleyi a rare bacteria causing infection in an immunocompromised patient. J Cancer Res Ther 2010;6:374-5. 9) Cacopardo, Stefani S, Cardì F, et al. Surgical site infection by Corynebacterium macginleyi in a patient with neurofibromatosis Type 1. Case Rep Infect Dis 2013:970678. 10) Kebbe J, Mador MJ. Corynebacterium macginleyi: a cause of ventilator associated pneumonia in an immunocompromised patient. Respir Med Case Rep 2015;16:154-6. 585
- 대한안과학회지 2019 년제 60 권제 6 호 - 11) lsuwaidi R, Wiebe D, urdz T, et al. Corynebacterium macginleyi conjunctivitis in Canada. J Clin Microbiol 2010;48:3788-90. 12) ezza enkaouha I, Le run C, Pisella PJ, et al. acterial flora in blepharitis. J Fr Ophtalmol 2015;38:723-8. 13) Eguchi H, Kuwahara T, Miyamoto T, et al. High-level fluoroquinolone resistance in ophthalmic clinical isolates belonging to the species Corynebacterium macginleyi. J Clin Microbiol 2008; 46:527-32. = 국문초록 = 코리네박테리움맥긴레이각막궤양 목적 : 3 개월이상결막염으로치료받은환자에서발생한 Corynebacterium macginleyi 에의한각막궤양 1 예가있어이를보고하고자한다. 증례요약 : 72 세여자가좌안의각막부종및혼탁의진행으로헤르페스각막염의심하에개인안과에서전원되었다. 내원 3 개월전부터좌안의결막충혈과통증을호소하고있었다. Levofloxacin 안약과 acyclovir 연고를사용하고있었다. 세극등현미경검사에서각막상부에서중앙에이르는 5.4 4.0 mm 크기의각막상피결손및기질침윤과함께각막후면의침착물을보여그람염색및배양검사를시행한결과, 결막과각막모두에서그람양성균이검출되고 Corynebacterium macginleyi 가동정되었다. Vancomycin 으로점안치료한후 3 개월째에각막에경한혼탁만을남기고완전히치료되었다. 결론 : 최근결막상주균인 Corynebacterium macginleyi 가결막염과안검염의주요원인균으로대두되고있는데, 장기간결막염을앓은환자에서발생한서서히진행하는각막염의경우에는원인균으로 Corynebacterium macginleyi 를고려해야하겠다. < 대한안과학회지 2019;60(6):582-586> 방소라 / So Ra ang 전북대학교의학전문대학원안과학교실 Department of Ophthalmology, Chonbuk National University Medical School 586