Original Article ISSN 975-745(Print) / ISSN: 88-06X(Online) http://dx.doi.org/777/kjutii.04.9..93 Korean J Urogenit Tract Infect Inflamm 04;9():93-98 0-03 년카테터유무에따른요로에서분리된효모의양상 류재형, 김태형, 권오주, 이미경 중앙대학교의과대학비뇨기과학교실, 진단검사의학교실 Profiles of Yeast Isolated from Urinary Tracts with and without Catheter during 0-03 Jae Hyung Ryu, Tae-Hyoung Kim, Oh Joo Kweon, Mi-Kyung Lee Departments of Urology and Laboratory Medicine, Chung-Ang University College of Medicine, Seoul, Korea Purpose: Indwelling urinary catheter is considered the most important risk factor for healthcare-associated urinary tract infection (UTI). The aim of the current study was to compare the prevalence of species distribution and susceptibilities of antifungals against clinical isolates of yeasts from funguria with and without urinary catheter. Materials and Methods: We analyzed 45,839 urine specimens collected from patients between 0 and 03. Species identification and antifungal susceptibility test to amphotericin B, fluconazole, voriconazole, and flucytosine were performed using the VITEK system (Biomérieux Inc.). Results: A total of,048 (.9%) urine specimens were yeast culture positive. The most frequent species was Candida albicans (49.0%), followed by C. tropicalis (8.6%), C. glabrata (.%), and Trichosporon asahii (7.%). C. tropicalis was isolated more frequently in catheterized urine than in voided urine (p<5). For C. albicans and C. glabrata, frequencies of non-susceptible to fluconazole or voriconazole were higher in catheterized urine than in voided urine. Conclusions: The results of this study suggest the possibility that urinary catheter may influence species distribution of yeast and antifungal susceptibilities. Further investigation is warranted to improve infection control strategies for healthcare-associated UTI. Keywords: Urinary tract infections; Urinary catheters; Yeasts; Microbial sensitivity tests Copyright 04, Korean Association of Urogenital Tract Infection and Inflammation. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution 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. Received: 8 October, 04 Revised: 7 October, 04 Accepted: 0 October, 04 Correspondence to: Mi-Kyung Lee Department of Laboratory Medicine, Chung-Ang University Hospital, 0, Heukseok-ro, Dongjak-gu, Seoul 56-755, Korea Tel: +8--699-79, Fax: +8--698-8630 E-mail: cpworld@cau.ac.kr 서 론 요로감염은무증상세균뇨, 신우신염, 방광염등의다양한 증상을나타내는질환으로, 최근침습성의료시술의증가, 노인인구의증가, 항균제사용과내성균의증가, 당뇨등의만성질환및면역저하환자의증가등으로인해지속적으로 93
94 Jae Hyung Ryu, et al. Yeasts from Urinary Tracts, 0-03 발생하고있다., 요로감염은병원감염 (hospital-acquired) 의 40-45% 를차지하고있으며, 항균제내성세균의전파와의료관련 (healthcare-associated) 패혈증의주요원인이될수있다. 또한병원감염에의한요로감염의약 80% 는요로카테터와관련되고있어, 카테터관련요로감염 (catheter-associated urinary tract infection, CAUTI) 은병원에서발생하는요로감염에서가장흔하고중요하다. 3 CAUTI의발생은관외의경로로카테터삽입시초기에직접균이접종되거나카테터삽입이후에회음부에있던균이카테터의외부표면을통하여상행하거나또는폐쇄배출체계 (closed drainage system) 의기능상실이나소변수집낭 (collection bag) 의오염으로인해소변이방광으로역류하여발생하는관내경로로설명되기도한다. 4 요로감염의원인균은지역이나병원에따라차이는있지만장내세균이가장많으며, 특히 Escherichia coli가가장높은빈도로분리되는것으로알려져있다. 그외에도 Enterococcus species (spp.), Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter spp., Proteus mirabilis, Staphylococcu spp. 및칸디다종 (Candida spp.) 등이많이분리되는것으로조사되었다.,5,6 사람에서정상상재균으로존재하는칸디다종은진균에의한요로감염의가장흔한원인균이며, 대부분의임상의들은진균에의한요로감염을칸디다종에의한요로감염으로인식하고있다. 7 진균에의한요로감염의빈도증가도광범위항생제투여, 요로유치카테터, 당뇨, 면역억제제투여, 장기입원, 고령, 여성, 정맥내카테터, 수술력등의위험인자와관련이있으며, 특히광범위항생제투여나지속적요로카테터삽입환자에서요로감염의위험이높은것으로보고되었다. 7-9 그러므로요로감염의원인균으로지속적으로분리되고있고특히의료관련요로감염의주요원인균으로그중요성이증가하고있는소변내효모의균종과항진균제내성양상은지역이나병원, 기간에따라차이가있을수있으므로그양상을감시하는것이중요하다. 이에본연구에서는 0 년부터 03 년까지소변배양에서분리된효모의양상을분석하고자, 요로카테터유무에따른효모의균종분포와항진균제감수성양상을조사하였다. 대상및방법 0년 월부터 03년 월까지중앙대학교병원임상미생물검사실에의뢰된소변배양검체 45,839건을대상으로후향적으로조사하였다. 채뇨는자가배뇨가가능한경우아침첫요를채취하는것을권장하고중간뇨를무균용기에채취하도록하였고 ( 중간뇨 ), 요로카테터를사용할경우카테터끝을알코올로닦은 후멸균주사기로채뇨하였다 ( 카테터뇨 ). 0 효모의균종동정은발아관시험또는 VITEK ID-YST 시스템 (BioMérieux Inc., Hazelwood, MO, USA) 을이용하여제조사의지침에따라시행하였다. 항진균제감수성시험은 VITEK- 시스템의 VITEK AST-YS0 (Biomérieux Inc.) 카드를이용하여시행하였으며, amphotericin B, fluconazole, voriconazole 과 flucytosine의 4가지약제를시험하였다. 각항진균제감수성검사결과는반응이끝난후 VITEK-의 Advanced Expert System software version VT-R03.0에의해자동판독후출력되었으며, 최소억제농도 (minimum inhibitory concentration, MIC) 는 Clinical and Laboratory Standards Institute (CLSI) 의기준에따라판정하였다., 즉, amphotericin B에대한감수성과내성은 MIC 가각각 μg/ml 이하와 μg/ml 이상으로판정하였다. Candida albicans, C. parapsilosis, C. tropicalis의 fluconazole과 voriconazole에대한감수성은 MIC 가각각 μg/ml 이하와 0. μg/ml 이하, 약용량의존감수성 (susceptible dose dependent, SDD) 은 4 μg/ml와 - μg/ml, 그리고내성은 8 μg/ml 이상과 μg/ml 이상으로판정하였고, 이외효모의 fluconazole과 voriconazole 에대한감수성은 MIC가각각 8 μg/ml 이하와 μg/ml 이하, SDD는 6-3 μg/ml와 μg/ml, 그리고내성은 64 μg/ml 이상과 μg/ml 이상으로판정하였다. Flucytosine의경우는 MIC가 4 μg/ml 이하면감수성, 8-6 μg/ml 사이면중간내성, 3 μg/ml 이상이면내성으로판정하였다. 통계적분석은 Statcalc (Epi Info version 3.5., Centers for Disease Control and Prevention, Atlanta, GA, USA) 을사용하여 chi-square 검증을하였으며, p<5를통계적으로유의한것으로판정하였다. 결과 0년부터 03년까지총 45,839건 ( 중간뇨 3,799건과카테터뇨 4,040 건 ) 의소변배양이의뢰되었고, 중간뇨의 34 검체 (34/3,799, %) 와카테터뇨의 94검체 (94/4,040, 6.5%) 에서효모가분리되어총,048검체 (,048/45,839,.9%) 에서배양양성결과를나타내었다. 균종분포는 C. albicans가가장많았고 (54균주, 49.0%), C. tropicalis (95균주, 8.6%), C. glabrata (8균주,.%), Trichosporon asahii (75균주, 7.%) 의순으로분리되었다 (Table ). 요로카테터유무에따른효모의분리비율은 C. tropicalis는카테터뇨에서, C. glabrata는중간뇨에서통계적으로유의하게높은빈도로분리되었다 (p<5; Table ). 통계적으로유의한차이를보이지는않았지만 C. albicans와 C. utilis는카테터뇨에비해중간뇨에서더많이분리되었고 T. asahii,
Jae Hyung Ryu, et al. Yeasts from Urinary Tracts, 0-03 95 C. famata 및 C. parapsilosis는중간뇨에비해카테터뇨에서더많이분리되었으며, 특히 C. parapsilosis는중간뇨에서는한균주도분리되지않았다 (Table ). 총,048 균주의효모에대한 amphotericin B, fluconazole, voriconazole과 flucytosine의 MIC는각각 μg/ml, μg/ml, - 4 μg/ml, - 64 μg/ml로분포하였으며, 균종별로차이를보였다. 의 Table. Species distribution of yeast isolates of urinary tract infections according to the specimen sampling technique Organisms (isolates no.) Candida albicans (54) C. tropicalis (95) C. glabrata (8) Trichosporon asahii (75) C. famata (5) C. utilis (43) C. parapsilosis () Cryptococcus laurentii (8) C. lusitaniae (5) C. krusei (3) C. guilliermondii () C. kefyr () Unidentified () Total (,048) *p<5. Isolates, n (%) Catheterized Voided urine urine 73 (55.3) 5 (.4) 4 (8.) 9 (6.8) 4 (3.0) 6 (4.5) (0.8) (0.8) (0.8) 34 (00) 44 (48.) 80 (9.7) 04 (.4) 66 (7.) 47 (5.) 37 (4.0) (.4) 8 (0.9) 4 () (0.) (0.) (0.) (0.) 94 (00) p-value 8 8* 3* 0.83 8 0.85 69 7 0.68 0.86 경우 T. asahii 4균주및 C. glabrata와 C. kefyr 각각 균주를제외한모든균종에서감수성이었다. 에대하여 SDD인균주는 C. albicans 6균주, C. krusei 균주및 C. tropicalis 균주였으며, 내성인균주는 C. albicans 와 T. asahii 가각각 균주였다. 에대하여 SDD인균주는 C. glabrata 6균주, C. albicans와 T. asahii가각각 균주였으며, 내성인균주는 C. albicans와 C. glabrata가각각 균주였다. Flucytosine 에대해서는 T. asahii 6균주, C. albicans 3균주및 C. krusei 균주가중간내성을보였고, C. albicans 8균주가내성이었다 (Tables, 3). 요로카테터유무에따른항진균제감수성결과는일부균종에서차이를보였다. 즉 C. albicans의경우중간뇨에서분리된균이 fluconazole 과 voriconazole에 00% 감수성인데비해, 카테터뇨에서분리된균은 fluconazole에 96.0%, voriconazole 에 99.3% 의감수성률을보였다. 또한 C. glabrata 의경우중간뇨에서분리된균이 voriconazole 에 00% 감수성인데비해, 카테터뇨에서분리된균은 voriconazole에 94.3% 의감수성률을보였다 (Tables, 3). 고찰 요로감염은외래와입원환자모두에서일생을통하여가장흔하게나타나는감염의하나로, 007년미국에서외래환자의 Table. Antifungal susceptibilities of 34 yeast isolates from voided urine specimens Species (isolates no.) Antifungal agent MIC (μg/ml) MICs by category (%) Range MIC 50 MIC 90 S SDD/I a R Candida albicans (73) C. tropicalis (5) C. glabrata (4) Trichosporon asahii (9) Others (3) Total (34) - - - 6 - - 64 - -8 - -6-6 - 64-8 0. 6 64 4 0 0 0 94.6 0 0 0 0 0 0 0 0 88.9 88.9 0 88.9 0 9.3 0 9.3 99.3 98.6 0 95.5.7. 7.7 7.7 3.0 MIC: minimum inhibitory concentration, S: susceptible, SDD: susceptible dose dependent, I: intermediate, R: resistant. a :For flucytosine, the available data do not permit the MIC results to be clearly categorized as either "susceptible" or "resistant"..7...5
96 Jae Hyung Ryu, et al. Yeasts from Urinary Tracts, 0-03 Table 3. Antifungal susceptibilities of 94 yeast isolates from catheterized urine specimens Species (isolates no.) Antifungal agent MIC (μg/ml) MICs by category (%) Range MIC 50 MIC 90 S SDD/I a R Candida albicans (44) C. tropicalis (80) C. glabrata (04) Trichosporon asahii (66) C. famata (47) C. utilis (37) C. parapsilosis () Others (7) Total (94) -6-4 -4-6 -4 - -8-4 - - -6-8 -4 0. 8 6 4 4 0 96.0 99.3 98. 0 99.4 0 0 99.0 0 94.3 0 95.5 98.5 98.5 93.9 0 0 0 0 0 0 0 0 0 0 0 0 94. 94. 0 88. 99.6 99.3 98.9 98.6 3.6 0. 0. 0.6 3.8.5 6. 5.9 5.9.8 MIC: minimum inhibitory concentration, S: susceptible, SDD: susceptible dose dependent, I: intermediate, R: resistant. a :For flucytosine, the available data do not permit the MIC results to be clearly categorized as either "susceptible" or "resistant"..6.0.9 4.5.5 0.3 0.9% 가요로감염으로병원을방문한것으로조사되었다. 3 또한 004년스위스의증상이있는입원환자를대상으로한연구에서는외래환자에비해훨씬높은빈도로요로감염이발생하였으며, 4시간이상카테터를삽입하고있는환자에서는 3.7%, 카테터를하지않은환자에서는 0.9% 에서요로감염이발생한것으로보고되었다. 4 최근국내의중환자실에대한전국병원감염감시체계결과보고에서는요로감염이병원감염의 53% 를차지하였고이들요로감염의 99% 가요로카테터와관련이있으며, 이들환자들로부터분리된균주의 44.% 가진균임을보고한바있다. 5 그러나아직까지는국내에서요로감염에대한병원과지역에따른역학정보, 특히진균의균종분포나항진균제감수성양상에관한자료가부족한상태이다. 이에본연구에서는 0년부터 03년까지요로카테터유무에따른소변분리효모의균종분포와항진균제감수성양상을조사함으로소변배양에서분리된효모의양상을분석하고자하였다. 본연구에서는총 45,839건의소변검체중.9% 에서효모가분리되었고, 카테터뇨에서의분리율 (6.5%) 이중간뇨에서의분리율 (%) 보다훨씬높았다. 이는진균에의한의료관련감염의독립적위험인자중의하나인유치요로카테터의영향으로생각할수있으며, 최근의조사에의하면유럽 66개병원환자의 7.5%, 6 미국 83개병원환자의 3.6% 가요로카테터를삽입하고있는것으로나타나 7 유치요로카테터의효과적인관리가의료관련요로감염을예방하고조절하는데매우중요할것으로생각되었다. 소변배양에서분리된효모의균종은 C. albicans가가장많았고 (49.0%) 그다음으로 C. tropicalis (8.6%), C. glabrata (.%), T. asahii (7.%) 의순으로분리되었다. 요로에서분리된칸디다종의균종분포는대부분의연구에서 C. albicans를가장많은원인균으로보고하였으며, 6,8,9,5,8 일부연구에서는 C. tropicalis가가장흔히분리되는것으로보고하기도하였다. 9,0 또한본연구에서 5번째로많이분리된 C.
Jae Hyung Ryu, et al. Yeasts from Urinary Tracts, 0-03 97 famata는치즈, 음식물, 환경등에존재하며사람에서는약 0.-% 의빈도로분리되고있는비교적흔하지않은균으로알려져있다. 8, 그러나최근자동화장비를사용한효모의균종동정에서일부칸디다균종이 C. famata로잘못동정되고있음이보고되어, 실제 C. famata의분리빈도는더낮을것으로생각되고있다. 즉다국가다기관감시연구를통해수집한 C. famata 33균주를염기순서분석등의여러가지방법으로다시동정하였을때 C. famata로동정된균주는없었고 C. guilliermondii (9균주), C. parapsilosis (4균주), C. orthopsilosis (균주), C. metapsilosis (균주) 로각각최종동정되었다. 그러므로본연구에서분리동정된 C. famata도다른칸디다종일가능성이높으며, 정확한균종분포확인을위하여추후보관된균주를대상으로추가적인방법으로확인할필요가있겠다. 한편요로카테터유무에따른효모의분리율을조사한결과, 중간뇨에비해요로카테터에서채취한소변에서 C. albicans와 C. glabrata를제외한대부분의효모가상대적으로더높은빈도로분리되었고, 특히 C. tropicalis 분리율이통계적으로유의하게높았으며 (p<5) C. parapsilosis는중간뇨에서는한균주도분리되지않았다. 반대로 C. albicans와 C. glabrata는카테터뇨보다중간뇨에서더높은비율로분리되었고, 특히 C. glabrata는통계적으로유의한차이를보였다 (p<5). 이는 C. tropicalis가다른균종에비해강한 biofilm 형성능 과요로카테터표면에대한부착능 3 을가진것과관련이있을것으로추측할수있다. 칸디다균종분포의변화는조사기간, 지역및병원에따라발생할수있으며, 특히이전항진균제에노출유무가주요인자로생각되고있다. 또한항진균제노출이외에도면역억제, 미숙, 중증질환, 광범위항생제치료, 고령등의다양한인자들이칸디다균종분포를변화시킬수있는것으로알려져있어, 4 본연구에서나타난중간뇨와카테터뇨에서효모의균종분포차이를정확하게분석하기위해서는항진균제나광범위항생제투여등과같은균종분포에영향을줄수있는인자들에대한조사와장기간에걸친효모의균종분포에대한감시가필요할것으로사료되었다. 효모에대한항진균제감수성검사는표준화된검사법이개발되어있고일부균종에대해서는판독기준도제시되어있다. 현재칸디다종에대한항진균제감수성검사의판독기준은임상적으로항진균제치료효과를예측하는데중요한정보가되고있으며, 항진균제감수성결과가항진균제치료에대한의사결정에서의역할이증가하면서최근에는좀더신속하게결과를보고하는방법과칸디다에사용하는전신성항진균제에대한종특이기준도제시되어있다.,5 본연구에서소변분리효모의 amphotericin B, fluconazole, voriconazole 과 flucytosine 에대한항진균제감수성결과는지금까지알려 진균종별항진균제감수성결과와유사하였다. 요로카테터유무에따른항진균제감수성은일부균종에서차이를보였는데, 카테터뇨에서분리된 C. albicans와 C. glabrata의 fluconazole 또는 voriconazole 비감수성비율이중간뇨에서분리된균에비해높게나타났다. 이는요로카테터를삽입하고있는환자들이대부분중증환자이거나수술등의침습성시술또는항진균제치료를받았을가능성이높아, 중간뇨에비해카테터뇨에서분리된균이 fluconazole과 voriconazole 에대한비감수성비율이높아졌을것으로추측된다. 그러므로요로카테터유무가효모의균종분포와항진균제감수성양상에영향을줄가능성이있으므로, 요로카테터등의요로감염의위험인자와관련한환자의임상양상, 역학정보, 이들에서분리되는효모의균종분포및항진균제감수성양상에대한지속적인감시가필요할것으로생각된다. 결론 요로감염은의료관련감염에서매우중요하며, 특히 CAUTI 는병원에서발생하는요로감염에서가장흔하고중요하다. 진균에의한요로감염은흔히칸디다종에의한요로감염으로인식되고있으며, 최근이들감염의빈도가지속적으로증가하고있다. 본연구에서는 0년부터 03년까지소변배양에서분리된효모중 C. albicans가가장많았고 (49.0%), 요로카테터유무에따른효모의분리비율은 C. tropicalis 카테터뇨에서, C. glabrata는중간뇨에서통계적으로유의하게높은빈도로분리되었다. 요로카테터유무에따른항진균제감수성은카테터뇨에서분리된 C. albicans 와 C. glabrata의 fluconazole 또는 voriconazole 비감수성비율이중간뇨에서분리된균에비해높게나타났다. 그러므로의료관련감염을감소시키기위한전략을향상시키기위해서는 CAUTI를조절하는것이필요하며, 이를위해서는요로카테터를삽입하고있는환자의임상양상, 역학정보, 이들에서분리되는효모의균종분포및항진균제감수성양상등에대한지속적인감시가필요할것으로생각된다. CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported. REFERENCES. Foxman B. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am 04;8:-3.
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