Korean J Lab Med 2010;30:20-7 DOI /kjlm Original Article Clinical Microbiology Comparison of the Efficacies of Silver-Containing D

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1 Korean J Lab Med 2010;30:20-7 DOI /kjlm Original Article Clinical Microbiology Comparison of the Efficacies of Silver-Containing Dressing Materials for Treating a Full-Thickness Rodent Wound Infected by Methicillin-resistant Staphylococcus aureus Jong Hoon Lee, M.D. 1, Jeong Don Chae, M.D. 2, Dong Gu Kim, M.D. 1, Sung Hee Hong, M.D. 1, Won Mi Lee, M.D. 3, and Moran Ki, M.D. 4 Departments of Plastic and Reconstructive Surgery 1, Laboratory Medicine 2, and Pathology 3, Eulji University School of Medicine, Eulji General Hospital, Seoul; Department of Preventive Medicine 4, Eulji University School of Medicine, Daejeon, Korea Background : Methicillin-resistant Staphylococcus aureus (MRSA) may cause infections during wound dressing. We aimed to compare the antibacterial activities and wound-healing effects of commercially available silver-coated or silver-impregnated wound dressings on MRSA-infected wounds. Methods : Full-thickness skin defects were made on the back of rats (N=108) and were infected with MRSA. The rats were divided into the following 6 groups according to the dressing used for the wounds: nanocrystalline silver (Acticoat ), silver carboxymethylcellulose (Aquacel -Ag), silver sulfadiazine (Medifoam silver ), nanocrystalline silver (PolyMem silver ), silver sulfadiazine (Ilvadon ), and 10% povidone iodide (Betadine ). We analyzed the wound sizes, histological findings, and bacterial colony counts for the groups. We also inoculated the silver materials on Mueller-Hinton agar plates containing MRSA and compared the inhibition zones in the agar plates. Results : The order of the rate of wound-size decrease was Acticoat >Aquacel -Ag>PolyMem silver >Medifoam silver >Ilvadon >Betadine. The histological findings revealed that the Acticoat showed more reepithelialization and granulation tissue formation and less inflammatory cell infiltration than the other materials. The order of the time required for wound healing was Acticoat >Aquacel -Ag>PolyMem silver >Ilvadon >Medifoam silver >Betadine. The bacterial colony counts reduced in all the groups, except in the Medifoam silver group. The order of the size of the inhibition zone was Acticoat >Aquacel -Ag>Ilvadon >PolyMem silver >Betadine >Medifoam silver. Conclusions : Silver-coated or silver-impregnated wound dressings can be used for treating MRSAinfected wounds. Considering its superior efficacy in comparison to the efficacies of other silver-coated or silver-impregnated wound dressings, Acticoat should be preferentially used for the treatment of MRSA-infected skin wounds. (Korean J Lab Med 2010;30:20-7) Key Words : Methicillin-resistant Staphylococcus aureus, Skin defect, Infection, Silver dressing 서 균주에따른적절한드레싱제제를선택하는것은상처치료에중요한과제이다. 1961년영국에서처음으로 methicillin-resistant Staphylococcus aureus (MRSA) 가동정된이후, 국내에 Received : February 16, 2009 Manuscript No : KJLM Revision received : October 12, 2009 Accepted : October 30, 2009 Corresponding author : Jeong Don Chae, M.D. Department of Laboratory Medicine, Eulji University School of Medicine, Eulji General Hospital, Hagye 1-dong, Nowon-gu, Seoul , Korea Tel : , Fax : chaejdon@hanmail.net 론 서도 MRSA 감염은증가하였으며, 상처치료시 MRSA는많은문제를발생시키는원인이되고있다 [1-3]. MRSA에사용될수있는드레싱방법중은 (silver) 함유드레싱제제를이용한방법을고려할수있는데은은고대로부터상처나화상치료에이용되었고수세기전부터궤양이나만성상처를치료하기위해국소적요법으로사용되고있으며넓은범위의항균력을지닌것으로알려져있다 [4]. 현재사용되고있는은함유드레싱제제들중각각의효과에대한보고는있으나은함유드레싱제제들의효과를서로비교한보고는적다. 이에저자들은 MRSA를접종한 Mueller-Hinton 배지에은함유드레싱제제들을붙여항균력정도를비교하였고, 흰쥐의 20

2 Silver Dressing of MRSA-infected Wounds 21 배부에형성한전층피부결손에 MRSA를접종시켜감염을유발한상처에은함유드레싱제제들을처치한군과임상에서일반적으로사용되고있는베타딘으로처치한대조군에서상처치유효능을비교함으로써향후 MRSA에효과적인드레싱제제의개발에대한초석을마련하고자하였다. 균을 0.1 ml씩점적하고, 2 2 cm 크기의바셀린거즈로상처를충분히덮어 MRSA균의성장을촉진하고상처의건조를막게하였다. 바셀린거즈위는투명한방수접착필름 (Opsite ; Smith & Nephew, London, UK) 으로밀봉한후테이프로고정하였다. 재료및방법 1. 실험재료 1) 실험동물생후 8주된 g Sprague-Dawley계암컷흰쥐 108 마리를생활조건을같게하여실험대상으로사용하였다. 2) 실험균주표준균주로 MRSA ATCC 43300을사용하였으며, 균부유액은 0.5 McFarland 탁도로맞추어사용하였다. 3) 실험제제은함유드레싱제제로는 nanocrystalline silver (Acticoat ; Smith & Nephew Healthcare, Hull, England), silver carboxymethylcellulose (Aquacel -Ag; ConvaTec, Bristol-Myers Squibb Company, Skillman, NJ, USA), silver sulfadiazine (Medifoam silver ; Biopol, Seoul, Korea), nanocrystalline silver (PolyMem silver ; Ferris, IL, USA), silver sulfadiazine (Ilvadon ; Ildong Pharm. Co. Ltd., Seoul, Korea) 그리고대조군으로베타딘 10% (Povidone iodide; Sungkwang Pharm. Co. Ltd., Bucheon, Korea) 을사용하였다. 2. 실험방법 1) Mueller-Hinton 배지에서드레싱제제별항균효과측정 Mueller-Hinton 배지 6개에 MRSA 표준균주를 0.5 Mc- Farland 탁도로맞추어접종한후위 6가지드레싱제제의거즈를 cm 크기로붙여 37 에서 24시간배양한후판독하였다. 항균효과는억제대의크기로비교하였다. 2) 흰쥐배부상처유도후균접종 108마리쥐들을마취시킨다음배부에있는털을제거한후알코올로소독하고 1 1 cm 크기의전층피부결손상처를만들었다. 만들어진상처에 0.5 McFarland 탁도로맞추어 MRSA 3) 드레싱종류별상처처치상처에균을접종하고 24시간후에 108마리의쥐를 18마리씩 6군으로나누어 Acticoat (Ac), Aquacel -Ag (Aq), Medifoam silver (M), PolyMem silver (P), Ilvadon (I), 베타딘 (B) 으로각각처치하였다. 필름을제거한후 Ac 군, Aq군, M군과 P군은 cm 크기로상처에드레싱제제를부착하였고, I군과 B군은같은크기의거즈에같은정도로약제를발라상처에부착하였다. 그후거즈를덮어필름으로밀봉한뒤테이프로고정하였다. 드레싱은 3일뒤인상처유발 4일째부터 3일간격으로같은방법으로시행하였다. 4) 상처면적측정상처유발후 4일째, 7일째그리고 10일째에소독된투명필름을상처에대고상처의경계를따라그린후스캔하여영상분석프로그램인 Image Tool Version 2.01 Alpha 4 (Microsoft Corporation, Redmond, WA, USA) 를이용하여측정하였다. 기준면적으로 1 1 cm 크기의정사각형을스캔하여면적을측정하였다. 측정한면적을 cm 2 로환산한후, 상처유발 1일째면적을 100% 로하고백분율로환산하여그변화를비교하였다. 4 일째에는각그룹별로 18마리씩, 7일째에는 12마리씩, 10 일째에는 6마리씩이대상이되었다. 5) 상처조직검사상처유발후 4일째, 7일째그리고 10일째에 3마리씩실험동물을희생시켜주변의상처조직과상처전체가포함되도록조직을채취하였다. 채취한조직을 10% 포르말린용액에 6시간이상고정한후 hematoxylin-eosin 염색을시행하여광학현미경하에서재상피화정도, 육아조직증식, 괴사및염증의정도를관찰하였다. 상처조직검사소견의정도에따라정량화하여비교하였다. 재상피화, 육아조직증식의형성정도를각각 0부터 3까지나누어수치화하였는데재상피화나육아조직증식이전혀형성되지않은경우를 0, 재상피화나육아조직증식이형성되지못한결손부분이 2/3 이상이면 1, 1/3-2/3이면 2, 1/3 이하인경우를 3으로하였다. 괴사및염증정도는 0부터 -3 까지나누어수치화하였고, 정상피부와같이괴사및염증이없는상태를 0으

22 Jong Hoon Lee, Jeong Don Chae, Dong Gu Kim, et al. 로정하고중성구와같은염증세포가군락형성이없이세포형태로만부분적으로나타나면 -1, 군락이뚜렷하지않고작은군락형태나세포형태로혼재되고있는상태를 -2, 큰군락을이루고있는상태를 -3 으로하였다.

3 22 Jong Hoon Lee, Jeong Don Chae, Dong Gu Kim, et al. 로정하고중성구와같은염증세포가군락형성이없이세포형태로만부분적으로나타나면 -1, 군락이뚜렷하지않고작은군락형태나세포형태로혼재되고있는상태를 -2, 큰군락을이루고있는상태를 -3 으로하였다. 재상피화, 육아조직증식정도각질층및상피층의괴사및염증정도의정량화된수치를합산한값을 -6 에서 6으로범위를정하였고값이클수록상처치유효과가좋은것으로가정하였다. 6) 상처세균배양상처유발후 4일째, 7일째그리고 10일째에 3마리씩실험동물을희생시켜개방상처의조직을생검하여균을배양하였다. 생검한조직중 1 g을조직혼합기 (tissue homogenizer) 로처치한후인산염완충식염수용액 0.5 ml를넣어 1,500 rpm으로 5분간원심분리하여세척하였다. 이러한세척과정을한번더반복하였다. 세척된현탁액을혈액한천배지에 ml 접종한후35 에서 24시간동안배양한후세균집락수를측정하였다. 3. 통계처치종류별항균효과에대한비교는일원배치분산분석 (oneway ANOVA test) 을시행하였고, 일별, 처치종류별상처면적변화에대한비교는이원배치분산분석 (two-way ANOVA test) 을시행하였다. 처치종류에따른상처조직검사결과와상처의세균배양비교는대상자수가적어서비모수검정방법인 Kruskal-Wallis test를시행하였다. 통계분석소프트웨어는 SPSS (SPSS for Windows 14.0, SPSS Inc., Chicago, IL, USA) 를이용하였다. 결과 1. Mueller-Hinton 배지에서드레싱제제별항균효과 M군을제외하고모든군에서억제대가관찰되어감수성이있는것으로나타났다 (Fig. 1). 6개배지에서억제대크기의순위는 Ac, Aq, I, P, B, M군의순서로모두같았고, 억제대의평균크기는 Ac군에서가장크게나타나 Ac 제제가가장항균력이좋은것으로나타났다 (Fig. 2). 각드레싱제제별억제대평균치의차이는통계적으로유의하였다 (One-way ANOVA, P<0.000). 2. 상처면적변화모든군에서시간이지남에따라상처면적이감소하였고 Ac, Aq, P, M, I, B군의순으로감소하였다. 7일째 6개군의상처면적의차이가유의하게나타났다 (two-way ANOVA, P<0.001) (Fig. 3). 3. 상처조직검사일자별관찰결과, 모든기간에서재상피화및육아조직형성 2.50 Aq Ac Fig. 1. Antibacterial effect of silver-based dressing materials in Mueller-Hinton agar. The antibacterial effect was evaluated by measuring the growth-inhibition zones on the agar plate. After 24 hr, additional inhibition zones were observed along the edges of the dressing material. Abbreviations: Ac, Acticoat ; Aq, Aquacel -Ag; P, PolyMem silver ; M, Medifoam silver. P M Diameter of restricted zone (mm) Ac Aq P M I B Dressing group Fig. 2. Error bars indicating the standard deviation for the antibacterial effects of silver dressing materials (Acticoat [Ac], Aquacel - Ag [Aq], PolyMem silver [P], Medifoam silver [M], Ilvadon [I], and Betadine [B] groups) in Mueller-Hinton agar. Statistically significant differences were observed among the groups (oneway ANOVA, P<0.001).

Silver Dressing of MRSA-infected Wounds 23 을보였고염증세포침윤이감소되어있는것으로나타났다 (Fig. 4).

상처치유효과는모든군이대조군인 B군보다좋았으며, 순위는 Ac, Aq, P, I, M군의순으로나타났다 (Fig. 5). Wound size change (%) 80.00 60.00 40.00 20.00 0.

Error bars indicating the standard deviation for wound size change (%) according to the day and type of wound

groups). The differences among the groups were statistically significant (two-way ANOVA, P<0.001). 4.

드레싱그룹별세균수의차이는통계적으로유의하였다 (Kruskal-Wallis test, P<0.001) (Fig. 6).

MRSA에감염된상처의치료에항생제를전신적으로투여하는방법이있으나이균은페니실린결합단백질 (penicillinbinding protein, PBP) 의변형으로인하여 b-lactam 항생제와 macrolide,

4 Silver Dressing of MRSA-infected Wounds 23 을보였고염증세포침윤이감소되어있는것으로나타났다 (Fig. 4). 4, 7, 10일째에모든그룹에서상처치유효과점수가증가하였고, 치유효과를정량화한수치를비교한결과군간에유의한차이가있었다 (Kruskal-Wallis test, P<0.001). 상처치유효과는모든군이대조군인 B군보다좋았으며, 순위는 Ac, Aq, P, I, M군의순으로나타났다 (Fig. 5). Wound size change (%) P Aq Ac M I B Day Fig. 3. Error bars indicating the standard deviation for wound size change (%) according to the day and type of wound dressing (Acticoat [Ac], Aquacel -Ag [Aq], PolyMem silver [P], Medifoam silver [M], Ilvadon [I], and Betadine [B] groups). The differences among the groups were statistically significant (two-way ANOVA, P<0.001). 4. 상처세균배양군별로세균수는시간이지날수록감소하였으나 Ac, Aq군은처음부터매우적었고, 그다음은 P, I군의순이었다. M군은대조군인 B군보다세균수가많았으나 10일째에는차이가없어졌다. 드레싱그룹별세균수의차이는통계적으로유의하였다 (Kruskal-Wallis test, P<0.001) (Fig. 6). 고찰 MRSA는병원내감염으로인한난치성폐렴, 심내막염이나균혈증을유발하여치명적인위협이될뿐아니라외과적수술부위나욕창, 화상, 당뇨발등연조직결손부에감염을일으킨다 [5, 6]. MRSA에감염된상처의치료에항생제를전신적으로투여하는방법이있으나이균은페니실린결합단백질 (penicillinbinding protein, PBP) 의변형으로인하여 b-lactam 항생제와 macrolide, clindamycin, tetracycline, aminoglycoside 등다른계열의항생제에서도내성을보인다 [5-7]. 또다른문제점은만성감염의경우만성육아조직성상처로인해항생제가충분히침투되지않고, 당뇨병이나고혈압등의합병증을동반하여혈관장애가있거나심한개방성골절등으로혈관손상이동반된경우충분한항생제가상처부위까지도달하지못해 Acticoat group Aquacel -Ag group PolyMem silver group Medifoam silver group Ilvadon group Betadine group Fig. 4. Histological findings in each group (hematoxylin and eosin stain, 200) at 10 days.

5 24 Jong Hoon Lee, Jeong Don Chae, Dong Gu Kim, et al. 5 Ac Aq M Grade (mean) P I M B Colony count (mean) B I P Aq Ac Day Day Fig. 5. Mean wound-healing grade by day and dressing groups (Acticoat [Ac], Aquacel -Ag [Aq], PolyMem silver [P], Medifoam silver [M], Ilvadon [I], and Betadine [B] groups). The differences among the groups were statistically significant (Kruskal-Wallis test, P<0.001). Fig. 6. Mean number of colonies ( 10 5 CFU/mL) by day and dressing groups (Acticoat [Ac], Aquacel -Ag [Aq], PolyMem silver [P], Medifoam silver [M], Ilvadon [I], and Betadine [B] group). The differences among the groups were statistically significant (Kruskal- Wallis test, P<0.001). 국소치료가중요하다 [6]. 저자들은 MRSA에대해국소적으로효과를보이는것으로알려진은을함유한다양한드레싱제제들의 MRSA에대한항균효과및상처치유효과를베타딘을대조군으로비교하였다. 은은 Ag 107 과Ag 109 의두개의동위원소가비슷한비율로자연에존재하며 Ag 1+, Ag 2+ 와Ag 3+ 의세가지산화상태가있고 Ag + 만이의료기구나의료용품의항균제용도로사용하기에안정하다 [8]. 은금속과대부분의은화합물은물, 체액, 조직삼출물과반응하여이온화됨으로써항균력이있는 Ag + 또는다른형태의생물학적활성은이온을유리하거나인접한생체조직에흡수된다. 은이온은단백질과음이온에강한결합력이있으며인접세포, 세균과진균표면의수용체군과도결합한다 [9]. 은성분이병원성미생물을효과적으로죽이기위해서는은이온을유리해야만한다. 은이온은항생제내성균을포함한광범위한미생물에대해살균작용을나타내며균에작용하는부위가다양하고매우저농도로작용하기때문에내성균이나타날확률이매우낮은것으로보고되고있다 [10-12]. 은을함유한드레싱제제로개발되어사용된것으로질산은과 silver sulfadiazine이있는데질산은은조직에대한자극현상을유발하여상처치유를오히려지연시키는단점이있어 1960년대이후에는주로 silver sulfadiazine이사용되어왔다 [13]. Silver sulfadiazine은 1968년화상상처에이용된이후현재도많이사용되고있으나이를상처부위에적용하였을때상처의삼출액에의해은성분이비활성화되기때문에드레싱을자 주교환하여야하는불편함이있으며상처를착색시키거나자극할수있고가성가피를형성하기도하며빠르게불활성화되는단점이있다 [13, 14]. 본연구에서도 Ilvadon (silver sulfadiazine) 은대조군인베타딘에비해 MRSA에대해항균력과상처치유에효과적인것으로나타났으나가성가피가형성되고착색의양상을보였으며 Medifoam silver 를제외한다른드레싱제제들에비해서항균력및상처치유효과가떨어지는양상을보였다. 본연구에서폴리우레탄폼드레싱제제인 Medifoam silver 와 PolyMem silver 도포함하였다. 기존의폴리우레탄폼드레싱제제는상처표면의습윤환경을유지하면서상처에서나오는삼출액을흡수하여상피세포의이동을빠르게하여재상피화를촉진시킨다는장점이있으나항생물질이없어감염된상처의적용에제한이있고가피의분해및분리를빠르게진행시키지못하는단점이있다 [15-17]. Medifoam silver 는기존의 Medifoam 제제에 silver sulfadiazine을첨가하여환부접촉면에도포한것으로흡수력을높이기위해 Medifoam 제제의접촉층을없애고대신흡수층에존재하는폴리우레탄미세구멍의크기를 mm 로작게하여상피세포가미세구멍안으로자라들어가지못하므로상처에붙지않게하였고 silver sulfadiazine 을미세구멍안에녹여넣어항균효과가나타나도록하였다 [18]. 그러나본연구에서는 MRSA에대한항균효과가 silver sulfadiazine뿐만아니라베타딘보다더적은것으로나타났으며상처치유효과에있어서도상처면적의감소는 silver

6 Silver Dressing of MRSA-infected Wounds 25 sulfadiazine보다빠른것으로나타났지만상처의조직검사에서는염증양상이더많아상처치유효능이떨어지는것으로나타났다. 이것은 silver sulfadiazine 농도와폼드레싱제제의흡수력과의상관관계에대해좀더고려할필요가있다고사료된다. 즉, silver sulfadiazine의농도를높이면감염예방에는좋겠지만흡수력이떨어질가능성이있으므로폴리우레탄폼드레싱제제의구조적문제를고려할필요가있다고사료된다. PolyMem silver 는제조사의보고에의하면반투과성얇은막을가진친수성폴리우레탄으로구성된 PolyMem 에작은입자의은 (nanocrystalline silver particle) 을첨가한것으로본연구에서는비슷한폼드레싱제제인 Medifoam silver 가대조군인베타딘에비해 MRSA에대해항균효과와상처치유에효과가적은것에비해 PolyMem silver 는효과적인것으로나타났다. 이러한차이가폴리우레탄폼드레싱에함유된 silver sulfadiazine과은나노입자간의 MRSA에대한항균효과및상처치유에대한차이가원인일가능성이있으나차이를보이는원인에대한연구는좀더필요할것으로사료된다. Acticoat 는 3층의폴리에틸렌메쉬 (polyethylene mesh), 나노은 (nanocrystalline silver) 과 2겹의레이온폴리에스테르 (rayon polyester) 로구성되어있는최근에개발된은을함유한많은드레싱제제중하나이다 [14]. 수일이상지속적으로일정한농도의은이온을 Ag + 에비하여상대적으로내구력이강하고자극효과가적은 Ag 0 형태로방출함으로써상처의할로겐화물 (halide) 와결합하지않아은성분이비활성화되지않으므로 Ag + 형태를기본으로하던제제들의단점이보완된것으로 [14, 19], 본연구에서도 Acticoat 가다른은함유드레싱제제들보다 MRSA에대해항균효과및상처치유효과가더좋은것으로나타났다. 그러나삼출물을흡수하는효과가없어 2차드레싱이필요하고증류수로드레싱을시행하는불편함이있으며드레싱후에착색이되는경향이있다. Aquacel -Ag는기존의 Aquacel 에은이온이함유되어있는것으로제조사에의하면삼출물을흡수하여 hydrofiber가녹으면함유되어있는은이온이방출되어항균효과를나타나게되는것으로기존의 Aquacel 이갖고있는상처의습윤환경조성및드레싱교환시통증이적으며세포독성이적다는장점은유지하면서은이온의항균효과가부가된드레싱제제이다. Aquacel -Ag는화상상처에적용하였을때 silver sulfadiazine에비해소독중통증이덜하고드레싱에걸리는시간이나교체횟수가적어가격대비효과면에서우수하며흉터도덜하다는보고도있으며 [20], S. aureus와 Pseudomonas aeruginosa 에대해 Aquacel -Ag, Acticoat, PolyMem silver 및다른은 함유드레싱제제의은함유량, 은방출량및항균효과를비교하였을때 Acticoat 가 Aquacel -Ag와 PolyMem silver 에비해은함유량이높고 Aquacel -Ag가 PolyMem silver 에비해은함유량이낮으며은방출량은 Acticoat 가가장높고 Aquacel -Ag가 PolyMem silver 에비해은방출량이낮지만항균효과는 Aquacel -Ag가 Acticoat 와비슷한정도로 PolyMem silver 에비해높다는보고도있다 [21]. 본연구에서도 S. aureus와 P. aeruginosa에대한보고와같이 MRSA에대해 Aquacel -Ag가 Acticoat 와비슷한정도로항균효과와상처치유효과가좋은것으로나타났으며 Acticoat 와유사하게나노은이함유된 PolyMem silver 보다는더효과가좋은것으로나타났다. 본연구에서 MRSA에감염된상처에대부분의은함유드레싱제제가대조군인베타딘보다유의하게상처치유효과가있으며항균효과도있는것으로보였으며은함유드레싱제제들간에도서로차이가있는것으로나타났다. 은함유드레싱제제들의 MRSA 균주에대한효과의정도는각실험적항목들마다조금씩차이가있었지만 Acticoat 는모든항목에서유의하게가장우수한효과를가지는것으로나타났으며나노은이함유된드레싱제제인 Acticoat 와 PolyMem silver 가 silver sulfadiazine이함유된드레싱제제인 Medifoam silver 와 Ilvadon 보다더효과적인것으로나타났으므로나노은이효과가있을것으로사료된다. 최근에나노입자를이용한다양한연구가이루어지고있어새롭게떠오르는생체재료로서다양한분야에서많이응용되고있고또한많은물질들이나노입자형태로만들어져서다양한연구에이용되고있다. 그러나극소수의나노물질만이생물학적연구에사용되고있다. 은나노입자의경우쉽게합성이가능하고작은입자크기로인하여세포표면으로흡수되는것이용이하다는장점에서생물학적연구에가장많이사용되고있다 [22]. 또한은자체가가지는뛰어난환원능력과항독성효과와더불어나노입자가가지는항균능력이합쳐져서각종생체재료의기본재료로서그가능성을시험받고있다 [23]. 그러므로, 향후효과적인은함유드레싱제제를개발할때는이러한구조및성질에대해충분한검토가필요할것으로사료된다. 저농도의은이온은피부착색이나세포독성이거의없다는연구결과도있으나배양된사람의상피세포를대상으로한실험에서는은함유드레싱이독성을나타낸다는보고도있고장기적으로인체에어떤영향을미치는지에대해서는아직까지알려진바가없다 [12, 24]. 본연구에서도상처의조직검사에서특별한이상소견을보이는은함유드레싱제제는없었으나 Acti-

7 26 Jong Hoon Lee, Jeong Don Chae, Dong Gu Kim, et al. coat 와같이은이온의함량이많은것으로알려져있는제제의경우는향후은함유드레싱제제들의안전성에대한연구가필요하다고사료된다. 본연구를통해은함유드레싱제제의 MRSA에대한항균효과및상처치유효과가있다는것이확실하게나타났지만효과적인드레싱제제의개발, 은함유드레싱의안전성및장기적인생체내침습성등에대해서는좀더장기적인연구기간과임상실험을병행하여연구결과를검증하는것이필요할것으로사료된다. 병원내감염의문제가되고있는 MRSA에감염된상처치유를하는방법으로은함유드레싱제제가효과적이며다양하게사용되고있는은함유드레싱제제들중 Acticoat 가항균효과나상처치유에있어효과적이다. 감염되지않은상처를치유하는방법으로많이사용되고있는폼드레싱제제에은입자가함유된은함유폼드레싱제제들중나노은입자가함유된 PolyMem silver 는 MRSA 감염상처치유에효과가있는것으로나타났으나 Acticoat 나 Aquacel-Ag 보다는효과가적은것으로나타났으며 silver sulfadiazine이함유된 Medifoam silver 는배지를이용한항균력검사에서효과가전혀없는것으로나타났다. 은함유드레싱제제들중은입자가함유된제제들보다나노은입자가함유된제제들이항균효과및상처치유효과가더좋은것으로나타났지만, 나노은입자가함유된드레싱제제중 Acticoat 는직접은이온이함유된 Aquacel-Ag 보다효과가좋은것으로나타났으나 PolyMem silver 는효과가적은것으로나타났다. 이것은폼드레싱과 hydrofiber 제제의창상에대한항균효과및창상치유효과를나타내기위한은이온의작용기전차이때문인것으로사료되므로효과적인은함유드레싱제제의개발은방법에대한차이를고려할필요가있다고사료된다. 그러나개체수가많지않았고드레싱제제의사용하는양이실제임상에서사용되는양과차이가있으므로좀더연구가필요할것으로사료된다. 또한실제임상에적용하기위해서는상처치유를위한항생제의사용및환자들의여러가지요인을고려하는것이필요하겠다. 요약배경 : Methicillin-resistant Staphylococcus aureus (MR- SA) 는상처드레싱에서문제가되는세균이다. 상업적으로사용되는은함유드레싱제제들의 MRSA에감염된상처에서의항균효과및상처치유효과에대해비교하고자하였다. 방법 : 108마리쥐의등에전층피부결손을형성하고 MRSA로감염을유발하였다. 쥐들은 nanocrystalline silver (Acticoat ), silver carboxymethylcellulose (Aquacel -Ag), silver sulfadiazine (Medifoam silver ), nanocrystalline silver (Poly- Mem silver ), silver sulfadiazine (Ilvadon ) 과 povidone iodide (Betadine ) 군으로나누어드레싱하였다. 상처크기, 조직소견, 세균집락수를분석하였다. 각군에서항균력은 Mueller-Hinton 배지에서억제대로평가하였다. 결과 : 상처크기는 Acticoat, Aquacel -Ag, PolyMem silver, Medifoam silver, Ilvadon, 베타딘군의순으로감소하였다. 조직소견에서 Acticoat 군이다른군들에비해재상피화및육아조직형성이뚜렷하였으며염증세포침윤이적었다. 상처치유효과는 Acticoat, Aquacel -Ag, PolyMem silver, Ilvadon, Medifoam silver, 베타딘군순으로좋았다. 세균집락수는 Medifoam silver 군을제외한모든군에서감소했다. 억제대는 Acticoat, Aquacel -Ag, Ilvadon, PolyMem silver, 베타딘, Medifoam silver 군순으로크게나타났다. 결론 : 은함유드레싱제제는 MRSA에감염된상처를치료하는데유용하게사용될수있다. 본실험에서나타난다양한은함유드레싱제제들을비교한결과에따라 Acticoat 는 MRSA 에감염된상처를치료하는데중요한역할을할수있을것으로사료된다. 감사본논문에서사용된실험제제들은저자들과이해관계가없음을밝힙니다. 참고문헌 1. Kim HB, Jang HC, Nam HJ, Lee YS, Kim BS, Park WB, et al. In vitro activities of 28 antimicrobial agents against Staphylococcus aureus isolates from tertiary-care hospitals in Korea: a nationwide survey. Antimicrob Agents Chemother 2004;48: Hernandez R. The use of systemic antibiotics in the treatment of chronic wounds. Dermatol Ther 2006;19: Attinger CE, Janis JE, Steinberg J, Schwartz J, Al-Attar A, Couch K. Clinical approach to wounds: debridement and wound bed preparation including the use of dressings and wound-healing adjuvants. Plast Reconstr Surg 2006;117(S7):S Jeong TK and Yang HJ. Effectiveness of nanocrystalline silver (Acticoat ) dressing at wound infected by multidrug resistant bacteria. J Korean Soc Plast Reconstr Surg 2007;34: ( 정광태및양호직. 다제

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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