224 YM Jo, et al. Pneumococcal and non-pneumococcal Streptococcal Pneumonia 서론 성인에서지역사회페렴의가장흔한원인균은폐렴사슬알균으로알려져있다 [1, 2]. 폐렴사슬알균 (Stre

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1 Original Article DOI: /ic Infect Chemother 2010;42(4): Infection & Chemotherapy 폐렴알균과기타연쇄구균에의한지역사회획득폐렴의임상상비교 조유미 송준영 최원석 허중연 노지윤 김우주 정희진고려대학교의과대학내과학교실감염내과 Comparison of Clinical Characteristics of Pneumococcal and non-pneumococcal Streptococcal Pneumonia Background: Although Pneumococcal (SPN) is the most common cause of community acquired, non pneumococcal streptococcal (NSPN) is also frequently reported. However, there are insufficient data on characteristics of NSPN which makes it difficult to decide treatment plans or to assess the prognosis. Materials and Methods: Between March 2002 and February 2009, medical records including clinical and epidemiological data on patients aged 18 years with community acquired streptococcal were reviewed retrospectively. Clinical characteristics were compared between community acquired NSPN and SPN. Results: During the 7 year study periods, 248 patients were hospitalized with community acquired streptococcal and 30 of them had NSPN. There were 12 cases of Streptococcus constellatus, 7 cases of S. anginosus, 4 cases of S. mitis, 3 cases of S. pyogenes, 2 cases of S. oralis, 1 case of S. alactolyticus and 1 case of S. agalactiae. There was no difference in percentage of patients with a chronic underlying disease between SPN and NSPN groups. The most common was chronic obstructive pulmonary disease (SPN 29.8%, NSPN 16.7%) followed by diabetes mellitus (SPN 22.0%, NSPN 13.3%). Bacteremia (SPN 7.3%, NSPN 20.0%, P=0.04) and empyema (SPN 1.4%, NSPN 53.3%, P<0.001) were more common in NSPN. However, there was no significant difference in the CURB 65 severity score and 30 day mortality between the two groups. According to multivariate analysis results, the significant risk factor for NSPN was the history of frequent alcohol drinking (Adjusted OR 3.81, 95% CI 1.36 to 10.67). Conclusion: Pneumonia caused by NPSN is more commonly accompanied by bacteremia and empyema compared to SPN, but there was no difference in the 30-day mortality between the two groups. NSPN should be considered if a patient with a history of chronic alcoholism presents with and pleural effusion, especially when Gram positive diplococci is seen in the sputum Gram stain. Key Words: Community-acquired, Pneumococcal, Streptococcus Yu Mi Jo, Joon Young Song, Won Suk Choi, Jung Yeon Heo, Ji Youn Noh, Woo Joo Kim, and Hee Jin Cheong Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea Copyright 2010 by The Korean Society of Infectious Diseases Korean Society for Chemotherapy Submitted: May 10, 2010 Revised: August 10, 2010 Accepted: August 11, 2010 Correspondence to Hee-Jin Cheong, M.D., Ph.D. Division of Infectious Disease, Department of Internal Medicine, Korea University College of Medicine, 97 Guro Dong-gil, Guro-gu, Seoul , Korea Tel: , Fax: heejinmd@medimail.co.kr

2 224 YM Jo, et al. Pneumococcal and non-pneumococcal Streptococcal Pneumonia 서론 성인에서지역사회페렴의가장흔한원인균은폐렴사슬알균으로알려져있다 [1, 2]. 폐렴사슬알균 (Streptococcus e, SPN) 은사슬알균 (Streptococcus spp.) 중한가지로폐렴을비롯한각종호흡기감염증을유발한다. 그러나 SPN 이외의 A, B, C, G 등다양한혈청군의사슬알균 (Non-pneumococcal Streptococcus, NSPN) 은호흡기감염증이외에도심내막염이나피부연조직감염증등다양한감염증과연관된다. 사슬알균폐렴은대부분 SPN 에의해발생하지만 NSPN 에의한폐렴도드물게보고되고있으며, A군, β- 용혈성사슬알균인 Streptococcus pyogenes 가 NSPN 폐렴의대부분을차지한다. A군, β- 용혈성사슬알균은주로급성인후염또는그와연관된합병증과관련되며, 폐렴과같은하부호흡기감염증은 SPN 에비해상대적으로드물다. 그러나영국에서시행되었던연구에서는 A군, β- 용혈성사슬알균에의한감염증중폐렴이 20% 를차지할만큼호흡기감염증의비중이적지않았다 [3]. B, C, G 군 β- 용혈성사슬알균은폐렴등의하부호흡기감염증을일으키기보다는면역저하가있는환자에서아급성심내막염등의주요원인균으로분리된다. 즉, 같은사슬알균이라도혈청군에따라연관되는주요감염증이다르다. 만성심폐질환, 만성간질환, 당뇨병, 알코올남용, 지라없음증, 종양등의기저질환은침습 SPN 폐렴의유의한위험인자로알려져있으나 [4-6], 상대적으로드물게발생하는 NSPN 폐렴에서는위험인자및예후인자가잘알려져있지않다. 이에저자들은본연구를통하여 NSPN 폐렴환자들에서기저질환, 치료효과등임상상을파악하고 SPN 폐렴과차이점을분석하고자하였다. 대상및방법 1. 연구대상 2002 년 3월부터 2009 년 2월까지 900 병상규모의일개수련병원에입원한 18 세이상의환자를대상으로하였고, 미생물배양결과를토대로호흡기검체 ( 객담, 기관지흡인액, 흉수 ) 또는혈액에서사슬알균이동정된환자를찾고, 이중에서단순흉부촬영에서폐렴침윤소견과함께기침, 객담, 발열등의호흡기및전신증상을동반한폐렴에합당한환자들중지역사회폐렴환자들을선별하여이들의의무기록을후향적으로조사하였다. 배양결과는입원초기에시행한최초의검사만을유의한것으로판단하였고, 반복된입원으로한환자가두번이상포함된경우에는입원간격이최소한달이상이면서지역사회폐렴에합당할때에만별도의 1예로간주하였다. 이들의성별, 나이, 기저질환, 입원력, 음주, 흡연등의인구학적요소와 3개월내입원력, 입원전항균제사용력, 합병증발생과사망유무, 입원기간등을조사하여 SPN 폐렴과 NPSN 폐렴의임상적특징을비교하였다. 2. 정의지역사회폐렴은입원당시에폐렴이있었거나입원후 48시간이내에흉부 X- 선검사상폐렴침윤이있었던경우로정의하였다. 일반적으로폐렴의원인균을규명할때혈액이나흉수등정상적으로무균상태인검체에서세균이동정될때명백한원인균으로판정할수있다. 그러나지역사회폐렴에서혈액에서원인균이동정되는경우는 5-14% 에지나지않아, 초기에경험적항균제로치료를시작하고객담도말과배양검사를참조하게된다 [7]. 최근의한연구에서는양질의객담으로시행한도말검사와일치하는배양검사의 SPN 폐렴에대한진단의예민도와특이도는각각 82% 와 93% 에이른다고보고한바있다 [8]. 저자들은연구대상검체중무균검체의제한된수를극복하고자양질의객담검체결과를포함하여본연구를진행하였다. 객담은현미경저배율시야에서 10 개미만의상피세포와 25개이상의백혈구를보이는 5 등급이상을적절한검체로간주하였고, 도말검사에서그람양성쌍알균이보이고, SPN 또는 NSPN 이단독으로배양되었던결과만을포함시켜폐렴원인균으로간주하였다. Legionella pneumophila 소변항원검사와, Chlamydia, Mycoplasma, Legionella 등에대한혈청검사결과양성인경우는분석에서제외하였다. SPN 폐렴은호흡기검체또는혈액에서 SPN 이동정된경우로, NSPN 폐렴은 SPN 을제외한사슬알균이동정된경우로정의하였다. 흡연력은하루 1갑이상흡연을하는경우로, 잦은음주력은주 5회이상음주를하는경우로정의하였다. 3. 항균제감수성검사항균제감수성검사는 VITEK 2로보고된결과를토대로 penicillin G, levofloxacin, cefotaxime, erythromycin, trimethoprim/ sulfamethoxazole 에대한내성을조사하였다. Penicillin G에대한내성은 SPN 에서 2008 년 1월개정된 CLSI (Clinical and Laboratory Standards Institute) 지침의기준에따라서 MIC 4 μg/ml 일때내성으로보는것이타당하지만, 2005 년이전에는감수성결과에 MIC 가보고되지않았던현실을고려하여 MIC 2 μg/ml 일때내성으로간주하였다. 그밖에, Viridans streptococci, S. milleri group 은 MIC 4 μg/ml 를기준으로하였으며, β- 용혈성사슬알균은 MIC 0.12 μg/ml 에해당되지않는비감수성그룹 (nonsusceptible category) 인경우내성으로간주하였다. Cefotaxime 에대한내성은 SPN, Viridans streptococci, S. milleri group 은 MIC 4 μg/ml 를기준으로하였고, β- 용혈성사슬알균은 MIC 0.5 μg/ml 에해당되지않는비감수성그룹인경우내성으로간주하였다 [9]. Trimethoprim/ sulfamethoxazole 에대한내성은 SPN 에대해서만조사하였다. 4. 통계처리통계프로그램은 SPSS 12.0 KO for Windows (SPSS Inc.) 를이용하였다. SPN 폐렴과 NSPN 폐렴의임상적특성은 chi-square test, Student s t-test, Wilcoxon s rank sum test 를이용하여비교하였고, NSPN 폐렴에대한 Odd ratio 분석에는 logistic regression test 를이용하였다. 개체수가적은경우 Fisher s exact test 를이용하였다. 통계적유의성판정은 P <0.05 을기준으로하였고, 신뢰구간은 95% 를기준

3 DOI: /ic Infect Chemother 2010;42(4): 으로하였다. 결과 1. 사슬알균폐렴의연도별발생추이 2002 년부터 2009 년까지 7 년간배양양성지역사회획득사슬알 균폐렴으로진단된환자는총 248 명이었고, 이중 NSPN 폐렴은 30 명이었다. NSPN 원인균은 Streptococcus constellatus 가 12예, S. anginosus 가 7예, S. mitis 가 4예, S. pyogenes 가 3예, S. oralis 가 2예, S. Case (No.) Table 1. Baseline Characteristics of Patients with Streptococcal Pneumonia No. (%) of patients (n=248) Characteristics Year Pneumococcal SPN Other streptococcal NSPN Figure 1. Annual cases of Streptococcal. SPN, Pneumococcal ; NSPN, Non-pneumococcal streptococcal. P value Age, years, mean Male to female ratio 2.5:1 1.5: Immunocompromised conditions a 65 (29.8) 4 (13.3) 0.06 Malignancy b 39 (17.9) 4 (13.3) 0.54 Chronic renal disease 8 ( 3.7) 0 ( 0 ) 0.60 Transplantation 1 ( 0.5) 0 ( 0 ) 1.00 Immune suppressive treatment c 44 (20.2) 3 (10.0) 0.18 Other chronic conditions d 109 (50.0) 11 (36.7) 0.18 Diabetes mellitus 48 (22.0) 4 (13.3) 0.27 Chronic heart disease 28 (12.8) 3 (10.0) 1.00 Liver cirrhosis 4 ( 1.8) 1 ( 3.3) 0.48 Chronic obstructive lung disease 65 (29.8) 5 (16.7) 0.13 Frequent alcohol drinking e 42 (19.3) 11 (36.7) 0.03 Smoking 99 (45.4) 12 (40.0) 0.58 Hospitalization within 3 months 32 (14.7) 7 (23.3) 0.28 Previous antibiotics within 2 weeks before hospitalization 64 (29.4) 10 (33.3) 0.66 a, d Some patients had more than one conditions. b Including hematologic malignancy. c Current immnune suppressive therapy including radiation, systemic steroids or chemotherapy. e Alcohol drinking more than five times a week. alactolyticus 와 S. agalactiae 가각각 1예였다. 사슬알균폐렴의연도별발생환자수는 명으로유의한차이를보이지않았으나 NSPN 폐렴은 2002 년부터 2008 년까지각각 1명, 6명, 4명, 4명, 2명, 2명, 11 명으로 2008 년도에급격한증가를보였고 2008 년 11 예중 7예가 S. constellatus 에의한폐렴이었다 (Fig. 1). 2. 사슬알균폐렴환자의임상적특징 248 명의사슬알균폐렴환자들의임상적특징은 Table 1과같다. SPN 폐렴군과 NSPN 폐렴군의평균나이는 62.7 세와 57.6 세로차이는없었고, 남녀비는 SPN 군이 2.5:1, NPSN 군이 1.5:1 로양군모두남자환자의비율이높았고양군간유의한차이는없었다. 유일한차이를보였던것은잦은음주력이있는환자의비율로 SPN 군과 NPSN 군에서각각 19.3% 와 36.7% 로 NPSN 군에서높은비율을보였다 (P=0.03). 만성기저질환이있는환자는양군에서각각 50.0% 와 36.7% 였으나유의한차이는없었으며, 이중가장흔한것은만성폐쇄성폐질환과당뇨병으로 SPN 군에서각각 29.8% 와 22.0%, NSPN 군에서각각 16.7% 와 13.3% 에서동반되었다. CURB-65 로나타낸폐렴의중증지표는양군간유의한차이는없었다. 사슬알균폐렴의흉부단순촬영소견은국소반점침윤에서다엽성침윤까지다양하였고, 흉수를동반한폐렴은 SPN 폐렴에서 22 예 (11.1%), NSPN 폐렴에서 17 예 (56.7%) 로 NSPN 폐렴에서유의하게많았다 (P<0.001). 균혈증 (SPN 폐렴 7.3%, NSPN 폐렴 20.0%) 과농흉 (SPN 폐렴 1.4%, NSPN 폐렴 53.3%) 은 NSPN 폐렴에서높은동반율을보였다 (P=0.04, P<0.001). 패혈쇼크, 기계환기유무, 급성신부전등의기타합병증은양군간차이는없었고 30일사망률도차이를보이지않았다. 그러나입원기간은 NSPN 폐렴에서유의하게길었다 (P<0.001) (Table 2). 흉수를동반한폐렴 39예중 27예에서흉수천자를시행하였고 (SPN 폐렴 11 예, NSPN 폐렴 16 예 ), 이중 16 예 (59.3%) 에서입원 2일내에 Table 2. Clinical Presentation and Outcome of Streptococcal Pneumonia No. (%) of patients (n=248) Clinical presentation Pneumococcal Other streptococcal P value CURB-65 score, mean [range] 2.0 [ ] 1.0 [ ] 0.74 Chest radiograph Localized patch infiltration 36 ( 16.5) 7 (23.3) Bilateral interstitial infiltration 39 ( 17.9) 5 (16.7) Lobar infiltration 80 (36.7) 11 (36.7) Multilobar infiltration 63 (28.9) 7 (23.3) Pleural effusion 22 ( 11.1) 17 (56.7) <0.001 Outcome Bacteremia 16 ( 7.3) 6 (20.0) 0.04 Shock 26 (11.9) 7 (23.3) 0.09 Empyema 3 ( 1.4) 16 (53.3) <0.001 Mechanical ventilation 25 (11.5) 4 (13.3) 0.76 Acute renal failure 44 (20.2) 5 (16.7) 0.81 Length of hospital stay, days, mean [range] 9 [ ] 18.5 [ ] < day mortality 9 ( 4.1) 3 (10.0) 0.17

4 226 YM Jo, et al. Pneumococcal and non-pneumococcal Streptococcal Pneumonia 시행하였고양군간시행시기의차이는없었다. 흉수천자검사에서 NSPN 폐렴에서유의하게 glucose 는낮았고 lactate dehydrogenase 는높았다 (Table 3). 사슬알균이동정된검체는혈액이 17 예 (SPN 11 예, NSPN 6예 ), 혈액과객담에서동시배양된경우가 5예 (SPN 5예 ), 흉수에서배양된경우가 16 예 (NSPN 16 예 ), 흉수와객담에서동시배양된경우가 1예 (SPN 1예 ), 객담, 기관지흡인액등에서만배양된경우가 209 예 (SPN 201 예, NSPN 8예 ) 였다. 3. 사슬알균폐렴원인균의항균제내성 항균제감수성결과 NSPN 은모두페니실린에감수성을보였고, SPN 은 114 예 (52.3%) 에서페니실린에내성을보였다. Erythomycin 에대한내성은 SPN 130 예 (59.6%) 와 NSPN 6예 (20.0%) 에서보였다. Cefotaxime 과 vancomycin 에내성을보인사슬알균은없었으며, levofloxacin 내성은 SPN 3예, NSPN 1예에서보였다. Trimethoprime/sulfamethoxazole 의경우 SPN 94예 (43.1%) 에서내성을보였다 (Table 4). 4. 비폐렴사슬알균 -사슬알균폐렴의위험인자단변량분석에서주 5회이상의잦은음주력이있는경우 NSPN 의위험도가 2.43 배증가하였고, 나이, 성별등을고려한다변량분석에서도잦은음주력은 NSPN 폐렴의유의한위험인자였다 (Adjusted OR 3.81, 95% CI ). 면역저하상태나기저질환동반유무는 NSPN 폐렴발생에영향을미치지않았고, 특히만성호흡기질환과당뇨병, 종양도 NSPN 폐렴과유의한관련이없었다 (Table 5). 고찰 본연구결과 2002 년부터 2009 년까지 NPSN 에의한지역사회폐렴 Table 3. Culture Results and Pleural fluid analysis in Streptococcal Pneumonia Pneumococcal Other streptococcal P value Pleural fluid characteristics No. of cases performed thoracentesis <0.05 No. of cases with gross pus 1 6 <0.05 White blood cell ( 10 9 /L), mean±sd ± ± Neutrophil count (%), mean±sd 63.3± ± Protein (g/dl), mean±sd 3.74± ± Glucose (mg/dl), mean±sd 87.1± ± LDH (IU/L), mean±sd ± ± ph, mean±sd 7.8± ± Sources of streptococcal isolates Blood 16 a Pleural fluid 1 b 16 <0.05 Sputum 186 a, b 5 <0.05 Bronchial aspiration SD, standard deviation; LDH, lactate dehydrogenase a In five cases, SPN cultured in both sputum and blood. b In one case, SPN cultured in both sputum and pleural fluid. 은총 30예가발생하여 SPN 에의한지역사회폐렴과평균 6:1 의비율로비교적균등한예가해마다발생하고있음을알수있었다. NSPN 폐렴의원인균분포는다양했으나 S. milleri group (SMG) 이 19 예 (63.3%, S. constellatus 12예, S. anginosus 7예 ) 로가장많았다. 사슬알균은그람양성쌍알균으로용혈양상에따라 α와 β군으로나뉜다. SPN 과 Viridans streptococci, SMG 등이 α- 용혈성사슬알균에해당되며, β- 용혈성사슬알균은다시 Lancefield group A, B, C, G 군등으로나눌수있다. SPN 이외의사슬알균폐렴이지역사회폐렴에서차지하는비중이나임상적특징에관한국내자료는매우드물다 년대후반에시행된 7개대학병원의후향적조사에의하면지역사회폐렴 246 예중 81예 (32.9%) 에서원인균을알수있었고 ( 도말검사와일치하는객담배양양성인경우도포함 ), 이중 19 예가 SPN, 4예가 NSPN 이었다. SPN 2예에서만알코올중독 (alcoholism, 명확한기준은제시되어있지않았다 ) 이있었고, 당뇨병은 SPN 6예, NSPN 2 예에서동반되어가장흔한기저질환이었다. SPN 의항균제내성률은병원별로 17-28% 정도로본연구에서조사된 52.3% 에비하면낮았다 [10]. 이후 2000 년대초반에원외폐렴에대한다기관전향적연구가시행되었고, 객담검사결과까지포함한분석에서총 585 예중 220 예에서원인균이동정되었고, 이중 SPN 이 59예 (26.8%) 로가장많았고, NSPN 은흉수에서배양된 group C Streptococci 단 1예였다. 기저질환은 SPN 폐렴의 50% 에서동반되었고, SPN 의페니실린내성률 (MIC 2 μg/ml ) 은 34.3% 였다 [11]. 사슬알균이호흡기주요상재균임을감안하면 NSPN 도적지않은수에서폐렴의원인이될것이라예상된다. Yamashiro 등은화농성객담을보이는사람이그렇지않은사람에비해 SMG 의인후집락율이높았고, SMG 의인후집락정도가높을수록 SMG 에대한혈청항체가가높았으며, 화농성가래가호전된후항체가가정상수치로떨어지 Table 4. Drug Susceptibility of Streptococcus isolated from Patients with Streptococcal Pneumonia (n=248) No. (%) of resistant strains a Drug Pneumococcal b Other streptococcal c Penicillin 114 (52.3) 0 Erythromycin 130 (59.6) 6 (20.0) Cefotaxime d 0 0 Vancomycin 0 0 Levofloxacin 3 ( 1.4) 1 ( 3.3) TMP/SMX e 94 (43.1) - a If the MIC criteria have only susceptible range, strains yielding results suggestive of a nonsusceptible category, we assumed the results as resistant. b MICs of SPN: penicillin resistance MIC 2 μg/ml, erythromycin resistance MIC 1 μg/ml, cefotaxime resistance MIC 4 μg/ml, vancomycin susceptible MIC 1 μg/ml, levofloxacin resistance MIC 8 μg/ml, TMP/SMX resistance MIC 4/76 μg/ml. c MICs of Streptococcus spp. Viridans Group including SMG Group, penicillin resistance MIC 4 μg/ml. MICs of Streptococcu spp. β-hemolytic Group: penicillin susceptible MIC 0.12 μg/ml, cefotaxime susceptible MIC 0.5 μg/ml. Otherwise same as SPN. d MIC results of cefotaxime were available in 74 cases of SPN and 14 cases of NSPN. e Trimethoprim/sulfamethoxazole.

5 DOI: /ic Infect Chemother 2010;42(4): Table 5. Univariate and Multivariate Analysis for Risk Factors Associated Non-Pneumococcal Streptococcal Pneumonia Variable No. (%) of patients Univariate analysis Multivariate analysis a OR (95% CI) P value OR (95% CI) P value Age 65 years 120 (48.4) 0.68 ( ) ( ) 0.79 Male gender 174 (70.2) 1.68 ( ) ( ) 0.11 Frequent alcohol drinking b 53 (21.4) 2.43 ( ) ( ) 0.01 Smoking 111 (44.8) 0.80 ( ) ( ) 0.50 Immunocompromised conditions c 69 (27.8) 0.36 ( ) ( ) 0.30 Malignancy d 43 (17.3) 0.71 ( ) Chronic renal disease 8 ( 3.2) Transplantation 1 ( 0.4) Immune suppressive treatment e 47 (19.0) 0.44 ( ) ( ) 0.70 Other chronic conditions f 120 (48.4) 0.58 ( ) ( ) 0.94 Diabetes mellitus 52 (21.0) 0.55 ( ) ( ) 0.46 Chronic heart disease 31 (12.5) 0.75 ( ) ( ) 0.92 Liver cirrhosis 5 ( 2.0) 1.85 ( ) Chronic obstructive lung disease 70 (28.2) 0.47 ( ) ( ) 0.37 a Blank result means excluded variables. Alcohol drinking more than five times a week. c, f Some patients had more than one conditions. Including hematologic malignancy. e Current immnune suppressive therapy including radiation, systemic steroids or chemotherapy. 는것을근거로원인균이동정되지않는급성세균성폐렴의상당수가 SMG 에의할것이라말한바있다 [12]. Shinzato 등은구강내혐기균이 SMG 의성장을촉진하고숙주의살균력을약화시켜 SMG 감염에대한상승작용을나타내므로 SMG 도중요한호흡기감염원이될수있음을언급한바있다 [13]. S. anginosus, S. intermedius 와 S. constellatus 를포함하는 SMG 는 11.8% 에서호흡기감염을일으키고 [14] 대부분농흉이나폐농양을동반하는것으로알려져있다 [15]. 지역사회폐렴원인균에서 SMG 가차지하는비율은 2-12% 에불과하지만, 47예의농흉을동반한지역사회폐렴에관한조사에의하면원인균중 50% 가 SMG 였다 [16]. S. pyogenes 를포함한 β- 용혈성 A군사슬알균은괴사근막염이나독소충격증후군같은피부연조직감염을주로유발하는것으로알려져있다, A군사슬알균이지역사회폐렴의드문원인이긴하지만 88명의 β- 용혈성사슬알균균혈증에대한연구에서 43% 가 A군사슬알균감염이었고 23% 가호흡기감염으로나타나 A군사슬알균도폐렴의적지않은원인이될수있음을알수있었다 [17]. 군대와같이폐쇄된곳에서단체생활을하는집단이나가족내에서 A군사슬알균폐렴의집단발생이간헐적으로보고된바있으며, 2002 년에는군훈련소에서 162 건의 A군사슬알균폐렴이대단위로발생한사례가있었다 [18]. 본연구에서는 S. pyogenes 폐렴이 3예였고, 이중 1예에서균혈증을동반하였다. β- 용혈성 C군사슬알균폐렴은드물게발생하나보고된증례들을보면주로흉수를동반했고 40세이하의젊고기저질환이적은환자에서발생하였다. 균혈증은많게는 75% 까지보고되었고농흉이나심내막염의합병증을동반하기도하였다 [19]. 본연구에서조사된 C군사슬알균폐렴은없었다. NSPN 폐렴발생의위험인자를분석해보았을때, 주 5회이상의잦은음주력이유의한위험인자였다 (Adjusted OR 3.81, 95% CI ). 미국에서 년에걸쳐시행된 5400 명의 A군사슬알 균감염에대한대규모역학연구에서센터마다차이는보였지만음주력이유의한관련이있었다 [20]. Fujiki 등또한 15 명의 SMG 호흡기감염증환자에대한연구에서 60% 가알코올남용력 (alcohol abuse) 이있음을보고하였다 [21]. NSPN 폐렴은특징적으로균혈증이나흉수, 농흉을동반한경우가 SPN 폐렴에비해많았다. SPN 폐렴이가장흔한지역사회폐렴이지만흉수, 특히농흉을동반하는경우는기타세균성폐렴에비해드문것으로알려져있다 [22, 23]. Light 등은 203 명의지역사회폐렴환자를대상으로연구를수행하였는데, 90명 (44%) 에서흉수가동반되었고 SPN 폐렴과기타세균성폐렴의비율이 2:3 정도였으나, 농흉등의합병흉수 10 예중 1예에서만 SPN 이동정되었다 [24]. 본연구에서흉수를동반한폐렴 39예중 17 예가 NSPN 폐렴이었고그중 15 예가 SMG 폐렴이었으며이중 14 예가농흉이었다. SMG 가농흉을흔히동반하는정확한기전에대해아직알려진바는없지만, SMG 의세포표면단백질이 fibronectin, platelet-fibrin, fibrinogen 과결합하는성질과 S. intermedius 의경우 hyaluronidase, DNase 와같은조직용해효소를배출하는것들이농양을특징적으로잘만드는기전으로설명되고있다 [25-29]. 쥐를이용한폐렴과피하농양동물모델들에서는 Fusobacterium 과같은혐기성균이분비하는물질들과 SMG 피막물질들이다형핵백혈구에의한포식작용을억제하는것이확인되어이는 SMG 가농양을형성하는데상승작용을할것이라는가설을뒷받침한다 [30-33]. 사슬알균폐렴의치료경과는원인균에따라유의한차이는없었다. 균혈증과농흉은 NSPN 폐렴에서더많았는데이것이 NSPN 폐렴에서입원기간을증가시킨한요인임을알수있었다 ( 균혈증또는농흉동반시입원기간중위수 14 일, 동반하지않은경우입원기간중위수 9일, P<0.001). 30일사망률은균혈증이나농흉을동반한침습폐렴의경우가 NSPN 폐렴에서더많았음에도양군간유의한차이를보이지않았

6 228 YM Jo, et al. Pneumococcal and non-pneumococcal Streptococcal Pneumonia 다 (P=0.17). 30일사망률에영향을미치는요인으로는폐렴의중증도를반영하는 CURB-65 점수가관련이있었다. CURB-65 점수가 2점이상인경우 30일사망률은 4.83 배증가하였다 (P=0.045). SPN 폐렴군과 NSPN 폐렴군의 CURB-65 점수는통계적으로유의한차이를보이지않았으며, 이로인한양군간에사망률의차이가없었던것으로생각된다. Penicillin 과 erythromycin 에대한항균제내성률은 NSPN 폐렴에서유의하게낮았다 ( 각각 SPN 폐렴 52.3% 와 59.6%, NSPN 폐렴 0% 와 20%). 지역사회폐렴의초기치료제로페니실린계열을포함한 β-lactam 과 macrolide 항균제가주로사용되는현실과, 페니실린내성 SPN 이 cephalosporin 이나 macrolide 항균제와교차내성을흔히동반하는것을감안하면, NSPN 폐렴원인균의항균제내성률이낮아 NSPN 폐렴의상대적으로빈번한침습합병증동반에도불구하고 SPN 폐렴과사망률에있어유의한차이가없는데기여하였을것으로추론할수있다 [34]. 그러나항균제내성률과폐렴의예후에대해서는아직까지논란의여지가많아이를뒷받침하기위해서는좀더객관적인자료가축적되어야할것이다 [35, 36]. 본연구의제한점은첫째, 배양양성폐렴에대해서만조사를하였기때문에전체지역사회획득폐렴의배양양성률을확인할수없었다는것이고, 둘째, 객담배양검체를포함하여 SPN 폐렴과 NSPN 폐렴을정의하였다는것이다. 호흡기검체배양균은단순상재균일가능성이높고본연구에서 SPN 배양양성검체의 82.6% (180 예 ) 가객담이어서 SPN 폐렴이과대평가되었을가능성이있다. 그러나, 최근의한연구에의하면지역사회폐렴원인균의객담배양율이 30% 미만으로나타났는데, NSPN 의일부는혐기성조건에서배양되는경우도있고, 일부증례를제외한대부분의경우에서 Viridans streptococci 를비롯한 α-용혈성사슬알균이구강내상재균으로보고되는현실을감안하면, NSPN 폐렴이과소평가되었을가능성도생각해볼수있다 [37]. 향후객담검사의진단적신빙성을높이기위해서객담의정량적중합효소연쇄반응법을활용하거나침습검체만을기준으로하는연구가필요하겠다. 셋째, 폐렴의사망률에영향을미치는기저질환과활동능력수준, 구강위생상태등사슬알균폐렴발생에영향을미칠수있는요인들에대해조사가보완되어야한다는점이다. 본연구에서조사된항목들은 SPN 폐렴에대한기존자료를참고로후향적으로조사하였기때문에실제 NSPN 폐렴에영향을미칠수있는항목은누락되었을가능성이있어이것만으로양군간에차이가없다고말하기는무리일수있다. 넷째, NSPN 폐렴의증례수가 30예로적고, 이중 19 예 (63.3%) 가 SMG 폐렴으로본연구에서조사된 NSPN 폐렴은 SMG 폐렴의특징을반영했을가능성이있다. 결국보다많은증례수의확보만이문제해결의실마리가될것이다. 결론적으로 NSPN 폐렴은사슬알균폐렴중소수를차지하지만 SPN 폐렴에비해균혈증, 농흉과같은합병증을흔히일으키고입원기간을연장시키지만이로인한사망률은 SPN 폐렴에비해높지않았다. 잦은음주력은 NSPN 폐렴의유의한위험요인으로잦은음주력이있는환자에서흉수를동반한폐렴이발생한경우 NSPN 폐렴을고려해야한다. 그러나 NSPN 폐렴의특징을객관화하고구체적인치료방침을마 련하기위해서는향후더많은자료가축적되어야할것이다. 참고문헌 1. Bartlett JG, Dowell SF, Mandell LA, File Jr TM, Musher DM, Fine MJ. Practice guidelines for the management of communityacquired in adults. Infectious Diseases Society of America. Clin Infect Dis 2000;31: Song JH, Oh WS, Kang CI, Chung DR, Peck KR, Ko KS, Yeom JS, Kim CK, Kim SW, Chang HH, Kim YS, Jung SI, Tong Z, Wang Q, Huang SG, Liu JW, Lalitha MK, Tan BH, Van PH, Carlos CC, So T; Asian Network for Surveillance of Resistant Pathogens Study Group. Epidemiology and clinical outcomes of communityacquired in adult patients in Asian countries: a prospective study by the Asian network for surveillance of resistant pathogens. Int J Antimicrob Agents 2008;31: Barnham M, Weightman N, Anderson A, Pagan F, Chapman S. Review of 17 cases of caused by Streptococcus pyogenes. Eur J Clin Microbiol Infect Dis 1999;18: Gentile JH, Sparo MD, Mercapide ME, Luna CM. Adult bacteremic pneumococcal acquired in the community. A prospective study on 101 patients. Medicina (B Aires) 2003;63: Laupland KB, Gregson DB, Zygun DA, Doig CJ, Mortis G, Church DL. Severe bloodstream infections: a population-based assessment. Crit Care Med 2004;32: Talbot TR, Hartert TV, Mitchel E, Halasa NB, Arbogast PG, Poehling KA, Schaffner W, Craig AS, Griffin MR. Asthma as a risk factor for invasive pneumococcal disease. N Engl J Med 2005;352: Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired in adults. Clin Infect Dis 2007;44 (Suppl 2):S Anevlavis S, Petroglou N, Tzavaras A, Maltezos E, Pneumatikos I, Froudarakis M, Anevlavis E, Bouros D. A prospective study of the diagnostic utility of sputum Gram stain in. J Infect 2009;59: Wikler MA. Performance standards for antimicrobial susceptibility testing: 19th informational supplement M100-S19. Wayne, PA: CLSI; Chung MH, Shin WS, Kim YR, Kang MW, Kim MJ, Jung HJ, Park SC, Pai H, Choi HJ, Shin HS, Kim EC, Choe KW, Kim S, Peck KR, Song JH, Lee K, Kim JM, Chong Y, Han SW, Lee KM. Etiology of

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