한국임상약학회지제 27 권제 2 호 Korean J Clin Pharm, Vol. 27, No. 3, 2017 Original Article Korean Journal of Clinical Pharmacy Official Journal of Korean College of Clinical Pharmacy pissn 1226-6051 eissn 2508-786X https://doi.org/10.24304/kjcp.2017.27.3.186 Korean journal of clinical pharmacy (Online) URL: http://www.ekjcp.org 건강보험청구자료를이용한외래급성호흡기계질환방문과항생제처방률변화분석 김지애 박주희 김보연 김동숙 * 건강보험심사평가원연구조정실약제정책연구팀 (2017년 2월 3일접수 2017년 9월 21일수정 2017년 9월 22일승인 ) The Trend of Acute Respiratory Tract Infections and Antibiotic Prescription Rates in Outpatient Settings using Health Insurance Data Jee-Ae Kim, Juhee Park, Bo-Yun Kim, and Dong-Sook Kim * Pharmaceutical Policy Research Team, Department of Research, Health Insurance Review & Assessment Service, Wonju 26465, Republic of Korea (Received February 3, 2017 Revised September 21, 2017 Accepted September 22, 2017) ABSTRACT Objectives: A significant concern has been raised about the emerging resistance that is largely caused by the excessive or inappropriate use of antibacterial agents for viral respiratory infections. This study investigated the trend of respiratory tract infections (RTIs) and the use of antibiotics. Methods: Utilizing the national level health insurance claims data from 2005 to 2008, we examined encounter days, antibiotic use, and the prescription rate for respiratory tract infections including upper respiratory tract infections (URTIs), lower respiratory tract infections (LRTIs), and otitis media in outpatient settings. The antibiotic use was measured as defined daily dose per 1,000 patients per day (DDD/1,000 patients/day). Results: The visit for URTI increased from 141,693,465 in 2005 to 120,717,966 in 2008 and the visit for LRTI decreased from 61,778,718 to 66,930,122. For RTIs, prescription rates of antibiotics decreased from 65.2% to 58.5% for URTIs and 76.9% to 68.3% for LRTIs from 2005 to 2008. The antibiotic use decreased to 20.85 DDD/1,000 patients/day after a significant increase of 22.01 DDD/1,000 patients/day in 2006. Among antibiotics, J01CR had the highest use- 7.93 DDD/1,000 patients/day followed by J01DC of 3.71 DDD/1,000 patients/day and J01FA of 3.2 DDD/1,000 patients/day. One notable trend is that J01FA presented a continuous increase in antibiotic use from 2.3 in 2005 to 3.26 DDD/1,000 patients/day in 2008. Conclusion: The use of antibiotics had poor compliance to guidelines for RTIs. Despite decrease in the use of antibiotics, prescription rates for URTIs were still about 50% indicating that the delayed prescribing antibiotics (or wait-and-see) were not observed. KEY WORDS: Respiratory tract infections, anti-bacterial agents, outpatients, prescription rate, use 1940년대항생제가발견되는획기적인사건이래로감염으로인한질병과사망은극적으로감소하는듯했으나, 항생제가개발된이후항생제내성이등장, 증가하는양상을보이고있어, 항생제가듣지않는 항생제이후의시대 에대한우려가제기되는시점에이르게되었다. 1,2) 항생제내성은피할수없는공중보건의문제로인식되는데, 항생제사용량증가는내성증가와양의상관성이있다고밝혀진바있어, 항생제내성을줄이기위해서는적정하게사용하는것이중요하다. 3,4) 외래항생항생제처방중대부분을차지하는것은호흡기계감염 (respiratory tract infections, RTIs) 으로, 호흡기계질환은제 처방의 75% 를차지하고 1,2) 특히상기도감염 (upper respiratory tract infections, URTIs) 과급성기관지염 (acute bronchitis) 은전체항생제처방의 21% 를차지하는것으로보고된다. 3) 따라서영국, 미국, 호주에서는호흡기계질환에서항생제사용에대한지침을개발하였고, 5-8) 국내질병관리본부에서도지침개발을의뢰하여, 향후발표할예정에있다. 호흡기계질환의항생제사용지침은기관지염, 인두염 / 편도염, 감기등은일반적으로대부분이바이러스가원인이기에자연치유되므로항생제치료가필요하지않지만, 항생제치료가필요한경우를감별하는방법과원인균에적합한항생제를선택하도록제시하고있다. 5-8) *Correspondence to: Dong-Sook Kim, Department of Research, Health Insurance Review & Assessment Service, 60 Hyeoksin-ro, Wonju-si 26465, Gangwon-do, Republic of Korea Tel: +82-33-739-0922, Fax: +82-33-811-7442, E-mail: sttone@hira.or.kr 186
187 / Korean J Clin Pharm, Vol. 27, No. 3, 2017 국내에서는의약분업이후, 2001년부터항생제처방률, 주사제처방률등을산출해, 의료기관에피드백하는약제급여적정성평가사업을실시하고있다. 항생제처방률평가지표는외래급성상기도감염의료기관내원일수대비항생제처방여부를산출하고있다. 급성상기도감염은한국표준질병사인분류의진단코드인 J00( 감기 ), J01( 급성부비동염 ), J02( 급성인두염 ), J03( 급성편도염 ), J04( 급성후두염및기관염 ), J05( 급성폐쇄성후두염및후두개염 ), J06( 상세불명부위의급성상기도감염 ) 이다. 이러한사업결과, 급성상기도감염항생제처방률은 2002년 73.33% 에서 2014년 43.73% 로감소하는성과를거두었다. 9) 그럼에도불구하고, 국내항생제사용량은 31.7 DDD/ 인구 1,000명 / 일 (DID) 로경제협력개발기구 (Organization for Economic Cooperation and Development, OECD) 12개국평균인 23.7 DDD/ 인구 1,000명 / 일 (defined daily dose/1,000 inhabitants/day, DID) 보다높다. 10) 이에정부는범부처 ( 국무조정실, 보건복지부, 기획재정부, 행정자치부등 8개부처 ) 차원의국무총리주재제 86회국가정책조정회의에서 국가항생제내성관리대책 (2016~2020) 을확정 발표 (2016.8.11.) 하고, 항생제사용을줄이기위한방안을발표한바있다. 11) 항생제내성관리대책의주요한골자로는급성상기도감염, 급성하기도감염, 피부감염등에서항생제사용지침개발을중점과제로제시하고있다. 향후항생제적정사용지침이개발되고지침사용이활성화되기위해서는국내급성호흡기계질환에서항생제처방의경향을분석하는것이선행되어야할것이다. 본연구는호흡기계질환양상의변화, 호흡기계질환에서항생제처방경향, 항생제사용량을분석하고자하였다. 연구방법 연구대상본연구에서는한국국민건강보험의 2005년 1월 ~2008년 12 월외래에서분석대상호흡기계질환으로진료받은환자의내역자료 ( 건강보험청구자료 ) 를활용하였다. 본연구에서는환자의일반적특성, 상병, 방문한의료기관특성, 의약품성분, 1일투약량 (1일투여량 1회투약량 ), 투여일수변수를활용하였다. 분석대상호흡기계질환은한국표준질병사인분류제5차개정 (international classification of diagnoses, 10th revision, ICD-10) 기준상병명을활용하였다 (Table 1). 단, 주상병기준이아니라, 분석대상호흡기계질환이주상병혹은부1상병에기재된대상으로모두분석하였다. 항생제는국제보건기구 (World Health Organization, WHO) collaborating center의 ATC(anatomical therapeutic chemical) 의 J01을대상으로하였다. 보편적으로사용되는 ATC 분류체계는신체기관, 작용기전, 화학구조, 약물학적및치료학적특성에따라세분되어있고, ATC 4단계 ( 화학적 ) 분류는 854개로구성되어있다. 12) J01은 anti-infectives for systemic use이므로, 경구제와주사제만을대상으로하였고, 2004~2008년도등재된의약품목록중 WHO의 ATC 분류에서 J01에해당하는항생제는 536 성분, 6,474 품목이다. Table 1. Acute Respiratory tract infections for the use of antibiotics. Classification URTI (upper respiratory tract infections) LRTI (acute-lower respiratory tract infections LRTI (chronic-lower respiratory tract infections Evaluation O Foreign Guideline OM (otitis media) O O O O O J00 J01 J02 J03 J04 J05 J06 J20 J21 J22 J40 J41 J42 H65 H66 H67 Diagnosis Acute nasopharyngitis [common cold] Acute sinusitis Acute pharyngitis Acute tonsillitis Acute laryngitis and tracheitis Acute obstructive laryngitis[croup] and epiglottitis Acute upper respiratory infections of multiple and unspecified sites Acute bronchitis Acute bronchiolitis Unspecified acute lower respiratory infection bronchitis, not specified as acute or chraconic Simple and mucopurulent chronic bronchitis Unspecified chronic bronchitis Nonsuppurative otitis media Suppurative and unspecified otitis media Otitis media in diseases classified elsewhere
건강보험청구자료를이용한외래급성호흡기계질환방문과항생제처방률변화분석 / 188 Table 2. Trend in visit and antibiotic prescriptions for specific respiratory tract, 2005-2008. Class Sum (% of all claims) 109,471,940 (16.4) No. of Visit (%) Antibiotic prescription rate, % 2005 2006 2007 2008 2005 2006 2007 2008 110,808,872 (15.9) 109,212,278 (15.3) 110,945,967 (15.3) 56.2 57.9 54.6 51.8 J00 Acute nasopharyngitis [common cold] 11,477,224 (10.5) 11,868,826 (10.7) 10,899,036 (10.0) 10,616,589 (9.6) 18.0 16.8 12.4 8.6 J01 Acute sinusitis 6,156,728 (5.6) 5,124,887 (4.6) 5,069,092 (4.6) 5,370,773 (4.8) 81.3 86.3 83.8 81.2 J02 Acute pharyngitis 8,298,233 (7.6) 7,750,638 (7.0) 7,448,247 (6.8) 7,454,750 (6.7) 51.7 46.2 41.8 37.0 J03 Acute tonsillitis 15,541,619 (14.2) 13,245,438 (12.0) 12,975,473 (11.9) 13,318,685 (12.0) 77.1 79.1 77.1 75.4 J04 Acute laryngitis and tracheitis 5,094,496 (4.7) 4,956,058 (4.5) 4,634,926 (4.2) 4,438,529 (4.0) 59.8 57.1 53.3 49.9 Acute obstructive laryngitis J05 [croup] & epiglottitis 179,991 (0.2) 159,816 (0.1) 162,361 (0.1) 162,158 (0.1) 67.8 71.3 67.9 66.0 Acute upper respiratory J06 infections of multiple & unspecified sites 12,709,624 (11.6) 12,647,194 (11.4) 12,695,070 (11.6) 12,778,115 (11.5) 39.5 34.7 30.3 26.5 Influenza due to identified J09 avian influenza virus J10 Influenza due to other identified influenza virus 170 (0.0) 11.2 35,822 (0.0) 31752 (0.0) 33,888 (0.0) 27,626 (0.0) 37.9 32.0 28.5 34.9 J11 Influenza, virus not identified 234,053 (0.2) 183,351 (0.2) 230,253 (0.2) 227,583 (0.2) 38.3 43.7 40.0 36.4 J12 Viral pneumonia, nec 46,400 (0.0) 48,700 (0.0) 46,348 (0.0) 36,059 (0.0) 66.6 72.5 66.1 60.8 J13 Pneumonia due to streptococcus pneumoniae Pneumonia due to J14 haemophilus pneumoniae 23,718 (0.0) 26,512 (0.0) 18,407 (0.0) 17,237 (0.0) 77.3 89.2 85.7 80.9 3,733 (0.0) 3,500 (0.0) 3,395 (0.0) 4,490 (0.0) 68.5 75.4 72.0 75.6 J20 Acute bronchitis 20,156,132 (18.4) 22,354,537 (20.2) 22,315,038 (20.4) 23,397,015 (21.1) 64.8 70.8 67.9 65.3 J21 Acute bronchiolitis 2,617,041 (2.4) 2,893,986 (2.6) 2,913,150 (2.7) 3,021,988 (2.7) 69.8 75.8 71.3 67.7 J22 J30 J31 Unspecified acute lower respiratory infection Vasomotor and allergic rhinitis Chronic rhinitis, nasopharyngitis & pharyngitis 1,066,610 (1.0) 1,303,858 (1.2) 1,347,912 (1.2) 1,407,912 (1.3) 66.7 74.0 71.3 68.3 7,951,937 (7.3) 8,538,135 (7.7) 9,040,489 (8.3) 9,509,953 (8.6) 32.6 33.6 28.9 24.4 2,073,744 (1.9) 2,128,853 (1.9) 2,011,089 (1.8) 1,811,670 (1.6) 62.8 69.9 69.1 66.1 J32 Chronic sinusitis 2,057,304 (1.9) 2,485,988 (2.2) 2,399,234 (2.2) 2,289,845 (2.1) 76.5 86.2 84.1 81.6 J33 Nasal polyp 27,563 (0.0) 28,521 (0.0) 31,849 (0.0) 28,201 (0.0) 47.0 49.9 47.3 43.6 J34 Other disorders of nose and nasal sinuses 721,651 (0.7) 763,942 (0.7) 822,641 (0.8) 850,235 (0.8) 58.2 62.4 60.2 57.1 Chronic diseases of tonsils J35 287,147 (0.3) 401,843 (0.4) 460,936 (0.4) 484,433 (0.4) 60.6 73.7 73.4 72.6 and adenoids J36 Peritonsillar abscess 1,036,348 (0.9) 1,240,704 (1.1) 1,272,376 (1.2) 1,252,337 (1.1) 83.3 93.5 91.7 90.1 J37 Chronic laryngitis and laryngotracheitis Disease of vocal cords and J38 larynx, nec J39 Other diseases of upper respiratory tract bronchitis, not specified as J40 acute or chronic 361,407 (0.3) 424,530 (0.4) 434,873 (0.4) 420,172 (0.4) 45.1 58.0 56.2 54.6 332,162 (0.3) 351,079 (0.3) 388,657 (0.4) 400,460 (0.4) 28.2 29.9 27.4 25.3 206,159 (0.2) 290,321 (0.3) 413,438 (0.4) 491,936 (0.4) 54.3 69.0 66.9 65.6 2,322,307 (2.1) 2,549,872 (2.3) 2,513,421 (2.3) 2,588,924 (2.3) 53.6 59.5 58.8 57.1
189 / Korean J Clin Pharm, Vol. 27, No. 3, 2017 Table 2. Trend in visit and antibiotic prescriptions for specific respiratory tract, 2005-2008(continued). Simple and mucopurulent J41 chronic bronchitis Unspecified chronic J42 bronchitis Nonsuppurative otitis H65 media Suppurative and H66 unspecified otitis media Otitis media in diseases H67 classified elsewhere 1,127,013 (1.0) 1,226,647 (1.1) 1,250,690 (1.1) 1,266,494 (1.1) 50.5 55.4 51.9 49.5 1,372,263 (1.3) 1,382,650 (1.2) 1,180,263 (1.1) 1,075,562 (1.0) 44.4 48.5 44.4 43.3 1,845,700 (1.7) 1,959,061 (1.8) 1,853,751 (1.7) 1,847,178 (1.7) 72.4 79.1 74.4 71.3 4,095,273 (3.7) 4,426,755 (4.0) 4,334,179 (4.0) 4,333,053 (3.9) 77.9 85.4 80.5 77.3 12,538 (0.0) 10,918 (0.0) 11,796 (0.0) 15,835 (0.0) 74.5 89.5 85.8 78.4 결과지표및통계분석주요결과지표는호흡기계질환에서의항생제처방률과사용량이다. 항생제처방률은호흡기계질환을주상병, 부1상병으로병의원을내원한내원일수대비항생제처방횟수를산출하였다. 호흡기계질환내원일당처방률을산출함에있어서, 급성상기도감염 (J00-J06), 하기도감염 (J20-J22, J40-J42), 기타호흡기계질환, 중이염 (H65-H67) 분류와각각의상병명별로빈도분석을실시하였다. 또한, 외래호흡기계상병으로병의원을방문한환자의총투약일수를계산하고자, 첫방문시점에서투약일수가종료되는날로부터재방문 ( 동일의료기관혹은타의료기관 ) 에대해서동일한에피소드로묶었다. 동일질환에피소드를구축함에있어서는다음과같은 4가지방식으로구현하였다. 1) 동일의료기관만 3일이내재방문한경우, 2) 동일의료기관만 7일이내방문한경우, 3) 동일및타의료기관을포함하여 3일이내재방문한경우, 4) 동일및타의료기관을포함하여 7 일이내재방문한경우. 항생제사용량 ( 단위 : DDD/ 환자 1,000명 / 일 ) 산출공식은다음과같다. 환자수는분석대상상병으로병의원을방문한환자수를적용하였다. 단, 각각의상병이모두포함된급성상기도감염환자수등은각각의상병별환자수를합산하지않고, 질병의중분류군에한번이라도포함된환자수를재산출하였다. 사용량 = 1 년동안소비된의약품의양 (mg) 1000 명 = DDD/1000 patients/day DDD(mg) 365 일 환자수 WHO에서성인 (70kg) 의하루유지용량을근거로단일제제의 DDD를산출하고있으며, 생물학적효용이제형별로다르므로, 동일한의약품이라도제형별로 DDD를달리결정하고있다. 12) 본연구에서는이러한 DDD를이용하여, DDD/ 환자 1,000명 / 년지표를사용하였다. 본연구의자료분석은 SAS 9.1 을사용하여빈도분석을실시하였다. 연구결과 호흡기계상병별항생제처방률변화외래호흡기계상병을주상병혹은부1상병으로청구된건중각세부상병별비중을살펴보면, 급성상기도감염중가장많은급성편도염 (J03) 은 2005년 14.2% 에서 2008년 12% 로, 감기는 2005년 10.5% 에서 2008년 9.6% 로감소하고있었다. 반면, 급성하기도감염중기관지염 (J20) 은 2005년 18.4% 에서 2008년 21.1% 로그비중이점차증가하는양상을보이고있었다 (Table 2). 호흡기계상병진료건의내원일당항생제처방률은급성부비동염 (J01) 에서 2005년 81.3% 에서 2008년 81.2% 로유사하지만, 급성인두염 (J02) 은 51.7% 에서 37% 로점차감소하고있었고, 급성편도염 (J03) 도미미하나 77.1% 에서 75.4% 로감소하고있었다 (Table 2). 항생제계열별사용량외래호흡기계질환으로병의원을방문하여항생제를처방받은환자의사용량은 DDD/ 환자 1,000명 / 일 (DID) 로는 2005년 20.38 에서 2006년 22.01, 2007년 20.42, 2008년 20.85로 2006년에는크게증가했으나, 이후감소하는것으로나타났다. 2008년기준베타락타마제포함페니실린계 (J01CR, combinations of penicillins, incl. beta-lactamase inhibitors) 는 7.93 DID 로가장많고, 2세대세팔로스포린계 (J01DC, second-generation cephalosporins) 는 3.71, 마크로라이드계 (J01FA, macrolide) 는 3.26이었다. 광범위페니실린계 (J01CA, penicillins with extended spectrum) 은 2005년 5.49 7.93 DID 였으나 2008년 2.57로크게감소하였다. 마크로라이드계 (J01FA, macrolides) 의항생제사용량은 2005년 2.3 DID에서 2008년 3.26으로지속적으로증가하고있었다 (Table 3). 영국의진료지침등에서는급성부비동염, 급성인두염, 급성기관지염, 급성중이염의대부분이바이러스성이므로, 일단항생제를사용하기전에관찰하라고권고하고있고, 항생제를
건강보험청구자료를이용한외래급성호흡기계질환방문과항생제처방률변화분석 / 190 Table 3. Antibiotics use by DID (DDD/1,000 patients/day), 2005-2008. ATC 2005 2006 2007 2008 sum of DDD sum of day DID sum of DDD sum of day DID sum of DDDsum of day DID sum of DDD sum of day DID J01A J01AA 1,733,633 889,210 0.16 1,689,477 848,656 0.16 1,358,972 688,542 0.12 1,072,785 570,819 0.09 J01B J01BA 149,607 248,654 0.01 155,759 254,899 0.01 126,664 214,158 0.01 114,939 190,807 0.01 J01C J01CA 58,788,947 58,929,666 5.49 58,476,829 55,925,405 5.41 39,991,240 39,149,633 3.66 29,187,751 30,620,368 2.57 J01CE 825 14,456 0 738 2,537 0 764 2,118 0 629 1,677 0 J01CF 1 3 0-14 - 37 - J01CR 64,853,328 104,006,008 6.06 72,509,775 110,709,600 6.71 77,932,865 115,819,968 7.13 89,992,981 127,995,451 7.93 J01D J01D 10,505-11,045-12,551-12,696 - J01DB 14,582,299 25,840,800 1.36 13,656,032 23,660,117 1.26 12,979,898 22,025,607 1.19 11,631,337 19,207,673 1.02 J01DC 32,082,896 53,660,906 3 33,477,221 53,859,956 3.1 35,041,765 55,652,287 3.2 42,145,911 65,514,544 3.71 J01DD 4,662,437 10,805,988 0.44 10,586,857 16,319,056 0.98 6,150,891 17,024,443 0.56 7,705,403 21,357,888 0.68 J01DE 155 157 0 160 175 0 135 147 0 157 222 0 J01DF 49 147 0 22 38 0 25 192 0 43 329 0 J01DH 514 1,272 0 894 2,020 0 1,317 2,546 0 1,096 2,137 0 J01E J01EC - - - 162 138 0 J01EE 4,579,324-4,217,657-3,605,083-3,021,443 - J01F J01FA 24,634,256 44,359,525 2.3 29,924,935 48,717,409 2.77 32,320,447 50,000,235 2.96 36,978,242 52,881,333 3.26 J01FF 1,877,949 5,862,499 0.18 1,729,652 5,293,703 0.16 1,596,860 4,828,751 0.15 1,575,971 4,767,973 0.14 J01G J01GA 14,005 9,699 0 16,698 12,375 0 15,073 10,624 0 16,601 11,345 0 J01GB 737,054 6,955,935 0.07 685,398 6,086,896 0.06 624,122 5,523,800 0.06 634,956 5,482,798 0.06 J01M J01MA 14,122,769 18,694,987 1.32 15,021,959 19,932,511 1.39 15,115,044 20,229,790 1.38 15,663,269 21,455,098 1.38 J01MB 29,080 34,925 0 21,330 20,366 0 6,225 5,542 0 20 23 0 J01R J01RA 355,234-348,966-298,485-271,923 - J01X J01XA 3,120 5,856 0 3,453 6,353 0 2,805 4,995 0 2,712 4,698 0 J01XB 3 2 0-25 9 0 18 12 0 J01XC 26,502 40,194 0 30,912 50,666 0 27,320 43,713 0 24,178 37,603 0 J01XD 456 128,970 0 569 148,083 0 498 156,970 0 605 166,235 0 J01XX 586 819 0 558 778 0 399 566 0 216 296 0 Total 218,300,470 335,435,741 20.38 237,989,229 346,429,267 22.01 223,293,354 335,300,769 20.42 236,749,980 353,575,566 20.85 J00: Acute nasopharyngitis [common cold], J01: Acute sinusitis, J02: Acute pharyngitis, J03: Acute tonsillitis, J04: Acute laryngitis and tracheitis, J05: Acute obstructive laryngitis[croup] and epiglottitis, J06: Acute upper respiratory infections of multiple and unspecified sites, J20: Acute bronchitis, J21: Acute bronchiolitis, J22: Unspecified acute lower respiratory infection, J40: bronchitis, not specified as acute or chraconic, J41: Simple and mucopurulent chronic bronchitis, J42: Unspecified chronic bronchitis, H65: Nonsuppurative otitis media, H66: Suppurative and unspecified otitis media, H67: Otitis media in diseases classified elsewhere 처방할경우 1차약제는 J01CA의 amoxicillin 사용을권고하고있다. 그러나, J01CR의 amoxicillin/clavulanate 의사용이모든급성호흡기계질환에서사용이많았고, 2세대세팔로스포린계 (J01DC, third-generation cephalosporins) 와마크로라이드계 (J01FA, macrolide) 의사용이컸다. 가장항생제사용량이많은질환인기관지염에서는베타락타마제포함페니실린계 (J01CR, combinations of penicillins, incl. beta-lactamase inhibitors) 이 2.06 DID, 마크로라이드계 (J01FA, macrolide) 가 1.00 DID, 2세대세팔로스포린계 (J01DC, third-generation cephalosporins) 가 0.97 DID 였고, 급성편도염에서도베타락타마제포함페니실린계가 1.82 DID, 2세대세 팔로스포린계가 0.89 DID 를차지했다 (Table 4). 호흡기계상병별투약일수및지연처방현황외래호흡기계상병에피소드별 ( 동일의료기관만 3일이내재방문, 동일의료기관만 7일이내재방문, 동일및타의료기관을포함하여 3일이내재방문, 동일및타의료기관을포함하여 7 일이내재방문 ) 항생제처방이이뤄진환자와투약일수분포를살펴보았다. 모든의료기관 3일이내재방문으로살펴보면, 급성부비동염 (J01) 으로 1번만항생제를처방받은비율은 76.78% 였고, 투여일수는 3.13일이었다. 기관지염 (J20) 또한 1번만병원을방문해처방받은비율은 62.6% 였다 (Table 5).
191 / Korean J Clin Pharm, Vol. 27, No. 3, 2017 Table 4. Antibiotics use by DID (DDD/1,000 patients/day) for specific respiratory tract, 2008. URTI LRIT OM ATC DID Total J01A J01C J01D J01F J01M J01AA J01CA J01CR J01DB J01DC J01DD J01FA J01FF J01MA J01 Acute sinusitis 2.92 0 0.31 1.53 0.06 0.36 0.07 0.47 0.01 0.1 J02 Acute pharyngitis 1.41 0.01 0.23 0.51 0.09 0.3 0.03 0.15 0.01 0.09 J03 Acute tonsilitis 4.15 0.01 0.51 1.82 0.27 0.89 0.05 0.33 0.04 0.21 J04 Acute laryngitis and trachettis 1.46 0.01 0.15 0.56 0.08 0.28 0.02 0.24 0.01 0.1 J05 Acute obstructive laryngitis(croup) and epiglottitis 0.04 0 0.01 0.02 0 0.01 0 0.01 0 0 J06 Acute upper respiratory infections of multiple and unspecified sites 1.51 0.01 0.25 0.56 0.09 0.29 0.02 0.16 0.01 0.1 J20 Acute bronchitis 5.59 0.03 0.76 2.06 0.29 0.97 0.12 1.00 0.04 0.31 J21 Acute bronchiolitis 0.58 0 0.06 0.21 0.02 0.11 0.03 0.13 0 0.02 J22 Unspecified acute lower respiratory infection 0.34 0 0.04 0.12 0.02 0.07 0.01 0.06 0 0.02 J40 Bronchitis, not specified as acute or chronic 0.65 0 0.06 0.21 0.03 0.12 0.02 0.12 0 0.07 J41 Simple and mucopurulent chronic bronchitis 0.28 0 0.03 0.07 0.02 0.06 0.01 0.05 0 0.04 J42 Unspecified chronic bronchitis 0.22 0 0.03 0.05 0.01 0.04 0.01 0.05 0 0.03 H65 Nonsuppurative otitis media 0.66 0 0.06 0.29 0.02 0.1 0.07 0.09 0 0.03 H66 Suppurative and unspecified otitis media 1.27 0 0.23 0.57 0.02 0.15 0.15 0.09 0 0.06 H67 Otitis media in diseases classfied elsewhere 0 0 0 0 0 0 0 0 0 0 ARTI : acute respiratory tract infections, URTI : upper respiratory tract infections, LRTI : lower respiratory tract infections, OM : otitis media 고찰및결론 본연구는약제급여적정성평가대상질환인급성상기도감염 (J00-J06) 뿐만아니라급성하기도감염, 중이염, 기타호흡기계질환내원일수변화, 호흡기계상병별항생제처방률과투여일수및항생제사용량을살펴보았다. 검토결과다음과같은함의점을도출할수있었다. 첫째, 호흡기계상병별내원일수변화를살펴보면, 가장많은비중을차지하고있는급성기관지염 (J20) 의내원일수는점점증가하는양상을보이고있었고, 편도염, 감기, 인두염은점차감소하고있었다. 이처럼급성하기도감염이증가하는현상이질병자체의변화인지, 급성상기도감염평가로인해급성하기도감염의청구경향이증가하는것인지에대해서는추가분석이필요하겠다. 둘째, 호흡기계질환에서 2008년항생제처방률은급성편도염 (J03) 75.4%, 급성부비동염 (J01) 81.2%, 급성기관지염 65.3% 로높은편이다. 물론, 호흡기계질환의항생제처방률이높은것은비단국내문제만이아니다. 과거미국에서도급성기관지염의항생제처방률은 1993년 82.2% 였으나, 미국질병통제예방센터 (centers for disease control and prevention, CDC) 는 1995년부터팜플렛등다각적교육자료를통해, 항생제적절사용캠페인을벌인결과, 1999년급성기관지염의항생제처방률은 29.3% 로감소하는효과가있었다. 셋째, 전체항생제사용은베타락타마제포함페니실린계 (J01CR, combinations of penicillins, incl. beta-lactamase inhibitors), 2세대세팔로스포린계 (J01DC, second-generation cephalosporins), 마크로라이드계 (J01FA, macrolide) 에서많이사용되고있는것으로나타났다. 괄목할만한점은마크로라이드계 (J01FA, macrolides) 의경우 2005년 2.3에서 2008년 3.26으로지속적으로증가하고있다는점으로, 광범위항생제사용이점차증가하고있었다. 호흡기계상병별항생제계열이어떻게사용되고있는지살펴본결과, 급성부비동염, 급성인두염, 급성기관지염, 급성중이염에서항생제를처방할경우외국에서는 1차로 amoxicillin, ampicllin을권고하고있으나, 급성호흡기계질환에서권고하는페니실린계항생제사용은낮은반면, 2세대, 3세대이상세파, 마크로라이드계항생제비중이지속적으로증가하고있는것으로나타났다. 넷째, 항생제에대한국내지침은현재소아급성상기도감염만개발되어있고, 향후성인의급성상기도감염과급성하기도감염에대해서도개발될예정이기에, 외국의항생제사용지침을기준으로국내항생제사용경향을분석한결과는다음과같다. 미국, 영국, 호주의항생제지침에서는급성부비동염의경우세균성혹은합병증위험이있을때처방하지만, 보통은항생제가불필요하다고권고하고있다. 또한항생제를처방한다면, 7일혹은 10일치료를제시하고있다. 급성인두염에대해서도 90% 가바이러스성이고, 인후배양법양성이나오고고열, 림프절비대등의 2가지이상의증세가있을때항생제를처방하고, 10일치료를권고하고있다. 급성기관지염또한 90% 가바이러스성이고, 만성기관지염이악화된경우에만항생제를처방하도록제시하고있다. 5-8) 그러나분석결과,
Table 5. The antibiotic prescription rate in same episode. Classification Dise ase Revisit only same medical institution No.of episode Only Within 3days Within 7days Antibiotic prescription Administration days Antibiotic prescription Administration days No.of First Second Third First Second Third episode Only First Second Third First Second Third J00 8,933,769 803,122 (9.54) 119,803 150,488 68,904 3.12 2.41 2.54 2.44 8,874,012 793,188 (9.54) 123,440 154,506 71,183 3.12 2.43 2.56 2.44 J01 9,299,657 5,930,622 (77.82) 1,636,691 1,620,785 799,296 3.16 2.49 2.77 2.61 9,226,228 5,844,583 (77.81) 1,660,987 1,647,687 834,137 3.16 2.50 2.78 2.62 J02 8,534,845 2,908,790 (37.75) 604,426 628,610 248,585 2.81 2.29 2.50 2.42 8,479,002 2,869,321 (37.71) 617,761 644,624 258,705 2.81 2.30 2.51 2.42 J03 17,323,063 11,162,511 (75.25) 2,486,275 2,395,355 797,523 2.73 2.25 2.45 2.38 17,010,286 10,746,354 (75.03) 2,633,776 2,554,447 907,087 2.74 2.27 2.46 2.38 J04 5,949,363 2,630,261 (50.87) 614,160 626,123 258,028 2.86 2.29 2.50 2.40 5,923,777 2,608,096 (50.85) 620,892 634,229 265,355 2.86 2.30 2.51 2.40 J05 188,088 96,586 (63.80) 31,861 31,985 15,460 2.92 2.21 2.54 2.48 187,158 95,834 (63.94) 32,077 32,227 15,754 2.92 2.22 2.54 2.48 J06 12,138,901 3,103,617 (27.85) 561,727 606,886 228,642 2.84 2.33 2.51 2.39 12,042,686 3,055,285 (27.83) 577,702 627,058 240,827 2.84 2.34 2.51 2.40 J20 26,049,593 14,062,465 (63.28) 3,456,027 3,566,428 1,543,829 2.92 2.40 2.60 2.51 25,566,278 13,563,884 (63.21) 3,606,133 3,738,7261,720,006 2.92 2.41 2.61 2.52 J21 3,092,565 1,567,996 (64.53) 547,086 566,022 350,666 2.94 2.40 2.60 2.49 3,062,977 1,543,777 (64.61) 551,507 571,398 365,088 2.94 2.41 2.61 2.50 J22 1,558,138 902,984 (67.39) 201,807 201,515 77,619 2.95 2.41 2.60 2.48 1,556,303 901,014 (67.39) 202,450 202,240 78,221 2.95 2.41 2.60 2.49 J40 2,542,839 1,312,515 (58.64) 268,506 269,062 113,486 3.13 2.39 2.56 2.44 2,536,157 1,306,218 (58.65) 270,593 271,465 115,293 3.13 2.39 2.57 2.44 J41 1,074,884 520,464 (54.61) 109,595 107,987 51,679 3.55 2.38 2.54 2.34 1,073,324 519,287 (54.63) 109,975 108,343 52,120 3.55 2.39 2.55 2.34 J42 715,473 308,614 (47.17) 63,454 61,537 33,283 4.16 2.37 2.51 2.29 714,374 307,943 (47.21) 63,696 61,736 33,513 4.16 2.38 2.52 2.30 H65 2,470,075 1,274,494 (71.88) 708,179 680,111 635,695 3.28 2.38 2.69 2.46 2,433,420 1,240,891 (71.84) 712,755 684,912 659,921 3.28 2.39 2.70 2.48 H66 4,307,042 2,336,425 (77.77) 1,287,064 1,227,356 1,046,836 3.20 2.43 2.73 2.52 4,201,142 2,231,247 (77.65) 1,303,680 1,245,0821,117,672 3.21 2.45 2.74 2.54 H67 12,744 6,380 (70.77) 3,674 3,526 2,777 2.84 2.39 2.58 2.61 12,742 6,378 (70.77) 3,674 3,527 2,778 2.84 2.39 2.58 2.61 건강보험청구자료를이용한외래급성호흡기계질환방문과항생제처방률변화분석 / 192
Table 5. The antibiotic prescription rate in same episode(continued). Classification Dise ase Revisit same or different medical institution No.of episode Only Within 3days Within 7days Antibiotic prescription Administration days Antibiotic prescription Administration days No.of First Second Third First Secon Third episode Only First Second Third First Second Third d J00 8,228,750 653,450 (8.99) 153,135 201,889 133,843 3.13 2.60 2.71 2.64 8,122,044 637,215 (8.98) 157,943 207,718 139,441 3.13 2.62 2.73 2.65 J01 7,745,243 4,219,030 (76.78) 2,055,008 2,051,892 1,661,464 3.11 2.71 2.91 2.84 7,600,850 4,072,265 (76.69) 2,078,704 2,080,798 1,755,627 3.11 2.72 2.91 2.85 J02 7,781,156 2,428,135 (37.23) 741,345 781,493 439,438 2.78 2.42 2.60 2.59 7,692,474 2,371,776 (37.18) 757,651 801,831 459,153 2.79 2.43 2.61 2.59 J03 15,822,324 9,484,443 (75.64) 3,042,533 2,939,476 1,375,212 2.70 2.37 2.55 2.54 15,384,841 8,938,553 (75.34) 3,216,559 3,129,167 1,557,385 2.71 2.38 2.55 2.54 J04 5,287,114 2,091,508 (50.15) 767,723 794,272 475,069 2.83 2.45 2.62 2.59 5,242,857 2,057,272 (50.12) 775,660 804,650 490,990 2.83 2.45 2.63 2.59 J05 168,816 77,640 (62.96) 36,902 37,163 24,187 2.87 2.36 2.64 2.64 167,619 76,726 (63.21) 37,143 37,472 24,551 2.88 2.36 2.64 2.64 J06 11,050,461 2,558,131 (27.20) 716,381 789,470 436,890 2.82 2.48 2.63 2.59 10,884,253 2,484,229 (27.19) 736,775 816,477 463,391 2.82 2.48 2.63 2.60 J20 22,656,163 10,802,696 (62.60) 4,322,656 4,506,547 2,996,850 2.89 2.55 2.70 2.68 21,801,036 10,028,273 (62.49) 4,488,081 4,709,620 3,402,775 2.90 2.56 2.71 2.69 J21 2,575,958 1,114,991 (63.76) 633,500 661,713 621,566 2.91 2.54 2.69 2.64 2,527,876 1,080,445 (63.91) 635,984 665,818 649,523 2.92 2.54 2.69 2.64 J22 1,370,489 707,929 (66.89) 260,006 262,242 153,748 2.93 2.55 2.71 2.69 1,367,256 704,765 (66.90) 260,808 263,247 155,105 2.94 2.56 2.72 2.69 J40 2,256,777 1,050,990 (57.89) 343,830 348,489 220,260 3.14 2.56 2.71 2.66 2,244,922 1,040,829 (57.90) 346,568 351,743 224,429 3.14 2.57 2.72 2.67 J41 933,823 404,502 (54.14) 142,268 141,799 101,156 3.62 2.64 2.79 2.67 931,039 402,555 (54.17) 142,700 142,270 102,200 3.62 2.65 2.80 2.68 J42 622,503 239,157 (46.04) 82,119 81,239 64,373 4.34 2.70 2.84 2.70 620,625 238,150 (46.10) 82,337 81,455 64,946 4.34 2.71 2.85 2.70 H65 1,816,109 718,110 (68.89) 735,630 711,877 1,132,862 3.21 2.59 2.80 2.70 1,757,334 677,093 (68.72) 730,237 707,382 1,183,767 3.20 2.60 2.81 2.72 H66 3,213,634 1,376,911 (76.78) 1,357,989 1,305,086 1,857,695 3.13 2.60 2.82 2.73 3,049,073 1,245,405 (76.45) 1,351,240 1,301,372 1,999,664 3.14 2.61 2.82 2.74 H67 9,960 4,124 (67.68) 3,718 3,556 4,960 2.77 2.48 2.59 2.69 9,957 4,121 (67.68) 3,718 3,556 4,962 2.77 2.48 2.59 2.69 193 / Korean J Clin Pharm, Vol. 27, No. 3, 2017 J00: Acute nasopharyngitis [common cold], J01: Acute sinusitis, J02: Acute pharyngitis, J03: Acute tonsillitis, J04: Acute laryngitis and tracheitis, J05: Acute obstructive laryngitis[croup] and epiglottitis, J06: Acute upper respiratory infections of multiple and unspecified sites, J20: Acute bronchitis, J21: Acute bronchiolitis, J22: Unspecified acute lower respiratory infection, J40: bronchitis, not specified as acute or chraconic, J41: Simple and mucopurulent chronic bronchitis, J42: Unspecified chronic bronchitis, H65: Nonsuppurative otitis media, H66: Suppurative and unspecified otitis media, H67: Otitis media in diseases classified elsewhere
건강보험청구자료를이용한외래급성호흡기계질환방문과항생제처방률변화분석 / 194 우리나라는대부분이 1회방문으로항생제가처방되고있었고, 투여일수는대체로 3일에그치고있었다. 급성부비동염 ((J01) 의 76.78% 가 1회방문에서처방되고있었고, 급성인두염 (J02) 은 37.23% 가 1방문에서처방되었다. 급성기관지염 (J20) 또한 90% 가바이러스성이라고제시되지만, 국내에서는 62.6% 가 1회방문에서처방되고있었다. 본연구는항생제적정사용방안을모색하기위한기초자료로서, 건강보험청구자료를이용하여, 호흡기계질환의변화와항생제처방률, 항생제사용량을산출하였다. 기존의표본자료와다르게본연구는 4년간의전수자료를사용하여, 호흡기계질환의변화양상을시간적변화에따라서정확하게분석했다는장점을갖고있다. 또한, 약제급여적정성평가에서수행하는급성상기도감염항생제처방률평가는주상병만을기준으로하기에, 고혈압, 당뇨와같은만성질환으로방문한환자가감기를동반하는경우평가대상에서제외된다는단점을안고있다. 이러하기에본연구는주상병과부1상병을모두검토해급성호흡기계질환이포함되는명세서를대상으로분석하였다. 그럼에도불구하고본연구에는다음과같은한계점이있다. 본연구는의료기관의처방전내역자료를활용하였기에, 실제환자가복용했는지여부에대해서는추적하지못했다는단점을가지고있다. 이러한점으로인해항생제처방이과다측정될우려가있기는하다. 또한, 2005년에서 2008년까지시간의변화외에청구양식의변화 ( 일자별청구 ) 와각종제도의변화 (2006년항생제처방률공개, 2007년선별등재제도도입 ) 등의큰제도개혁이이뤄진바있다. 이외에도가계경제수준등의변화가의료기관방문일수변화에도영향을미쳤을수있다. 또한, 건강보험청구자료는검사결과를확인할수없기때문에, 실제세균성이기때문에항생제를처방한경우를포함하고있다. 그러나, 일반적으로외국지침에서제시하는세균성의비율에대비한다고하더라도, 국내호흡기계상병별항생제처방률은상당히높은수준이다. 이는본연구결과가항생제를처방받은호흡기계질환이아니라, 호흡기계상병으로의료기관을내원한경우를대상으로하였기에, 상당히의의가크다고할수있겠다. 그럼에도분석시점이상당히지나서, 본연구결과가여전히그러한지에대해서는최근의자료로업데이트한연구가필요하다고하겠다. 인체에서의항생제사용량증가는내성의증가를유발할수있고, 내성균의전파로인한세계적보건위협을해결하기위한노력이필요한시점이다. 항생제사용감소방안마련을위해, 불필요한항생제사용이발생하는영역에대한탐구활동이선행되는추가연구가활발히이뤄져야하겠다. 참고문헌 1. McCaig DJ, Stewart D, Harvey Y, et al. An assessment of antibiotic therapy of urinary tract infection in elderly, hospitalised patients. Health Bull 1995;53:359-64. 2. Akkerman AE, Wouden JC, Kuyvenhoven MM, et al. Antibiotics prescribing for respiratory tract infections in Dutch primary care in relation to patient age and clinical entities. J Antimicrob Chemother 2004;54: 1116-21. 3. Cantrell R, Young FY, Martin BC. Antibiotic prescribing in ambulatory care settings for adults with colds, upper respiratory tract infections and bronchitis. Clin Ther 2002;24:170-182. 4. World Health Organization (WHO). Antimicrobial Resistance Global Report on Surveillance 2014. Available from http://www.who.int/drugresistance/documents/surveillancereport/en/. Accessed January 17, 2017. 5. National Institute for Health and Clinical Excellence (NICE). Respiratory tract infections - antibiotic prescribing. NICE clinical guideline 69. July 2008. Available from https://www.nice.org.uk/guidance/cg69. Accessed December 14, 2016. 6. National Prescribing Service (NPS). Management of specific respiratory tract infections; 2009. Available from http://ww2.i2p.com.au/ article/nps-media-releases-june-2009?ed=3?fullscreen. Accessed December 2, 2016. 7. Wong DM, Blumberg DA, Lowe KG. Guidelines for the use of antibiotics in acute upper respiratory tract infections. Am Fam Physician 2006;74:956-66. 8. Scottish Intercollegiate Guideline Network (SIGN). Community management of lower respiratory tract infections in adults: A national clinical guideline; 2002. Available from http://www.sign.ac.uk/guidelines/ fulltext/59/index.html. Accessed January 8, 2016. 9. Health insurance review & assessment service. Drug use evaluation 2001~2010. Available from https://www.index.go.kr/com/cmm/fms/ FileDown.do?apnd_file_id=1449&apnd_file_seq=5. Accessed October 1, 2016. Available from https://www.index.go.kr/com/cmm/ fms/filedown.do?apnd_file_id=1449&apnd_file_seq=5. Accessed October 1, 2016. 10. Organization for Economic Co-operation and Development (OECD). OECD Health Statistics 2016. Available from https://www.oecd.org/ els/health-systems/health-data.htm. Accessed December 11, 2016. 11. National Policy Coordination Meeting. Advisory group on integrated surveillance of antimicrobial resistance (2016~2020. Available from http://www.motie.go.kr/common/download.do?fid=bbs&bbs_cd_ n=81&bbs_seq_n=158481&file_seq_n=1. Accessed October 26, 2016. 12. World Health Organization (WHO). Anatomical Therapeutic Chemical (ATC) Classification System: Guidelines for ATC Classification and DDD Assignment: WHO Collaborating Center for Drug Statistics Methodology, 2014. Available from https://www.whocc.no/atc_ddd_ index/. Accessed December 7, 2016. 13. Mainous AG 3rd, Hueston WJ, Davis MP, et al. Trend in antimicrobial prescribing for bronchitis and upper respiratory infections among adults and children. Am J Public Health 2003;93:1910-4.