한국임상약학회지제 22 권제 4 호 Kor. J. Clin. Pharm., Vol. 22, No. 4. 2012 외래호흡기계질환에서항생제사용에대한후향적평가방안 김동숙 1 배그린 1 김수경 1 이학선 1 김윤진 1 이숙향 2 * 1 건강보험심사평가원연구조성실, 2 아주대학교약학대학 (2012 년 9 월 26 일접수 2012 년 11 월 21 일수정 2012 년 11 월 23 일승인 ) Retrospective Drug Utilization Review of Antibiotics for Respiratory Tract Infection(RTI) in Ambulatory Outpatient Care Dong-Sook Kim 1, Green Bae 1, Su-Kyeong Kim 1, Hak-Seon Lee 1, Yoon Jin Kim 1, and SukHyang Lee 2 * 1 Department of Research, Health Insurance Review & Assessment Service, Seoul 137-927, Korea 2 College of Pharmacy, Ajou University, Suwon 443-749, Korea (Received September 26, 2012 Revised November 21, 2012 Accepted November 23, 2012) As respiratory tract infections (RTI) account for about 60% of all antibiotic prescriptions in outpatient care setting, there are significant concerns about emerging resistance that are largely due to the excessive or inappropriate use of antibacterial agents for viral respiratory infections. This study was aimed to develop retrospective drug utilization review (DUR) program of antibiotics for RTIs using Delphi methods. Retrospective DUR criteria of antibiotics for RTIs were identified based on clinical practice guidelines and opinion of experts. Expert panel members were clinical doctors and pharmacists and Delphi method was applied by survey on 16 members of panels. The claim data from Korean Health Insurance Review & Assessment (HIRA) were used to examine trends in outpatient antibiotic prescription between Janunary to December of 2008. As results, Quality index for RTI was assessed for the claim type, antibiotics use of quantity, duration, number and cost. Antibiotic prescription rate for RTIs, Defined Daily Dose (DDD), and duration of antibiotics use were more recognized as significant quality index by experts' opinion. Use of first line agents suggested by guidelines was low and duration of antibiotics use was shorter compared to the recommendations. Antibiotics were over prescribed for RITs. However, dose and duration of antibiotics were under-used. Key words - Respiratory Tract Infections (RTI), Antibiotics, Drug Utilization Review (DUR) 호흡기계감염 (respiratory tract infections, RTIs) 은일반의 (general practitioner, GP) 가외래항생제처방대상질환의 75% 를차지하고 1), 상기도감염 (upper respiratory tract infection, URI), 급성기관지염 (acute bronchitis) 이전체항생제처방질환의 21% 를차지한다. 2) 미국에서도일차의료에서전체처방약물중항생제처방이차지하는비중은 12~14% 로보고되고있다. 2) 국내에서도 2008년 1월 ~12월의료보험청구자료에서외래진료후항생제처방명세서를분석한결과, 호흡기계질환은내원일수의 92.8%( 명세서의 93.1%) 로대부분을차지했고, 분석대상호흡기계질환 (J00~J06, J20~J22) 은내원일수의 61%( 명세서의 60.3%) 를차지했다. 3) Correspondence to : 이숙향아주대학교약학대학경기도수원시영통구원천동산 5 번지 Tel: +82-31-219-3443, Fax: +82-31-219-3435 E-mail: suklee@ajou.ac.kr 임상연구결과를체계적으로고찰한 Arroll 등 (2009) 은상기도감염에대한항생제사용의편익이불충분하다고보고하였고 4), Reveiz 등 (2010) 은급성후두염 (acute laryngitis) 에서항생제사용에대한체계적문헌고찰에서, 2개연구가조건을충족시켰고, 항생제가급성후두염치료에서는편익이없는것으로제시하였다. 5) Ahovuo-Saloranta A 등 (2009) 은급성부비동염 (acute maxillary sinusitis) 에서항생제효과에대한체계적문헌고찰을수행한결과, 7일이상급성부비동염에서미미한치료효과가있으나, 항생제없이치료받은대상자의 80% 가 2주안에개선되었다고밝혔다. 6) Smith 등 (2010) 은급성기관지염에서항생제처방이더좋은결과를가져올수있다고제시하였으나 7), Staykova T 등 (2009) 은소아의급성세기관지염에서는항생제처방을지지할근거를찾지못했다고하였다. 8) Spinks 등 (2010) 은인후통 (sore throat) 에서항생제사용의편익을검토한결과, 27개의연구가기준을충족시켰고, 상대적편익은있으나, 절대적편익은적은 (modest) 편이었다. 9) 그러나이러한질환의경우항 291
292 Kor. J. Clin. Pharm., Vol. 22, No. 4, 2012 Fig. 1. Process of Developing the Evaluation Plan. 생제효과가미미하거나의학적이득이없음에도불구하고처방되고있다. 2) 국내외호흡기계질환에대한항생제사용지침에서는급성부비동염 (sinusitis) 에서는항생제를처방하지않고, 만성부비동염이나합병증의위험이있을경우처방하도록하고있다. 인두염 (pharyngitis) 에서도바이러스성인두염에대해서는항생제를쓰지않고, 세균성에대한임상적근거가있을경우항생제를처방하도록하고있다. 기관지염 (bronchitis) 은대부분이바이러스성이므로, 항생제를처방할필요가없다. 11-21) 이에따라, 2001년부터의사의청구내역에대한후향적평가의필요성이제기되었고약제급여적정성평가사업을실시하게되었다. 건강보험시심사평가원에서는약제급여적정성평가를통해항생제총량과급성상기도감염에대한항생제처방을관리하고있으나 10), 보다구체적으로상병별, 항생제별적정성향상을위한세부관리기준이마련되어있지못하며, 바이러스성호흡기감염에도불필요한항생제사용이높은것으로나타났다. 특히, 세팔로스포린계 3세대나퀴놀론계과같이부적정사용으로인한내성등사회적비용문제가더욱클수있으므로, 이를적정하게관리할세부기준및관리방안이연구될필요가있다. 본연구는외래호흡기계질환에서사용하는항생제에대한후향적평가방안을모색하고자하였다. 이를위해델파이기법을이용하여공식적합의를도출하였고, 이결과를적용해후보지표값별로국내항생제사용량을분석하였다. 연구대상및방법 평가지표 ( 안 ) 개발과정평가지표 ( 안 ) 을개발하기위해주요외국의진료지침과외 국의질지표를검토하고, 문헌고찰결과에따라항생제를적절히사용할질환, 용량, 투여기간등에대한지표 ( 안 ) 를개발하였다. 또한, 심사평가원심사위원, 관련보건의료전문가등으로자문단을구성하였고, 전문가조사를통해지표를선정하였다. 전문가패널구성및델파이조사학계의자문을구하여 16명의전문가패널을선정하였다. 구성은호흡기계질환을진료하는전문과목을중심으로 5개학회 ( 소아과학회, 결핵및호흡기학회, 이비인후과학회, 가정의학과학회, 대한감염학회 ) 의각 1인씩, 5개개원의협회 ( 소아과, 내과, 이비인후과, 가정의학과, 일반의 ) 각 1인씩, 학계전문가 2인, 임상약학전문가 2인, 건강보험심사평가원심사위원 2인으로구성되었다. Nominal group method 1, 2라운드는우편조사방식으로진행하였다. 1라운드에서 10명이상의패널이동의할경우그항목에대해서는완료하고, 그렇지않은항목에대해서는 2 라운드로진행하고, 2라운드에서는 1라운드에서나타난결과를정리하여전문가패널에게제공하였고, 2라운드에서도 1 라운드와마찬가지로진행하였다. 연구결과 외국의지침및지표검토항생제남용으로내성이증가하게되자, 각국에서는항생제내성을억제하고자, 호흡기계질환을중심으로항생제의적정사용에대한지침을발표하였다. 항생제적정사용지침은호흡기계질환중바이러스성질환에서있어서불필요한항생제사용을감소하는것, 항생제치료가필요한감염질환
외래호흡기계질환에서항생제사용에대한후향적평가방안 293 Table 1. Guidelines on the Use of Antibiotics for Respiratory Tract Diseases in Other Countries (Regarding Immediate Prescription) Disease Korea 1) U.S 2) Canada 3) U.K 4) Australia 5) Acute otitis media (Children) 48-72 hours, Wait and see without prescribing antibiotics <6 months 6 months - 2 years a) 2 years or older *otitis media with effusion Sinusitis d) e) *Acute: *Adult, chronic Pharyngitis f) Bronchitis /Nonspecific cough Bronchiolitis /Nonspecific URI <24 months <24 months 2 years or older b) Aural discharge 2 years or older c) <6 months 6 months -2 years *otitis media with *otitis media with 2 years or older effusion effusion *Acute: *Immediate prescription if the disease affects the whole body or there is a risk of complication Delayed prescription f) g) N/A N/A : Immediate prescription, : Prescribe when it is confirmed, it is bacterial or there is clear clinical evidence, : Antibiotics is not recommended. Note: 1) Korea - Kim SW. Upper Respiratory Infections in Audult. J Korean Med Assoc 2010; 53(1): 10-19. 28) 2) U.S - Diagnosis and management of otitis media in children. National Guideline Clearinghouse Guideline Synthesis 2010. 11) - Wong DM, Blumberg DA, Lowe LG. Guidelines for the use of antibiotics in acute upper respiratory tract infections. Am Fam Physician 2006; 74: 956-66. 12) 3) Canada - Guideline for the diagnosis and treatment of acute otitis media in children.. 2001. 18) - Guideline for the diagnosis and management of acute bacterial sinusitis. AMA 2001. 19) - Guideline for the diagnosis and management of acute pharyngitis. 2010. 20) - Guideline for the management of acute bronchitis.2001 - Guideline for the management of acute exacerbation of chronic bronchitis(aecb). 2001. 21) 4) U.K - National Institute for Health and Clinicl Excellenc(NICE). Respiratory tract infections - antibiotic prescribing. NICE clinical guideline 69. July 2008. 13) - Diagnosis and management of childhood otitis media in primary care. 14) - Management of sore throat and indication for tonsillectomy. 15) - Respiratory tract infections-antibiotic prescribing: Prescribing of antibiotics for self-limiting respiratory tract infections in adults and children in primary care. NICE. 2008. 16) - Guidance for the care of NHS patients in Leeds. 2008. 17) - CKS website (http://cks.nhs.uk) 29) 5) Australia - Clinical audit: management of specific respiratory tract infection 30) a) For 6-month ~ 2-year children, even though it is not confirmed, if symptoms are serious, antibiotics is prescribed. For 2-year or older children, when it is confirmed and is accompanied by symptoms, antibiotics is prescribed. b) For 2-year or older children, when it is confirmed and is accompanied by symptoms, antibiotics is prescribed. c) Prescribe after 72 hours d) If it is acute and bacterial, and symptoms are not improving or serious. prescribe antibiotics. e) If it is acute and bacterial, and symptoms are not improving for 10 days or serious. prescribe antibiotics. f) Acute pharyngitis includes quinsy and acute pharyngotonsillitis. g) For children, wait and see for 14 days and then prescribe antibiotics. 의경우원인균에적합한항생제를선택하는것을주로다루고있다. 의사를대상으로하는외국의호흡기감염질환에대한지침을검토한결과는아래와같다. 미국의 Centers for Disease Control and Prevention(CDC) 은여러관련부처와협력하여적절한항생제사용과관련한지침을제공하고있다. 미국의 CDC와학회등에서입원영역에서는감염방지를위한지침을제공하고있고, 외래영역의상기도감염에있어서적절한항생제사용과관련한지침을제공하고있다. 성인의급성상기 도감염, 비특이적상기도감염, 급성비부비동염 (rhinosinusitis), 급성인두염 (pharyngitis), 합병증이없는급성기관지염 (bronchitis) 에대한적절한항생제사용원칙, 기침진단및관리에대한 American College of Chest Physicians (ACCP) 지침을제공하고있다. 소아에대해서는소아상기도감염에대한항생제사용원칙, 기침진단및관리, 삼출성중이염진단및관리, 인두염, 급성부비동염 (sinusitis), 기관지염, 감기에대한항생제사용원칙지침을제공하고있다. 11),12) 영국의 National Institute for Clinical Excellence(NICE) 에서
294 Kor. J. Clin. Pharm., Vol. 22, No. 4, 2012 Table 2. First Choice of Antibiotics and Its Dose for Respiratory Tract Diseases Disease Korea 1) U.S 2) Canada 3) U.K 4) Australia 5) Acute otitis media (Children) Acute sinusitis Acute pharyngitis Bronchitis Amoxicillin, high dose a) Amoxicillin/clavulanate *penicillin allergy (Type 1 hypersensitivity reaction) Erythromycin Clarithromycin Azithromycin *penicillin allergy(not Type 1) Cefnir,Cefpodoxime,Cefuroxime *Parenteral :Ceftriaxone Penicillin V Penicillin G benzathine Amoxicilin Ampicillin penicillin allergy EM,clindamycin, 1G cepha Penicillin V Penicillin G benzathine Amoxicilin Ampicillin penicillin allergy EM,clindamycin, 1G cepha *When acute bronchitis lasts more than 10 days Amoxicillin macrolides *Acute exacerbation of chronic bronchitis macrolides β-lactamase inhibitor 2G, 3G oral cepha Amoxicillin, high dose b) Amoxicillin/clavulanate *penicillin allergy(type 1 hypersensitivity reaction) Clarithromycin Azithromycin c) *penicillin allergy (not Type 1) Cefnir,Cefpodoxime,Cefuroxime *parenteral :Ceftriaxone *Antibiotics within 6 weeks Amoxicillin β-lactam allergy EM-sulfisoxazole *Antibiotics within 6 weeks, Improvement within 48-72 hours X, relapse Amoxicillin/clavulanate Clarithromycin Amoxicillin *penicillin allergy Erythromycin Amoxicillin Amoxicillin d) Amoxicillin e) Doxycyclin(>12 β-lactam allergy Clindamycin TMP/SMX Macrolides Penicillin V (Veetids) Penicillin G benzathine azithromycin β-lactam allergy EM-sulfisoxazole TMP/SMX Penicillin V Amoxicilin (Under 10 years) β-lactam allergy Clindamycin Amoxicillin/clavulanate *Acute exacerbation of chronic bronchitis Amoxicillin 500 mg β-lactam allergy Doxycycline Tetracycline TMP/SMX years) Macrolides (EM, clarithromycin) Penicillin V Amoxicillin 500 mg Doxycycline Amoxicillin Amoxicillin/clavulanate penicillin allergy cefuroxime cefaclor Amoxicillin Amoxicillin/clavulanate penicillin allergy Cefuroxime, Cefaclor Doxycyclin (>8 years) Penicillin V Benzathine penicillin f) *Acute exacerbation of chronic bronchitis Amoxicillin β-lactam allergy Doxycycline 는감염관리, 호흡기감염에대한지침을제공하고있고 13)-17), 스코틀랜드의 Scottish Intercollegiate Guideline Network (SIGN) 에서는소아의기관지염, 소아의중이염, 인후염및성인의하기도감염에관한지침을제공하고있다. NICE는일차및지역사회관리에서감염관리, 보건의료인관련성감염예방, 호흡기감염에대한항생제처방을제공하고있고, SIGN은소아에서의기관지염, 일차의료영역에서소아의중이염진단및관리, 인두통 (sore throat) 관리와편도선절제술적응증, 성인의하기도감염에대한관리에대한지침을제공하고있다. 캐나다의 Alberta Medical Association에서는 Toward Optimized Practice 웹사이트를통해, 급성세균성부비동염 (sinusitis) 진단및관리, 급성기관지염관리, 급성인두염 (pharyngitis) 진단및관리, 만성폐쇄성폐질환 (chronic obstructive pulmonary disease, COPD) 의악화방지, 급성중이염진단및관리, 지역사회획득폐렴의진단및관리 ( 성인, 소아 ), 장기요양원 (nurshing home) 에서의획득성폐렴에대한진단및관리등질환별로임상진료지침을제공하고있다. 18)-21) 호주의 Office for Aboriginal and Torres Strait Islander Health(OATSIH) 에서는중이염에대한권고사항을제공하고, 주정부인 New South Wales Health Department에서도소아의중이염에대한가이드라인, 소아의인후염에대한가이드라인, 소아의상기도감염에대한지침을제공하고있다. 영국, 프랑스는항생제의적정사용을관리하기위해, 의사를대상으로항생제사용을모니터링한결과를제공하고있고, 이를인센티브지급에활용하기도한다. 호주, 캐나다에서는적절한의약품을사용할수있도록교육자료를제공하고있었고, 캐나다, 미국에서는호흡기계질환에서항생제처방에대해평가지표를산출해제공하며, 후향적 DUR (Drug Utilization Reveiw) 혹은인센티브지급에활용하기도한다. 외국의호흡기계질환에대한항생제지표를정리한결과는 Table 3과같다. 영국 Prescribing Support Unit(PSU) 에서는국내와유사하게항생제의품목수, 비용제네릭항생제처방률등의지표와권고항생제사용에대한비율을진료소 (practice) 혹은일반의 (GP) 에게제공하고있다. 22,23) 프랑스건강보험공단의
외래호흡기계질환에서항생제사용에대한후향적평가방안 295 Table 3. Antibiotics Prescribing Indicators in Other Countries U.K 1) France 2) 3) Canada4) Australia (Retrospective DUR) U.S 5)6) Index Cost and number of antibiotics, generic prescription rate, rate of "approved antibiotics" against all antibiotics, list of antibiotics with an increasing prescription rate (amoxycillin, erythromycin, trimethoprim, penicillin V), Quinolones-cost or use reduction, rate of cephalosporin against penicillin Antibiotics prescription rate Prescription of antibiotics for nonspecific upper respiratory infection Prescription of antibiotics for acute otitis media Prescription of recommended antibiotics for acute pharyngitis Prescription of recommended antibiotics for acute sinusitis and chronic sinusitis Prescription of recommended antibiotics for acute otitis media Prescription of antibiotics for a child with upper respiratory infection Prescription of antibiotics for an adult with acute bronchitis Rate of 2-month - 12-year children with oozing otitis media that do not receive antibiotics prescription Note: 1) PSU(Prescribing Support Unit); Asworth et al., 2002 22) ; Campbell et al., 2000 23) 2) France, SIAM 24) 3) Australia, NPS 25) 4) Canada, Alberta drug utilization program 27) 5) U.S., NCQA(National Committee for Quality Assurance)'s IHA(Intergrated Healthcare Association) California Pay for Performance Program Measurement Year 2009 P4P Draft Manual 26) 6) AHRQ(Agency for Healthcare Research and Quality) 31) 진료정보시스템 (SIAM) 에서도항생제처방률을의사별로통보하고있고 24), 호주의 National Prescription Service Limited (NPS) 는의사에게비특이적상기도감염에서항생제처방, 급성중이염에서항생제처방에대한지표를의사스스로산출하도록처방지표를정의하고있다. 25) 미국 National Committee for Quality Assurance(NCQA) 의 Intergrated Healthcare Association(IHA) California Pay for Performance(P4P) Program에서는 2009년상기도감염소아의항생제처방, 급성기관지염이있는성인에대한항생제처방을지표로가감지급을하고있다 26). 반면, 캐나다의 Alberta drug utilization program은후향적 DUR 프로그램으로서급성인두염, 급성부비동염, 만성부비동염, 급성중이염에서권고항생제를처방하고있는지를살펴보고있다. 27) 후보지표에대한델파이조사결과 16명의전문가를대상으로, Table 4와같이호흡기계질환별로항생제를평가하는것이필요한지질문하였다. 호흡기계질환에대해항생제를처방하지않고관찰하는것이필요한지, 항생제를적절하게사용하는것이중요한지에대해 5점척도로질의한결과, 급성코인두염 ( 감기 ), 바이러스가확인되지않은인플루엔자, 급성인두염, 다발성및상세불명부위의급성상기도감염에대해서항생제를처방하지않고관찰하는것에대해 3점이상응답자가 15명, 14명, 13명, 13명으로대부분이관찰하는필요성을인지하고있었다. 반면, 급성폐쇄성후두염 ( 크루프 ) 및후두개염, 비화농성및상세불명의중이염에대해서는항생제처방없이관찰하는것에대해서 3점이상답한응답자는 3명으로항생제가필요하다고판단하는수준이높았다. 급성부비동염, 급성후두 염및기관염, 상세불명의급성하기도감염에대해서도 3점이상답한응답자가 5명으로나타났다. 항생제의적절사용에대해서는다발성및상세불명부위의급성상기도감염, 달리분류되지않은바이러스성폐렴, 상세불명의급성하기도감염에대해서 3점이상응답자가 14 명이었고, 대부분이호흡기계질환에서항생제의적절사용을평가하는것에대해동의하고있었다. 후보지표별전문가조사결과, 문제의중요성과개선필요성에대해서 3점이상응답자가 9명이상이많아, 대체로후보지표별평가지표의적절성에대해동의하고있는것으로나타났다. 특히질환별항생제처방, 일일사용량 (Defined Daily Dose, DDD) 를기준으로한사용량, 항생제투여일수에대해서는대부분이평가의필요성에대해높게인지하고있었다. 다만, 항생제중 cephalosporin의비중에대해서는문제의중요성이낮아, 2세대이상으로범주를국한할필요가있겠다. 후보지표값산출평가지표는청구행태, 항생제투여여부, 선택, 사용량, 투여기간및품목수, 비용으로구분하여산출하였다. 항생제투여여부는항생제사용이권고되지않는급성편도염, 급성인두염, 급성기관지염, 화농성중이염에서항생제비처방혹은지연처방전략, 혹은항생제처방없이관찰하는지판단하고자, 항생제처방률을살펴보았다. 항생제선택은 Table 3 에제시한항생제권고기준과캐나다앨버타의후향적 DUR 기준을사용하였다. 항생제사용량, 투여기간, 비용은명세서 ( 처방전 ) 단위로산출하였다. 분석자료는 2008년외래호흡기계질환으로병원을방문해진료받고청구한내역을활용
296 Kor. J. Clin. Pharm., Vol. 22, No. 4, 2012 Table 4. Delphi Results of Antibiotics Prescription for Respiratory Tract Diseases code diagnosis 3 points or higher Wait-and see No. of Respondents 3 points or higher Proper use No. of Respondents J00 acute nasopharyngitis(common cold) 15 15 10 16 J01 acute sinusitis 5 15 12 16 J02 acute pharyngitis 13 15 13 16 J03 acute tonsilitis 6 15 12 16 J04 acute laryngitis and tracheitis 5 15 11 16 J05 acute obstructive laryngitis and epiglotitis 3 14 10 15 J06 acute upper respiratory infections of multiple and unspecified sites 13 15 14 16 J09 influenza due to identified avian influenza virus 12 14 10 15 J10 influenza due to other identified influenza virus 14 15 11 16 J11 influenza, virus not identified 12 15 13 16 J12 viral pneumonia, nec 9 15 14 16 J20 acute bronchitis 10 15 15 16 J21 acute bronchiolitis 8 15 12 16 J22 unspecified acute lower respiratory infection 6 15 14 16 J40 bronchitis, not specified as acute or chronic 9 15 13 16 J41 simple and mucopurulent chronic bronchitis 7 15 11 16 J42 unspecified chronic bronchitis 10 15 13 16 H65 nonsuppurative otitis media 10 14 12 15 H66 suppurative and unspecified otitis media 3 14 9 15 하였다. 상병이나질환분류시분석대상호흡기계상병외의호흡기계타상병을포함하는경우는제외하였다. 지표 2-2의세부상병별소아의항생제처방률은외래호흡기계질환을주상병혹은부1상병으로청구된내역자료를이용하여산출하였다. 급성기관지염 (J20) 에서상급종합병원의경우 56.6% 인데비해, 병원 67.8%, 종합병원 67.6%, 의원급 61.5% 로높게나타났다. 급성세기관지염 (J21) 에서도상급종합병원이 51% 인데비해, 병원급이 79.9% 로가장높았고, 의원급 70%, 종합병원 69% 로병원급의항생제처방률이높게나타났다. 지표 2-3의주상병기준호흡기감염질환분류별항생제처방률은급성상기도감염에서항생제처방률은종합병원이 53.3% 로가장높게나타났는데, 약제급여적정성평가에서 2008년 4/4분기기준으로의원급이 55.5% 로가장높고, 병원이 46.2% 인데비해서큰차이를보이고있다. 이는분석대상호흡기계상병외의호흡기계타상병을제외하였기때문인것으로판단된다. 지표 4의권고항생제선택에대해서는상급종합병원에서가장낮았고, 보건기관이대체로높게나타났다. 급성부비동염의경우권고항생제인 amoxicillin, erythromycin, TMP/ SMX 처방이 23.8% 였고, 급성기관지염의 amoxicllin, doxycycline, tetracycline, TMP/SMX 처방비율은 20.3%, 중이염의 amoxicillin, erythromycin, TMP/SMX 처방비율은약 20~24% 로낮았으나, 급성인두염에서는 penicillinv, penicilling benzathine, amoxicillin, clindamycin, erythromycin 처방비율이 47.1% 였다. 그러나 β-lactam allergy가있는경우사용해야하는 clindamycin, erythrmycin을 allergy 여부를판단하지않은채처방했을가능성이높으며, 전반적으로권고항생제처방이낮은것으로판단된다. 지표 5의특정항생제처방비중에있어서, fluoroquinolone의비중이급성상기도감염에서조차 12% 로높을뿐만아니라, 의원급에서상급종합병원 4.6% 에비해 12.4% 로상당히빈번하게처방하는것으로나타났다. Macrolide도비슷한데, 급성상기도감염에서 13.6% 로높고, 의원급이 13.9% 로더높은수준이었다. 반면, penicillin의경우급성상기도감염에서의원급의경우 24.7% 로상급종합병원 4.6% 에비해대체로높은수준이었다. 일일상용량 (DDD) 을기준으로한, 18세이상환자의사용량은대체로 1미만으로 1일상용량보다적은것으로나타났으며, 과소용량으로투여되는문제점이나타났다. 호흡기감염질환에서항생제투여일수는급성기관지염은 2.9일로호흡기감염에투여되는항생제사용기간권고일수인 7-10일에못미치는것으로나타났다.
외래호흡기계질환에서항생제사용에대한후향적평가방안 297 Table 5. Delphi Results of Antibiotics Prescribing Indicators for Respiratory Tract Diseases Indicators 1. For respiratory tract diseases 1), monthly requests rate of acute upper / lower respiratory infections Claims behavior 2-2. For respiratory tract sub-diseases 2), Administratiodren rate of antibiotics prescription for chil- 2-3. Antibiotics prescription rate for upper respiratory infections based on main diseases Selection of Antibiotics 2-1. For respiratory tract sub-diseases 2), rate of antibiotics prescription Formula Number of visits due to acute upper respiratory infection (J00-J06) Number of visits due to acute lower respiratory infection (J20-J22,J40-J42) Total number of antibiotics prescriptions For relevant sub-diseases 2), number of visits Total number of antibiotics prescriptions For relevant sub-diseases 2), number of visits of children under age 18 Total number of antibiotics prescriptions For main disease, number of visits Importance 3 points or higher No. of Respo ndents Need for Improvement 1 Round 2 Round 3 points or higher No. of Respo ndents 3 points or higher No. of Respo ndents 100 9 16 9 16 7 10 100 14 16 12 16 14 16 100 13 15 12 15 14 15 100 11 16 10 16 14 16 3. For respiratory tract sub-diseases 2), Total number of injection antibiotics prescriptions 100 rate of injection antibiotics prescription For relevant diseases 2), number of visits 15 16 11 16 11 16 4. For respiratory tract sub-diseases 2), selection of recommended antibiotics 4-1. For J01(acute sinusitis), rate of prescribing amoxicillin, erythromycin, TMP/SMX 11 16 9 16 9 15 4-2. For J02 (acute pharyngitis) group A beta-hemolytic streptococcus(gabhs), rate of prescribing penicillin V. For children under age 10, rate of prescribing amoxicillin - For patients with β-lactam allergy, rate of prescribing clindamycin, erythromycin 4-3. For J20 (acute bronchitis) which is developed from chronic bronchitis, rate of prescribing amoxicillin - For patients with β-lactam allergy, rate of prescribing doxycyclin, tetracycline, TMP/SMX 4-4. For H65 (non-suppurative otitis media), rate of prescribing amoxicillin, erythromycin, TMP/SMX, clarithromycin 4-5. For H66 (suppurative otitis media and unclear otitis media), rate of prescribing amoxicillin, erythromycin, TMP/SMX, clarithromycin Total number of prescribing 1st choice antibiotics For relevant sub-diseases 2), number of prescriptions 100 5. Rate of certain antibiotics among antibiotics used for respiratory diseases 1 5-1. Rate of fluoroquinolone for respiratory diseases 5-2. Rate of macrolide for respiratory diseases 5-3. Rate of cephalosporin for respiratory diseases 5-4. Rate of amoxicillin-clavulanic acid for respiratory diseases 5-5. Rate of penicillin for respiratory diseases Number of prescribing fluoroquinolone, macrolide, penicillin, amoxicillin-clavulanic acid, cephalosporin For relevant sub-diseases 2), number of p rescribing antibiotics 100 12 16 11 16 8 15 9 16 9 16 9 15 13 16 12 16 8 14 13 16 11 16 10 14 11 16 12 16 11 15 12 16 9 16 12 15 7 16 9 16 11 16 13 16 11 16 11 16 13 16 11 16 10 16
298 Kor. J. Clin. Pharm., Vol. 22, No. 4, 2012 Table 5. Delphi Results of Antibiotics Prescribing Indicators for Respiratory Tract Diseases(continued) Antibiotics Use 6. Dose for patients with age 18 or older based on the DDD(Defined Daily Dose) Admin- 7. Number of administration days for istra- tion respiratory diseases1) days and 8. Number of antibiotics for respiratory number diseases 1) Cost monitoring 9. Cost of each antibiotics for respiratory diseases 1) 10. Cost of antibiotics against administration days for respiratory diseases 1) Sum of defined daily doses For relevant sub-diseases 2), number of prescribing antibiotics with age 18 or older patients Number of administration days For relevant sub-diseases 2), number of visits for diseases 2) Number of antibiotics For relevant sub-diseases 2), number of visits for diseases 2) Cost of antibiotics For relevant sub-diseases 2), number of antibiotics Cost of antibiotics 100 13 16 11 16 10 16 100 14 16 13 16 15 16 100 12 16 12 16 11 16 11 16 9 16 8 16 12 16 9 16 10 16 Note: 1) Respiratory diseases are J00~J06, J20~J22, J40~J42, H65~H67 for main diseases and sub-diseases 1. 2) Based on 2-digit diseases in the fifth revision of Korea's standard cause of death classification 3) Recommended antibiotics use standards in table 4 are the same as table 2. * Index 6 is excluded from the 2nd investigation ** Standard deviation or dispersion are used to see data distribution. However, as they increase if the mean becomes bigger, to correct this, the fluctuation index is calculated by dividing dispersion by mean. Table 6. Result of Antibiotics Prescribing Indicators for Respiratory Tract Diseases Claims behavior For relevant sub-diseases 2), administration days of antibiotics Administration Indicators Total CV Types of insitution Tertiary hospital Clinic 1. For respiratory tract diseases 1), monthly requests rate of acute upper / lower respiratory infections 9.1±135.8 14,495.2 1.7±1.6 11.0±151.7 2-1. For respiratory tract sub-diseases 2), rate of antibiotics prescription (%) - acute bronchitis(j20) 57.4±30.0 52.3 53.2±13.5 57.8±30.4 - acute bornchiolitis(j21) 67.7±28.0 41.4 50.6±18.8 67.6±28.3 - unspecified acute lower respiratory infection(j22) 66.7±30.8 46.2 49.9±17.6 66.8±49.5 - bronchitis, not specified as acute or chronic(j40) 52.9±31.7 60.0 36.8±17.7 54.2±32.9 - simple and mucopurulent chronic bronchitis(j41) 50.8±32.8 64.7 32.7±16.5 51.0±33.3 - unspecified chronic bronchitis(j42) 46.4±32.4 69.8 33.3±13.8 47.7±33.3 - nonsuppurative otitis media(h65) 76.7±23.9 31.2 55.5±14.7 76.3±24.1 - suppurative and unspecified otitis media(h66) 81.7±19.4 23.8 61.0±13.8 81.6±19.3 2-2. For respiratory tract sub-diseases 2), rate of antibiotics prescription for children (%) - acute bronchitis(j20) 65.3±28.8 44.1 56.6±17.9 65.1±29.2 - acute bornchiolitis(j21) 70.2±27.1 38.6 51.0±21.0 70.0±27.4 - unspecified acute lower respiratory infection(j22) 71.9±29.0 40.3 54.6±27.2 71.5±29.2 - bronchitis, not specified as acute or chronic(j40) 69.0±28.6 41.4 57.9±24.4 70.4±29.0 - simple and mucopurulent chronic bronchitis(j41) 73.1±29.4 40.2 61.3±31.8 73.0±29.7 - unspecified chronic bronchitis(j42) 78.4±27.0 34.4 62.0±25.7 79.1±26.9 - nonsuppurative otitis media(h65) 78.7±22.9 29.1 58.8±15.9 78.6±23.1 - suppurative and unspecified otitis media(h66) 85.4±17.1 20.1 70.8±13.2 85.4±17.2 2-3. Antibiotics prescription rate for upper respiratory infections based on main diseases (%) - acute upper respiratory disease 50.0±29.7 59.5 49.7±11.7 51.4±30.2 - acute lower respiratory disease 59.1±30.0 50.7 52.3±16.0 60.2±30.2 - other upper respiratory disease 41.0±29.6 72.3 46.5±12.2 41.2±30.1 - influenza 80.3±21.9 27.3 61.2±13.9 80.8±21.7 - otitis media 86.3±16.2 18.7 62.8±13.9 86.4±15.8
외래호흡기계질환에서항생제사용에대한후향적평가방안 299 Table 6. Result of Antibiotics Prescribing Indicators for Respiratory Tract Diseases(continued) Selection of Antibiotics 3. For respiratory tract sub-diseases 2), rate of injection antibiotics prescription (%) - acute bronchitis(j20) 10.6±20.5 193.1 0.9±0.9 11.3±21.3 - acute bornchiolitis(j21) 5.9±17.8 300.6 0.4±0.7 6.2±18.6 - unspecified acute lower respiratory infection(j22) 10.1±23.7 234.7 0.3±0.8 10.8±24.3 - bronchitis, not specified as acute or chronic(j40) 8.1±20.1 247.9 0.1±1.0 9.1±12.6 - simple and mucopurulent chronic bronchitis(j41) 8.0±20.2 254.4 0.6±1.9 8.9±21.7 - unspecified chronic bronchitis(j42) 7.1±19.4 275.1 0.5±0.9 8.1±20.9 - nonsuppurative otitis media(h65) 15.1±29.9 198.6 1.5±1.7 16.2±31.0 - suppurative and unspecified otitis media(h66) 20.8±31.8 152.9 2.9±3.4 21.9±32.4 4. For respiratory tract sub-diseases 2), selection of recommended antibiotics (%) 4-1. For J01(acute sinusitis), rate of prescribing amoxicillin, erythromycin, TMP/SMX 23.8±29.0 121.5 9.3±8.8 24.2±29.3 4-2. For J02 (acute pharyngitis) group A beta-hemolytic streptococcus(gabhs), rate of prescribing penicillin V. For children under age 10, rate of prescribing amoxicillin - For patients with β-lactam allergy, rate of prescribing clindamycin, erythromycin 47.1±33.4 70.9 19.6±11.5 46.5±33.2 4-3. For J20 (acute bronchitis) which is developed from chronic bronchitis, rate of prescribing amoxicillin - For patients with β-lactam allergy, rate of prescribing doxycyclin, tetracycline, TMP/SMX 4-4. For H65 (non-suppurative otitis media), rate of prescribing amoxicillin, erythromycin, TMP/SMX, clarithromycin 4-5. For H66 (suppurative otitis media and unclear otitis media), rate of prescribing amoxicillin, erythromycin, TMP/SMX, clarithromycin 5. Rate of certain antibiotics among antibiotics used for respiratory diseases (%) 20.3±28.1 138.3 6.1±7.0 20.3±28.0 24.3±25.7 105.7 8.4±8.1 24.4±25.7 20.5±22.2 108.1 9.5±7.2 20.4±21.9 5-1. Rate of fluoroquinolone for respiratory diseases 12.1±20.4 168.4 10.3±6.9 12.4±21.1 - acute upper respiratory disease 12.0±20.6 171.3 4.6±3.2 12.4±21.3 - acute lower respiratory disease 14.7±23.2 157.7 13.8±10.1 14.6±23.5 - otitis media 16.7±23.2 139.2 9.5±7.3 16.3±22.9 5-2. Rate of macrolide for respiratory diseases 15.1±19.0 126.2 18.1±8.5 15.4±19.4 - acute upper respiratory disease 13.6±18.7 137.6 13.7±7.8 13.9±19.2 - acute lower respiratory disease 22.2±24.0 108.2 28.2±12.6 22.4±24.4 - otitis media 12.7±17.4 136.9 6.0±4.1 12.7±17.4 5-3. Rate of cephalosporin for respiratory diseases 37.8±30.7 81.4 45.7±12.0 37.4±30.9 - acute upper respiratory disease 88.5±31.2 81.1 46.6±14.9 38.2±31.4 - acute lower respiratory disease 36.9±31.0 84.2 34.4±12.8 36.0±31.1 - otitis media 40.8±30.1 73.7 60.1±14.3 39.5±29.8 5-4. Rate of amoxicillin-clavulanic acid for respiratory diseases 39.3±29.3 74.6 18.7±10.9 39.0±29.2 - acute upper respiratory disease 41.8±30.2 72.1 27.5±13.0 41.5±30.2 - acute lower respiratory disease 37.6±29.1 77.4 17.0±11.5 37.2±28.9 - otitis media 49.8±28.8 57.9 17.0±13.3 49.7±28.5 5-5. Rate of penicillin for respiratory diseases 22.0±28.8 131.0 3.2±3.9 22.3±29.1 - acute upper respiratory disease 24.3±29.8 122.7 4.6±4.9 24.7±30.2 - acute lower respiratory disease 19.8±27.3 137.9 3.7±4.7 20.0±27.4 - otitis media 19.5±23.5 120.7 1.7±3.0 19.4±23.0
300 Kor. J. Clin. Pharm., Vol. 22, No. 4, 2012 Table 6. Result of Antibiotics Prescribing Indicators for Respiratory Tract Diseases(continued) Antibiotics Use Administration days and number Cost monitoring 6. Patient episodes with prescribing antibiotics for respiratory diseases 1) (DDD/1,000 /population/day) - acute bronchitis(j20) 0.84±0.31 36.8 0.87±0.15 0.84±0.28 - acute bornchiolitis(j21) 0.83±0.31 36.8 0.81±0.21 0.83±0.30 - unspecified acute lower respiratory infection(j22) 0.83±0.27 32.0 0.89±0.22 0.83±0.26 - bronchitis, not specified as acute or chronic(j40) 0.83±0.28 33.7 0.83±0.20 0.83±0.28 - simple and mucopurulent chronic bronchitis(j41) 0.82±0.28 34.2 0.75±0.29 0.82±0.28 - unspecified chronic bronchitis(j42) 0.82±0.30 36.6 0.78±0.18 0.82±0.30 - nonsuppurative otitis media(h65) 0.81±0.29 35.2 0.64±0.14 0.81±0.28 - suppurative and unspecified otitis media(h66) 0.82±0.30 36.2 0.62±0.15 0.82±0.30 7-1. Number of administration days for respiratory diseases 1) (day) - acute bronchitis(j20) 2.9±1.4 48.7 4.4±1.3 2.9±1.3 - acute bornchiolitis(j21) 2.7±1.2 43.7 4.5±3.2 2.7±0.9 - unspecified acute lower respiratory infection(j22) 3.0±1.7 56.8 6.7±4.3 2.9±1.3 - bronchitis, not specified as acute or chronic(j40) 3.3±2.2 66.5 7.2 ± 3.9 3.3±2.1 - simple and mucopurulent chronic bronchitis(j41) 4.5±4.5 100.2 9.2±6.4 4.5±4.4 - unspecified chronic bronchitis(j42) 4.7±4.3 92.7 10.4±6.5 4.6±4.3 - nonsuppurative otitis media(h65) 3.0±1.6 51.8 4.7±1.2 3.0±1.4 - suppurative and unspecified otitis media(h66) 3.0±1.7 57.6 4.1±1.4 3.0±1.6 7-2. Number of administration days for respiratory diseases 1) (day) - acute upper respiratory disease 3.0±1.3 43.4 4.5±1.0 2.9±1.2 - acute lower respiratory disease 3.1±1.6 51.0 5.7±3.1 3.0±1.4 - other upper respiratory disease 3.4±1.7 49.4 7.4±1.4 3.3±1.5 - influenza 3.0±2.1 69.7 5.9±2.2 3.0±2.0 - otitis media 3.0±1.6 53.4 4.3±1.3 3.0±1.4 8. Number of antibiotics for respiratory diseases1) ( 단위 : items) - acute bronchitis(j20) 1.1±0.2 19.7 0.9±0.1 1.1±0.2 - acute bornchiolitis(j21) 1.0±0.2 18.8 0.8±0.1 1.1±0.2 - unspecified acute lower respiratory infection(j22) 1.1±0.2 22.4 0.9±0.1 1.1±0.2 - bronchitis, not specified as acute or chronic(j40) 1.0±0.3 24.4 0.8±0.1 1.1±0.2 - simple and mucopurulent chronic bronchitis(j41) 1.1±0.3 25.4 0.9±0.2 1.1±0.2 - unspecified chronic bronchitis(j42) 1.1±0.3 25.2 0.8±0.1 1.1±0.2 - nonsuppurative otitis media(h65) 1.1±0.3 25.6 0.8±0.1 1.2±0.3 - suppurative and unspecified otitis media(h66) 1.2±0.3 25.3 0.8±0.1 1.2±0.3 9. Cost of each antibiotics for respiratory diseases 1) (KRW) - acute upper respiratory disease 4,321±14,248 329.7 15,658±2,977 4,072±15,036 - acute lower respiratory disease 4,550±3,824 84.0 18,797±8,156 4,201±3,505 - other upper respiratory disease 4,790±3,998 83.5 23,892±8,392 4,396±3,284 - influenza 6,362±5,840 91.8 24,809±9,502 5,721±5,104 - otitis media 5,175±22,122 427.5 18,981±4,619 4,873±23,170 10. Cost of antibiotics against administration days for respiratory diseases 1) (KRW) - acute upper respiratory disease 1,355±2,842 209.7 2,401±218 1,322±3,005 - acute lower respiratory disease 1,376±603 43.8 2,350±419 1,335±578 - other upper respiratory disease 1,403±607 43.3 2,677±320 1,361±580 - influenza 1,887±876 46.4 2,944±441 1,831±845 - otitis media 1,528±2,825 184.9 2,411±399 1,503±2,964
외래호흡기계질환에서항생제사용에대한후향적평가방안 301 Fig. 2. Retrospective DUR of Canadian Alberta. 고찰및결론 본연구는외래호흡기계질환에서사용하는항생제에대한후향적평가방안을모색하고자하였다. 이를위해델파이기법을이용하여공식적합의를도출하였고, 이결과를적용해후보지표값별로국내항생제사용량을분석하였다. 16명의전문가로구성한델파이조사결과, 급성코인두염 ( 감기 ), 바이러스가확인되지않은인플루엔자, 급성인두염, 다발성및상세불명부위의급성상기도감염에대해서항생제를처방하지않고관찰하는것에대해대체로동의하고있었으나, 급성폐쇄성후두염 ( 크루프 ) 및후두개염, 비화농성및상세불명의중이염에대해서는항생제가처방되어야한다고판단하는것으로나타났다. 후보지표별전문가조사결과, 문제의중요성과개선필요성에대해서 3점이상응답자가 9명이상이많아, 대체로후보지표별평가지표의적절성에대해동의하고있는것으로나타났다. 특히질환별항생제처방, 일일사용량 (Defined Daily Dose, DDD) 을기준으로한사용량, 항생제투여일수에대해서는대부분이평가의필요성에대해높게인지하고있었다. 2008년외래호흡기계질환으로병원을방문해진료받고청구한내역을활용하여, 후보지표값을산출한결과, 첫째, 국내에서는처방지연전략을대체로사용하고있지않은것으로판단된다. 급성기관지염뿐만아니라, 급성상기도감 염에서도여전히호흡기계질환에서항생제처방률은높게나타났다. 둘째, 급성부비동염, 급성인두염, 급성기관지염, 중이염에서권고항생제처방비율을살펴본결과, 전반적으로권고항생제처방이낮은것으로나타났다. 이는특정항생제처방비중을살펴볼때도, fluoroquinolone, macrolide의비중이높았고, 특히의원급에서처방비중이높은것으로나타나, 개선이필요한것으로판단된다. 셋째, 일일상용량 (DDD) 을기준으로한, 18세이상환자의사용량은대체로 1 미만으로나타나, 과소용량으로투여되고, 급성기관지염투여일수는 2.9일로나타났으나, 본연구의분석단위가처방전이므로 3일미만인것으로제시되었다. 그러나동일질환코드를가진환자를단위로에피소드를묶었음에도, 투여일수는권고일수인 10일에비해, 못미치는것으로나타나, 항생제의과소사용이문제점으로제시되었다. 처방을 3일정도하고재방문을권유하는경우가포함될수있으며이에대한분석을위하여연속처방에대한통합을하여평가를할필요성를고려할필요가있다. 즉, 호흡기계질환의경우환자의의료기관방문수준이높고, 의료기관이동이많아급성기관지염에서조차 3일이내로처방하는비율이높은것으로나타났다. 이는외국에서주치의를방문하거나처방전리필등을통해, 환자단위로처방이관리되는것과달리, 과소사용이빈번할수있다는문제점이다. 본연구는항생제가처방되는질환의대부분을차지하고있는급성호흡기계질환에서항생제사용에대한관리방안
302 Kor. J. Clin. Pharm., Vol. 22, No. 4, 2012 을도출하고자하였다. 그러나본연구는다음과같은제한점을갖고있다. 첫째, 환자의항생제치료기간이권고기간에못미치는문제점이있으나, 주치의제도가도입되지않은실정에서의료기관별로정책수행이어렵다는한계를안고있다. 최근만성질환자가투약을지속적으로하는것의중요성이제기됨에따라, 건강보험심사평가원에서는고혈압, 당뇨환자의투약지속성을의료기관별로평가, 관리하게되었으나, 급성호흡기계질환과같은급성질환에대해서환자단위의후향적평가를도입하는것은어려운실정이다. 이에환자단위분석보다는의료기관별처방전단위의후향적평가를중심으로검토하였다. 둘째, 단순히특정상병에대해서항생제처방에대한후향적평가가필요한영역과지표만을개발하였으나, 평가지표로도입할경우처방행태변화를고려하지않았다는제한점을갖고있다. 상기도, 급성기관지염으로평가대상을묶을경우, 만성기관지염등다른질환으로진단명을변경할우려가있다. 감사의말씀 본논문은질병관리본부와건강보험심사평가원에서 2010 년수행한 외래호흡기계상병별항생제별평가방안연구 연구의일환으로수행되었음. 참고문헌 1. 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. Journal of Antimicrobial Chemotherapy 2004; 54: 1116-1121. 2. Cantrell R, Young FY, Martin BC. Antibiotic prescribing in ambulatory care settings for adults with colds, upper respiratory tract infections and bronchitis. Clinical Therapeutics 2002; 24(1): 170-182. 3. 김동숙, 배그린, 김수경등. 외래호흡기계상병별항생제별평가방안연구. 건강보험심사평가원 질병관리본부용역과제 2010. 4. Arroll B, Kenealy T. Antibiotics for the common cold and acute purulent rhinitis. Cochrane Database of Systematic Reviews 2005; Issue 3. Art. No.: CD000247. DOI: 10.1002/ 14651858.CD000247.pub2. 5. Reveiz L, Cardona AF, Ospina EG. Antibiotics for acute laryngitis in adults. Cochrane Database of Systematic Reviews 2007; Issue 2. Art. No.: CD004783. DOI: 10.1002/ 14651858.CD004783.pub3. 6. Ahovuo-Saloranta A, Rautakorpi U-M, Borisenko OV, et al., Antibiotics for acute maxillary sinusitis. Cochrane Database of Systematic Reviews 2008; Issue 2. Art. No.: CD000243. DOI: 10.1002/14651858.CD000243.pub2. 7. Smith SM, Fahey T, Smucny J, et al., Antibiotics for acute bronchitis. Cochrane Database of Systematic Reviews 2004; Issue 4. Art. No.: CD000245. DOI: 10.1002/14651858. CD000245.pub2. 8. Staykova T, Black PN, Chacko EE, et al., Prophylactic antibiotic therapy for chronic bronchitis. Cochrane Database of Systematic Reviews 2003; Issue 1. Art. No.: CD004105. DOI: 10.1002/14651858.CD004105. 9. Spinks A, Glasziou PP, DelMar CB. Antibiotics for sore throat. Cochrane Database of Systematic Reviews 2006; Issue 4. Art. No.: CD000023. DOI: 10.1002/14651858. CD000023.pub3. 10. 건강보험심사평가원. 약제적정성평가결과. 2005. 11. Diagnosis and management of otitis media in children. National Guideline Clearinghouse Guideline Synthesis 2010. 12. Wong DM, Blumberg DA, Lowe LG. Guidelines for the use of antibiotics in acute upper respiratory tract infections. Am Fam Physician 2006; 74: 956-66. 13. National Institute for Health and Clinicl Excellenc(NICE). Respiratory tract infections - antibiotic prescribing. NICE clinical guideline 69 2008. 14. Diagnosis and management of childhood otitis media in primary care. A National clinical Guideline No 66 2003. 15. Management of sore throat and indication for tonsillectomy. A National clinical Guideline 2010. 16. Respiratory tract infections-antibiotic prescribing: Prescribing of antibiotics for self-limiting respiratory tract infections in adults and children in primary care. NICE. 2008. 17. Guideline for the care of NHS patients in Leeds. 2008. 18. Guideline for the diagnosis and treatment of acute otitis media in children. AMA 2001. 19. Guideline for the diagnosis and management of acute bacterial sinusitis. AMA 2001. 20. Guideline for the diagnosis and management of acute pharyngitis. AMA 2010. 21. Guideline for the management of acute exacerbation of chronic bronchitis(aecb). AMA 2001. 22. Ashworth M, Armstrong D, Lloyd D, et al., The effects on GP prescribing of joining a commissioning group. Journal of Clinical Pharmacy and Therapeutics 2002; 27 issue 3: 221-228. 23. Campbell SM, Cantrill JA, Roberts D. Prescribing
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