Pediatr Infect Vaccine Aug;25(2): pissn eissn Original Article 30 일이상 90 일미만의발

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1 Pediatr Infect Vaccine Aug;25(2): pissn eissn Original Article 30 일이상 90 일미만의 변정희, 송보경, 김영아, 고훈, 유석동, 임택진, 박수은 부산대학교어린이병원소아청소년과 The Factors Affecting the Use of Empirical Antibiotics in Febrile Infants from 1 Month to Less than 3 Months Joung-Hee Byun, Bo Kyung Song, Young A Kim, Hoon Ko, Suk dong Yoo, Taek Jin Lim, Su Eun Park Department of Pediatrics, Pusan National University Children's Hospital, Yangsan, the Republic of Korea Received: Sep 12, 2017 Revised: Jan 11, 2018 Accepted: Jan 17, 2018 Correspondence to Su Eun Park Department of Pediatrics, Pusan National University Children's Hospital, 20 Geumo-ro, Yangsan 50612, the Repulblic of Korea. psepse@naver.com Copyright 2018 The Korean Society of Pediatric Infectious Diseases This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ORCID ids Suk dong Yoo Su Eun Park ABSTRACT Purpose: This study investigated the factors affecting the use of empirical antibiotics in febrile infants from 1 month to less than 3 months. Methods: We retrospectively reviewed the medical records of hospitalized previously healthy infants with fever in Pusan National University Children's Hospital from January 2010 to December Clinical features, laboratory findings and antibiotic therapy were analyzed. Respiratory viruses were identified by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) and were reported after 1 3 days. Enterovirus were identified by real time polymerase chain reaction (PCR) and were reported in several hours. Results: The 129 of 366 subjects used empirical antibiotics and 237 patients didn't used empirical antibiotics. Empirical antibiotics were used more frequently when the fever was longer before admission, respiratory symptoms and ill being appearances were present and C-reactive protein was elevated. The rate of readmission was low in the group not used empirical antibiotics. Most of the patients detected by enterovirus PCR in cerebrospinal fluid didn't used empirical antibiotics. The results of respiratory virus multiplex RT-PCR showed no difference in the use of empirical antibiotics. Conclusions: In our study, empirical antibiotic prescriptions were affected not respiratory virus multiplex RT-PCR but enterovirus PCR. If multiplex RT-PCR were reported more rapid turn around time, it will affect antibiotic use. Keywords: Fever; Infant; Anti-bacterial agents Conflict of Interest No potential conflict of interest relevant to this article was reported. 91

2 Author Contributions Conceptualization: Park SE; Data curation: Byun JH; Formal analysis: Yoo SD, Kim YA; Investigation: Byun JH; Methodology: Lim TJ; Project administr: Park SE; Resources: Park SE; Software: Song BK; Supervision: Park SE; Validation: Ko H; Visualization: Byun JH; Writing - original draft: Byun JH; Writing - review & editing: Byun JH, Park SE. 서론 소아에서발열은매우흔한증상이다. 3개월미만의발열이있는영아에서세균감염은 8 10% 정도로, 대부분의경우에뇌척수액배양검사등과같은침습적검사와항생제투여가필요하지않지만, 1) 발열만있는상태로병원또는응급실을방문하였을때균혈증, 세균수막염, 요로감염등과같은심각한세균감염과의구별이쉽지않고세균감염에의한합병증을우려하여어린영아에게침습적검사를시행하고경험적항생제를투여하게된다. 2) 이와같은진단및치료적접근방법은약 25년전에몇몇전문가단체가제안하였던것으로최근에도이를따르는경우가많다. 그중에서도발열이있는생후 1개월이내신생아는세균감염과바이러스감염의구분이임상적으로어려워혈액, 소변, 뇌척수액배양을시행하고대부분경험적항생제를사용한다. 그러나국소증상이없는 1 3개월발열이있는영아중많은수는바이러스질환이고, 최근에는세균백신인 b형헤모필루스인플루엔자백신과폐구균단백결합백신의사용으로세균감염의빈도가감소하여영아의발열에바이러스가차지하는비율이더높아졌고급성호흡기감염영아에서는 90% 까지바이러스원인으로보고된다. 3-5) 최근바이러스진단법이향상되어진료현장에서보다빠르고정확하게바이러스감염을진단할수있게되었고, 6) 어린영아에게시행되는침습적검사의부정적영향과불필요한항생제사용으로인한문제점도고려하여야한다. 7) 발열로병원을방문한영아에서조기에바이러스감염을진단할수있다면침습검사의시행을줄일수있고항생제사용도감소시킬수있다는국외보고가있다. 8) 본연구는부산대학교어린이병원에발열을주소로입원한생후 30일이상 90일미만의영아에서입원시경험적항생제를사용한군과사용하지않은군을나누어임상양상과검사소견을조사하였고, 경험적항생제사용결정과중단에영향을미치는요인을분석하였다. 방법 1. 대상 2010년 1월부터 2016년 12월까지발열을주소로부산대학교어린이병원에입원한생후 30일이상 90일미만의영아를대상으로하였다. 발열은체온계로측정한액와또는고막체온이 38.0 C 이상인경우로정의하였다. 미숙아, 선천심장질환, 선천소화기질환, 유전대사질환환자와처음부터중환자실로입원한환자및가와사키병의심환자는연구대상에서제외하였다. 연구대상환자중에서심각한세균감염일가능성이높은고위험군을분류하기위하여 Philadelphia criteria를사용하였으며 4), 처음소변검사에서백혈구 >10개 /HPF, 뇌척수액검사에서백혈구 >8개 /mm 3, 또는단순흉부방사선사진에서침윤이있는환자는대상에서제외하였다. 본연구는양산부산대학교병원임상시험심사위원회 (Institutional Review Board [IRB]) 에서 심의면제받았다 (IRB No ). 92

3 2. 방법의무기록을후향적으로검토하여입원시경험적항생제를사용한군과사용하지않은두군으로분류하였고, 연령, 성별, 발열기간, 동반증상, 입원기간, 진찰소견, 검사결과, 항생제사용변경시이유, 최종진단및퇴원후 2주이내재입원율을분석하였다. 경험적항생제의사용결정은환자를직접진료한의사의판단에따랐다. 대상환자들은모두단순흉부방사선사진, 혈액검사, 소변검사를시행하였고뇌척수액천자는모든환자에게권유하였고보호자가동의하는경우에시행하였으며뇌척수액천자를시행하였을경우뇌척수액분석검사, 배양검사, enterovirus polymerase chain reaction (PCR) 등을시행하였다. 뇌척수액으로시행한 enterovirus PCR 검사는 4 6시간후보고되었다. 입원 24시간이내에비강인두도말검체를채취하여다중역전사중합효소연쇄반응검사 (multiplex reverse transcriptase polymerase chain reaction [RT-PCR]) 를시행하였다. 2010년 1 월부터 2013년 5월까지는 Seeplex TM RV 7 kit (Seegen Inc., Seoul, Korea) 를사용하여바이러스 7종, 즉 adenovirus (ADV), human metapneumovirus (hmpv), respiratory syncytial virus (RSV), influenza virus type A and B, parainfluenza virus (PIV), rhinovirus (RV) 을검사하였고, 2013년 6월부터 2016년 12월까지는 AdvanSure RV real-time RT-PCR kit (LG Life Sciences, Seoul, Korea) 를사용하여바이러스 13종, 즉 ADV, hmpv, RSV type A, B, influenza virus type A and B, PIV type 1, 2, 3, RV A, B, C, coronavirus 229E/NL63, OC43, bocavirus (hbov) 를검사하였다. 본기관에서검사결과는주 3회보고되며, 검체접수에서결과보고까지 1 3일소요되었다. 혈액배양에서균이동정되면균혈증으로진단하였고 1회혈액배양에서 coagulase-negative Staphylococcus가동정된경우는오염균으로간주하였다. 9) 소변검사는모두도뇨관으로채취하였고단일세균이 50,000 colony forming unit (CFU)/mL 이상배양된경우요로감염으로진단하였다. 10) 본기관에서는혈액배양검사는 48시간배양후균동정이되지않으면 2일간음성으로중간보고되며 5일배양후최종결과보고되고, 소변배양검사는 24시간배양후균동정되지않으면음성으로보고되고, 뇌척수액배양검사는 48시간배양후까지세균이자라지않으면음성으로보고된다. 최종진단명을분류할때상기도감염에는감기, 비인두염, 편도선염을포함하였고 11,12) 하기도감염은기관지염, 급성세기관지염및폐렴을포함하였다. 13) 급성상기도감염과하기도감염에서급성중이염이합병된경우진단명은급성중이염으로분류하였다. 요로감염과균혈증이다른질환 ( 상기도감염, 하기도감염, 장바이러스수막염등 ) 과동반되었을경우요로감염과균혈증으로분류하였다. 1주일미만발열이있으면서병력청취와신체진찰을하여도발열을설명할수없는경우국소증상없는발열 (fever without localizing signs) 로분류하였다. 3) 퇴원 2 주이내재입원한환자는선행질환의악화, 치료실패여부, 치료에따른합병증이 있는지분석하였다. 3. 통계통계분석은 SPSS version 21.0 (IBM Co., Armonk, NY, USA) 을사용하였고범주형변수비교는 Pearson's χ 2 test를사용하였고, 연속형변수의평균비교는 Student's t-test를사용하였으며 P-value가 0.05 미만인경우통계적으로유의하다고해석하였다. 93

4 결과 1. 연구대상자특징연구대상자는총366명으로남자는 205명 (56.0%), 여자는 158명 (43.2%) 이고남녀비는1.3:1 이었으며, 입원시경험적항생제를사용한환자는 129명 (35.2%), 사용하지않은환자는 237 명 (64.8%) 으로경험적항생제를사용하지않은환자가많았다. 뇌척수액검사는보호자가검사를동의하지않은 68 명을제외한 298 명 (81.4%) 에서시행되었고 respiratory virus multiplex RT-PCR 은 316 명 (86.3%) 에서시행되었다. 2. 경험적항생제를사용한군과사용하지않은군의임상양상비교경험적항생제를사용한군과사용하지않은군의평균나이는각각 61.44±15.4일, 60.59±17.9 일로두군간유의한차이가없고성별역시차이가없었다. 입원전발열기간은각각 2.5±1.5 일, 1.9±1.2일로경험적항생제를사용한군이길었으며 (P 0.001), 입원기간역시각각 6.1±2.5 일, 4.7±1.7일로경험적항생제를사용한군이길었다 (P 0.001). 경험적항생제를사용한군에서사용하지않은군에비해호흡기증상있는환자 (79 명, 61.2%) 와아파보이는환자 (46 명, 35.7%) 가많았으며통계적으로유의하였다 (P and <0.001, respectively). 소화기증상을보이는환자는두군간의미있는차이가없었다 (Table 1). 3. 경험적항생제를사용한군과사용하지않은군의검사소견비교두군의검사소견을비교하였고, 백혈구수, 분획백혈구비율, 혈색소, 혈소판수는유의한차이가없었으며, C-반응단백은경험적항생제를사용한군에서 2.6±3.1 mg/dl, 항생제를사용하지않은군에서 0.8±0.9 mg/dl으로경험적항생제를사용한군에서유의하게높았다 (P 0.001). 뇌척수액검사를시행한 298 명중 84 명에서 enterovirus PCR 검사가양성이었으며그중 경험적항생제를사용한환자수는 2 명, 항생제를사용하지않은환자수는 82 명으로대부분 항생제를사용하지않았고통계적으로유의하였다 (P 0.001). Respiratory virus multiplex RT-PCR 검사를시행한 316 명중 218 명에서바이러스가검출되었고, 경험적항생제를사용한군 78 명 (60.5%), 항생제를사용하지않은군 140 명 (59.1%) 으로 유의한차이가없었다 (P=0.084; Table 2). Table 1. Comparison of characteristics and clinical manifestation of febrile infants by classification group Characteristics Empirical antibiotic use (n=129) No empirical antibiotic use (n=237) P-value Age (day) 61.44± ± Male:female ratio (Male %) 80:49 (62.0) 125:112 (52.7) Clinical symptoms Days of fever (day) 2.5± ±1.2 <0.001 Respiratory symptoms 79 (61.2) 86 (36.3) <0.001 GI symptoms 9 (7.0) 16 (6.8) Ill being appearance 46 (35.7) 17 (5.9) <0.001 Duration of hospitalization (day) 6.1± ±1.7 <0.001 Data are presented as median±standard deviation or number (%). Abbreviations: GI, gastrointestinal. 94

5 Table 2. Comparison of initial laboratory values of febrile infants by classification group Values Empirical antibiotic use (n=129) No empirical antibiotic use (n=237) P-value WBC count (/µl) 10,657.3±4, ,753.5±3, Segmented neutrophil (%) 38.6± ± Lymphocyte (%) 46.2± ± Hemoglobin (g/dl) 18.4± ± Platelet counts (10 3 /µl) 380.6± ± C-reactive protein (mg/dl) 2.6± ±0.9 <0.001 Enterovirus PCR (CSF) detected 2 (1.6) 82 (34.6) <0.001 Multiplex RT-PCR detected 78 (60.5) 140 (59.1) Respiratory syncytial virus 26 (52.9) 25 (24.4) Rhinovirus 15 (22.1) 47 (43.3) Parainfluenza virus 6 (8.8) 18 (17.8) Human metapneumovirus 13 (19.1) 5 (5.6) Adenovirus 3 (4.4) 4 (4.4) Influenza virus type A 4 (5.9) 8 (8.9) Influenza virus type B 0 (0) 3 (3.3) Coronavirus 0 (0) 6 (6.7) Human bocavirus 1 (1.5) 7 (7.8) Coinfection 10 (14.7) 17 (18.9) Data are presented as median±standard deviation or number (%). Abbreviations: WBC, white blood cell; PCR, polymerase chain reaction; CSF, cerebrospinal fluid; RT-PCR, reverse transcriptase polymerase chain reaction. 4. 경험적항생제를사용한군과사용하지않은군의최종진단명과재입원률비교혈액배양검사에서 Streptococcus agalactiae가 2명의환자에서동정되어균혈증으로최종진단되었고 2명모두경험적항생제를사용하였고두명모두진찰시아파보이고, C-반응단백상승이있어균동정되기전에경험적항생제를시작하였다. 5 명의환자에서 Staphylococcus epidermidis 가동정되었으나 C- 반응단백상승도없고아파보이지 않아경험적항생제를사용하지않은군이었고혈액배양검사를다시시행하였고두번째 혈액배양검사에서균이동정되지않아오염균으로간주하였다. 처음소변검사에서백혈구 >10개 /HPF인경우는연구대상에서제외하였고입원당시소변검사는이상이없었으나, 소변배양검사에서균이동정되어요로감염으로진단된환자가 19명있었다. 19명모두단일세균이 100,000 CFU/mL 이상배양되었고, Escherichia coli가 12명, Enterococcus faecalis와 Klebsiella pneumoniae가각각 3명, Klebsiella oxytoca가 1명에서배양되었다. 경험적항생제를사용한군에서요로감염이 15명 (11.6%) 으로사용하지않은군의 4명 (1.8%) 보다유의하게많았다 (P 0.001). 뇌척수액으로시행한 enterovirus PCR 검사에서양성으로검출된 84 명의환자중 2 명은 소변배양검사에서균이동정되어요로감염으로최종진단하였고뇌척수액배양검사에서 세균이동정되어세균수막염으로진단된환자는없었다. 상기도감염은경험적항생제를사용한군 30 명 (23.3%), 항생제를사용하지않은군 77 명 (32.5%), 하기도감염은경험적항생제를사용한군 14 명 (10.9%), 항생제를사용하지않은군 18 명 (7.6%) 로상기도감염과하기도감염모두두군사이유의한차이는없었다. 95

6 Table 3. Comparison of final diagnosis and readmissions of febrile infants by classification group Characteristics Empirical antibiotic use (n=129) No empirical antibiotic use (n=237) P-value Bacteremia 2 (1.6) 0 (0) Urinary tract infection 15 (11.6) 4 (1.7) <0.001 Bacterial meningitis 0 0 Enterovirus meningitis 2 (1.6) 80 (33.7) <0.001 URI* 30 (23.3) 77 (32.5) LRI 14 (10.9) 18 (7.6) Acute otitis media 18 (14) 3 (1.3) <0.001 Fever without localizing sign 38 (29.5) 57 (24.1) Change the use of antibiotics 78 (60.5) 2 (0.8) Readmissions <2 wk 6 (4.7) 2 (0.8) Data are presented as number (%). *Upper respiratory infection included common cold, nasopharyngitis, tonsillitis, pharyngotonsilitis; Lower respiratory infection included pneumonia, acute bronchiolitis; The 78 patients stopped the antibiotics after confirmation of culture results and 2 patients discontinued the antibiotics after breathing sound improvement in group of empirical antibiotic use. The 2 patients started antibiotics because urine cultures showed bacterial growth in group of no empirical antibiotic use. Abbreviations: URI, upper respiratory infection; LRI, lower respiratory infection. 급성중이염은경험적항생제를사용한군 18 명 (14%), 항생제를사용하지않은군 3 명 (1.3%) 으로경험적항생제를사용한군에서많았다 (P 0.001). 국소증상없는발열은경험적항생제를사용한군 38 명 (29.5%), 항생제를사용하지않은군 57 명 (24.1%) 으로유의한차이가없었다 (P=0.260) (Table 3). 경험적항생제를사용한군 129명에서 78명 (60.5%) 은입원중에항생제를중단한것으로조사되었다. 항생제중단시기와이유를분석하였을때, 76명은혈액배양, 소변배양, 뇌척수액배양결과를확인후중단하였고 2명은청진소견호전후중단하였다. 항생제를중단한 78명의환자에서배양검사가모두음성인것이확인되는평균보고시간은 31.5±17.5 시간이었고, respiratory virus multiplex RT-PCR 의평균보고시간은 54.5±10.5시간이었으며, 항생제평균사용일은 3.5±1.2일이었다. 배양검사결과확인후항생제를중단한 76명의환자중에서 61명은 respiratory virus multiplex RT-PCR 결과보고가배양검사보고보다빨리되었고, 17명은배양검사음성확인후 respiratory virus PCR 결과가보고되었다. 2주이내재입원한환자는경험적항생제를사용한군 6명 (4.7%), 경험적항생제를사용하지않은군 2명 (0.8%) 으로항생제를사용한군에서유의하게많았고 (P 0.017), 3명은호흡기증상악화로 3명은항생제사용후설사로재입원하였다. 경험적항생제를사용하지않은군에서재입원한환자는 2명이었고, 1명은호흡기증상악화로입원하였고, 1명은 enterovirus 수막염진단후소변배양에서 E. coli 100,000 CFU/mL 동정되었는데입원후발열이없어무증상세균뇨로항생제사용하지않고퇴원후다시발열있어재입원하여요로감염으로항생제치료를받았다. 경험적항생제를사용하지않은환자군은항생제를처음부터사용한군과비교하여질병의재발또는악화로다시입원하는비율이낮았다. 고찰 본연구는발열을주소로입원한생후 30 일이상 90 일미만의영아를대상으로항생제투여 결정에영향을주는요인을알아보고자, 항생제를사용해야할이유가명확한증상또는 96

7 징후가있거나소변검사와뇌척수액검사에서세균감염의가능성이있는영아를제외한후, 경험적항생제를사용한군과사용하지않은군으로나누어비교분석하였다. 경험적항생제를사용한군이호흡기증상이있는환자와아파보이는환자의비율이높았으며, 발열기간과입원기간이길었다. 경험적항생제를사용한환자군에서최종진단에서요로감염, 균혈증등심각한세균감염으로확인된환자수가많았는데, 이환자들의평균백혈구수는 12,292.5±5,171.3/μL 으로백혈구상승이있었고평균 C-반응단백이 4.78±8.41 mg/dl으로상승되어있었다. 경험적항생제를사용하지않은환자에서균혈증, 세균수막염환자는없었고요로감염이 4명진단되었다. 그중 1명은입원중항생제치료를시작하였고 3명은입원후발열이없어무증상세균뇨가능성을고려하여항생제사용하지않고퇴원하였으며그중 1명만다시발열이있어재입원하여항생제치료를하였고 4명중위중한합병증이생긴환자는없었다. 경험적항생제를사용하지않은군에서재입원한환자가유의하게더적었으며균혈증, 세균수막염등위중한세균감염환자도없었다. 예방적항생제를사용하고퇴원후재입원한 6명의환자중 3명은기존질환의악화로입원하였지만 3명은항생제사용으로인한합병증으로입원하였다. 1 3개월발열있는영아의많은수는바이러스질환이고세균감염은 8 10% 정도로적으며대부분의경우에뇌척수액검사등과같은침습적검사와항생제투여가필요하지않다는보고가있는데 1) 본연구에서는경험적항생제가 129명 (35.2%) 으로높은비율의환자에서사용되었고이들중 78명 (60.5%) 의환자는항생제사용이필요없다고판단되어입원중항생제를중단하였다. 예방적항생제를사용하지않은환자중치료실패로인한재입원하는경우도유의하게적었고, 치료실패로인한합병증이보고되지않은점들은종합하여, 1 3개월발열이있는영아에서아파보이지않고진찰소견과검사소견에특이소견이없을때항생제사용을하지않고배양검사를기다릴수있다. 본연구에서뇌척수액검사는 298명 (81.4%) 으로많은수의환자에서시행되었고세균수막염으로진단된환자는없었다. 다른연구에서아파보이지않는영아의바이러스질환에서세균수막염의빈도는매우드물다보고되고 14,15) Mintegi 등의연구에서 16) 척수천자와항생제처방없이응급실에서진료후외래에서추적관찰한환자들을분석하였고 0.1% 가세균감염이고세균수막염환자는없었다. 어린영아에게침습적인검사를시행하고경험적항생제투여를권고하던진단및치료적접근방법은약 25년전에권고된것으로 2) 고전적인 criteria의변화가필요하며침습적인검사를줄일필요가있다. 1) 입원시검사에서농뇨가없는환자만연구대상에포함하였는데배양검사결과요로감염으로진단된환자가 19명이었다. 이는농뇨가없다고요로감염을완전히배제할수없다는다른연구결과와일치한다. 17) 그람음성간균등의감염을예방할수있는백신은아직개발되지않았고영아의세균감염에서많은비중을요로감염이차지하며소아의바이러스질환환자중 2% 에서요로감염이동반되었다는보고도있으므로 18) 발열있는영아에서소변검사와소변배양검사는필요하다. 본연구의검사소견에서 C- 반응단백상승이있을때항생제사용이많았고뇌척수액검사에서 enterovirus PCR 이검출된 84 명중요로감염이동반된 2 명을제외한 82 명은경험적항생제를 97

8 사용하지않았다. 국내연구에서수막염에서 enterovirus PCR 을검출한결과항생제사용과 입원기간이감소했다는보고가있는데 19) enterovirus PCR 은수시간내보고되는장점이있고 그로인해항생제사용을줄이는데도움이된다. 그에반해 respiratory virus multiplex RT-PCR를통해바이러스가검출된것은경험적항생제를사용한군과사용하지않은두군간유의한차이가없었고호흡기바이러스종류에따라서도두군간차이가없었다. Respiratory Multiplex RT-PCR은의료기관별로차이는있으나통상적으로결과보고되는데 1 3일걸리고, 본연구에서결과가보고되는평균시간은 52.5±12.5시간이었다. Brittain-Long 등 20) 은 multiplex RT-PCR 결과를하루이내로빨리보고받는군과 8 12일로지연보고받는군으로나누어두군간의항생제처방비율을비교하는무작위대조군연구를하였는데, RT-PCR 결과를하루이내에빨리보고받는군에서첫방문시항생제시작하는비율이적었다. Burstein 등 21) 은캐나다의 16개의료기관소아과의사에게시나리오를짜서설문조사를하였는데 3주와 5주의어린영아가무병소발열로방문하였을때바이러스검사결과가보고되는경우와바이러스검사를시행하지않았을경우로나눠입원치료여부, 경험적항생제의사용여부, 입원기간등의답변을분석하였다. 바이러스검사를시행하였고바이러스가검출된경우항생제처방을적게하겠다는답변비율이높았다. 그리고바이러스검사결과보고시간에따른검사시행여부를물었을때 6 시간이내보고된다면 59% 에서검사를시행할것이라하였고 24시간이상소요된다면 32% 에서시행할것이라하여검사보고시간이짧을수록검사시행률이높을것임을시사하였다. 위의연구들을종합하고인플루엔자신속항원검사가응급실을방문한소아의항생제사용과입원율을감소시켰다는국외연구와 22,23) enterovirus PCR이경험적항생제사용결정에영향을주는점을볼때 respiratory virus multiplex RT-PCR 결과를더신속하게보고받는다면항생제사용을줄이는데도움이될것으로판단된다. 본연구의제한점으로는외래나응급실방문후진찰소견과검사소견이양호하여항생제를사용하지않고외래추적관찰한영아를포함하지않아항생제사용률이실제보다높게평가되었을가능성이있다. 또한단일기관조사로대상환자수가많지않고후향적연구로, 경험적항생제를시작하거나중단하는데정해진규정이없고진찰한의사주관에따라이뤄졌다는한계점이있다. 외래를재방문하지않은환자와퇴원후합병증으로타병원에방문한환자는포함시키지않아재입원율분석에도제한점이있다. 그러나이번연구는30일이상 90일미만의발열이있는어린영아를대상으로의사의경험적항생제의사용결정에영향을끼치는요인을분석하였다는것에의의가있다. 앞으로전향적연구가필요하며, 항생제사용에영향을주는요소에대해인과관계를분명하게밝힐수있을것이다. Respiratory virus multiplex RT-PCR결과보고가더신속하게보고되는전향적연구를한다면바이러스질환이의심되는아파보이지않는영아에서항생제사용을줄이는데도움이될것이다. REFERENCES 1. DePorre AG, Aronson PL, McCulloh RJ. Facing the ongoing challenge of the febrile young infant. Crit Care 2017;21:68. 98

9 2. Baraff LJ, Bass JW, Fleisher GR, Klein JO, McCracken GH Jr, Powell KR, et al. Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Ann Emerg Med 1993;22: Nield LS, Kamat D. Fever without focus. In: Kilegman RM, Stanton BF, St. Geme JW III, Schor NF, Behrman RE, editors. Nelsons textbook of pediatrics. 20th ed. Philadelphia: Elsevier, 2016: Filho EM, de Carvalho WB. Current management of occult bacteremia in infants. J Pediatr (Rio J) 2015;91:S61-6. CROSSREF 5. Park JS. Acute viral lower respiratory tract infections in children. Korean J Pediatr 2009;52: CROSSREF 6. Choi EH, Lee HJ, Kim SJ, Eun BW, Kim NH, Lee JA, et al. The association of newly identified respiratory viruses with lower respiratory tract infections in Korean children, Clin Infect Dis 2006;43: Shah SS, Volk J, Mohamad Z, Hodinka RL, Zorc JJ. Herpes simplex virus testing and hospital length of stay in neonates and young infants. J Pediatr 2010;156: Templeton KE. Why diagnose respiratory viral infection? J Clin Virol 2007;40 Suppl 1:S Rahkonen M, Luttinen S, Koskela M, Hautala T. True bacteremias caused by coagulase negative Staphylococcus are difficult to distinguish from blood culture contaminants. Eur J Clin Microbiol Infect Dis 2012;31: Elder JS. Urinary tract infections. In: Kilegman RM, Stanton BF, St. Geme JW III, Schor NF, Behrman RE, editors. Nelsons textbook of pediatrics. 20th ed. Philadelphia: Elsevier, 2016: Cherry JD, Nieves DJ. The common cold. In: Feigin RD, Cherry JD, Demmler-Harrison GJ, Kaplan SL, editors. Feigin and Cherry's textbook of pediatric infectious diseases. 6th ed. Philadelphia: Saunders/ Elsevier, 2009: Cherry JD. Pharyngitis. In: Feigin RD, Cherry JD, Demmler-Harrison GJ, Kaplan SL, editors. Feigin and Cherry's textbook of pediatric infectious diseases. 6th ed. Philadelphia: Saunders/Elsevier, 2009: Denny FW, Clyde WA Jr. Acute lower respiratory tract infections in nonhospitalized children. J Pediatr 1986;108: Levine DA, Platt SL, Dayan PS, Macias CG, Zorc JJ, Krief W, et al. Risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections. Pediatrics 2004;113: Melendez E, Harper MB. Utility of sepsis evaluation in infants 90 days of age or younger with fever and clinical bronchiolitis. Pediatr Infect Dis J 2003;22: Mintegi S, Gomez B, Martinez-Virumbrales L, Morientes O, Benito J. Outpatient management of selected young febrile infants without antibiotics. Arch Dis Child 2017;102: Kim SH, Lyu SY, Kim HY, Park SE, Kim SY. Can absence of pyuria exclude urinary tract infection in febrile infants? About 2011 AAP guidelines on UTI. Pediatr Int 2016;58: Greenhow TL, Hung YY, Herz AM, Losada E, Pantell RH. The changing epidemiology of serious bacterial infections in young infants. Pediatr Infect Dis J 2014;33: Jin D, Heo TH, Byeon JH, Kim GH, Kim MK, Eun SH, et al. Analysis of clinical information and reverse transcriptase-polymerase chain reaction for early diagnosis of enteroviral meningitis. Korean J Pediatr 2015;58: Brittain-Long R, Westin J, Olofsson S, Lindh M, Andersson LM. Access to a polymerase chain reaction assay method targeting 13 respiratory viruses can reduce antibiotics: a randomised, controlled trial. BMC Med 2011;9: Burstein B, Dubrovsky AS, Greene AW, Quach C. National survey on the impact of viral testing for the ED and inpatient management of febrile young infants. Hosp Pediatr 2016;6:

10 22. Noyola DE, Demmler GJ. Effect of rapid diagnosis on management of influenza A infections. Pediatr Infect Dis J 2000;19: Poehling KA, Zhu Y, Tang YW, Edwards K. Accuracy and impact of a point-of-care rapid influenza test in young children with respiratory illnesses. Arch Pediatr Adolesc Med 2006;160: 요약 목적 : 본연구는 30 일이상 90 일미만의발열이있는영아에서경험적항생제사용에미치는요소를조사하였다. 방법 : 2010 년 1 월부터 2016 년 12 월까지부산대학교어린이병원에발열이있는이전에건강했던영아를대상으로임상양상, 검사소견, 항생제사용에대해의무기록을후향적으로분석하였다. 호흡기바이러스는다중역전사중합연쇄반응검사로검출하여 1 3 일후보고되었고, enterovirus 는중합연쇄반응검사로검출하여수시간만에보고되었다. 결과 : 366 명의대상자중 129 명은경험적항생제를사용하였고 237 명은경험적항생제를사용하지않았다. 입원전발열기간이긴경우와호흡기증상이있을때, 아파보일때, CRP 상승시경험적항생제사용이많았다. 경험적항생제를사용하지않은환자의재입원율이낮았다. Enterovirus polymerase chain reaction (PCR) 이검출된대부분의환자는경험적항생제를사용하지않았다. Respiratory virus multiplex reverse transcriptase (RT)-PCR 결과는경험적항생제사용에차이를보이지않았다. 결론 : 본연구에서 respiratory virus multiplex RT-PCR 은항생제처방에영향을주지않았고 enterovirus PCR 은항생제처방에영향을주었다. Respiratory virus multiplex RT-PCR 결과가신속하게보고된다면항생제사용에영향을줄것이다. 100

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