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병원약사회지 (27), 제 34 권제 4 호 J. Kor. Soc. Health-syst. Pharm., Vol. 34, No. 4, 433 ~ 442 (27) Original Article 국내지역사회획득폐렴원인균의경험적항균제에대한내성현황 하혜민 a, 김윤숙 b, 안정미 c, 천부순 a, 인제대학교약학대학 a, 인제대학교해운대백병원약제부 b, 인제대학교상계백병원약제부 c The Resistance to Empirical Antibiotics among Pathogens Causing Community-Acquired Pneumonia in Korea Hye Min Ha a, Yoonsook Kim b, Jung Mi Ahn c, and Pusoon Chun a, College of Pharmacy, Inje University, 97 Inje-ro, Gimhae, Gyeongnam 5834, Republic of Korea a Division of Pharmacy, Inje University Haeundae Paik Hospital, Haeundae-ro 875, Haeundae-gu, Busan, Korea b Division of Pharmacy, Inje University Sanggye Paik Hospital, Dongil-ro 342, Nowon-gu, Seoul, Korea c Background : Antibiotic resistance has become a serious threat to manage community-acquired pneumonia (CAP). Despite the rapid emergence of drug-resistant organisms, there are no updated guidelines for the initial antibiotic management of CAP. This study was conducted to investigate the resistance of isolated pathogens to empirical antibiotics consistent with recommendations from the 29 guidelines on the management of CAP. Methods : A retrospective clinical analysis was conducted, using electronic medical records of the CAP patients, between January 24 and December 25, at three teaching hospitals in Korea. The patterns of prescribing empirical antibiotics and the resistance of isolated pathogens to antibiotics were analyzed. Results : A total of 68 patients were analyzed. The most common pathogen was Acinetobacter baumannii (5.5%), followed by Streptococcus pneumoniae (5.5%), Klebsiella pneumoniae (3.%), Pseudomonas aeruginosa (3.%), Staphylococcus aureus (.9%), and Haemophilus influenza (4.8%). 투고일자 27.6.25; 심사완료일자 27.7.27; 게재확정일자 27.9.8 교신저자천부순 Tel:55-32-3886 E-mail:pusoon@inje.ac.kr - 433 -

JKSHP, VOL.34, NO.4 (27) A. baumannii exhibited high resistance rates (8-92%) to ciprofloxacin, levofloxacin, meropenem, and piperacillin/tazobactam, while H. influenzae showed high rates (%) of sensitivity to the drugs. S. pneumoniae had a high level of resistance (9.3%) to azithromycin and a low resistance rate (.5%) to ceftriaxone. K. pneumoniae and P. aeruginosa showed a high level of sensitivity to ciprofloxacin (9.9% vs. 86.4%) and piperacillin/tazobactam (9% vs. 88.9%). The resistance rate of S. aureus to ciprofloxacin was 65%, while the sensitivity rate of S. pneumoniae to levofloxacin was 96.2%. Conclusion : For the initial antibiotic management of CAP due to A. baumannii, the empirical use of ciprofloxacin, levofloxacin, meropenem, or piperacillin/tazobactam is not recommended. Moreover, azithromycin is inappropriate for empirical antibiotics to treat CAP, due to S. pneumoniae. Routine use of ciprofloxacin for empiric treatment of CAP due to S. aureus should also be avoided. [Key words] Antibiotic resistance, Community-acquired pneumonia, Empirical antibiotics 의학기술의발달과다양한항균제의개발에도불구하고국내폐렴에의한사망률은지난 년간꾸준히증가해왔으며, 25년폐렴으로인한사망률은인구 만명당 28.9명으로전체사망원인중 4위, 감염으로인한사망원인으로는 위이었다. ) 지역사회획득폐렴 (community-acquired pneumonia, CAP) 은병원획득폐렴 (hospital-acquired pneumonia, HAP) 에대립되는용어로지역사회에서얻은폐렴을일컫는다. 2) 국내지역사회획득폐렴의경우 Streptococcus pneumoniae에의한감염이가장흔하여환자의약 27-44% 에서원인균으로밝혀졌으며그외정형폐렴 (typical pneumonia) 의원인균으로 Acinetobacter spp., Haemophilus influenza, Klebsiella spp., Pseudomonas spp., Staphylococcus aureus 등과비정형폐렴 (atypical pneumonia) 의원인균으로 Chlamydophila pneumoniae, Legionella spp., Mycoplasma pneumoniae 등이보고되었다. 3)-6) 세균에의한폐렴으로의심되는환자가발생하면원인균진단이이루어지기전에경험적항균제치료를시작한다. 치료성과를높이기위해 28년대한화학요법학회, 대한감염학회, 대한결핵및호흡기학회가공동으로 지역사회획득폐렴의치료지침권고안 을개발하여 29년에발표하였으며초기경험적치료시항균제 의선택에관한권고안을제공하고있다. 7) 입원을요하지않는환자 에서의경험적항균제는 β-lactam 단독, β-lactam과 macrolide의병용, respiratory fluoroquinolone 단독요법을권고하는데, β-lactam으로는 amoxicillin, amoxicillin-clavulanate, cefpodoxime, cefditoren을, macrolide로는 azithromycin, clarithromycin, erythromycin, roxithromycin을, respiratory fluoroquinolone으로는 gemifloxacin, levofloxacin, moxifloxacin을사용할것을권고한다. 일반병동으로입원하는환자 의경우는 입원을요하지않는환자 에서의항균요법과크게차이가없으며 amoxicillin 대신에 ampicillin/ sulbactam을, 경구제 cefpodoxime, cefditoren 대신에주사제 cefotaxime, ceftriaxone의사용을권고한다. 일반병동으로입원하는환자 에게사용이권고되는 macrolides, respiratory fluoroquinolones은 입원을요하지않는환자 에서사용이권고되는항균제와동일하며 fluoroquinolones은경구제뿐만아니라주사제의사용도권고된다. 중환자실로입원하는환자 로 Pseudomonas의감염이의심되지않는경우는 β-lactam (cefotaxime, ceftriaxone, ampicillin/ sulbactam, amoxicillin/clavulanate) 과 azithromycin 의병용혹은β-lactam (cefotaxime, ceftriaxone, - 434 -

하혜민 : 국내지역사회획득폐렴원인균의경험적항균제에대한내성현황 ampicillin/sulbactam) 과 fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin) 의병용을권고한다. 반면, Pseudomonas 감염이의심되는환자에게는 antipneumococcal, antipseudomonal β-lactam (cefepime, piperacillin/tazobactam, imipenem, meropenem) 과 ciprofloxacin이나 levofloxacin 을병용하거나 antipneumococcal, antipseudomonal β-lactam과 aminoglycoside의두가지약물에 azithromycin이나 antipneumococcal fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin) 을병용할것을권고한다. 7) 급증하는항균제내성균의출현과확산은폐렴치료에큰걸림돌이되고있으며지역사회획득폐렴은항균요법에도불구하고사망률이 2-4% 에이른다. 7),8) 지역사회획득폐렴의주요원인균으로알려진 S. pneumoniae의경우 erythromycin에대한국내내성률은 8.6%, azithromycin과 clarithromycin에대한아시아지역에서의내성률은각각 77.4%, 74.2% 로보고되었다. 9) 국내 S. pneumoniae의 fluoroquinolones에대한내성의경우 2-2년에모은균주를대상으로한조사에서 ciprofloxacin에대한내성률은 6.5% 로나타났으나 gemifloxacin, levofloxacin, moxifloxacin에대한내성은발견되지않았다. ) 그러나 22-26년에모은 S. pneumoniae 균주의 3.8% 는 levofloxacin에, 2.% 는 moxifloxacin에감수성이없는것으로나타나국내에서이들 fluoroquinolones 에대한내성이증가하고있는것으로드러났다. ) K. pneumoniae의경우 29-2년사이 cefotaxime, ceftazidime, ceftriaxone 등 3세대 cephalosporins 에대한내성률이우리나라의경우 4.7% 이었던반면미국은 23% 이었던것으로보고되었으며 doripenem, ertapenem, imipenem, meropenem 등 carbapenems에대한내성률은우리나라에서는.3% 이었던것으로보고되었으나미국의경우는 % 로보고되었다. 2) 이처럼폐렴원인균의항균제에대한내성이증가하고있음에도불구하고지역사회획득폐렴의초기치료를위한경험적항균요법에관한지침은 28년에개발되어제공되고있다. 따라서본연구는경험적항균제의처방양상을조사하고국내에서발생한지역사회획득폐렴환자에게사용한경험적항균제의내성현황을 파악하기위해수행되었다. 연구방법. 연구대상 24년 월 일부터 25년 2 월 3일까지의기간중인제대학교부산백병원, 상계백병원, 해운대백병원에내원하여폐렴상병코드 J-2으로항균제를투여받은환자중원인균의진단결과및투여한항균제에대한원인균의내성검사결과를가지는환자를대상으로하였다. 동일환자의치료를위해초기항균제를사용후항균제를변경하여투약한경우는연구대상에서제외했다. 입원당시에는폐렴이없었으나입원 48 시간이후에폐렴이발생한병원획득폐렴환자와기도삽관후 48 시간이경과하고발생한기계환기관련폐렴 (ventilator-associated pneumonia, VAP) 환자는연구대상에서제외했다. 반면, 보건의료관련폐렴 (healthcare-associated pneumonia, HCAP) 환자를지역사회획득폐렴환자와구분하여연구대상자에서제외하지는않았다. 3) 본연구는인제대학교생명윤리위원회 (Institutional Review Board) 의승인을얻은후수행되었다 ( 과제번호 : 2-424-AB-N-- 2623-HR-345). 2. 자료수집및평가전자의무기록 (electronic medical record, EMR) 을후향적으로검토하여자료를수집하였다. 환자의성 (sex), 나이, 원인균진단전에최초로투여된항균제의성분및항균제개수의자료를수집하여경험적항균제의처방양상살펴보고, 환자의성및나이와투여한항균제개수의관련성을분석했다. 진단된원인균과, 원인균진단전에투여한항균제에대한원인균의내성검사결과를수집하여사용한경험적항균제에대한원인균의내성현황을분석하였다. 3. 통계분석수집된자료의통계분석은 SPSS(ver. 24, IBM - 435 -

JKSHP, VOL.34, NO.4 (27) Corp. Armonk, NY, USA) 를이용하여수행하였다. 환자의나이는평균과표준편차로나타내었고사용한항균제의개수와원인균의진단횟수는절대수치와백분율로나타냈다. 사용한경험적항균제의개수와나이와의인과성을비교하기위해서는 Pearson 상관분석및일원배치분산분석 (one way ANOVA) 을수행하였다. 통계적유의수준은 p.5로설정하였다. 연구결과. 대상환자특성 24년 월 일부터 25년 2 월 3일까지의기간에폐렴상병으로항균제를투여받은환자중원인균의진단결과및투여한항균제에대한원인균의내성검사결과를가지는환자는 68명이었으며모두가입원환자이었다. 이중원인균진단전초기경험적치료를위해항균제를 개만투여한환자가 98명 (58.3%) 으로가장많았으며 2개를투여한환자는 59명 (35.%), 3개를투여한환자는 명 (6.5%) 이었다. 전체환자의평균나이는 69.5±4.9세였으며환자의 72% 가 65 세이상이었고남성환자가 67.9% 로여성환자보다많았다. 치료를위해초기에사용한경험적항균제의개수는전체환자의나이와상관이없었으며 (r=.28, p=.98), 이러한경향은 65세이상환자와 65세미만환자, 남성환자와여성환자로분류하여수행한하위분석에서도관찰되었다 (Table ). 2. 경험적항균요법의약물구성및사용빈도경험적치료를위해항균제를단독요법으로사용한경우 piperacillin/tazobactam, ciprofloxacin, ceftriaxone이다빈도약물이었으며 (Table 2), 2제요법의경우는 ceftriaxone과 azithromycin의병용이가장많았다 (Table 3). 3제요법의경우는 azithromycin, ceftriaxone, levofloxacin, 혹은 piperacillin/ tazobactam을포함하는항균요법이대부분이었다 (Table 4). 3. 진단된원인균의경험적항균제에대한감수성및내성원인균의진단결과를가지는전체 68명의환자에서가장흔히진단된균은 Acinetobacter baumannii (5.5%) 와 Streptococcus pneumoniae (5.5%) 이었으며그뒤를이어 Klebsiella pneumoniae (3.%), Pseudomonas aeruginosa (3.%), Staphylococcus aureus (.9%), Escherichia coli (8.9%), Haemophilus influenza (4.8%) 의순으로진단되었다. S. pneumoniae 외4종의 Streptococcus sp. 와 S. aureus 외 4종의 Staphylococcus sp. 이각각 6% 와 4.2% 를차지했으며 Klebsiella oxytoca를비롯한 7종의세균이전체진단된원인균의 7.% 에달했다. 초기경험적치료를위해사용한항균제에대한진단된원인균의내성을분석한결과 A. baumannii는 ceftriaxone에대해 (84%), S. pneumoniae는 azithromycin Table. Patient characteristics according to the number of the initial empirical antibiotic The number of the initial empirical antibiotics Total (n=68) (n=98) 2 (n=59) 3 (n=) p-value Age of total subjects 69.5±4.9 68.4±5.9 7.4±2. 74.2±.7.255 Subjects aged 65 years (N) 76.8±6.5 (2) 76.3±5.8 (7) 77.5±7. (4) 76.6±9. ().67 Subjects aged 65 years (N) 52.±4. (47) 48.4±5.6 (28) 57.7±9.4 (8) 5. ().89 Age of male subjects (N) 7.4±4.9 (4) 68.±6.8 (66) 73.2±.9 (43) 69.8±9.8 (5).29 Age of female subjects (N) 7.9±2.8 (54) 69.±3.9 (32) 74.2±9.9 (6) 72.±3.3 (6).44 Age is expressed as mean±sd in years; (N) denotes the number of patients in each subgroup - 436 -

하혜민 : 국내지역사회획득폐렴원인균의경험적항균제에대한내성현황 Table 2. The frequency of the initial empirical antibiotics used as monotherapy β-lactams Macrolides Fluoroquinolones Glycopeptides Other The initial empirical antibiotics used as monotherapy Number of patients, n=98 penicillin piperacillin/tazobactam 3 (3.6%) antipneumococcal, antipseudomonal carbapenem meropenem 6 (6.%) 4th generation cephalosporin cefepime (%) ceftriaxone 2 (2.4%) 3rd generation cephalosporins cefotaxime (%) st generation cefazolin (%) azithromycin 2 (2%) clindamycin 2 (2%) antipneumococcal, antipseudomonal ciprofloxacin 2 (2.4%) levofloxacin 7 (7.%) vancomycin 6 (6.%) colistin (%) Table 3. The frequency of the initial empirical antibiotics used as dual therapy The initial empirical antibiotics used as dual therapy Number of patients, n=59 ceftriaxone + azithromycin 22 (37.3%) β-lactam + macrolide β-lactam + fluoroquinolone Antipneumococcal, antipseudomonal β-lactam + macrolide Antipneumococcal, antipseudomonal β-lactam + fluoroquinolone Others ceftriaxone + clarithromycin 5 (8.5%) ceftriaxone + clindamycin 3 (5.%) ceftriaxone + levofloxacin 2 (3.4%) cefotaxime + ciprofloxacin (.7%) cefpodoxime + levofloxacin (.7%) piperacillin/tazobactam + clindamycin 2 (3.4%) piperacillin/tazobactam + azithromycin (.7%) ceftazidime + azithromycin (.7%) meropenem + clindamycin (.7%) piperacillin/tazobactam + ciprofloxacin 7 (.9%) piperacillin/tazobactam + levofloxacin 6 (.2%) piperacillin/tazobactam + moxifloxacin (.7%) piperacillin/tazobactam + cefpodoxime (.7%) meropenem + [colistin, teicoplanin, or vancomycin] 3 (5.%) ceftriaxone + vancomycin (.7%) ampicillin + netilmicin (.7%) - 437 -

JKSHP, VOL.34, NO.4 (27) (9.3%) 에대해높은내성률을보였다. 반면, S. pneumoniae의경우 ceftriaxone에대해서는낮은내성률 (.5%) 을나타내었다 (Fig. ). 다빈도원인균의 ciprofloxacin, levofloxacin, meropenem, piperacillin/tazobactam에대한내성을분석했을때 A. baumannii는 4가지약물모두에높은내성률을가진반면H. influenzae는 4가지약물모두에높은감수성을보였다. K. pneumoniae와 P. aeruginosa가 ciprofloxacin과 piperacillin/ tazobactam에대해높은감수성을가진반면 S. aureus는 ciprofloxacin에 대해다소높은내성률을나타내었다. S. pneumoniae 는 levofloxacin에대해높은감수성을보였다 (Table 5). 고찰본연구는지역사회획득폐렴의초기치료를위해원인균진단결과가나오기전에경험적치료로사용되는항균요법의약물구성과사용빈도를파악하고사용한경험적항균제에대해높은빈도로진단된원인균의내 Table 4. The frequency of the initial empirical antibiotics used as triple therapy The empirical antibiotics used as triple therap Number of patients, n= β-lactam + macrolide + antipneumococcal fluoroquinolone Antipneumococcal, antipseudomonal β-lactam based Other amoxicillin/clavulanate + azithromycin + levofloxacin 2 (8.2%) ceftriaxone + azithromycin + levofloxacin 2 (8.2%) cefotaxime + azithromycin + levofloxacin (9.%) piperacillin/tazobactam + azithromycin + ceftriaxone 2 (8.2%) piperacillin/tazobactam + azithromycin + cefpodoxime (9.%) piperacillin/tazobactam + levofloxacin + colistin (9.%) cefepime + azithromycin + levofloxacin (9.%) ceftriaxone + vancomycin + ciprofloxacin (9.%) Acinetocacter baumannii Streptococcus pneumoniae Fig. Resistance of Acinetobacter baumannii and Streptococcus pneumoniae to azithromycin and ceftriaxone. A. Baumannii showed a high resistance rate to ceftriaxone while S. pneumoniae was highly resistant to azithromycin. - 438 -

하혜민 : 국내지역사회획득폐렴원인균의경험적항균제에대한내성현황 Table 5. The susceptibility and resistance of the most frequently isolated organisms to the initial empirical antibiotics The initial empirical antibiotics Organism Meropenem Number of cases (%) Piperacillin/tazobactam Number of cases (%) Ciprofloxacin Number of cases (%) S I R S I R S I R S Levofloxacin Number of cases (%) I R Acinetobacter baumannii 5 (9.2) 2 (8.8) 4 (6.7) 2 (83.3) 2 (7.7) 24 (92.3) 4 (5.4) 22 (84.6) Escherichia coli - - - (9.7) 4 - - (8.3) (73.3) (26.7) - Haemophilus influenzae 6 () () 8 5 () () Klebsiella pneumoniae - - - 8 (9) (5) (5) 2 (9.9) 2 - - (9.) - Pseudomonas aeruginosa - - - 6 (88.9) (5.6) (5.6) 9 (86.4) 2 (9.) (4.5) - - - Staphylococcus aureus - - - - 7 - - (35) 3 (65) - - - Streptococcus pneumoniae - - - - - - - - - 25 (96.2) (3.8) S, sensitive; I, intermediate; R, resistant; -, not defined 성현황을분석하고자국내 3개의대학병원에서수행되었다. 본연구에서분석된환자중경험적항균제로항균제를 개만사용한환자가전체의과반수를넘었으며환자의 35.% 는 2제요법을, 6.5% 는 3제요법을사용했다. 사용된경험적항균요법의항균제개수와환자의나이간에유의한인과관계는발견되지않았다. 국내에서 28년에개발된 지역사회획득폐렴의치료지침권고안 은치료성과를높이기위해폐렴이진단된후환자의입원여부를결정하여 입원을요하지않는환자, 일반병동으로입원하는환자, 중환자실로입원하는환자 에따라적절한항균요법을사용할것을권고하고있다. 7) 본연구에서폐렴의상병으로항균제를투여받고원인균의진단결과를가지는환자는모두가입원환자이었지만폐렴의중증도에따라 일반병동으로입원한환자 와 중환자실로입원한환자 로분류하고그에따른처방의적절성을평가하지못한한 계점을지닌다. 이는본연구가환자의전자의무기록을후향적으로분석한연구이며, 본연구에포함된환자의입원실이폐렴의중증도만으로결정되지못한점때문이다. 본연구에는지역사회획득폐렴환자뿐아니라보건의료관련폐렴 (healthcare-associated pneumonia, HCAP) 환자까지포함되었다고볼수있다. 보건의료관련폐렴은입원후 48 시간이내채취된검체에서호흡기계배양결과양성을나타난환자들중최근에보건의료기관을이용한환자, 폐렴발생 9일내에 2일이상병원에입원한환자, 장기요양시설에거주하는환자, 폐렴감염발생 3일이전에항균제를정맥으로투여받은환자, 항암제치료를받은환자, 상처치료를받은환자, 혈액투석환자중어느하나에해당되는경우를일컫는다. 2) 26년에개정된 Infectious Diseases Society of America and the American Thoracic Society (IDSA/ATS) 지침서는, 보건의료관 - 439 -

JKSHP, VOL.34, NO.4 (27) 련폐렴의경우지역사회획득폐렴과유사하게지역사회에서빈번히발생하고, 대부분의환자가초기에응급실을통해내원하는것등을고려하여지역사회획득폐렴의지침에보건의료관련폐렴을포함할것을제안하고있다. 4) 따라서본연구가지역사회획득폐렴과보건의료관련폐렴을분리하지못한단점을가지기는하나이부분이본연구의목표및의의를약화시키는요인은아니라고믿어진다. 본연구에서지역사회획득폐렴의원인균으로 A. baumannii와 S. pneumoniae가각각 5% 정도의빈도로가장흔하게진단되었고뒤를이어 K. pneumoniae와 P. aeruginosa가각각 3.%, S. aureus가.9%, E. coli가 8.9%, H. influenza가 4.8% 의빈도로진단되었다. 이러한결과는 2-28년에발표된국내에서수행된 4개의선행연구에서그람양성균인 S. pneumoniae의검출빈도가 27-44% 정도였으며 3)-6) P. aeruginosa의경우는 3개의연구에서 6- % 정도로검출된것 4)-6) 과다소대조적이다. 이는본연구가 2차및 3차의료기관에서수행된연구였다는것으로부분적으로해석되어진다. 3) S. pneumoniae 의항균제에대한내성을분석했을때 ceftriaxone에대해서는낮은내성률을가진반면 azithromycin에대해서는높은내성률 (9.3%) 을보였다. S. pneumoniae의 azithromycin에대한높은내성률은이미선행연구에서도보고되었다. 9) 따라서 지역사회획득폐렴의치료지침권고안 이β-lactam과 azithromycin 의병용을권고하고있지만 S. pneumoniae에의한감염이의심되는경우 ceftriaxone에 azithromycin을추가하는항균요법은효과에대한재평가가필요하다고사료된다. 본연구에서 ceftriaxone은경험적항균요법의단독요법중약 2% 의빈도로사용되었다. Azithromycin의경우는단독요법의약 2% 로사용되었으며 2제요법의약 37% 에서 ceftriaxone과병용되었고, 3% 에서 piperacillin/tazobactam 혹은 ceftazidime과병용되었다. 반면, 3제요법의약 82% 에서타약물과병용되었다. S. pneumoniae의 fluoroquinolones에대한내성의경우 2-2년에모은균주를대상으로한조사에서 levofloxacin에대한내성은발견되지않았던것으로보고되었으나 ) 22-26년에모은균주의 3.8% 가 levofloxacin에감수성 이없는것으로나타났고 ) 본연구에서는 3.8% 가 levofloxacin에대해내성을보였다. 본연구에서 levofloxacin은단독항균요법의약 7% 의빈도로사용되었으며 2제요법의약 5%, 3제요법의약 64% 에서타약물과병용되었다. 한편, 본연구에포함된환자에서높은빈도로진단된 E. coli, H. influenza, K. pneumoniae, P. aeruginosa는모두 piperacillin/ tazobactam과 ciprofloxacin에대해높은감수성을보여주었다. Piperacillin/tazobactam은경험적항균요법의단독요법중약 3% 의빈도로처방되고 2제요법의약 29%, 3제요법의약 36% 에서타약물과병용되었으며, ciprofloxacin의경우는단독요법중약 22% 의빈도로처방되고 2제요법의약 4%, 3제요법의약 9% 에서타약물과병용되었다. E. coli, H. influenza, K. pneumoniae, P. aeruginosa에의한감염이의심되는폐렴에경험적항균요법으로 piperacillin/tazobactam 혹은 ciprofloxacin을사용하는것은적절하다고판단된다. 더하여, H. influenza는 levofloxacin과 meropenem에도 % 의감수성을보여두약물은 H. influenza에의한폐렴이의심되는경우사용이적극권장된다고하겠다. Meropenem은단독항균요법의약 6% 빈도로사용되었으며 2제요법의약 7% 에서타약물과병용되었으나 3제요법으로는사용되지않았다. 지역사회획득폐렴에서 A. baumannii의진단률은선행연구간에도차이를보여낮게는 % 미만으로보고되었는가하면높게는 4.8% 까지도보고되었다. 4),6) 초기경험적항균제에대한 A. baumannii의내성현황을분석했을때 ceftriaxone, ciprofloxacin, levofloxacin, meropenem, piperacillin/tazobactam 모두에대해높은내성률 (8-92%) 을보였다. A. baumannii의다약제내성현황은이미선행연구를통해서도보고되었다. 5),6) 그러므로, A. baumannii에의한폐렴이의심되는경우이러한항균제를사용하는것에대한재고가필요하다고여겨진다. 본연구는적은환자수를대상으로한후향적연구로지역사회획득폐렴환자중경험적항균제를투여받고항균제에대한원인균의내성검사결과를가지는환자만분석하였기에본연구결과가제시하는진단된원인균의종류및진단빈도가지역사회획득폐렴환자전체에서나타나는양상을반영한다고볼수는 - 44 -

하혜민 : 국내지역사회획득폐렴원인균의경험적항균제에대한내성현황 없다. 이러한한계점에도불구하고, 본연구는지역사회획득폐렴의초기치료를위한경험적항균제의처방양상을살펴보고사용한항균제에대한진단된원인균의내성현황을파악하여 28년에개발된국내권고안에따른경험적항균요법의사용이적절한가를알아보고자한것에중요한의의가있다고하겠다. 결론 A. baumannii는 ceftriaxone, ciprofloxacin, meropenem, piperacillin/tazobactam 모두에대해높은내성률을보이므로 A. baumannii에의한폐렴이의심되는경우이들항균제를사용하는것에대한재고가필요하다. S. pneumoniae의경우는 azithromycin에대해높은내성률을가지므로 β-lactam 항균제에 azithromycin을추가하는항균요법에대한재평가가필요하다. 한편, E. coli, H. influenza, K. pneumoniae, P. aeruginosa는 piperacillin/ tazobactam과 ciprofloxacin에대해높은감수성을보였으며특히 H. influenza는 levofloxacin과 meropenem에도높은감수성을가지므로이들항균제의사용이적절한것으로판단된다. 참고문헌 ) KOSIS. Report on the cause of death statistics. Available from: http://kosis.kr/ups/ ups_list.jsp 2) Won CW. Community Acquired Pneumonia. Korean J Fam Med. 2;3:53-. 3) Woo JH, Kang JM, Kim YS, et al. A prospective multicenter study of communityacquired pneumonia in adults with emphasis on bacterial etiology. Korean J Infect Dis 2;33:-7. 4) Yu CW, Park CW, Hwang BY, et al. Clinical features and prognosisof communityacquired pneumonia in the elderly patients. Korean J Infect Dis. 2;32:22-8. 5) Sohn JW, Park SC, Choi YH, et al. Atypical pathogens as etiologic agents in hospitalized patients with community-acquired pneumonia in Korea: a prospective multi-center study. J Korean Med Sci. 26;2:62-7. 6) Song JH, Oh WS, Kang CI, et al. Epidemiology and clinical outcomes of community-acquired pneumonia in adult patients in Asian countries: a prospective study by the Asian network for surveillance of resistant pathogens. Int J Antimicrob Agents 28;3:7-4. 7) Song J-H, Jung K-S, Kang MW, et al. Treatment guidelines for communityacquired pneumonia in Korea: An evidencebased approach to appropriate antimicrobial therapy. Infect Chemother. 29;4:33-53. 8) Ayukekbong JA, Ntemgwa M, Atabe AN. The threat of antimicrobial resistance in developing countries: causes and control strategies. Antimicrob Resist Infect Control. 27;6:47. 9) Jung SI, Kim NY, Son JS, et al. Changing trends in antimicrobial resistance among invasive pneumococcal pathogens in Asian countries: Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study. Infect Chemother. 24;36:-. ) Song JH, Jung SI, Ko KS, et al. High prevalence of antimicrobial resistance among clinical Streptococcus pneumoniae isolates in Asia (an ANSORP study). Antimicrob Agents Chemother. 24;48: 2-7. ) Shin JH, Jung HJ, Kim HR, et al. Prevalence, characteristics, and molecular epidemiology of macrolide and fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae at five tertiarycare hospitals in Korea. Antimicrob Agents Chemother. 27;5:2625-7. - 44 -

JKSHP, VOL.34, NO.4 (27) 2) World Health Organization. Antimicrobial resistance: global report on surveillance 24. Available from: http://www.who.int/ drugresistance/documents/surveillancereport/en/ 3) American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospitalacquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 25;7:388-46. 4) Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospitalacquired and Ventilator-associated Pneumonia: 26 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 26;63: e6-. 5) Park HJ, Kim JM, Kim KH, Kim DS. Current analysis of Acintobacter baumannii infection among pediatric patients in a single-centered study. Korean J Pediatr Infect Dis. 2;8:23-3. 6) Lee K, Lee MA, Lee CH, et al. Increase of ceftazidime-and fluoroquinolone-resistant Klebsiella pneumoniae and imipenemresistant Acinetobacter spp. in Korea: analysis of KONSAR study data from 25 and 27. Yonsei Med J. 2;5:9-. - 442 -