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Korean J Crit Care Med 2013 August 28(3):173-179 / http://dx.doi.org/10.4266/kjccm.2013.28.3.173 원 저 인공호흡기치료중기관분비물배양검사에서 Carbapenem-Resistant Acinetobacter baumannii 가동정된환자의임상적특성 부산대학교의학전문대학원내과학교실 목정하ㆍ김미현ㆍ이광하ㆍ김기욱ㆍ박혜경ㆍ이민기 Clinical Characteristics in Patients with Carbapenem-Resistant Acinetobacter baumannii Isolates from Tracheal Secretions Jeong Ha Mok, M.D., Mi Hyun Kim, M.D., Kwangha Lee, M.D., Ki Uk Kim, M.D., Hye-Kyung Park, M.D. and Min Ki Lee, M.D. Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea Background: This study was conducted to evaluate the clinical characteristics and outcomes of mechanically ventilated patients with carbapenem-resistant Acinetobacter baumannii (CRAB) isolates from tracheal secretions in a medical intensive care unit (ICU) of a university hospital. Methods: We conducted a retrospective study from January 2009 to June 2012. Results: Among the patients who had isolates cultured from tracheal secretions, 130 patients (34.8%) had CRAB isolates. Their mean age was 65 ± 14 yr and 74.6% were male. The ICU and hospital mortality was 51.5% and 60.0%, respectively. According to physician s clinical decision, antibiotics were changed in order to cover CRAB in 75 (57.7%) patients. The total duration of antibiotics use was 12.2 ± 8.1 days. Of patients with antibiotics change to cover CRAB, 70 patients (93.3%) had Clinical Pulmonary Infection Score of 6 and over. However, there was no significant difference in hospital mortality between patients with antibiotics change against CRAB and those without change. In multivariable analysis, only Acute Physiology and Chronic Health Evaluation II score was related to hospital mortality of patients with CRAB. Conclusions: In this study, changing antibiotics to cover CRAB by physician s clinical decision only did not influence hospital mortality; further studies would be necessary to investigate how to use antibiotics against CRAB isolates cultured from tracheal secretions. Key Words: Acinetobacter baumannii, carbapenem, intensive care unit. 서 논문접수일 :2013 년 3 월 5 일, 수정일 :2013 년 5 월 9 일 (1 차 ), 2013 년 6 월 18 일 (2 차 ), 승인일 :2013 년 6 월 20 일책임저자 : 이광하, 부산시서구구덕로 179 부산대학교병원내과우편번호 : 602-739 Tel: 051-240-7743, Fax: 051-245-3127 E-mail: jubilate@pusan.ac.kr 본연구는 2012 년도부산대학교병원임상연구비지원으로이루어졌음. 론 173 중환자실에입원한환자는광범위항균제를많이사용하여다약제내성세균감염의발생위험이높다.[1] 역학적환경에따라동정되는균주의차이는있으나, 국내병원에서분리되는임상적으로중요한다약제내성세균으로는 Methicillin-resistant Staphylococcus aureus (MRSA), Extended spectrum beta-lactamase (ESBL) 생성그람음성균, Vancomycin-resistant Enterococci (VRE), Carbapenem-resistant Pseudomonas 및 Acinetobacter species 등이있다.[2] 이러한다약제내성세균감염은입원기간이나사망률의증가와연관이있고, 광범위항균제사용으로인한다른다약제내성세균발생의위험인자가된다.[2,3] 이중 Acinetobacter baumannii는중환자실의철저한감염관리대책에도불구하고감염빈도가늘어나고있다.[2] 특히광범위항균제인 carbapenem계항균제의사용으로이에대해내성을보이는 carbapenem-resistant A. baumannii (CRAB) 가인공호흡기치료를받는환자의기관분비물에서많이동정되고있으며, 이로인한인공호흡기연관폐렴발생시중환자실재원기간과사망률의증가가보고되고있다.[2-5] 하지만 CRAB는인공호흡기치료를받는환자에서오염균또는단순집락균으로검출되는경우가많아실제인공

174 대한중환자의학회지 : 제 28 권제 3 호 2013 호흡기연관폐렴의원인균인지명확하게감별하기가힘들고이로인해치료여부를결정하기힘든경우가많다. 기관분비물검출세균에대해정량적배양검사를시행하는경우인공호흡기연관폐렴의원인균감별에도움이될수있으나, 실제부산지역의대학병원에서는기관분비물에서검출된세균에대해일상적으로정량적배양검사를시행하지않고있기때문에의사의임상적판단에따라 CRAB 를치료하는경우가많다. 하지만이러한임상적판단에의해 CRAB 치료를결정한경우환자들의치료결과가어떻게달라지는지에대한보고는드물다. 따라서본연구는부산지역의한대학병원내과계중환자실에서인공호흡기치료를받았던환자들을대상으로기관분비물에서 CRAB가동정된환자들의임상적특성을조사하고, 동정된 CRAB에대해항균제감수성결과에의거하여의사의임상적판단에따라치료한경우환자들의치료결과가어떻게달라지는지알아보고자하였다. 대상및방법 1) 연구대상 2009년 1월 1일부터 2012년 6월 30일까지본원내과계중환자실에여러원인의호흡부전으로입원하여인공호흡기치료를받았던성인환자 ( 만 18세이상 ) 중기관분비물미생물배양검사에서 CRAB가동정된환자를대상으로후향적의무기록분석을시행하였다. 본연구는본원임상시험심사위원회심의를통과하였다 (E-2012113). 2) 연구방법대상환자들의인구학적인특성, 기저질환, 중환자실입원시의주진단, 실험실검사결과, 기관절개술의시행여부, 인공호흡기치료기간, 중환자실및병원재원일수를조사하였고, 중환자실및병원사망률도조사하였다. 중환자실입원첫 24시간동안환자의중등도는 Acute Physiology and Chronic Health Evaluation (APACHE) II 점수로,[6] 동반된장기의기능부전은 Sequential Organ Failure Assessment (SOFA) 점수로평가하였다.[7] 기관분비물배양검사당시인공호흡기연관폐렴의동반여부는 Clinical Pulmonary Infection Score (CPIS) 로평가하였고,[8] CPIS가 6 점이상인경우인공호흡기연관폐렴의가능성이높은것으로정의하였다. 또한환자들의동반된모든기저질환을점수화하기위해 Charlson s Comorbidity Index (CCI) 를계산하였다.[9] 기관분비물배양검사에서동정된 CRAB는 Murray and Washington Sputum Grading System을기준으로 group 5에해당되는 ( 현미경 100배시야에서상피세포 10개미만, 백혈구 25개초과 ) 경우만연구에포함시켰으며,[10] 또한인공호흡 기치료도중기관분비물에서 2회이상 CRAB가동정되는경우는처음동정된 CRAB만분석에포함시켰다. 항균제에대한감수성검사는디스크확산법을이용하여검사하였으며, 결과는 susceptible과 resistant로보고하였다. CRAB 치료는의사의임상적판단에의해시행하였으며, 임상적판단에의한 CRAB 치료시작은 CRAB가동정된시점에서기존항균제를 3일이상사용함에도불구하고실험 실검사, 흉부방사선검사및증상의악화가있는경우로정의하였다. 항균제감수성검사결과에서감수성이있는것으로보고된항균제를 CRAB 치료에사용하였으며, 두가지이상항균제를병합하여 CRAB를치료한경우최소한가지이상의감수성이있는항균제를병합요법에포함시켰다. 또한모든환자에대해 CRAB 치료전과후의항균제사용력을조사하였으며, CRAB 검출이후중환자실입원기간동안동반검출된다른다약제내성세균과이세균의치료항균제에대해서도조사하였다. 병원퇴원시생존여부에따라생존군, 사망군으로나누었고, 무망퇴원 (hopeless discharge) 은사망군으로분류하였다. 3) 통계분석 통계분석은 SPSS 20.0 version (SPSS TM Inc; Chicago, IL, USA) 을사용하였다. 연속변수는평균과표준편차로계산하고독립표본 t검정을이용하여분석하였으며, 명목변수는카이제곱검정과피셔의정확확률검정법을이용하여분석하였다. 생존에영향을미친인자를조사하기위해로지스틱회귀분석을실시하였다. p값은 0.05 미만인경우를통계학적으로유의한것으로간주하였다. Table 1. Diagnosis of Enrolled Patients on Initial Intensive Care Unit Admission Diagnosis Total (n = 130) Respiratory failure 112 (86.1) Pneumonia 93 (71.5) Hemoptysis 8 (6.2) Acute exacerbation of chronic lung disease 6 (4.6) Pulmonary tuberculosis 5 (3.8) Hepatobiliary infection 5 (3.8) Gastrointestinal disease* 5 (3.8) Soft tissue, bone infection 5 (3.8) Others 3 (2.4) All data are expressed as number (%). *Gastrointestinal disease include gastrointestinal bleeding (n = 3), and colitis (n = 2). Other disease include acute kidney injury (n = 1), Henoch Schonlein purpura (n = 1), and hemolytic uremic syndrome (n = 1).

목정하외 5 인 :Carbapenem-Resistant Acinetobacter baumannii in a Intensive Care Unit 175 결 Table 2. Antibiotic Susceptibility of Carbapenem-Resistant Acinetobacter baumannii Antibiotics Total (n = 130) Colistin* 106 (81.5) Minocycline 80 (61.5) Amikacin 12 (9.2) Tobramycin 7 (5.4) Trimethoprim-sulfamethoxazole 4 (3.1) Netilmycin 2 (1.5) Isepamicin 1 (0.8) All data are expressed as number of susceptible isolates (%). *After exam for colistin resistance regularly, no carbapenem-resistant Acinetobacter baumannii isolates resistant to colistin were revealed. All isolates susceptible to minocycline were also susceptible to colistin. 과 1) CRAB 가동정된환자의임상적특성 대상기간동안내과계중환자실에입원한 1,440명의환자중 374명의기관분비물에대해세균배양검사가시행 되었으며, 이중 130명 (34.8%) 에서 CRAB가동정되었다. 중환자실입원후 CRAB가동정되기까지의기간은 8.9 ± 6.6 ( 평균 ± 표준편차 ) 일이었으며, 11명 (8.5%) 의환자는 CRAB 균혈증도동반되었다. 환자들의중환자실입원당시가장흔한진단명은폐렴이었다 (Table 1). 동정된 CRAB의항균제감수성검사상 106건 (81.5%) 에서 colistin에감수성을보였고, 80건 (61.5%) 에서 colistin과 minocycline에감수성을보였다 (Table 2). Colistin과 minocycline에대해일상적으로항균제감수성검사를시행한 2010년이후의환자 83건 (63.8%) 만을대상으로하였을경우 colistin에내성을보이는경우는없었다. CRAB가동정되기전 14일이내의항균제사용력 ( 두가지이상의항균제를병합하여사용한경우는각각중복해서기록 ) 을조사하였을때 quinolone계항균제사용이 94명 (72.3%) 으로가장많았으며, 다음으로 carbapenem계항균제 77명 (59.2%), glycopeptide계항균제 71명 (54.6%), 3세대 cephalosporin계항균제 48명 (36.9%), antipseudomonal penicillin계항균제 ( 모두 piperacillin/tazobactam) 38명 (29.2%) 순이었고, 121명 (93.1%) 의환자가두가지이상의항균제를병합하여사용한것으로조사되었다. Table 3. Comparison of Clinical Characteristics and Outcomes between Patients Who Underwent Antibiotics Change to Cover Carbapenem-Resistant Acinetobacter baumannii and Who Did Not Variables Total (n = 130) Antibiotics change (n = 75) No antibiotics change (n = 55) p value Age, years 65.0 ± 13.8 65.5 ± 14.5 64.3 ± 12.7 0.617 Male gender 97 (74.6) 54 (72.0) 43 (78.1) 0.547 Tracheostomy 53 (40.8) 40 (53.3) 13 (23.6) 0.001 APACHE II score on ICU admission day 20.8 ± 6.0 20.0 ± 6.1 21.8 ± 5.7 0.087 SOFA score on ICU admission day 8.4 ± 3.1 7.9 ± 2.9 9.0 ± 3.1 0.031 Charlson s Comorbidity Index 2.0 ± 1.4 1.9 ± 1.2 2.2 ± 1.6 0.207 Serum albumin, g/dl 2.6 ± 0.4 2.6 ± 0.4 2.6 ± 0.3 0.834 Serum total bilirubin, mg/dl 1.7 ± 2.7 1.5 ± 1.7 2.0 ± 3.7 0.303 Serum creatinine, mg/dl 1.2 ± 1.1 1.2 ± 1.0 1.3 ± 1.2 0.448 Serum C-reactive protein, mg/dl 12.6 ± 8.2 13.5 ± 8.9 11.2 ± 7.2 0.102 Ratio of PaO 2 to FiO 2 227.7 ± 121.2 211.1 ± 95.8 250.3 ± 146.9 0.088 Requirement for vasopressor 50 (38.5) 27 (36.0) 23 (46.0) 0.585 Requirement for renal replace therapy 26 (20.0) 13 (17.3) 13 (23.6) 0.385 Clinical Pulmonary Infection Score 7.3 ± 1.5 7.7 ± 1.4 6.9 ± 1.5 0.004 Clinical Pulmonary Infection Score 6 113 (86.9) 70 (93.3) 43 (78.2) 0.017 Total duration of MV, days 27.1 ± 31.2 32.8 ± 30.2 19.4 ± 30.9 0.015 Total ICU LOS, days 26.5 ± 27.9 30.4 ± 25.1 21.1 ± 30.6 0.061 Total hospital LOS, days 52.4 ± 47.1 52.1 ± 35.7 52.7 ± 59.5 0.936 ICU mortality 67 (51.5) 37 (49.3) 30 (54.5) 0.597 Hospital mortality 78 (60.0) 45 (60.0) 33 (60.0) 1.000 All data are expressed as mean ± standard deviation for continuous variables and number (%) for categorical variables. Statistical significance was tested by Student's t-test for continuous variables and the Chi-square test or Fisher's exact test (for small numbers) for categorical variables. All laboratory results and parameters related mechanical ventilator are based on date of tracheal secretion collect. APACHE: Acute Physiology and Chronic Health Evaluation; SOFA: Sequential Organ Failure Assessment; MV: mechanical ventilation; ICU: intensive care unit; LOS: length of stay.

176 대한중환자의학회지 : 제 28 권제 3 호 2013 CRAB가동정된환자들의중환자실및병원사망률은각각 51.5% 와 60.0% 였다. 2) CRAB 치료를위해항균제를변경한환자들의임상적특성과치료결과 75명 (57.7%) 의환자가의사의임상적판단에의해동정된 CRAB에의한폐렴또는기관기관지염으로추정하고이에대한치료를목표로항균제를변경하였다. 항균제변경시점은 CRAB 동정이후 1.7 ± 1.8일이었고, 변경항균제의평균사용기간은 12.2 ± 8.1일이었다. CRAB 감염치료에사용한항균제는 cefoperazone/sulbactam과 minocycline의병합요법이 31명 (41.3%) 으로가장많았고, colistin 23명 (30.7%), colistin과다른항균제 (minocycline, rifampin, aminoglycoside, ampicillin/sulbactam) 의병합요법 11명 (14.7%), minocycline 4명 (3.1%), minocycline과다른항균제 (tigecycline, aminoglycoside) 의병합요법 3명 (2.3%), 기타항균제 (ampicillin/sulbactam, aminoglycoside) 3명 (2.3%) 순이었다. 55명 (42.3%) 의환자는 CRAB가동정되었으나의사의임상적판단에의해항균제를변경하지않았고, 이들이 CRAB 동정이후사용한항균제는 carbapenem계항균제 41명 (74.5%), quinolone계항균제 32명 (58.2%), glycopeptide계항균제 28명 (50.9%) 순이었으며, 53명 (96.4%) 의환자가두가지이상의 항균제를병합하여사용하였다. 동정된 CRAB에대해항균제를변경한군과변경하지않은군을비교시항균제를바꾼환자의 CPIS가더높았고 CPIS가 6점이상인환자및기관절개술을시행한환자의비율이더많았다. 또한 SOFA점수는더낮았으며인공호흡기치료기간은더길었다. 하지만중환자실및병원사망률에있어통계학적인차이는없었다 (Table 3). 전체대상환자 130명중 36명 (27.7%) 의기관분비물에서 CRAB 동정이후중환자실체류기간동안다른다약제내성세균이함께동정되었으며, 항균제변경군은 27명 (36.0%), 비변경군은 9명 (16.0%) 으로항균제변경군에서 CRAB 동정이후다른다약제내성세균의동반빈도가의미있게높았다 (p = 0.009). 동반된다약제내성세균은 ESBL 생성그람음성균이 13명 (36.1%) 으로가장많았고, 다음으로 MRSA 12명 (33.3%), carbapenem-resistant Pseudomonas aeruginosa 7명 (19.4%) 순이었다. 동반된다약제내성세균의치료는 30명 (83.3%) 에서시행되었으며, carbapenem계항균제및 glycopeptide계항균제를주로사용하였다. 3) CRAB가동정된환자의예후분석전체환자들을생존군과사망군으로나누어비교하였을때사망군의 APACHE II 점수와 CCI가더높았다 (Table 4). 하지만다변량로지스틱회귀분석시 APACHE II 점수만 Table 4. Comparison of Clinical Characteristics between Survivors and Non-Survivors at Hospital Discharge Variables Survivors at hospital discharge (n = 52) Non-survivors at hospital discharge (n = 78) p value Age, years 63.9 ± 13.6 65.6 ± 13.9 0.498 Male gender 40 (76.9) 57 (73.0) 0.684 Tracheostomy 23 (44.2) 30 (38.5) 0.586 APACHE II score on ICU admission day 18.5 ± 5.0 22.4 ± 6.2 <0.001 SOFA score on ICU admission day 7.8 ± 3.0 8.7 ± 3.1 0.104 Charlson s Comorbidity Index 1.6 ± 1.2 2.3 ± 1.5 0.012 Serum albumin, g/dl 2.6 ± 0.4 2.6 ± 0.4 0.735 Serum total bilirubin, mg/dl 1.5 ± 1.5 1.9 ± 3.3 0.418 Serum creatinine, mg/dl 1.1 ± 1.1 1.3 ± 1.1 0.266 Serum C-reactive protein, mg/dl 11.2 ± 8.1 13.5 ± 8.2 0.125 Ratio of PaO 2 to FiO 2 234.4 ± 94.2 223.2 ± 136.6 0.608 Requirement for vasopressor 20 (38.5) 30 (38.5) 1.000 Requirement for renal replace therapy 7 (13.5) 19 (24.4) 0.179 Clinical Pulmonary Infection Score 7.4 ± 1.6 7.3 ± 1.5 0.963 Total duration of MV, days 23.7 ± 23.8 29.4 ± 35.2 0.303 Total ICU LOS, days 22.8 ± 12.4 28.9 ± 34.4 0.224 Total hospital LOS, days 56.7 ± 37.6 49.5 ± 52.6 0.400 Antibiotics change for CRAB 30 (57.7) 45 (57.7) 1.000 All data are expressed as mean ± standard deviation for continuous variables and number (%) for categorical variables. Statistical significance was tested by Student's t-test for continuous variables and the Chi-square test or Fisher's exact test (for small numbers) for categorical variables. All laboratory results and parameters related mechanical ventilator are based on date of tracheal secretion collect. APACHE: Acute Physiology and Chronic Health Evaluation; SOFA: Sequential Organ Failure Assessment; MV: mechanical ventilation; ICU: intensive care unit; LOS: length of stay; CRAB: carbapenem-resistant Acinetobacter baumannii.

목정하외 5 인 :Carbapenem-Resistant Acinetobacter baumannii in a Intensive Care Unit 177 Table 5. Multivariable Analysis for Factors Associated with Hospital Mortality in Patients with Carbapenem-Resistant Acinetobacter baumannii Variables Odds ratio (95% CI) p value APACHE II score on ICU admission day 1.111 (1.036 1.192) 0.003 Charlson s Comorbidity Index 1.330 (0.989 1.790) 0.060 Serum C-reactive protein, mg/dl 1.046 (0.997 1.097) 0.066 SOFA score on ICU admission day 0.924 (0.783 1.090) 0.350 Requirement for renal replace therapy 1.156 (0.406 3.293) 0.786 Statistical significance was tested by multivariable logistic regression analysis. CI: confidential interval; APACHE: Acute Physiology and Chronic Health Evaluation; SOFA: Sequential Organ Failure Assessment. 이 CRAB가동정된환자의병원사망과연관이있는것으로나타났으며, 의사의임상적판단에의한항균제변경은병원사망에영향이없는것으로분석되었다 (Table 5). CPIS 가 6점이상인환자 113명 (86.9%) 만을대상으로분석하였을경우에도동일한결과를보였다. 고찰본연구는인공호흡기치료중기관분비물배양검사에서 CRAB가동정된환자의특성을알아보고, 의사의임상적판단에의해 CRAB 치료를결정한경우치료결과에어떠한차이가있는지조사한연구이다. 본연구에서기관분비물에서동정된 CRAB에대해치료를실시한군에서 CPIS가더높았고 CPIS가 6점이상인환자의비율이더많았다. 즉환자의임상증상, 실험실검사, 흉부방사선검사결과가불량한경우임상적으로 CRAB에의한감염증으로판단하고항균제를변경하여 CRAB 치료를시작하는경우가많았다. 하지만항균제를변경하지않은군과비교시병원사망률에있어의미있는차이는없었으며, 또한다변량분석에서이러한의사의임상적판단에의한항균제변경은환자의예후에영향이없는것으로분석되었다. 이는동정된 CRAB가인공호흡기연관폐렴의원인균인지명확하지않았다는점이가장큰이유로생각된다. 또한의사의임상적판단에근거하여항균제를변경한경우, 동반되는다른다약제내성세균의빈도가높았으며이역시동정된 CRAB가인공호흡기연관폐렴의원인균인지명확하지않은상태에서항균제를변경하였기때문으로생각된다. NHSN (National Healthcare Safety Network) surveillance algorithm 프로그램에서는 Murray and Washington Sputum Grading System을기준으로 group 5에해당되는 ( 현미경 100배시야에서상피세포 10개미만, 백혈구 25개초과 ) 호흡기검체에서균주가동정되는경우 Possible ventilator-associated pneumonia (VAP) 로정의하며, 기관내흡인물정량적배양검사에서 10 5 CFU/ml 이상의균주가동정되는경우 `Probable VAP 로정의하고있다.[11] 따라서기관분비 물에서 CRAB가동정되는경우임상적판단외에도정량적배양검사와같이인공호흡기연관폐렴의원인균감별에도움이되는검사를진단과치료결정에보조적인방법으로사용하는것이좋을것으로생각된다. 하지만많은의료기관에서실제일상적으로기관분비물에서동정된세균에대해정량적배양검사를시행하지않고있기때문에이러한경우어떠한기준에근거하여 CRAB 치료를결정하는것이좋을지에대한논의가필요할것이다. 인공호흡기연관폐렴의 36%, 중환자실에서발생하는병원내폐렴의약 20% 는 A. baumannii에의한다고한다.[2] 또동정되는 A. baumannii의 80% 이상이다약제내성세균인 CRAB이며, CRAB 감염에의한폐렴은사망률이더높은것으로알려져있다.[2,12] A. baumannii의다약제내성위험인자는중환자실입원및광범위항균제사용이다.[13] 따라서 A. baumannii의내성을줄이기위해서는광범위항균제의무분별한사용을제한하는것이중요하며, 항균제의회전전략을사용하는것도고려해볼수있다.[14,15] 또한 CRAB를포함한다약제내성세균을신속하게진단, 보고할수있는검사기법이나, 원내시스템이뒷받침되어야한다. 그리고발생한 A. baumanii는병원내환경에서장시간생존할수있고, 의료인이나환자사이에전파될수있기때문에철저한병원감염관리가필수적이다.[4,16] 본연구에서중환자실환자의 CRAB 동정비율은 34.8% 였다. 상체거상, 매일진정제의휴약과기관발관의평가, 궤양성소화기질환및하지정맥혈전증의예방과같은 ventilator bundle intervention을모든인공호흡기치료환자에게적용하였고, 또한인공호흡기의주기적관리 ( 일주일간격의인공호흡기회로, 필터교체 ), 폐쇄형흡인팁의사용과 3일간격의교체, 그리고 CRAB 동정시적용되는접촉격리 ( 손씻기, 환자접촉시장갑과가운착용, 매일의료물품및개인물품소독, 가능한격리병상사용등 ) 등중환자실감염관리를연구기간동안꾸준히유지하였으나 CRAB의동정빈도는변화가없었다. 따라서이러한감염관리대책이실제얼마나정확하고철저하게수행되는지평가가필요할것이다. 본연구는몇가지제한점이있다. 첫번째로연구에사

178 대한중환자의학회지 : 제 28 권제 3 호 2013 용된자료가단순의무기록이고, 이를후향적으로분석하였기때문에결과분석에한계가있었다. 두번째로항균제를병합하여 CRAB를치료한경우일부약제의항균제감수성결과를알수없었으며, 또한병합약제간상승효과에대한정보를알수없었다. CRAB 감염의치료는 polymixin 계열의항균제인 colistin이일차치료제로권고되고있으나,[4,17] 다양한약제의병합요법으로 CRAB를치료한많은보고가있으며,[18-20] 최근에는 cefoperazone/sulbactam과 minocycline을병용할경우 CRAB에대한상승효과가발생한다는결과가보고되기도하였다.[21,22] 본연구에서도 cefoperazone/sulbactam과 minocycline 병합요법을많이사용하였다. 항균제감수성검사결과에서 minocycline에대해감수성이있는경우에만병합요법으로치료하였으나, sulbactam의항균제감수성결과및두항균제의상승효과에대한자료가없어본연구에서병합요법이실제치료효과에영향을미쳤을가능성에대해서는추가적인연구가필요하다. 결론적으로본연구에서인공호흡기치료를받는환자의기관분비물에서 CRAB 동정빈도는약 35% 정도였으며, 의사의임상적판단에근거하여 CRAB 치료를시행하는것은환자의예후에영향이없었다. 제한된검사실환경의의료기관에서인공호흡기치료중동정된 CRAB에대해어떠한기준에근거하여치료를결정하는것이좋을지에대한추가적인연구가필요하다. 참고문헌 1) Fridkin SK: Increasing prevalence of antimicrobial resistance in intensive care units. Crit Care Med 2001; 29(4 Suppl): N64-8. 2) Chung DR, Song JH, Kim SH, Thamlikitkul V, Huang SG, Wang H, et al; Asian Network for Surveillance of Resistant Pathogens Study Group: High prevalence of multidrug-resistant nonfermenters in hospital-acquired pneumonia in Asia. Am J Respir Crit Care Med 2011; 184: 1409-17. 3) Wunderink RG, Niederman MS: Update in respiratory infections 2011. Am J Respir Crit Care Med 2012; 185: 1261-5. 4) Munoz-Price LS, Weinstein RA: Acinetobacter infection. N Engl J Med 2008; 358: 1271-81. 5) Maniatis AN, Pournaras S, Orkopoulou S, Tassios PT, Legakis NJ; Bacterial Resistance Study Group: Multiresistant Acinetobacter baumannii isolates in intensive care units in Greece. Clin Microbiol Infect 2003; 9: 547-53. 6) Knaus WA, Draper EA, Wagner DP, Zimmerman JE: APACHE II: A severity of disease classification system. Crit Care Med 1985; 13: 818-29. 7) Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al: The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. on behalf of the working group on sepsis-related problems of the European society of intensive care medicine. Intensive Care Med 1996; 22: 707-10. 8) Luyt CE, Chastre J, Fagon JY: Value of the clinical pulmonary infection score for the identification and management of ventilator-associated pneumonia. Intensive Care Med 2004; 30: 844-52. 9) Charlson ME, Pompei P, Ales KL, MacKenzie CR: A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373-83. 10) Murray PR, Washington JA: Microscopic and baceriologic analysis of expectorated sputum. Mayo Clin Proc 1975; 50: 339-44. 11) Device-associated module: Ventilator-associated event protocol. National Healthcare Safety Network 2013. Available from http://www.cdc.gov/nhsn/pdfs/pscmanual/10-vae_final.pdf 12) Park II, Kim IK, Koo HC, Han JP, Kim YM, Lee MG, et al: Clinical characteristics and prognosis of Acinetobacter nosocomial pneumonia between MDR and non-mdr. Tuberc Respir Dis 2006; 61: 13-9. 13) Lee SO, Kim NJ, Choi SH, Hyong Kim T, Chung JW, Woo JH, et al: Risk factors for acquisition of imipenem-resistant Acinetobacter baumannii: a case-control study. Antimicrob Agents Chemother 2004; 48: 224-8. 14) Gruson D, Hilbert G, Vargas F, Valentino R, Bui N, Pereyre S, et al: Strategy of antibiotic rotation: long-term effect on incidence and susceptibilities of gram-negative bacilli responsible for ventilator-associated pneumonia. Crit Care Med 2003; 31: 1908-14. 15) Ma JE, Kim SK, Kang MK, Jeong YY, Kim HC, Lee JD, et al: Change of antibiotics resistance pattern of microorganism cultured in tracheal aspirate in mechanical ventilated patients after antibiotics restriction policy. Korean J Crit Care Med 2008; 23: 25-9. 16) Song JH: Current status and future strategies of antimicrobial resistance in Korea. Korean J Med 2009; 77: 143-51. 17) Karageorgopoulos DE, Falagas ME: Current control and treatment of multidrug-resistant Acinetobacter baumannii infections. Lancet Infect Dis 2008; 8: 751-62. 18) Bassetti M, Repetto E, Righi E, Boni S, Diverio M, Molinari MP, et al: Colistin and rifampicin in the treatment of multidrug-resistant Acinetobacter baumannii infections. J Antimicrob Chemother 2008; 61: 417-20. 19) Mutlu Yilmaz E, Sunbul M, Aksoy A, Yilmaz H, Guney AK, Guvenc T: Efficacy of tigecycline/colistin combination in a pneumonia model caused by extensively drug-resistant Acinetobacter baumannii. Int J Antimicrob Agents 2012; 40: 332-6. 20) Lim SY, Park SY, Jeon K, Suh GY, Kim S, Peck KR, et al: Extreme drug resistant Acinetobacter nosocomial ventilator-associated pneumonia treated successfully with tigecycline and amikacin in intensive care unit: a case report. Korean J Crit Care Med 2009; 24: 176-80. 21) Pei G, Mao Y, Sun Y: In vitro activity of minocycline alone

목정하외 5 인 :Carbapenem-Resistant Acinetobacter baumannii in a Intensive Care Unit 179 and in combination with cefoperazone-sulbactam against carbapenem-resistant Acinetobacter baumannii. Microb Drug Resist 2012; 18: 574-7. 22) Jang HJ, Kim MN, Lee K, Hong SB, Lim CM, Koh Y: The comparative efficacy of colistin monotherapy and combination therapy based on in vitro antimicrobial synergy in ventilator-associated pneumonia caused by multi-drug resistant Acinetobacter baumannii. Tuberc Respir Dis 2009; 67: 212-20.