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1 대한내과학회지 : 제 75 권제 2 호 2008 특집 (Special Review) - 노인호흡기질환의효과적관리 노인폐렴 한림대학교의과대학내과학교실호흡기내과 정기석 Pneumonia in the elderly patients Ki-Suck Jung, M.D. Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University College of Medicine, Korea Community-acquired pneumonia (CAP) is one of major medical illness and leading causes of death in the elderly patients. They account for the majority of CAP-related hospital admission, and suffer from more severe degree of illness that often requires broad-spectrum antibiotics and intensive care unit (ICU) admission. Recently, the incidence and mortality of CAP is rising. Therefore, the economic and clinical burden is expected to increase consistently at present time and also in the future. Although Streptococcus pneumoniae is still the most common pathogen identified, pneumonia in elderly patients is different from that in younger patients, with regard to the etiology, clinical course, and treatment response. The most striking characteristic of pneumonia in older patients is its clinical presentation: classic symptoms are often absent. Therefore, appropriate diagnosis and treatment can be delayed. When approaching the treatment for pneumonia in older patients, patients with healthcare-associated pneumonia (HCAP) should be distinguished from those with CAP. Patients with HCAP are at high risk for multidrug-resistant (MDR) pathogens and tend to have much more severe illness due to multiple co-morbidities and decreased functional status, which are associated with poor outcome. Prevention should also be implemented, focusing on smoking cessation, aspiration prevention, and influenza and pneumococcal vaccination. (Korean J Med 75: , 2008) Key Words: Community-acquired pneumonia; Healthcare-associated pneumonia; Elderly patients 서론노인환자들은입원을필요로하는지역사회폐렴의대부분을차지한다. 이들은젊은성인에비해, 긴입원기간을필요로하고, 동반질환이많으며, 중환자실치료를받아야하는경우가빈번하다. 폐렴은노인환자들의주된사망원인으로우리나라의통계를보면 2006년폐렴에의한사망이 10만명당 9.4명으로전체연령에서는사망원인의 10위를차지하고있으나 70세이상에서는 6위를차지한다 1). 미국에서는 65세이상에서 5번째로많은사망원인이된다 2). 고령화사회가진행됨에따라노인인구에대한건강비용도증가하 고있는데, Niederman 등의보고에의하면, 노인환자가전체지역사회폐렴의 1/3을차지하지만치료비용은 50% 이상을차지하였다 3). 폐렴치료는폐렴의중증도, 동반질환, 원인균에따라다를수있지만, 노인에서는폐렴의원인과임상양상, 치료에대한반응이젊은환자와차이가난다. 또, 노인환자에서는요양원등의집단수용시설거주자나장기적으로혈액투석을받는환자들이많은데, 이들에서발생한폐렴은건강관리-관련폐렴 (healthcare-associated pneumonia, HCAP) 으로따로분류하고있고, 이들은병원균의종류와항생제감수성양상이지역사회폐렴과는다르다. 지역사회폐렴의사망률은

2 - The Korean Journal of Medicine: Vol. 75, No. 2, Table 1. Clinical symptoms in the older patients with pneumonia Fernadez-Sabe et al 22) Riquelme et al 23) El-Solh 21) (n=305) (n=101) (n=104) Fever 207 (68%) 64 (64%) 56 (54%) Purulent Sputum 160 (53%) 52 (52%) Chills 136 (45%) Pleuritic Chest Pain 111 (37%) 13 (13%) Altered Mental Status 64 (21%) 45 (45%) 60 (58%) Myalgia 24 (8%) Headache 20 (7%) Dyspnea 71 (71%) 84 (81%) Cough 67 (67%) 47 (46%) Asthenia 58 (58%) Anorexia 50 (50%) 외래환자의경우는 1% 이내이지만 4, 5), 입원하는환자에서는 8~15% 정도로크게증가하게되고 6, 7), HCAP이나중환자실로의입원이필요한경우에서는 40% 이상의사망률을보일수있다 8). 현재우리나라에서는대한결핵및호흡기학회에서 2005 년에폐렴지침을발간하였고 9), 외국에서는 2007년미국감염학회 (Infectious Disease Society of America) 와흉부학회 (American Thoracic Society) 에서공동으로발간한지침이있다 10). 이들지침서를포함하여최근에나온노인폐렴에대한중요문헌들을바탕으로노인폐렴의특징및진단과치료에대해소개하고자한다. 병태생리폐렴은병원균이숙주의방어능력을넘어서는경우즉, 병원성이강한균이거나, 균수가많거나, 환자의균에대한저항능력이떨어지는경우에발생한다. 노인에서폐렴이잘생기는것은고령의나이보다는동반된질환때문이라는견해가많은데, 영양결핍, 종양, 만성폐질환, 심장질환, 간질환, 흡연등이숙주의방어기전을저해할수있다. 나이가증가함에따라흉벽의유순도가감소하고, 탄성이증가하며, 호흡근의힘이약해진다. 점막의섬모운동과기침반사의감소로인해객담배출이줄어들어세균의배출도감소되게된다 11). 노인에서는구강인두내에세균의집락화가증가하는데, 주된균은 Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli이고, 중증환자에서는장내그람음성세균 (enteric gram-negative organism) 과 S aureus가흔하다 12, 13). 거동이어렵거나요실금, 만성심폐질환, 다수의동 반질환 (co-morbidities), 영양결핍이있는환자에서는그람음성균에의한집락화가증가한다 14). 또, 노인에서는흡인 (aspiration) 이쉽게일어나는데연하장애가주된원인이고, 특히뇌졸증이나알츠하이머등의신경계질환에서많다. 몇몇연구에서는 ACE억제제로기침을유도하여폐렴의발생을감소시켰다는보고도있다 15, 16). 연하장애를가진환자들이영양결핍도흔한데, 알부민등의지표들이지역사회폐렴의발생과도관련이있다. Fry 등에의하면노인폐렴환자들은만성심장질환, 만성폐질환, 당뇨병등의적어도 1개이상의동반질환을가지고있다고하였는데, 이런질환들은숙주의방어기전을떨어뜨릴뿐만아니라활동능력도감소시킨다 17). 이런활동능력의감소와침상생활등의의존적인생활방식은결국노인환자의사망률을높이게된다 18). 임상적특징노인폐렴에서폐렴의특징적인임상증상이종종나타내지않는다는것은오래전부터잘알려져왔다. 즉, 오한이없고, 기침과객담이적으며, 이학적소견이뚜렷하지않다는점이다 19). 대신에혼돈이나무기력증, 기저질환의악화등으로나타나는경우가많다. 기저질환인만성폐쇄성폐질환, 당뇨, 심부전등은감염된사실을가릴수있고, 이들의기능부전이폐렴의첫번째증상으로표현될수있다. Metlay 등에의하면노인환자에서는젊은환자보다증상이적었으나, 증상의기간은더길었으며, 발열과흉막통증이흔한젊은환자와는달리빈호흡이더흔하였다 20). 다른보고들에서도특징적인폐렴증상이외에호흡곤란, 섬망, 급

3 - Ki-Suck Jung: Pneumonia in the elderly patients - Table 2. Etiologic pathogens for pneumonia in older patients 40) Outpatient and non-icu inpatients ICU Patients Streptococcus pneumonia, Hemophilus influenzae, Morexalla catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella spp., Enteric gram-negative organisms, Staphylococcus aureus, Anaerobes Streptococcus pneumonia (including DRSP), Mycoplasma pneumoinae, Chlamydia pneumoniae, Legionella spp., Enteric gram-negative organisms (including Pseudomonas spp.) Hemophilus influenzae, Staphylococcus aureus (including MRSA), Influenza and other viruses If risks for drug resistance are not present Healthcare-associated Pneumonia (HCAP) Streptococcus pneumoniae (including DRSP), Mycoplasma pneumoinae, Chlamydia pneumoniae, Legionella spp., Hemophilus influenzae, Influenza and other viruses, Enteric gram-negative organism (Escherichia coli, Klebsiella pneumonia) If risks are present (recent antibiotics, poor functional status) All of the Above, plus Drug-resistance gram-negative organisms, Pseudomonas aeruginosa, Acinetobacter spp., Staphylococcus aureus (including MRSA) 성혼돈, 저산소증의빈도도높았다 ( 표 1) 21-23). 노인환자에서발열이흔하지않는이유도기초온도가낮고, 온도조절능력이감소되어열성반응이무뎌지기때문이다. 한연구에의하면노인환자에서내원전평균증상기간이 6.1일이었다는보고가있고 24), 응급실에서의항생제투여가 4시간이상지연될수있다는보고가있다 25). 이런결과들은노인폐렴에서는진단을놓치기쉽고, 치료가지연되어예후가좋지않다는점을말해준다고볼수있다 24, 25). 원인균지역사회폐렴의흔한원인균은 Streptococcus pneumonia, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Hemophilus influenzae 등으로알려져있다 10). 우리나라에서는입원환자를대상으로한연구를보면 S pneumoniae (26.8%), K pneumoniae (18.1%), Pseudomonas aeruginosa (11.8%), S aureus (11.4%) 가흔하다 9). 이외에다른원인으로는 Legionella spp., 혐기성세균, 바이러스가있고, 상황에따라서는약물내성 S. pneumoniae (Drug-resistant S pneumoniae, DRSP) 의가능성도고려해야한다. DRSP 는이전의항생제치료, 알코올중독, 면역저하, 만성심폐질환등의동반질환이있는환자에서발생할수있다 ( 표 2). 장내그람음성균과 P aeruginosa는지역사회폐렴에서흔한원인균은아니다. 하지만요양원에거주했거나, 최근의입원한과거력이있는경우, 투석을받는경우, 흡인의위험성이높은경우에는높은비율로검출되고있다 26). 아직까지 이들의빈도에대해서는논란의여지가있지만, 나이자체보다는동반질환의유무와관련이있을것으로보고있다. C pneumonia, M pneumonia, Legionella spp. 등의비정형균도지역사회폐렴의중요한원인으로노인보다는젊은성인에서빈도가높다고알려져있지만, 반대로노인에서더높다는보고도있다 27), 특히 Lieberman 의연구를보면, 비정형균이혼합감염의형태로 38.4% 까지검출되고있어폐렴의치료에있어서이점은꼭주지해야된다고본다 28). 요양원에서도 C pneumoniae, Legionella spp. 에의한집단감염이발생할수있고, rhinovirus 같은바이러스감염도집단으로발생할수있다. 중환자실에입원하는중증의지역사회폐렴에서도 S pneumoniae가가장흔한원인이라는점은비슷하다. 하지만 Legionella spp. S aureus, 그람음성균의빈도가높다는특징이있다 21, 29, 30). 노인에서의중증폐렴을대상으로한 El-Solh 등의연구를보면, 고전적인지역사회폐렴환자에서는 S pneumonia (14%), 그람음성균 (17%), Legionella spp. (7%), S aureus (7%) 가흔하였고, 요양원거주자로건강관련폐렴에해당하는환자에서는 S aureus (29%), 그람음성균은 (18%), S pneumonia (9%) 가흔하였다 21). 흡인성폐렴에서는장내그람음성균이 50%, S. aureus가 10%, 혐기성세균은 11.6% 이었다 29). 중증의폐렴에서는다제내성균 (Mutidurg-resistant organisms, MDR organism) 이 19% 에서만발견되었는데주로중증의질환, 6개월이내에항생제사용, 일상생활수행능력의감소가있는환자에서발생하였다 29)

4 - 대한내과학회지 : 제 75 권제 2 호통권제 576 호 HCAP의정의는 2005년 ATS/IDSA의원내폐렴지침에포함되었다. 여기서는지역사회폐렴이아닌원내폐렴과유사하게치료해야된다고하였으나, 다분히다제내성균과 methicillin-resistant S. aureus (MRSA) 의가능성을염두해두었기때문이다 31). El-Solh 등은다제내성균의위험인자는 1) 중증의폐렴, 2) 3~6 개월이내의항생제사용 3) 일상생활수행능력의감소세가지이다. 따라서이중두가지이상이있으면원내폐렴과유사하게광범위항생제로치료하고, 한가지이내인경우에는지역사회폐렴과같이치료하는것이바람직하다고한다. 실제로요양원의많은환자에게광범위항생제는불필요하며, 좁은범위의항생제로도충분히회복될수있다는근거가있다 32). 진단방법발열과함께기침, 객담등의하부호흡기감염증상이있는경우, 특히정신상태의변화나영양실조등이동반되어있는경우에는반드시폐렴의가능성을생각해야한다. 새로운 IDSA/ATS 지침서에서는감염이의심되는모든환자에서는폐렴의존재와중증도를파악하기위해흉부방사선을촬영하도록권유하고있다. 이는폐렴의범위를확인하고다른진단과의감별을위해서라도중요하다. 혈액배양검사는모든입원환자가대상이될수있고, 특히중증폐렴환자에게는반드시시행해야한다. 이전의항생제치료력이있는경우에는양성률이반으로감소될수있다. 따라서항생제투여전에검체를얻는것이중요하다. 노인환자에서는객담배출이어려워검체를얻기가쉽지않은데, 항생제투여이전에시행되어야하고, 실험실로빠르게이송될수있어야한다. 2004년에배포된대한결핵및호흡기학회의폐렴치료지침이나 2007년 IDSA/ATS 지침에서는적절히채취되고검사되어객담의질이보장될수있는경우에한하여서는검사를시행하도록권유하고있다 10). 중증의환자에서는 S pnumoniae와 Legionella에대한소변항원검사가시행되어야하고, 혈청검사는역학연구에는유용성이있으나폐렴환자의진단및치료과정에서는크게도움이되지않는다. 흉수가있는경우는진단적천자를실시해야한다. 예후인자및중증도평가중증도를평가하는것은환자의예후를평가하고치료장소를결정하며의료장비사용및치료방향의결정에도움을준다. 폐렴에특이적인평가척도로는 Pneumonia Severity Index (PSI) 및 CURB-65가있다. PSI는나이, 동반질환, 생화 학검사, 이학적소견등에점수를매겨환자를 5개의군으로나누는데, 높은군에속할수록사망률이증가한다. CURB-65는 1) confusion 2) BUN (>19.6 mg/dl) 3) 호흡수 (>30/min) 4) 수축기혈압 (<90 mm Hg) 혹은이완기혈압 (<60 mm Hg) 5) 나이 ( 65세) 의다섯가지지표로구성되어있다. PSI는저위험도의환자를확인하는데더적합하지만노인환자에서는다소맞지않을수있다는보고가있다. 이는폐렴의중증도보다는나이와동반질환에너무무게를두었기때문으로본다 33, 34). 반대로 CURB-65는고위험도의환자를확인하는데도움이된다 35). CURB-65를노인폐렴환자에적용할경우, 젊은환자군보다는수행능력이떨어지지만, 사망률예측에있어서 PSI 보다민감도가높았다고 Lim 등은보고하였다 36). 외래에서는 BUN 결과를얻기어려워이를제외한 CRB-65를이용할수있는데, CRB-65와 CURB-65 를같이이용한경우 30일사망률및입원의필요성, 기계호흡의필요성을예측할수있고, 정주용항생제의투여기간및입원기간에대해서도예측이가능하다는보고가있다 37). 하지만 PSI와 CURB-65의두가지점수체계가임상적인결정과정에있어서절대적인기준은될수없다. 따라서적극적치료의여부와치료장소등을결정할때는반드시환자개인의뜻과, 임상적요소및사회적요소를같이고려해서판단해야한다. 입원결정병원입원은환자에게반드시이로운것은아니다. 침상생활의시간이늘어나면서정맥혈전증, 카테터관련감염, 다제내성균에의노출등의위험성이따르게된다. 따라서환자가원하는바와입원치료가얻는이점을고려해서결정해야한다. 임상적으로는질환이중증이거나동반질환의악화, 사망률이높은경우에는입원치료를고려한다. 하지만입원이필요하다는것과사망률이높다는것은같은의미가아니다. 낮은사망률의환자일지라도탈수증세를보이거나호흡치료가필요한경우, 또, 심혈관계의지속적인감시나치료적산소농도의적절한조절이필요한경우에는입원이필요할수있다. PSI score 가 class IV & V의환자인경우입원을고려해볼수있는데, 앞에서말한대로점수체계에의한기준은보조적수단일뿐이지, 임상적결정의절대적인기준이될수는없다. 중증의폐렴에서도중환자실입원의필요성을결정하는데아직완벽한기준이없다. 1993년 ATS 지침에서는중증폐렴의정의에대해열가지의기준 ( 보조기준 6개, 주기준 4개 ) 을제시하였는데이중하나이상을

5 - 정기석 : 노인폐렴 - Table 3. Criteria for severe community-acquired pneumonia 10) Major Criteria Invasive mechanical ventilation Septic shock with the need for vasopressors Minor Criteria a Respiratory rate b 30 breaths/min PaO 2/FiO 2 ratiob 250 Multilobar infiltrates Confusion/disorientation Uremia (BUN level, 20 mg/dl) Leukopenia c (WBC count, <4,000 cells/mm 3 ) Thrombocytopenia (platelet count, <100,000 cells/mm 3 ) Hypothermia (core temperature, <36 ) Hypotension requiring aggressive fluid resuscitation BUN, blood urea nitrogen; PaO 2/FiO 2, arterial oxygen pressure/fraction of inspired oxygen; WBC, white blood cell a Other criteria to consider include hypoglycemia (in nondiabetic patients), acute alcoholism/alcoholic withdrawal, hyponatremia, unexplained metabolic acidosis or elevated lactated level, cirrhosis, and asplenia b A need for noninvasive ventilation can substitute for a respiratory rate 30 breaths/min or a PaO 2/FiO 2 ratio 250 c As a result of infection alone 만족하면중증폐렴으로정의하였다 38). 하지만이런방법은민감도와특이도가너무낮았고, 후에 Ewig 등이이를수정하여두가지의주기준과세가지의부기준으로바꾸었다 39). 새로나온 2007년 IDSA/ATS 지침에서는이전과같은두가지의주기준을이용하였으나, 부기준에서는이전의 ATS 기준에 CURB를추가시켰다. 여기서는주기준이 1개이상만족하거나혹은부기준이 3개이상있으면중증폐렴으로정의하고있고, 이런경우중환자실로의입원을권유하고있다 ( 표 3) 10). 앞으로이기준도전향적연구를통해검증되어야할것이다. 1. 일반적인접근 치 지역사회폐렴에서는진단법이빠르지않고정확성이높지않아미생물학적결과를근거로항생제치료를하기란어렵다. 따라서가장가능성이높은균들에대해경험적인치료를시작한다. 노인환자들에서는요양원에거주하는환자들이많이있으므로먼저지역사회폐렴과 HCAP으로나누 료 고, 가능성이있는균에따라다시세분화한다. 따라서권장되는치료는각군마다다르다고할수있다 ( 표 4). 지역사회폐렴은집에서거주하면서 HACP의위험요소를가지지않는환자가해당되고, 외래치료환자, 일반병실입원치료환자, 중환자실입원치료환자의세군으로나누어지게된다. HCAP은 2가지기준즉, 1) 폐렴의중증도와 2) 다제내성균에대한위험인자에따라 4개의치료군으로나눌수있다 ( 그림 1). 2. 지역사회폐렴의경험적치료모든지역사회폐렴환자는기본적으로폐렴구균과비정형균에대한경험적치료를시행해야한다. 또, 65세이상의노인에서는 DRSP의위험성이증가하므로이에대한치료도고려해야한다 10, 40). 이군에서는중증의폐렴이아니라면장내그람음성균은주된원인균이되지않는다. 장내그람음성균의위험인자를가진환자들은대부분 HCAP환자군에속하게된다. 사용하는항생제로는경구용 fluoroquinolone 단독이나 β-lactam 제제와 macrolide 의병합한치료를시행한다 ( 표 4) 10, 40). 중환자실이아닌일반병실로입원하는환자에서는 quinolone 단독치료나 β-lactam 제제에 macrolide를병합한치료를시행하면되겠다. β-lactam 제제에서 cefuroxime은사용하지않는게좋고, ertapenem은 non-pseudomonas 그람음성균에사용할수있다. 추천되는정주용 macrolide 는 azithromycin (500 mg daily) 이있다. 중증의지역사회폐렴환자는앞의두군과는치료가다르다. 대부분이중환자실로입원하게되는데이런경우엔 Legionella를포함한비정형균과 DRSP에대한치료를시행해야한다. 또, 아직안정성과효과, 적절한용량에대한연구가없기때문에이런환자들에서단독치료는피하는것이좋다. 모든중증지역사회폐렴환자에서 P aeruginosa와장내세균에대한치료를시행할필요는없으나다음의네가지요소즉, 1) 기관지확장증 2) 중증의만성폐쇄성폐질환 3) 최근의항생제치료 4) 최근의스테로이드치료중한가지이상이존재하는경우에 P aeruginosa와장내그람음성균에대한치료를시행한다 10, 40). P aeruginosa의위험요소가없다면 β-lactam 제제에 azithromycin이나 quinolone(levofloxacin 혹은 moxifloxacin) 을병합하여치료하고, 반대로 P aeruginosa 의위험요소가있는환자라면 anti-pseudomonal β-lactam에 aminoglycoside와 azithromycin ( 혹은 quinolone) 을병합하여사용한다. 다른대안으로는위의 β-lactam에 ciprofloxacin이

6 - The Korean Journal of Medicine: Vol. 75, No. 2, Table 4. Initial empiric therapy for pneumonia in older patients 40) Community-acquired pneumonia Outpatient Fluoroquinolone orally (gemifloxacin, levofloxacin a, moxifloxacin) β-lactam (high-dose amoxicillin b, amoxicillin-clavulanate, cefuroxime, cefpodoxime) Non-ICU inpatients Fluoroquinolone intravenously (levofloxacin a, moxifloxacin) β-lactam (ceftriaxone, cefotaxime, ampicillin/sulbactam, ertapenem) PLUS a macrolide (azithromycin intravenously) or doxycycline ICU-admitted No pseudomonal risk β-lactam (ceftriaxone, cefotaxime, ampicillin/sulbactam) PLUS a macrolide (azithromycin) or quinolone (levofloxacin a, moxifloxacin) Pseudomonal risks Anti-pseudomonal β-lactam (cefepime, imipenem, meropenem, piperacillin/tazobactam) PLUS anti-pseudomonal quinolone (ciprofloxacin, levofloxacin) OR Anti-pseudomonal β-lactam (cefepime, imipenem, meropenem, piperacillin/tazobactam) PLUS aminoglycoside (amikacin, gentamicin, tobramycin) PLUS a macrolide (azithromycin) or a quinolone (levofloxacin a, moxifloxacin) Healthcare-associated Pneumonia Non-severe illness 0-1 risk for MDR pathogens Fluoroquinolone or β-lactam/macrolide orally 2 risk pathogens Intravenous therapy with cefepime, ertapenem, levofloxacin a plus consider MRSA and/or additional gram-negative coverage Severe illness 0-1 risk for MDR pathogens Treat the same as severe CAP in ICU with no pseudomonal risks 2 risks for MDR pathogens Dual pseudomonal therapy plus MRSA coverage; Anti-pseudomonal β-lactam (cefepime, imipenem, meropenem, piperacillin/tazobactam or if penicillin allergic aztreonam) PLUS an aminoglycoside (amikacin, gentamicin, tobramycin) or a quinolone (ciprofloxacin or levofloxacin a, especially if concerned about atypical pathogens) PLUS vancomycin or linezolid a For patients with normal renal function, the 750-mg dose is currently recommended. b High-dose amoxicillin is 1 g three daily 나 levofloxacin (750 mg) 을병합하여사용한다. 지역사회폐렴의경험적치료에서비정형균을고려해야하는이유에는여러근거자료들이있는데, 적지않은빈도 에서혼합감염의형태로발생한다는보고가있고 28), β- lactam 단독보다는 macrolide나 quinolone의병합치료시사망률이더낮았으며 41, 42), 폐렴구균균혈증환자에서도 β

7 - Ki-Suck Jung: Pneumonia in the elderly patients - Figure 1. Proposed algorithm for Healthcare-associated pneumonia (HCAP) therapy. All patients with HCAP should be divided on the basis of severity of illness and the risk factors for multidrug-resistant pathogens (MDR pathogens). lactam 단독치료보다는병합치료가사망률을더낮추었다는보고들이있다 43-45). 이러한결과의기전은아직확실하지는않으나 1) 비정형균의중복감염 2) 두항생제의상승작용 3) macrolide 의항염증효과때문일것으로생각되고있다. DRSP의정의를살펴보면, 이전에미국의 NCCLS (National Committee for Clinical Laboratory Standards) 에서제시한내성기준은환자의임상경과및생존률과잘맞지않았다 46, 47). 이에따라미국질병통제예방센터 (Centers for Disease control and Prevention) 의 DRSP 치료연구그룹에서새로운기준을제시하였는데, MIC가 1 μg/ml인경우감수성, 2 μg/ml인경우중등도내성, 4 μg/ml인경우를고도내성으로하였다. 이들은 MIC 2 μg/ml인경우 β- lactam 제제로충분히치료할수있고, 4 μg/ml인경우가임상적으로의미있는고도내성임을제시하였다 47). 여러지침에서는 DRSP 가의심되는상황에이라면부적절한치료의가능성이적은 cefotaxime 이나 ceftriaxone 을사용하도록권유하고있다. 우리나라에서도 penicillin에내성으로분류된균주라도 cephalosporin에는모두감수성을보였고, MIC 4 μg/ml인경우가아니라면 cephalosporin 등의경험적항생제로치료할수있다는보고가있다 48). Cefuroxime 은 DRSP 균혈증환자에서나쁜예후를보였다는연구가있어, 입원치료의경우경험적항생제로는사용하지않는게좋다 49). 최근의항생제치료력도중요하다. 3개월이내에항생제를사용했던과거력이있다면이와는다른종류의항생제를사용하는것이좋다. Vanderkooi 등은 3,339명의폐렴환자를대상으로한연구에서 cephalosporin한 penicillin, macrolides, trimethoprim-sulfamethoxazole, quinolones 치료를받았던과거력이있는환자에서는같은항생제에대해저항성의발현이높았다는보고를하였고, 이중에서도 levofloxacin 의이가장큰관련성을보였다 50). Quinolone 제제는경구로투여해도약효가동일하여폐렴환자를외래에서치료할수있다는장점이있다. Moxifloxacin과 levofloxacin를비교할때심혈관계부작용에있어서둘다비슷한정도의안정성을보이지만치료 3~5 일째의반응에있어서는 moxifloxacin이좀더빠르다는보고가있다 51, 52). 다재내성그람음성균에대한위험요소가 1개이하인요양원폐렴환자에서도 levofloxacin 단독으로도안전하게치료할수있었다는연구가있어, 심하지않은 HCAP 환자에서도위험요소가 1개이하라면 quinolone 단독치료를시행할수있겠다 32, 40). 하지만노인환자에서 quinolone의

8 - 대한내과학회지 : 제 75 권제 2 호통권제 576 호 안정성이문제가되기도하는데 gatifloxacin 은고혈당이나저혈당을일으킬수있고 53), sparfloxacin은 QT prolongation 을일으킬수있어사용이제한되고있다. 3. HCAP 의경험적치료 2005년 ATS/IDSA 지침에따르면 HCAP 환자는다제내성그람음성균과 MRSA 의위험성이있으므로지역사회폐렴의치료지침을따르지말고, 원내폐렴 (Hospital-acquired pneumonia, HAP) 과비슷한방법으로치료할것을권유하였다 54). 하지만여기에는환자들이정주용항생제로치료받았다는가정이내포되어있다. 여기에는중증이아닌환자도포함될수있고, 다재내성그람음성균이아닌오히려비정형균과같은지역사회폐렴의위험요소를가진환자가포함될수있으며, 경구용항생제로치료받았던환자들도포함될수있다. 또, 중증도에관계없이집이나요양원에서치료받기를원하는환자도포함되게된다. 따라서이러한이질적인집단의성격으로인해일부는원내폐렴과같이일부는지역사회폐렴과같이치료할필요가있다. 만일모든 HCAP 환자를원내폐렴환자처럼치료한다면광범위항생제를불필요하게남용하는결과를가져올수있을것이다. 실제로건강관련폐렴환자에서 ciprofloxacin, levofloxacin, cefepime, ertapenem 을이용한단독치료의효과를입증한연구들이있었다 32, 55, 56). 또, 요양원같은집단수용시설에서는 Legionella spp. 나 C pneumoniae 같은비정형균에의한감염이생길수있는데원내폐렴의치료지침으로는이런균들에대한치료가안될수있다는위험성이있다 40). HCAP의치료에서 Niederman 등은환자군을먼저질환의중증도에따라나누었고 (severe or non-severe illness), 다음단계로다제내성균의위험요소가 1개이하인군과 2개인군으로세분화하였다 ( 그림 1) 40). 첫째로, 중증이아니면서위험요소가 1개이하인경우에는다제내성균의위험성이없으므로외래치료를하는지역사회폐렴처럼경구용항생제를사용할수있다. 단, 노인이므로 DRSP와비정형균에대한치료가되어야함을주의해야한다. 따라서이군의치료에서는 fluoroquinolone 단독이나 β-lactam과 macrolide 병합요법을사용할수있겠다. 둘째로, 중증이아니면서위험요소가 2개이상인경우는여전히지역사회폐렴균에목표를두어야하지만다제내성그람음성균과 MRSA 감염의가능성을고려해야한다. 따라서환자를입원시켜 ertapenem, cefepime, levofloxacine 등의단독치료를시행해볼수있고, 비정형균을고려한다면 levofloxacin이추천된다. 만약 MRSA 의가능성이있다면 vancomycin이나 linezolid를추가할수있겠다. 이환자군에서 P. aeruginosa 감염이의심되는경우에는 anti-pseudomonal β- lactam에 aminoglycoside 나 anti-psedomonal quinolone (ciprofloxacin, levofloxacin) 을병합한두가지항생제를사용하도록한다 32, 40). 셋째로, 중증의폐렴이면서위험요소가 1개이하인경우에는중증지역사회폐렴환자처럼 β-lactam 항생제에 quinolone이나 macrolide 를병합하여사용한다. 넷째로, 중증의폐렴이면서위험요소가 2개인경우에는 3종류의항생제를사용하는데 anti-pseudomonal effect를가진항생제두가지와 vancomycin 등의 MRSA 에대한항생제를같이사용하도록한다. 물론비정형균이의심된다면병합요법에서 aminoglycoside 대신 quinolone을사용하도록한다 32, 40). 치료반응폐렴환자에서는임상적호전여부가치료기간을결정하게되고입원환자에서는정주용항생제의기간도결정하게되는데, 이러한임상적반응은숙주의면역기능, 원인균의병원성, 경험적치료의적절성에달려있다. 임상적반응 ( 안정화 ) 의정의는기침, 객담, 발열등의증상이호전되고, 경구섭취가가능하며, 백혈구수치가호전된경우를의미한다. 지역사회폐렴으로입원한환자들의 50% 이상에서는대개 3 일이내에반응을보인다 57, 58). 이단계에서는경구용항생제로바꾸어퇴원을시킬수있는데, 항생제의기간은최소한 5일정도를사용하도록하고, 적어도발열이없는기간이 2~3일은되어야한다 10). 노인에서는면역기능의저하로젊은환자보다는호전속도가느리다. 치료지침을따르는경우, 빠른회복을가져올수있다는보고가있으나, 심부전이나만성폐쇄성폐질환이있는경우는지연반응을보일수있다 57). 초기의치료실패와관련된인자를보면 1) 65세이상의나이 2) 다엽성폐렴 3) PSI 점수 >90 4) Legionella 폐렴 5) 그람음성균폐렴 6) 부적절한항생제의사용이관련이있다. 초기의경험적치료에실패한군에서는반응군에비해합병증의발생률이높고, 사망률도더크다 58). 방사선학적호전은대개임상적증상의호전보다늦게온다. 많은환자들에서는 4~6 주에걸쳐방사선의호전을보인다. 따라서임상적악화소견을보이지않는다면흉부방사선을자주촬영할필요는없다. 노인에서는특히중증의질환, 알콜중독, 만성폐쇄성폐질환, 균혈증, 다수의동반질환이있는경우방사선학적호전이느리다 59). 70세이상의폐렴환자를조사한연구에서는 3주째에는 35%, 6주에는 62%, 12주에는 75% 의환자에서방사선학적인회복을보였

9 - 정기석 : 노인폐렴 - 고, 원인균에서는장내그람음성균인경우가 12주째에 54.8% 로가장느린회복소견을보여주었다 60). 환자가치료에대한반응을보이지않는경우엔가능성있는다양한원인을찾아야한다. 그예로는 1) 부적절한항생제 2) 드문원인균 3) 농흉, 심내막염, 뇌수막염, 폐색전증등의합병증 4) 비감염성폐질환등이있다 59). 치료에지연반응을보이거나반응이없는경우에는흉부 CT, 기관지내시경, 혈청검사등을시행해볼수있고, 드물게폐조직검사도고려할수있다. 예방 Jackson 등에의하면폐렴발생의 31% 는현재의흡연과관계가있다고하였다. 따라서금연이폐렴의예방에중요한방법이된다. 또, 노인에서는뇌졸증혹은치매등의질환을가지고있는경우가적지않아흡인의위험성이높다. 따라서이런환자들에서는흡인을줄이기위한노력이중요하다. 영양결핍또한하나의위험인자이므로충분한영양공급이이루어지도록해야한다 61). 폐렴의예방에서가장중요한방법은예방접종이다. 인플루엔자백신은호흡기감염에의한입원률과사망률을감소시키는것으로되어있는데 62, 63) influenza A (H3N2 & H1N1) 와 influenza B의세가지 strain 으로이루어져있고, 접종대상은 65세이상, 만성적인내과질환소유자, 의료업종사자들이된다. 계란에과민반응이있는경우는접종의금기사항이며, 소변이로인해매년유행바이러스주가바뀌므로매년가을마다재접종이필요하다. 만약인플루엔자유행이생기면예방접종을받지않는자는즉시예방접종을받고, 동시에예방적화학치료를시작하는것이좋다. 노인들에게는독성이적은 osteltamivir나 zanamivir 가선호된다 40). 폐렴구균백신은폐렴구균감염의 85~90% 를차지하는 23가지혈청형에대한 purified capsular polysaccharide를가지고있다. 65세이상의정상면역기능을가진환자에서는그효과가 75% 까지보고되었으나겸상적혈구빈혈증, 만성신부전, 면역글로불린결핍, 림프종, 백혈병, 다발성골수종등의면역기능저하환자에서는효과가확실하지않다 10). 일반적으로재접종은권장되지않는데, 첫번째접종이 5년이전에시행된 65세환자이거나 65세이전에예방접종을시행받은환자에서는일회의재접종을시행하도록한다. 만약 65세이후에첫접종을시행받은경우에는해부학적이상이나면역기능저하상태가아니라면재접종은필요없다 10). 급성감염이나임신또는모유수유경우에는백신접종이권장되지않는다. 폐렴으로입원한모든환자에서퇴원시에폐렴 구균백신을접종시키는것도좋은효과를볼수있을것으로보고있다. 폐렴구균백신과인플루엔자백신은서로다른곳에동시접종이가능하다. 요 지역사회폐렴은노인에서더흔하고사망률도높으며심각한경제적비용을초래한다. 노인폐렴은젊은성인과는자연경과나임상경과가달라치료에있어서다르게접근할필요가있다. 많은경우임상증상이특이적이지않아진단이쉽지않고, 치료또한지연되기쉽다. 따라서기저질환을포함한임상증상의악화를보이는경우에는폐렴의가능성을항상생각해야한다. 외래와입원치료의결정은 CURB-65나 PSI를참고로여러가지요인들을고려하여야한다. 경험적항생제를선택할때는먼저지역사회폐렴인지 HCAP인지를구분하고, 환자의동반질환이나건강상태를종합적으로고려하여적절하고항생제를빠른시간내에투여하여야좋은치료결과를얻게된다. 폐렴을예방하기위해서는흡인의기회를줄이고, 금연및예방접종을권한다. 중심단어 : 노인 ; 폐렴 약 REFERENCES 1) 통계청 사망원인통계연보 :( 2) Pneumonia and influenza death rates-united States, MMWR Morb Mortal Wkly Rep 44: , ) Niederman MS, McCombs JS, Unger AN, Kumar A, Popovian R. The cost of treating community-acquired pneumonia. Clin Ther 20: , ) Almirall J, Morato I, Riera F, Verdaguer A, Priu R, Coll P, Vidal J, Murgui L, Valls F, Catalan F, et al. Incidence of community-acquired pneumonia and Chlamydia pneumoniae infection: a prospective multicentre study. Eur Respir J 6:14-18, ) Woodhead MA, Macfarlane JT, McCracken JS, Rose DH, Finch RG. Prospective study of the aetiology and outcome of pneumonia in the community. Lancet 1: , ) Kaplan V, Angus DC, Griffin MF, Clermont G, Scott Watson R, Linde-Zwirble WT. Hospitalized community-acquired pneumonia in the elderly: age- and sex-related patterns of care and outcome in the United States. Am J Respir Crit Care Med 165: , ) Lim WS, Macfarlane JT, Boswell TC, Harrison TG, Rose D, Leinonen M, Saikku P. Study of community acquired

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