심사사례 성균관의대강북삼성병원감염내과 염준섭

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1 폐렴및호흡기질환의치료와 심사사례 성균관의대강북삼성병원감염내과 염준섭

2 서 론 미국 : 매년 560만명의환자발생 -- 20% 입원 사망률 - 외래에서치료가능한환자 : 1-5% - 입원치료가필요한환자 : 25% - 국내 ( 사망원인통계결과 ) : 2001년 ; 6.1명 /10만명, 1991년 ; 5.1명 /10만명 50-90% 가외래에서치료 30-40% 는원인을밝혀내지못함 획일적치료지침수립의어려움 : 환자, 지역사회, 병원등의특성에따라복잡 2

3 항생제선택의어려움 1. Difference in clinical signs and symptoms for bacterial and viral etiology: not clear 2. Obtaining uncomplicated specimens: difficult 3. Even when specimens are obtained, microbiological results are inconclusive approximately 50% of the time 3

4 Pathogenesis of CAP Aspiration of oropharyngeal secretion: descend Inhalation and spread along mucous membrane Hematogenous spread: Staphylococcus Contiguous spread 4

5 Etiologic agents in CAP Etiologic agents Cases(%) Bacteria S. pneumoniae Haemophilus influenzae Moraxella catarrhalis S.aureus Other gram-negative species Atypicals Mycoplasma spp. Chlamydia spp. Legionella spp. Viruses Aspiration pneumonia No diagnosis AJM 2004;117:39s-50s 5

6 Etiology of CAP by Disease Severity Ambulatory patients S. pneumoniae M. pneumoniae H. influenzae C. pneumoniae Respiratory virus Hospitalized (Non-ICU) S. pneumoniae M. Pneumoniae C. pneumoniae H. influenzae Legionella spp Aspiration Respiratory virus ICU (Severe) S. pneumoniae, Legionella spp H. influenzae Aerobic G(-) rods S. aureus Lancet 2003;362:

7 국내원외폐렴의주요원인균 대한감염학회 ( ) - 경기지역 9개대학병원을대상, 전향적연구 - 16세이상의원외폐렴환자 - 585명중 191예 (32.6%) 에서 220균주동정 : S. pneumoniae 59예 (26.8%) : K. pneumoniae 40예 (18.1%) : P. aeruginosa 26예 (11.8%) : E. cloacae 11예 (5.0%) : H. influenzae 11예 (5.0%) 7

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13 노인에서의원외폐렴 ( ) No. of patients 원인균 <65 years old ³65 years old (N=95) (N=119) Defined 38 (40%) 56 (47%) S. pneumoniae S. aureus 4 9 H. influenzae 5 6 K. pneumoniae 1 11 P. aeruginosa 2 3 Other G(-) bacilli 6 7 M. tuberculosis 3 1 M. pneumoniae 3 2 Others 1 4 Not-defined 57 (60%) 63 (53%) ( 유등, 감염 32: ,2000) 13

14 원외폐렴치료지침수립시고려할사항 원외폐렴의주요원인균은무엇인가? 주요원인균에대한항생제감수성양상은? 14

15 주요원인균에대한항생제감수성양상 병상규모에따른 S. pneumoniae 의항생제내성률 Antibiotics % of isolates resistant by hospital group Large Seoul-Medium Non-Seoul Medium Mean (n=762) (n=676) (n=749) (n=2187) Penicillin Erythromycin Cotrimoxazole Fluoroquinolone Tetracycline Large,³1000beds; Medium,<1000beds (Lee K, et al., YMJ 41: , 2000) 15

16 Definition of hospital-acquired acquired Pneumonia Clinical diagnosis Occurring > 48 hrs after admission Presence of new lung infiltration Clinical evidence is of an infectious origin - fever - purulent sputum - leukocytosis Exclusion - heart failure, atelectasis, thromboembolism, drug reaction, hemorrhage, ARDS, etc (Am J Respir Crit Care Med 1995;153:1711) 16

17 Microbiology Fraction Pathogens 55-85% Gram (-) bacilli EGNB P. aeruginosa Acinetobactor spp. Enterobacter spp % Gram (+) cocci S. aureus 40-60% polymicrobial In patients requiring prolonged mechanical ventilation in ICUs, P. aeruginosa and Acinetobactor acount for 30 to 50% of HAP. These pathogens are uncommon in non-icu setting. (Chest 2001;119:373S) 17

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19 Onset Early Late Onset time Major pathogens < 5 days 5 days S. pneumoniae P. aeruginosa H. influenzae Acinetobactor spp. M. catarrhalis Enterobacter spp. Antibiotic resistance Mortality MSSA low low MRSA high high (Infect Control Hosp Epidemiol 1992;13:515, Chest 1995;108:1655) 19

20 ICU surveillance Type of infection Pn UTI BSI SSI Others (Korean Society for Nosocomial Infection Control 2003) 20

21 ICU surveillance Common pathogens in pneumonia S. aureus Acinetobacter spp. P. aeruginosa K. pneumoniae 9.1 Enterobacter spp. 3.9 Others (Korean Society for Nosocomial Infection Control 2003) 21

22 ICU surveillance Gram-positive cocci 100% 90% MSSA : 9 80% 70% 60% 50% 40% 30% 20% 10% MRSA : 91 Non-VRE : 79.9 VRE : % 1 2 S. aureus Enterococcus spp. (Korean Society for Nosocomial Infection Control 2003) 22

23 ICU surveillance Acinetobacter spp. 100% 90% % 70% 60% % 40% % 20% 10% 0% CAZ 29.7 IMP Resistant Susceptible (Korean Society for Nosocomial Infection Control 2003) 23

24 ICU surveillance Pseudomonas aeruginosa 100% 90% 80% 70% % 50% 40% 30% 20% % 0% CIPR PIP CAZ IMP Resistant Susceptible (Korean Society for Nosocomial Infection Control 2003) 24

25 ICU surveillance Klebsiella pneumoniae 100% 90% 80% 70% 60% % % 30% 20% 10% % CAZ CIPR IMP Resistant Susceptible (Korean Society for Nosocomial Infection Control 2003) 25

26 ICU surveillance Enterobacter spp. 100% 90% 80% 70% 60% 50% 40% % 20% 10% 0% CAZ CIPR IMP Resistant Susceptible (Korean Society for Nosocomial Infection Control 2003) 26

27 Diagnosis of CAP

28 Base line Chest X ray! For diagnosis of pneumonia infiltrates is necessary For detecting alternative diagnosis or associated conditions To predict pathogens To assess severity Baseline to assess response 28

29 False negative results on Chest X-ray Dehydration Evaluation during the first 24 hours Pneumonia due to Pneumocystis carinii Pneumonia with profound neutropenia 29

30 DDx of lesion on CXR Congestive heart failure Pulmonary embolism Pulmonary edema Vasculitis Pulmonary malignancy Reactive airway diseases Atelectasis 30

31 Laboratory exam Outpatients sputum Gram stain is desirable culture for conventional bacteria is optional Inpatients etiologic diagnosis is recommended 31

32 Exam for in-patients CBC Blood cultures (before treatment) : 5-14% positive rate for hospitalized CAP : most common isolate is S. pneumoniae : yield of positive blood culture results is halved by prior antibiotics Gram stain and culture of sputum Chemistry (BUN/creatinine, glucose, electrolyte, bilirubin, and liver enzyme) O2 saturation AFB smear (in Korea) 32

33 Sputum Sample: Pros & Cons Pros Optimal Antibiotic Selection Detect resistance and monitor trends antibiotic costs Cons Not all patients can provide sample (up to 30%) Interpretation is observer dependent Doesn t detect atypicals Epidemiology Strategy for changing IV to PO Low yield (40 to 60% of results are negative) 33

34 Sputum Examination Adequate sputum <10 squamous epithelial cells & >25 PMNLs/LPF Interpretation large amount of epithelial cells; contamination many PMNLs; suggestion of infection many PMNLs & many bacteria; typical pneumonia a few PMNLs & a few bacteria; not infection or atypical pneumonia a few PMNLs & many bacteria; colonization 34

35 Diagnostic accuracy Diagnostic of pathogenic role, regardless of specimen source Bacteria Legionella species Mycobacteria Mycobacterium tuberculosis Viruses Influenza Respiratory syncytial virus HantavirusParainfluenzaAdenovirus Parasites - Stongylodes species, T. gondii Fungi Pneumocystis carinii Histoplasma gondii Coccidioides Non diagnostic if recovered from usual respiratory specimens a Virtually all other bacteria, including Norcardia and Actinomyces species Mycobacteria other than M. tuberculosis Cytomegalovirus Herpes simplex virus Candida species Aspergillus species Zygomycetes species Blastomyces dermatitidis Cryptococcus neoformans 35

36 Definite Diagnosis of Pneumonia Blood culture positive for a pathogen Pleural fluid, transtracheal, transthoracic specimen culture positive Culture positive from respiratory secretions of a likely pathogen that does not colonize the upper airway (M. tuberculosis, Legionella, influenza, P. carinii) 4 fold rising in titer of Ab to M. pneumoniae Isolation of L. pneumophila, a 4 fold rising in titer of Ab or urinary Ag (+) positive direct fluorescent Ab testing for legionella and a titer 1:256 serum or urine positive for S. pneumoniae Ag 36

37 Possible Diagnosis of Pneumonia Compatible clinical symptoms + detection (by staining or culture) of likely pulmonary pathogen in respiratory secretions (expectorated sputum, bronchoscopic aspirate, or quantitatively cultured BAL fluid) With semiquantitative culture, the pathogen should be recovered in moderate to heavy growth 37

38 Invasive Procedures Trans-tracheal aspiration - upper respiratory tract 의 contamination 을피할수있다. - sensitivity(>90%) 는높지만, specificity 가떨어진다. - complications : puncture or laceration of trachea, hypoxemia ( paroximal cough) subcutaneous or mediastinal emphysema, death Percutaneous transthoracic lung puncture - CT-guided fine needle insertion - 비교적 tolerable 하지만 diffuse lesion 인경우나 ventilator 를가지고있는환자에서는사용할수없다. Fiberoptic bronchoscopy - lower respiratory tract 의 secretion 을얻는 standard invasive method - safe and well tolerable - diffuse lung lesion 이유용 - specimen collection by protected double-sheathed brush(psb) : 항생제투여전에실시해야 bronchoalveolar lavage(bal) : 80% sensitivity in some pathogens transbronchial lung biopsy(tblb) : 40-60% 의진단율 38

39 Open lung biopsy - immunocompromised patient 에서 bronchoscopy 로얻은 specimen 으로도진단이안된경우 - 진단률 : 25-80% Examination of pleural effusion - Patient hospitalized with pneumonia and pleural effusion : 40% - Laboratory tests : total cell count with differential, Gram stain, cultures, ph, glucose - Gram stain and culture of pleural fluid : etiologic diagnosis - Pleural biopsy in pneumonia : little value only DDx with tuberculosis, tumors, pulmonary emboli, collagen disease 39

40 Other test Urinary Ag test for S. pneumoniae & Legionella Mycoplasma serology Chlamydia serology Thoracentesis with stain, culture, and ph and leukocyte count differential (pleural fluid) Induced sputum: optional (recommended for detection of M. tuberculosis or Pneumocystis carinii) 40

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44 Treatment 44

45 경험적치료시고려사항 치료받게되는장소 ( 환자의중증도와관련 ) ; 외래, 일반병실, 중환자실 기존심폐질환유무 Drug-resistant S. pneumoniae 위험요인이있는가 그람음성장내세균감염의위험요인이있는가 Pseudomonas aeruginosa 감염의위험이있는가 45

46 Drug-resistant S. pneumoniae 위험요인이있는가 65세이상 최근 3개월내 β-lactam 항생제사용 면역저하질환 스테로이드 동반되는다른질환이있는경우 46

47 그람음성장내세균감염의위험요인이있는가 요양원에거주 기존심폐질환 다른질환을갖고있는경우 최근에항생제치료를받은적이있는사람 Pseudomonas aeruginosa 감염의위험이있는가 기관지확장증과같은구조적인폐질환 prednisone 10 mg/day 이상의용량으로투여 최근한달사이에 7 일이상광범위항생제투여 47

48 대표적인외국의 CAP 치료 guideline CDC (Centers for Disease Control and Prevention), 2000 ATS (American Thoracic Society), 2007 IDSA (Infectious Diseases Society of America), only for pneumococcus, 2007 한국성인지역사회폐렴 guideline (2005, 2009) ; 호흡기학회, ATS guideline 외국의 HAP guideline ATS/IDSA

49 외래에서치료받는환자 일반병실에입원하여치료받는환자 중환자실에입원하여치료받는환자 49

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61 치료기간 원인균, 치료반응, 동반질환및폐렴의합병증을고려해서적절한치료기간을결정한다. 최소 5일간치료하고, 치료전에는적어도 3일간열이없어야하며하기사항중 2가지이상의소견은없어야함. 61

62 Duration of Treatment The presence of coexisting illness and/or bacteremia, the severity of illness at the onset of antibiotic therapy, and the subsequent hospital course should be considered in determining the duration of antibiotic therapy S.pneumoniae and other bacterial infections Generally 7-10 days M. pneumoniae and C. pneumoniae days Leginnaire s disease days in immunocompetent patients > 14 days in patients chronically treated with corticosteroids 62

63 Management of HAP 63

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74 흔히보는조정사례 Candida pneumonia Chest x-ray 판독상 pulmonary edema 혹은정상인경우 Pseudomonas pneumonia 가아닌경우에도장기간병합요법시행 Vancomycin 의경험적투여 미생물학적근거가없이장기간사용 미생물학적원인규명을위한노력이전혀없는경우 부적절한용량으로투여 다제내성 Acinetobacter, Pseudomonas 폐렴에서내성항균제의사용 Respiratory quinolone(moxi, gati 등 ) 을 beta-lactam 항생제와병용투여한경우 74

75 흔히보는조정사례 항생제사용기간 흡인성폐렴에서혐기균을 cover 하기위해 Tazocin 혹은 carbapenem(meropenem, imipenem) 과 clindamycin/metronidazole 을병합투여하는경우 적절하지못한검체 (sputum grade 5 가아닌경우 ) 에서동정되는미생물을근거로장기간항생제를투여한경우 객담에서동정되는미생물이바뀔때마다항생제를변경투여 장기간의항생제를사용하였으나 chest x-ray 판독상전혀호전 / 악화가관찰되지않는경우 감염내과 / 호흡기내과의권유와달리항생제를사용하는경우 IV to oral switch 시항균범위가다른항생제를사용하는경우 75