DOI: 10.4046/trd.2011.70.2.105 ISSN: 1738-3536(Print)/2005-6184(Online) Tuberc Respir Dis 2011;70:105-112 CopyrightC2011. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved. 의료기관관련폐렴 전북대학교의과대학 1 내과학교실, 2 임상의학연구소이흥범 1,2, 한효진 1,2 Review Healthcare-Associated Pneumonia Heung Bum Lee, M.D., Ph.D. 1,2, Hyo Jin Han, M.D. 1,2 1 Department of Internal Medicine, 2 Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Korea Pneumonia is frequently encountered in the clinical fields, both as a cause for admission and as a complication of the underlying disorder or as the course of treatment. Pneumonia is the second most common hospital-acquired infection and is associated with the highest morbidity and mortality rates among hospital-acquired infections. The guidelines for the management of hospital-acquired pneumonia by the American Thoracic Society include identifying individuals who have recently received antibiotics therapy or have been in medical facilities; these individuals are at higher risk for infection with multiple drug resistant organisms. Individuals, who have acquired pneumonia according to this clinical scenario, have what is known as healthcare-associated pneumonia (HCAP). Patients with HCAP should be considered to have potentially drug-resistant pathogens and should receive broad spectrum empiric antibiotic therapy directed at the potentially resistant organisms. In this paper, the diagnosis, risk factors, and treatment of HCAP are discussed. Key Words: Healthcare; Pneumonia 서 폐렴은크게지역사회획득폐렴 (community-acquired pneumonia, CAP) 과병원획득폐렴 (hospital-acquired pneumonia, HAP) 으로분류할수있다. 이러한분류의근거는역학적특성, 즉감염장소에따라주요원인균의차이가있고이로인하여감염균의항균제에대한내성의정도가다르기때문이다. 여러역학적근거를바탕으로폐렴을좀더세분화하면, HAP는입원 48 72시간이후의원내감염으로의한병원획득폐렴과기계호흡시작 48 72시간이후기관 Address for correspondence: Heung Bum Lee, M.D., Ph.D. Department of Internal Medicine, Chonbuk National University Medical School, San 2-20, Geumam-dong, Deokjin-gu, Jeonju 561-180, Korea Phone: 82-63-250-1685, Fax: 82-63-250-1633 E-mail: lhbmd@jbnu.ac.kr Received: Dec. 28, 2010 Accepted: Dec. 28, 2010 론 삽관환자에서발생하는인공호흡기연관폐렴 (ventilatorassociated pneumonia, VAP) 으로분류할수있으며, 최근고령화와만성질환자의증가등으로각종보건관련시설을정기적으로이용하는인구가크게증가하게되면서병원에입원하지않았으나광범위한의료서비스를받고있는 CAP의일부환자들은의료기관관련폐렴 (healthcareassociated pneumonia, HCAP) 이라고새로이분류할수있다 (Table 1) 1,2. 1996년미국흉부학회에서 HAP에관한진료지침 3 을내놓은이후, 2005년미국흉부학회와감염학회에서새로이발표된연구결과를토대로 HCAP 과 VAP 를포함한 HAP 에관한새로운치료지침 2 을제시하였는데, 지침서에서는 HCAP 의위험인자로 1) 최근 90일이내에 2일이상의입원, 2) 만성질환을앓는노인들을위한전문요양시설의수용인, 3) 최근 30일이내에항균제나항암제투여, 또는창상치료를받은적이있는경우, 그리고 4) 최근 30일이내에병원을방문하였거나혹은혈액투석중인환자등을들었으며, HCAP 가 CAP 에비하여 HAP, VAP 과유사한 105
HB Lee et al: Management of healthcare-associated pneumonia Table 1. Pneumonia types based on clinical characteristics Pneumonia type Community-acquired pneumonia (CAP) Healthcare-associated pneumonia (HCAP) Hospital-acquired pneumonia (HAP) Ventilator-associated pneumonia (VAP) Characteristics In the first 48 hr of hospital admission In CAP patients with recent contact with the health system 48 72 hr after hospital admission 48 72 hr after endotracheal intubation 임상적특성과항균제에내성을가진균에의해발생할가능성이매우높기때문에진단과치료에있어 HAP에준할것을권고하였다. 본글에서는 2005년미국흉부학회지침서 2 를기본으로최근발표된 HCAP의역학과치료의주안점등에대해서설명하고자한다. 역학 (Epidemiology) 폐렴은감염과관련된사망의가장많은원인으로알려져있으며, HAP는원내감염중두번째로흔하게발생하지만사망률에있어서는가장높다고알려져있고, 그사망률은 20 50% 정도이다 4,5. 역사적으로 2001년 Morin과 Hadler 6 는 12개월이내의입원기왕력이나혹은복막ㆍ혈액투석, 입원전거치한요로또는혈관내장치가의료시설관련감염 (healthcareassociated infection) 과밀접한관련이있으며, 기저질환을가진환자군에서기저질환을갖지않은환자군에비하여 Methicillin-resistant Staphylococcus aureus (MRSA)- 혈류감염이높다고보고하였다. 이후 2002년 Friedman 등 7 은의료시설관련혈류감염 (healthcare-associated bloodstream infection) 이병원감염 (nosocomial infections) 과유사한환자의기저질환과감염원, 원인균과감수성패턴, 사망률등을보였고, 이러한결과는의료시설관련혈류감염은병원감염과같은부류 (category) 로분류하여치료할것을뒷받침한다고주장하였다. 한편 2004년 Tacconelli 등 8 은 MRSA 균혈증 (MRSA bacteremia) 역학조사에서입원첫 24시간이내에발생한 MRSA 균혈증양성환자는모두의료시설관련 MRSA strains (healthcare-associated MRSA strains) 였으며, 지역사회연관종 (true community-acquired strains) 은확인되지않았다고보고하였고, 이는의료시설관련과실질적인지역사회연관감염 (true community-acquired infections) 의치료에는이를감별하여치료하는것이필요하다는점을강조하였다. 이 러한지역사회감염과병원감염과의사이에서일정기간혹은정기적인의료시설을이용하는환자에서발생하는감염, 특히폐렴을이해하고적절한치료를위하여 2005 년미국흉부학회와감염학회 2 에서 HCAP 을정의하고치료와관련된지침서를제정하게되었다. 현재까지진행된 HCAP 과관련된역학적연구는대단위연구에서조차 HCAP 의진단기준이각기다르게규정되어있어대상환자의다양성 (heterogeneous population) 이문제시되는실정이고내성균감염과관련된위험인자역시연구마다차이를보이고있기때문에 2,7,9-14 HCAP에확실한임상적인실체 (entity) 를정하기란쉽지않다. 그러나여러연구를종합하여볼때최근 90일이내의입원기왕력이나, 만성질환환자를위한전문요양시설의의료서비스, 자가정맥주사치료, 장기적인투석등은의미있는위험인자로생각된다. 병인 (Pathogenesis) HCAP 을포함한 HAP 의발생은하부기도에침입한미생물의양과병원성, 그리고숙주의반응과관련된다. 폐침범은구인두기관혹은드물지만소화기관에상재하는미생물의미세흡인이주된경로이며, 입원환자의상재균은주변환경과관련되어있다 15. 인공환기환자의가장흔한경로로는호흡장비 (respiratory devices) 나오염된물등을포함한주변병원소 (reservoir) 와의직접접촉이다 16. 이런오염은철저한기구소독에도불구하고발생할수있는데이는의료진의오염된손을통해감염이전파될수있기때문이다. 또한환자의기저질환으로인한면역력의저하나영양결핍, 약물이나장관영양등으로위내산도 (gastric ph) 의변화로인한상부위장관의환경변화역시폐렴의위험성을높인다 17. 106
Tuberculosis and Respiratory Diseases Vol. 70. No. 2, Feb. 2011 미생물학 (Microbiology) HCAP 을포함한 HAP의미생물학적원인은세균이대부분을차지하며, 많은경우에서혼합감염 (polymicrobial) 양상을보이고, 특히내성균의위험성이높다. 주요원인균주로는호기성그람음성간균인 Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter spp., Enterobacter spp. 등과그람양성구균인 Staphylococcus aureus 등이며, 구강내문제와같은특별한경우가아니라면일차원인균으로서혐기성균은드물다. 또한면역력이크게저하된환자가아니라면바이러스나진균은흔하지않다. 2005년 Kollef 등 9 의보고에의하면 CAP에비하여 HCAP 의원인균으로 MRSA와 P. aeruginosa가약 2배정도유의하게높고, Streptococcus pneumoniae와 Haemophilus influenzae 는유의하게낮았으며, CAP과비교하여 HCAP 의사망률또한의미있게높았다고보고하였다. Shorr 등 14 은항생제내성균주와관련된네가지인자를 1) 최근의입원 (4점), 2) 요양병원수용자 (3점), 3) 장기간의혈액투석 (2점), 4) 중환자실입원 (1점) 으로점수화하여합산점수가 6점이상인경우내성균주의가능성이 75% 이상, 3 5점인경우 55%, 3점미만인경우 20% 미만이라는연구결과를발표하였고이를기초로하여불필요한항생제의사용을억제하고적절한항생제치료를시작할것을주장하였다. 그러나흥미롭게도 2009 년 Shindo 등 13 이일본에서시행한단일기관연구결과는서구와달리 MRSA 는유의한차이를보이지않았으나 Pseudomonas spp. 는 HCAP 에서높게, 비정형성세균은 CAP에서유의하게높은양성률을보였다. 이들의연구결과는 50% 정도에서원인균을동정할수없었고, CAP 으로분류된환자의약 20% 정도에서 90일이전에이미항균제가사용되었던점을고려해야하지만, 지역적으로우리와비슷한일본의연구결과는국내의 CAP, HCAP 의치료에참고하여야할것으로생각된다. 또한본연구에서는 CAP에서보다는 HCAP 에서흔하게약제내성균이분리 (isolation) 되었으며, 이러한결과는초기항균제치료실패와부적절한초기항균제선택과관련하여 HCAP 의높은사망률이관련되어있을것으로생각된다. 진 HAP, VAP, HCAP 의임상적소견은때로비특이적이 단 기때문에 HAP, VAP, HCAP 의임상적진단은경우에따라서쉽지않다. 그러나 38 o C 이상의고열이나화농성객담, 백혈구증가증이나백혈구감소증, 산소포화도가떨어지는등의임상소견과함께흉부방사선촬영결과새로운병변이발생하거나악화되는경우에는반드시폐렴을고려해야한다. 또한어느정도한계가있으나, 흉부방사선소견이나객담의양상, 진찰소견등이원인균을예측하는데도움을주는경우도있다 (Table 2) 1. 미생물학적검사는폐렴의심환자에서폐렴을진단하는것은물론적합한배양검사를통해초기에적절한항균제치료를시작함과동시에사용중인항균제의점감 (de-escalation) 에유용하다. 폐렴의진단과원인균확인에있어하기도분비물배양검사가필수적이지만중환자실에입실한환자에게는비침습적인하기도분비물배양검사이외에도혈액배양, 소변 Legionella 항원검사, 폐렴구균항원검사뿐만아니라가능하다면침습적인기관지폐포액에대한배양등도시행할수있다 (Table 3) 1,18-22. HCAP 의진단에있어가장먼저고려하여야할점은 CAP 환자에서의료시설관련성의유무를확인하는것이고또한관련자체보다는의료시설관련인자중 HCAP 의위험인자여부를다시평가하는것이다. 그러나앞에서언급한것처럼 HCAP 의위험인자는너무나다양하여역학적으로위험인자를확실하게결정하는데에는현재까지논란이있는실정이다. 그러나최근까지의연구결과를종합하면 1) 3개월이내의광범위항생제의사용, 2) 중환자실입원, 3) 장기간요양병원수용, 4) 3개월이내의입원기왕력등은항생제내성과관련이있는것으로인정되고있어이러한인자는 HCAP의진단에주요한인자로생각된다. 치료적절한초기항균제투여는 HCAP 을비롯한 HAP의생존율을향상시킨다. 특히환자도착 4시간이내의적절한항균제투여는사망률과재원기간을줄이고, 이는폐렴의중증점수 (pneumonia severity index score) 23 가높은군에서더욱뚜렷하다고 24 보고되었다. 그러나, 확실한진단이어렵기때문에, 확진이전에임상적의심만으로치료를시작한경우, 중복감염 (superinfection) 과항균제의독성및내성균출현의위험성이있다. 따라서경험적항균제투여후 48 72시간이지난뒤에는환자의임상상태와검사실결과를종합하여항균제변경이나중단등을고려 107
HB Lee et al: Management of healthcare-associated pneumonia Table 2. Common clinical associations for pneumonia etiologies Clinical condition Co-morbidity Postinfluenza COPD Alcoholism Acquired immunodeficiency syndrome Intravenous drug abuse Endobronchial obstruction Nursing home residents Recent antibiotics treatment Sputum characteristics Mucopurulent Scanty watery Rusty Currant jelly Foul-smelling Few bacteria, many WBC Physical examination Pulse-temperature dissociation Frunculosis Herpes labilais Periodontal disease Clinical, radiological disparity Suspicious pneumonia etiologies S. aureus, S. pneumoniae, Influenza, H. influenzae K. pneumoniae, M. catarrhalis, S. pneumoniae, Legionella spp. K. pneumoniae, S. pneumoniae, anaerobes, M. tuberculosis Pneumocystis jirovecii, Cytomegalovirus, M. tuberculosis, nontuberculous Mycobacterium S. aureus, anaerobes, P. jirovecii, M. tuberculosis Anaerobes S. pneumoniae, H. influenzae, S. aureus, anaerobes, M. tuberculosis, C. pneumoniae Drug-resistant Streptococci, Pseudomonas spp. Bacterial, occasionally viral or Mycoplasma Mycoplasma, other atypical S. pneumoniae K. pneumoniae Mixed anaerobes Legionella Viral, Mycoplasma, Legionella Staphylococcus S. pneumoniae Aspiration of oral flora Viral, Mycoplasma COPD: chronic obstructive pulmonary disease; WBC: white blood cell. Table 3. Clinical indications for more extensive diagnostic testing Indication Blood culture Sputum culture Legionella UAT Pneumococcal UAT Other* Intensive care unit admission o o o o A Cavitary infiltrates o o B Leukopenia o o Active alcohol abuse o o o o Chronic severe liver disease o o Severe obstructive/structural lung disease o Pleural effusion o o o o C *A: Endotracheal aspirate if intubated, possibly bronchoscopy or nonbronchoscopic bronchoalveolar lavage; B: Fungal and tuberculosis cultures; C: Thoracentesis and pleural fluid cultures. UAT: urinary antigen tests (This Table is reprinted from the article by Mandell et al. 1 [2007, p. 27-72]). 하여야한다 (Figure 1). 임상적으로 HCAP이의심되어항균제투여를결정하였다면경험적항균제선택에있어다제내성균에대한위험도를평가하여야한다. 다제내성의위험성이높지않은경우에는 CAP 의경우에서처럼원인이될만한주요원인균에대한항균제로 ceftriaxone 또는 respiratory quinolones, 또는 Ampicillin/sulbactam 또는 Ertapenem 과같은제한적항균제중한가지를선택하여, 단독요법으로 우선투여한다 (Table 4). 그러나다제내성균의위험성이있다면광범위, 복합항균제로시작하여야하고, 이후배양검사및감수성검사결과에따라항균제범위를좁혀나가야한다. 이러한치료순서 (algorithm) 는 HAP, VAP, HCAP 모두에서동일하게적용된다. 다제내성균의정도와빈도는병원마다또한중환자실마다가지고있는각각의특성과최근항균제치료를받았던환자의분포와같은지역적특성에영향을받기때문 108
Tuberculosis and Respiratory Diseases Vol. 70. No. 2, Feb. 2011 Figure 1. Algorithm for the current management recommendations for HCAP. HCAP: healthcare-associated pneumonia; MDR: multi drug resistant (This Figure is reprinted from the article by ATS and IDSA 2 [2005, p. 388-416]). Table 4. Recommendations for initial, broad-spectrum, empiric therapy for HCAP with no risk factors for MDR pathogens Potential pathogens Initial, empiric, mono-antibiotic therapy S. pneumoniae Ceftriaxone H. influenzae OR Methicillin-sensitive S. aureus Levofloxacin, Moxifloxacin, or Ciprofloxacin Antibiotics-sensitive enteric G ( ) bacilli OR E. coli Ampicillin-Sulbactam K. pneumoniae OR Enterobacter species Ertapenem Proteus species Serratia marcescens This Table is reprinted from the article by ATS and IDSA 2 [2005, p. 388-416]. 에, 치료에있어이러한특정감수성패턴을인지하여이에맞는적절한초기항균제를선택하는것이매우중요하다. 다제내성균에의한폐렴의위험성이높은환자측인자로는 1) 최근 90일이내항균제를투여받은경우, 2) 최근 5일이상입원하였거나, 3) 그지역사회나특정병원에서항균제내성빈도가높은경우, 4) 면역력이저하된자나혹은면역억제치료를받고있는경우, 5) 최근 90일이내에 2일이상입원치료를받은경험이있거나, 장기요양시설수용자, 항균제를포함한자가치료를받은경우, 최근 30일이내에혈액투석이나창상치료를받은경우와같은여러 HCAP 과관련된위험인자를가진경우이다. 또한중증의만성기저질환이있는환자의경우에도다제내성균의위험도는높아진다. 그러나다제내성균을가진가족과의단순접촉의경우에는위험성이높지않다 25. 다제내성균인 P. aeruginosa, K. pneumoniae, Acinetobacter spp. 에대해서는 antipseudomonal cephalosporin (cefepime, ceftazidime) 또는 antipseudomonal carbepenem (imipenem 또는 meropenem) 또는 ß-Lactam/ ß-lactamase inhibitor (piperacillin-tazobactam) 에 antipseudomonal fluoroquinolone (ciprofloxacin 또는 levofloxacin) 또는 aminoglycoside (amikacin, gentamicin, 또는 tobramycin) 를병합하고, 만약 MRSA 가흔한병원감염균이라면 linezolid 또는 vancomycin 을반드시우선적으로선택, 추가해야한다. 2005년미국흉부학회에서도 MRSA에대해 linezolid나 vancomycin을고려할것을권고하고있으며, linezolid 는신기능장애가있거나그러할위험성이높은환자에있어우월하다 26-28. 또한 extended-spectrum β-lactamase (ESBL) 양성 K. pneumoniae와 Acinetobacter spp. 에대해서는 3세대 cephalosporin 단독사용은피해야하며, carbepenem 이우선적으로추천된다 (Table 5). 다제내성균에대해서는초기에정맥주사로광범위항균제의병합치료를시작해야하고, 이후배양검사결과및감수성검사결과에따라항균제를조정하여원인균에맞도록항균범위를좁혀나가야한다. 또한경험적항균제투여후에는초기항균제시작 72시간후환자상태를평 109
HB Lee et al: Management of healthcare-associated pneumonia Table 5. Recommendations for initial, broad-spectrum, empiric therapy for HCAP with risk factors for MDR pathogens Potential MDR pathogens Initial, broad-spectrum, combination antibiotic therapy MDR G ( ) bacilli Anti-pseudomonal cephalosporin (Cefepime, Ceftazidime) P. aeruginosa OR K. pneumoniae Anti-pseudomonal carbapenem (Imipenem or Meropenem) E. coli OR Anti-pseudomonal penicillin (Piperacillin-tazobactam) Plus Anti-pseudomonal fluoroquinolone (Ciprofloxacin or Levofloxacin) OR Aminoglycoside (Amikacin, Gentamicin, or Tobramycin) ESBL (+) K. pneumoniae Carbapenem Acinetobacter species OR Carbapenem+Aminoglycoside Non-MDR G ( ) bacilli Fluoroquinolone (Ciprofloxacin or Levofloxacin) L. pneumophilia OR Macrolide (Azithromycin) MDR G (+) cocci Add Linezolid or Vancomycin MRSA (if MRSA is suspected or there is a high incidence locally) HACP: healthcare-associated pneumonia; MDR: multi drug resistant; MRSA: Methicillin-resistant Staphylococcus aureus (This Table is reprinted from the article by ATS and IDSA 2 [2005, p. 388-416]). Figure 2. Recommendations for assessing response to initial antibiotic therapy, de-escalation and stopping antibiotics in patients with suspected HCAP. HCAP: healthcare-associated pneumonia; WBC: white blood cells; CXR: chest X-ray; SaO 2: oxygen saturation; Cxs: complications; Dx: diagnosis; Tx: treatment (This Figure is reprinted from the article by ATS and IDSA 2 [2005, p. 388-416]). 가하여항균제를중단하거나또는배양및감수성검사에근거하여점감하여항균제노출을최소화하여야한다 (Figure 2). 임상적으로호전되면서혈역학적으로안정화되고경구복용이가능하다면경구용으로교체하여투여할수있다. 만약원인균이규명되었다면배양및감수성결과에근거하여경구용으로교체하며, 만약원인균이규명되지않았다면이전정맥주사와동일한항균제로교체 하거나같은종류 (class) 의항균제중폐투과력이좋은항생제로교체한다. 항균제투여기간은임상적반응에따라달라진다. 과거의표준투여기간은특히 Pseudomona spp. 와같은치료하기힘든균주에초점이맞춰졌기때문에 14 21 일정도였으나, 최근의추세는새로운내성균의출현을염려하여좀더단기간의코스인 7일정도를추천하고있다. 실제 110
Tuberculosis and Respiratory Diseases Vol. 70. No. 2, Feb. 2011 여러연구에서 8일과 15일항균제사용후 28일째사망률을비교하였을때두군간의의미있는차이는없었으며, 오히려항생제사용기간이짧으면서도다제내성균의빈도가더낮게보고되었다 29. 그러나 Pseudomona spp. 와같은그람음성간균이원인인경우에는단기간사용한군에서사망률에는차이가없었지만재발률이의미있게높았다 29. 일부보고에서는, 항균제투여후 3일째되는날임상적폐감염점수 (Clinical Pulmonary Infection Score, CPIS score) 30 등의재평가를통해항균제의지속여부를결정하는것이항균제의양이나투여기간을줄이는데도움이된다고말하고있다. 따라서모든의료기관관련폐렴을포함한병원획득폐렴환자는첫경험적항균제투여후 72시간후에증상의호전여부와배양검사를확인할것을권고하고있다. 일반적으로임상적호전에는 48 72 시간정도소요되기때문에, 이시기에아주빠르게악화되지만않는다면굳이항균제를바꿀필요는없다 31,32. 만약원인균이동정되었다면감수성결과에따라항균제를점감 (de-escalation) 한후총 7일간유지하고, P. aeruginosa가동정되었다면 15일이상유지할것을권장한다 33. 만약임상적으로는호전되었으나원인균이규명되지못한경우에는 Pseudomona spp. 와 MRSA에대한항균제를중단하여항균범위가좁은항균제로유지하고, 72시간후에도임상적으로호전이없으면서내성균이동정된경우에는배양및감수성결과에따라항균제를변경하면서, 폐외의다른감염원은없는지, 폐렴의합병증이생겼는지를평가한다. 결론 2005년과 2007년미국흉부학회와감염학회에서는다제내성위험성이없는 HCAP 의경우에는주요원인균에대한 CAP의진료지침이유용하지만, 다제내성이의심되는상황에서는 HAP나 VAP처럼광범위항균제의병합치료를권장하고있다. 아직까지 HCAP 에대한임상적근거는제한적인실정이지만향후이러한문제는좀더표준화된연구를통해해결될것으로기대된다. 결론적으로 HCAP의진단에는 CAP 환자중의료시설관련성의유무와항생제내성균주의위험성이높은인자의관련성을확인하여이에대한적극적인치료가필요할것으로생각된다. 참고문헌 1. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44:S27-72. 2. American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005;171:388-416. 3. Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventive strategies. A consensus statement, American Thoracic Society, November 1995. Am J Respir Crit Care Med 1996;153:1711-25. 4. Kung HC, Hoyert DL, Xu J, Murphy SL. Deaths: final data for 2005. Natl Vital Stat Rep 2008;56:1-120. 5. DeFrances CJ, Lucas CA, Buie VC, Golosinskiy A. 2006 National Hospital Discharge Survey. Natl Health Stat Report 2008;30:1-20. 6. Morin CA, Hadler JL. Population-based incidence and characteristics of community-onset Staphylococcus aureus infections with bacteremia in 4 metropolitan Connecticut areas, 1998. J Infect Dis 2001;184:1029-34. 7. Friedman ND, Kaye KS, Stout JE, McGarry SA, Trivette SL, Briggs JP, et al. Health care--associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med 2002;137:791-7. 8. Tacconelli E, Venkataraman L, De Girolami PC, DAgata EM. Methicillin-resistant Staphylococcus aureus bacteraemia diagnosed at hospital admission: distinguishing between community-acquired versus healthcare-associated strains. J Antimicrob Chemother 2004;53:474-9. 9. Kollef MH, Shorr A, Tabak YP, Gupta V, Liu LZ, Johannes RS. Epidemiology and outcomes of healthcare-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest 2005;128: 3854-62. 10. Carratalà J, Mykietiuk A, Fernández-Sabé N, Suárez C, Dorca J, Verdaguer R, et al. Health care-associated pneumonia requiring hospital admission: epidemiology, antibiotic therapy, and clinical outcomes. Arch Intern Med 2007;167:1393-9. 11. Micek ST, Kollef KE, Reichley RM, Roubinian N, Kollef MH. Health care-associated pneumonia and community-acquired pneumonia: a single-center experience. 111
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