Etiology of community-acquired pneumonia and diagnostic yields of microbiological methods: a 3-year prospective study in Norway

BMC Infectious Diseases - Tập 15 - Trang 1-11 - 2015
Jan C Holter1,2,3, Fredrik Müller4,3, Ola Bjørang5, Helvi H Samdal5,6, Jon B Marthinsen7,8, Pål A Jenum5,3, Thor Ueland2,3,9, Stig S Frøland2,10,3, Pål Aukrust2,10,3,9, Einar Husebye1,3, Lars Heggelund1,3
1Department of Internal Medicine, Vestre Viken Hospital Trust, Drammen, Norway
2Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
3Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
4Department of Microbiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
5Department of Medical Microbiology, Vestre Viken Hospital Trust, Drammen, Norway
6Department of Microbiology, Oslo University Hospital Ullevaal, Oslo, Norway
7Department of Radiology, Vestre Viken Hospital Trust, Drammen, Norway
8Department of Radiology, Hospital of Southern Norway HF, Kristiansand, Norway
9K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway
10Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway

Tóm tắt

Despite recent advances in microbiological techniques, the etiology of community-acquired pneumonia (CAP) is still not well described. We applied polymerase chain reaction (PCR) and conventional methods to describe etiology of CAP in hospitalized adults and evaluated their respective diagnostic yields. 267 CAP patients were enrolled consecutively over our 3-year prospective study. Conventional methods (i.e., bacterial cultures, urinary antigen assays, serology) were combined with nasopharyngeal (NP) and oropharyngeal (OP) swab samples analyzed by real-time quantitative PCR (qPCR) for Streptococcus pneumoniae, and by real-time PCR for Mycoplasma pneumoniae, Chlamydophila pneumoniae, Bordetella pertussis and 12 types of respiratory viruses. Etiology was established in 167 (63%) patients with 69 (26%) patients having ≥1 copathogen. There were 75 (28%) pure bacterial and 41 (15%) pure viral infections, and 51 (19%) viral–bacterial coinfections, resulting in 126 (47%) patients with bacterial and 92 (34%) patients with viral etiology. S. pneumoniae (30%), influenza (15%) and rhinovirus (12%) were most commonly identified, typically with ≥1 copathogen. During winter and spring, viruses were detected more frequently (45%, P=.01) and usually in combination with bacteria (39%). PCR improved diagnostic yield by 8% in 64 cases with complete sampling (and by 15% in all patients); 5% for detection of bacteria; 19% for viruses (P=.04); and 16% for detection of ≥1 copathogen. Etiology was established in 79% of 43 antibiotic-naive patients with complete sampling. S. pneumoniae qPCR positive rate was significantly higher for OP swab compared to NP swab (P<.001). Positive rates for serology were significantly higher than for real-time PCR in detecting B. pertussis (P=.001) and influenza viruses (P<.001). Etiology could be established in 4 out of 5 CAP patients with the aid of PCR, particularly in diagnosing viral infections. S. pneumoniae and viruses were most frequently identified, usually with copathogens. Viral–bacterial coinfections were more common than pure infections during winter and spring; a finding we consider important in the proper management of CAP. When swabbing for qPCR detection of S. pneumoniae in adult CAP, OP appeared superior to NP, but this finding needs further confirmation. ClinicalTrials.gov Identifier: NCT01563315 .

Tài liệu tham khảo

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 Suppl 2:S27–72. Lim WS, Baudouin SV, George RC, Hill AT, Jamieson C, Le Jeune I, et al. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 2009;64 Suppl 3:iii1–55. Spindler C, Stralin K, Eriksson L, Hjerdt-Goscinski G, Holmberg H, Lidman C, et al. Swedish guidelines on the management of community-acquired pneumonia in immunocompetent adults–Swedish Society of Infectious Diseases 2012. Scand J Infect Dis. 2012;44(12):885–902. File TM. Community-acquired pneumonia. Lancet. 2003;362(9400):1991–2001. Ruiz M, Ewig S, Marcos MA, Martinez JA, Arancibia F, Mensa J, et al. Etiology of community-acquired pneumonia: impact of age, comorbidity, and severity. Am J Respir Crit Care Med. 1999;160(2):397–405. Brown JS. Geography and the aetiology of community-acquired pneumonia. Respirology. 2009;14(8):1068–71. Woodhead M. Community-acquired pneumonia in Europe: causative pathogens and resistance patterns. Eur Respir J Suppl. 2002;36:20s–7. Bartlett JG. Diagnostic tests for agents of community-acquired pneumonia. Clin Infect Dis. 2011;52 Suppl 4:S296–304. Schreiner AD, Digranes A. Bacteriology of acute lower respiratory tract infections. J Infect. 1979;1 Suppl 2:23–30. Johansson N, Kalin M, Giske CG, Hedlund J. Quantitative detection of Streptococcus pneumoniae from sputum samples with real-time quantitative polymerase chain reaction for etiologic diagnosis of community-acquired pneumonia. Diagn Microbiol Infect Dis. 2008;60(3):255–61. Johansson N, Kalin M, Tiveljung-Lindell A, Giske CG, Hedlund J. Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. Clin Infect Dis. 2010;50(2):202–9. Luchsinger V, Ruiz M, Zunino E, Martinez MA, Machado C, Piedra PA, et al. Community-acquired pneumonia in Chile: the clinical relevance in the detection of viruses and atypical bacteria. Thorax. 2013;68(11):1000–6. Sangil A, Calbo E, Robles A, Benet S, Viladot ME, Pascual V, et al. Aetiology of community-acquired pneumonia among adults in an H1N1 pandemic year: the role of respiratory viruses. Eur J Clin Microbiol Infect Dis. 2012;31(10):2765–72. Huijskens EG, van Erkel AJ, Palmen FM, Buiting AG, Kluytmans JA, Rossen JW. Viral and bacterial aetiology of community-acquired pneumonia in adults. Influenza Other Respi Viruses. 2013;7(4):567–73. van Gageldonk-Lafeber AB, Wever PC, van der Lubben IM, de Jager CP, Meijer A, de Vries MC, et al. The aetiology of community-acquired pneumonia and implications for patient management. Neth J Med. 2013;71(8):418–25. Templeton KE, Scheltinga SA, van den Eeden WC, Graffelman AW, van den Broek PJ, Claas EC. Improved diagnosis of the etiology of community-acquired pneumonia with real-time polymerase chain reaction. Clin Infect Dis. 2005;41(3):345–51. Pavia AT. What is the role of respiratory viruses in community-acquired pneumonia?: What is the best therapy for influenza and other viral causes of community-acquired pneumonia? Infect Dis Clin North Am. 2013;27(1):157–75. File Jr TM. New diagnostic tests for pneumonia: what is their role in clinical practice? Clin Chest Med. 2011;32(3):417–30. Kirkpatrick MB, Bass Jr JB. Quantitative bacterial cultures of bronchoalveolar lavage fluids and protected brush catheter specimens from normal subjects. Am Rev Respir Dis. 1989;139(2):546–8. Bartlett JG, Dowell SF, Mandell LA, File Jr TM, Musher DM, Fine MJ. Practice guidelines for the management of community-acquired pneumonia in adults. Infectious Diseases Society of America. Clin Infect Dis. 2000;31(2):347–82. Greiner O, Day PJ, Bosshard PP, Imeri F, Altwegg M, Nadal D. Quantitative detection of Streptococcus pneumoniae in nasopharyngeal secretions by real-time PCR. J Clin Microbiol. 2001;39(9):3129–34. Andre P, Caro V, Njamkepo E, Wendelboe AM, Van Rie A, Guiso N. Comparison of serological and real-time PCR assays to diagnose Bordetella pertussis infection in 2007. J Clin Microbiol. 2008;46(5):1672–7. Guiso N, Berbers G, Fry NK, He Q, Riffelmann M, Wirsing von Konig CH. What to do and what not to do in serological diagnosis of pertussis: recommendations from EU reference laboratories. Eur J Clin Microbiol Infect Dis. 2011;30(3):307–12. Albrich WC, Madhi SA, Adrian PV, van Niekerk N, Mareletsi T, Cutland C, et al. Use of a rapid test of pneumococcal colonization density to diagnose pneumococcal pneumonia. Clin Infect Dis. 2012;54(5):601–9. Kais M, Spindler C, Kalin M, Ortqvist A, Giske CG. Quantitative detection of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in lower respiratory tract samples by real-time PCR. Diagn Microbiol Infect Dis. 2006;55(3):169–78. Principi N, Terranova L, Zampiero A, Manzoni F, Senatore L, Rios WP, et al. Oropharyngeal and nasopharyngeal sampling for the detection of adolescent Streptococcus pneumoniae carriers. J Med Microbiol. 2014;63(Pt 3):393–8. Angeles Marcos M, Camps M, Pumarola T, Antonio Martinez J, Martinez E, Mensa J, et al. The role of viruses in the aetiology of community-acquired pneumonia in adults. Antivir Ther. 2006;11(3):351–9. Jennings LC, Anderson TP, Beynon KA, Chua A, Laing RT, Werno AM, et al. Incidence and characteristics of viral community-acquired pneumonia in adults. Thorax. 2008;63(1):42–8. Lieberman D, Shimoni A, Shemer-Avni Y, Keren-Naos A, Shtainberg R, Lieberman D. Respiratory viruses in adults with community-acquired pneumonia. Chest. 2010;138(4):811–6. Johnstone J, Majumdar SR, Fox JD, Marrie TJ. Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation. Chest. 2008;134(6):1141–8. Charles PG, Whitby M, Fuller AJ, Stirling R, Wright AA, Korman TM, et al. The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy. Clin Infect Dis. 2008;46(10):1513–21. Apisarnthanarak A, Mundy LM. Etiology of community-acquired pneumonia. Clin Chest Med. 2005;26(1):47–55. Gabutti G, Rota MC. Pertussis: a review of disease epidemiology worldwide and in Italy. Int J Environ Res Public Health. 2012;9(12):4626–38. Blystad H, Anestad G, Vestrheim DF, Madsen S, Ronning K. Increased incidence of Mycoplasma pneumoniae infection in Norway 2011. Euro Surveill. 2012;17(5). http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20074. Cesario TC. Viruses associated with pneumonia in adults. Clin Infect Dis. 2012;55(1):107–13. Jartti T, Jartti L, Ruuskanen O, Soderlund-Venermo M. New respiratory viral infections. Curr Opin Pulm Med. 2012;18(3):271–8. Ruuskanen O, Lahti E, Jennings LC, Murdoch DR. Viral pneumonia. Lancet. 2011;377(9773):1264–75. Ruuskanen O, Jarvinen A. What is the real role of respiratory viruses in severe community-acquired pneumonia? Clin Infect Dis. 2014;59:71–3. Oosterheert JJ, van Loon AM, Schuurman R, Hoepelman AI, Hak E, Thijsen S, et al. Impact of rapid detection of viral and atypical bacterial pathogens by real-time polymerase chain reaction for patients with lower respiratory tract infection. Clin Infect Dis. 2005;41(10):1438–44. Karhu J, Ala-Kokko TI, Vuorinen T, Ohtonen P, Syrjala H. Lower respiratory tract virus findings in mechanically ventilated patients with severe community-acquired pneumonia. Clin Infect Dis. 2014;59:62–70. Lim WS, Macfarlane JT, Boswell TC, Harrison TG, Rose D, Leinonen M, et al. Study of community acquired pneumonia aetiology (SCAPA) in adults admitted to hospital: implications for management guidelines. Thorax. 2001;56(4):296–301. Hernes SS, Quarsten H, Hagen E, Lyngroth AL, Pripp AH, Bjorvatn B, et al. Swabbing for respiratory viral infections in older patients: a comparison of rayon and nylon flocked swabs. Eur J Clin Microbiol Infect Dis. 2011;30(2):159–65. Pollock NR, Duong S, Cheng A, Han LL, Smole S, Kirby JE. Ruling out novel H1N1 influenza virus infection with direct fluorescent antigen testing. Clin Infect Dis. 2009;49(6):e66–8. Stralin K, Olcen P, Tornqvist E, Holmberg H. Definite, probable, and possible bacterial aetiologies of community-acquired pneumonia at different CRB-65 scores. Scand J Infect Dis. 2010;42(6–7):426–34.