1887

Abstract

Determination of pneumococcal load by quantitative PCR may be useful for diagnostic and prognostic purposes. We hypothesized that higher pneumococcal load would be associated with increased pneumonia severity. Therefore, we tested serum, sputum and urine specimens from 304 adults with community-acquired pneumonia by using a quantitative pneumococcal real-time PCR assay. The association between pneumococcal load and disease severity was assessed using several markers of severity: CURBage score, PSI risk class, intensive care unit admission, in-hospital death and admission duration. For PCR-positive specimens, the bacterial loads were higher in sputum specimens [median 8.55×10 copies ml; interquartile range (IQR) 4.70×10–4.69×10 copies ml] than either serum (median 180 copies ml; IQR 165–8970 copies ml) or urine (median 623 copies ml; IQR 510–650 copies ml). Detection of pneumococcal DNA in serum was associated with severe disease, and there was evidence of a dose–response effect with increased bacterial load being associated with increased severity. The same observations were not observed for other specimen types. This study adds to an increasing body of evidence suggesting that determination of pneumococcal load has a clinical utility. Further work is needed to determine whether measuring pneumococcal load in respiratory specimens from adults will differentiate colonization from coincidental carriage.

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2012-08-01
2019-10-23
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References

  1. Abdeldaim G. M., Strålin K., Olcén P., Blomberg J., Herrmann B.. ( 2008;). Toward a quantitative DNA-based definition of pneumococcal pneumonia: a comparison of Streptococcus pneumoniae target genes, with special reference to the Spn9802 fragment. . Diagn Microbiol Infect Dis 60:, 143–150. [CrossRef][PubMed]
    [Google Scholar]
  2. Abdeldaim G., Herrmann B., Korsgaard J., Olcén P., Blomberg J., Strålin K.. ( 2009;). Is quantitative PCR for the pneumolysin (ply) gene useful for detection of pneumococcal lower respiratory tract infection?. Clin Microbiol Infect 15:, 565–570. [CrossRef][PubMed]
    [Google Scholar]
  3. Abdeldaim G., Herrmann B., Mölling P., Holmberg H., Blomberg J., Olcén P., Strålin K.. ( 2010;). Usefulness of real-time PCR for lytA, ply, and Spn9802 on plasma samples for the diagnosis of pneumococcal pneumonia. . Clin Microbiol Infect 16:, 1135–1141. [CrossRef][PubMed]
    [Google Scholar]
  4. Azzari C., Cortimiglia M., Moriondo M., Canessa C., Lippi F., Ghiori F., Becciolini L., de Martino M., Resti M.. ( 2011;). Pneumococcal DNA is not detectable in the blood of healthy carrier children by real-time PCR targeting the lytA gene. . J Med Microbiol 60:, 710–714. [CrossRef][PubMed]
    [Google Scholar]
  5. British Thoracic Society ( 1987;). Community-acquired pneumonia in adults in British hospitals in 1982–1983: a survey of aetiology, mortality, prognostic factors and outcome. . Q J Med 62:, 195–220.[PubMed]
    [Google Scholar]
  6. Carrol E. D., Guiver M., Nkhoma S., Mankhambo L. A., Marsh J., Balmer P., Banda D. L., Jeffers G., White S. A.. & other authors ( 2007;). High pneumococcal DNA loads are associated with mortality in Malawian children with invasive pneumococcal disease. . Pediatr Infect Dis J 26:, 416–422. [CrossRef][PubMed]
    [Google Scholar]
  7. Carvalho M. G., Tondella M. L., McCaustland K., Weidlich L., McGee L., Mayer L. W., Steigerwalt A., Whaley M., Facklam R. R.. & other authors ( 2007;). Evaluation and improvement of real-time PCR assays targeting lytA, ply, and psaA genes for detection of pneumococcal DNA. . J Clin Microbiol 45:, 2460–2466. [CrossRef][PubMed]
    [Google Scholar]
  8. Dagan R., Shriker O., Hazan I., Leibovitz E., Greenberg D., Schlaeffer F., Levy R.. ( 1998;). Prospective study to determine clinical relevance of detection of pneumococcal DNA in sera of children by PCR. . J Clin Microbiol 36:, 669–673.[PubMed]
    [Google Scholar]
  9. Fine M. J., Auble T. E., Yealy D. M., Hanusa B. H., Weissfeld L. A., Singer D. E., Coley C. M., Marrie T. J., Kapoor W. N.. ( 1997;). A prediction rule to identify low-risk patients with community-acquired pneumonia. . N Engl J Med 336:, 243–250. [CrossRef][PubMed]
    [Google Scholar]
  10. Jennings L. C., Anderson T. P., Beynon K. A., Chua A., Laing R. T. R., Werno A. M., Young S. A., Chambers S. T., Murdoch D. R.. ( 2008;). Incidence and characteristics of viral community-acquired pneumonia in adults. . Thorax 63:, 42–48. [CrossRef][PubMed]
    [Google Scholar]
  11. Laing R., Slater W., Coles C., Chambers S., Frampton C., Jackson R., Jennings L., Karalus N., Mills G.. & other authors ( 2001;). Community-acquired pneumonia in Christchurch and Waikato 1999–2000: microbiology and epidemiology. . N Z Med J 114:, 488–492.[PubMed]
    [Google Scholar]
  12. Lim W. S., van der Eerden M. M., Laing R., Boersma W. G., Karalus N., Town G. I., Lewis S. A., Macfarlane J. T.. ( 2003;). Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. . Thorax 58:, 377–382. [CrossRef][PubMed]
    [Google Scholar]
  13. Marchese A., Esposito S., Coppo E., Rossi G. A., Tozzi A., Romano M., Da Dalt L., Schito G. C., Principi N.. ( 2011;). Detection of Streptococcus pneumoniae and identification of pneumococcal serotypes by real-time polymerase chain reaction using blood samples from Italian children ≤ 5 years of age with community-acquired pneumonia. . Microb Drug Resist 17:, 419–424. [CrossRef][PubMed]
    [Google Scholar]
  14. Messmer T. O., Sampson J. S., Stinson A., Wong B., Carlone G. M., Facklam R. R.. ( 2004;). Comparison of four polymerase chain reaction assays for specificity in the identification of Streptococcus pneumoniae. . Diagn Microbiol Infect Dis 49:, 249–254. [CrossRef][PubMed]
    [Google Scholar]
  15. Muñoz-Almagro C., Gala S., Selva L., Jordan I., Tarragó D., Pallares R.. ( 2011;). DNA bacterial load in children and adolescents with pneumococcal pneumonia and empyema. . Eur J Clin Microbiol Infect Dis 30:, 327–335. [CrossRef][PubMed]
    [Google Scholar]
  16. Murdoch D. R., Laing R. T. R., Mills G. D., Karalus N. C., Town G. I., Mirrett S., Reller L. B.. ( 2001;). Evaluation of a rapid immunochromatographic test for detection of Streptococcus pneumoniae antigen in urine samples from adults with community-acquired pneumonia. . J Clin Microbiol 39:, 3495–3498. [CrossRef][PubMed]
    [Google Scholar]
  17. Murdoch D. R., Anderson T. P., Beynon K. A., Chua A., Fleming A. M., Laing R. T. R., Town G. I., Mills G. D., Chambers S. T., Jennings L. C.. ( 2003;). Evaluation of a PCR assay for detection of Streptococcus pneumoniae in respiratory and nonrespiratory samples from adults with community-acquired pneumonia. . J Clin Microbiol 41:, 63–66. [CrossRef][PubMed]
    [Google Scholar]
  18. Murray P. R., Washington J. A. I.. ( 1975;). Microscopic and baceriologic analysis of expectorated sputum. . Mayo Clin Proc 50:, 339–344.[PubMed]
    [Google Scholar]
  19. Neill A. M., Martin I. R., Weir R., Anderson R., Chereshsky A., Epton M. J., Jackson R., Schousboe M., Frampton C.. & other authors ( 1996;). Community acquired pneumonia: aetiology and usefulness of severity criteria on admission. . Thorax 51:, 1010–1016. [CrossRef][PubMed]
    [Google Scholar]
  20. Peters R. P. H., de Boer R. F., Schuurman T., Gierveld S., Kooistra-Smid M., van Agtmael M. A., Vandenbroucke-Grauls C. M. J. E., Persoons M. C. J., Savelkoul P. H. M.. ( 2009;). Streptococcus pneumoniae DNA load in blood as a marker of infection in patients with community-acquired pneumonia. . J Clin Microbiol 47:, 3308–3312. [CrossRef][PubMed]
    [Google Scholar]
  21. Rello J., Lisboa T., Lujan M., Gallego M., Kee C., Kay I., Lopez D., Waterer G. W..for DNA-Neumococo Study Group ( 2009;). Severity of pneumococcal pneumonia associated with genomic bacterial load. . Chest 136:, 832–840. [CrossRef][PubMed]
    [Google Scholar]
  22. Rodríguez M. A., González A. V., Gavín M. A., Martínez F. M., Marín N. G., Blázquez B. R., Moreno J. C.. ( 2011;). Invasive pneumococcal disease: association between serotype, clinical presentation and lethality. . Vaccine 29:, 5740–5746. [CrossRef][PubMed]
    [Google Scholar]
  23. Sheppard C. L., Harrison T. G., Morris R., Hogan A., George R. C.. ( 2004;). Autolysin-targeted LightCycler assay including internal process control for detection of Streptococcus pneumoniae DNA in clinical samples. . J Med Microbiol 53:, 189–195. [CrossRef][PubMed]
    [Google Scholar]
  24. Suzuki N., Seki M., Nakano Y., Kiyoura Y., Maeno M., Yamashita Y.. ( 2005;). Discrimination of Streptococcus pneumoniae from viridans group streptococci by genomic subtractive hybridization. . J Clin Microbiol 43:, 4528–4534. [CrossRef][PubMed]
    [Google Scholar]
  25. Vu H. T. T., Yoshida L. M., Suzuki M., Nguyen H. A. T., Nguyen C. D. L., Nguyen A. T. T., Oishi K., Yamamoto T., Watanabe K.. & other authors ( 2011;). Association between nasopharyngeal load of Streptococcus pneumoniae, viral coinfection, and radiologically confirmed pneumonia in Vietnamese children. . Pediatr Infect Dis J 30:, 11–18. [CrossRef][PubMed]
    [Google Scholar]
  26. Waterer G., Rello J.. ( 2011;). Why should we measure bacterial load when treating community-acquired pneumonia?. Curr Opin Infect Dis 24:, 137–141. [CrossRef][PubMed]
    [Google Scholar]
  27. Werno A. M., Murdoch D. R.. ( 2008;). Laboratory diagnosis of invasive pneumococcal disease. . Clin Infect Dis 46:, 926–932. [CrossRef][PubMed]
    [Google Scholar]
  28. Whatmore A. M., Efstratiou A., Pickerill A. P., Broughton K., Woodard G., Sturgeon D., George R., Dowson C. G.. ( 2000;). Genetic relationships between clinical isolates of Streptococcus pneumoniae, Streptococcus oralis, and Streptococcus mitis: characterization of “atypical” pneumococci and organisms allied to S. mitis harboring S. pneumoniae virulence factor-encoding genes. . Infect Immun 68:, 1374–1382. [CrossRef][PubMed]
    [Google Scholar]
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