Current Concepts of Severe Pneumococcal Community-acquired Pneumonia

  • M. Luján
  • C. Muñoz-Almagro
  • J. Rello
Conference paper


Community-acquired pneumonia (CAP) is a major health problem, even in developed countries, being the leading cause of death due to infectious diseases in the USA [1]. CAP has a wide clinical spectrum of severity: up to 80% of patients are successfully managed in primary care, but 1 % of patients with CAP are classified as having severe disease, needing intensive care unit (ICU) admission, with 20–50% dying despite all available support and treatment options being utilized. Streptococcus pneumoniae is the most common cause of CAP, enclosing the subset group of patients having severe disease [2]. Moreover, bacteremia is not uncommon in pneumococcal CAP (20%) and has been associated with increased severity and mortality compared with non-bacteremic pneumonia [3].


Invasive Pneumococcal Disease Pneumococcal Pneumonia Pneumococcal Bacteremia Combination Antibiotic Therapy Pneumococcal Surface Protein 
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  1. 1.
    Garibaldi RA (1985) Epidemiology of community-acquired respiratory tract infections in adults: incidence, etiology and impact. Am J Med 78:32S–38SCrossRefGoogle Scholar
  2. 2.
    Torres A, Serra-Batlles J, Ferrer A, et al (1991) Severe community-acquired pneumonia. Epidemiology and prognostic factors. Am Rev Respir Dis 144:312–318PubMedGoogle Scholar
  3. 3.
    Musher D, Alexandraki I, Gravis EA, et al (2000) Bacteremic and non-bacteremic pneumococcal pneumonia: a prospective study. Medicine 79:210–221PubMedCrossRefGoogle Scholar
  4. 4.
    Tilghman RC, Finland M (1937) Clinical significance of bacteremia in pneumococcal pneumonia. Arch Intern Med 59:602–619Google Scholar
  5. 5.
    Knaus WA, Zimmerman JE, Wagner DP, et al (1981) APACHE-acute physiology and chronic health evaluation: a physiologically based classification system. Crit Care Med 9:591–597PubMedCrossRefGoogle Scholar
  6. 6.
    Fine MJ, Smith MA, Carson CA, et al (1996) Prognosis and outcomes of patients with community-acquired pneumonia: a meta-analysis. JAMA 75:134–141CrossRefGoogle Scholar
  7. 7.
    Fine MJ, Auble TE, Yealy DM, et al (1997) A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 336:243–250PubMedCrossRefGoogle Scholar
  8. 8.
    Roson B, Carratala J, Fernandez-Sabe N, et al (2004) Causes and factors associated with early failure in hospitalized patients with community-acquired pneumonia. Arch Intern Med 164:502–508PubMedCrossRefGoogle Scholar
  9. 9.
    Menendez R, Torres A, Zalacaín R, et al (2004) Risk factors of treatment failure in community acquired pneumonia: implications for disease outcome. Thorax 59: 960–965PubMedCrossRefGoogle Scholar
  10. 10.
    Lujan M, Gallego M, Fontanals D, et al (2004) Prospective observational study of bacteremic pneumococcal pneumonia: Effect of discordant therapy on mortality. Crit Care Med 32:625–631PubMedCrossRefGoogle Scholar
  11. 11.
    Musher DM, Rueda-Jaimes AM, Graviss EA, Rodriguez-Barradas MC (2006) Effect of pneumococcal vaccination: a comparison of vaccination rates in patients with bacteremic and nonbacteremic pneumococcal pneumonia. Clin Infect Dis 43:1004–1008PubMedCrossRefGoogle Scholar
  12. 12.
    Vila-Corcoles A, Ochoa-Gondar O, Hospital I, et al (2006) Protective effects of the 23-valent pneumococcal polysaccharide vaccine in the elderly population: the EVAN-65 study. Clin Infect Dis 43:860–868PubMedCrossRefGoogle Scholar
  13. 13.
    De Schutter I, Malfroot A, Pierard D, Lauwers S (2006) Pneumococcal serogroups and sero-types in severe pneumococcal pneumonia in Belgian children: theoretical coverage of the 7-valent and 9-valent pneumococcal conjugate vaccines. Pediatr Pulmonol 41:765–770PubMedCrossRefGoogle Scholar
  14. 14.
    Bone RC (1996) Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med 24:1125–1128PubMedCrossRefGoogle Scholar
  15. 15.
    Roy S, Knox K, Segal S, et al (2002) MBL genotype and risk of invasive pneumococcal disease: a case-control study. Lancet 359:1569–1573PubMedCrossRefGoogle Scholar
  16. 16.
    Fidler KJ, Wilson P, Davies JC, et al (2004) Increased incidence and severity of the systemic inflammatory response syndrome in patients deficient in mannose binding lectin. Intensive Care Med 30:1438–1445PubMedCrossRefGoogle Scholar
  17. 17.
    Kadioglu A, Andrew PA (2004) The innate response to pneumococcal lung infection: the untold story. Trends Immunol 25:143–149PubMedCrossRefGoogle Scholar
  18. 18.
    Currie AJ, Davidson DJ, Reid GS, et al (2004) Primary immunodeficiency to pneumococcal infection due to a defect in Toll-like receptor signaling. J Pediatr 144:512–518PubMedCrossRefGoogle Scholar
  19. 19.
    Quasney M, Waterer GW, Dahmer MK, et al (2004) Association between surfactant protein B+1580 polymorphism and the risk of respiratory failure in adults with community-acquired pneumonia. Crit Care Med 32:1115–1119PubMedCrossRefGoogle Scholar
  20. 20.
    Mira JP, Cariou A, Grall F, et al (1999) Association of TNF2, a TNFalpha promoter polymorphysm, with septic shock susceptibility and mortality: a multicenter study. JAMA 282: 561–568PubMedCrossRefGoogle Scholar
  21. 21.
    Waterer GW, Quasney MW, Cantor RM, Wunderink RG (2001) Septic shock and respiratory failure in community-acquired pneumonia have different TNF polymorphism associations Am J Respir Crit Care Med 163:1599–1604PubMedGoogle Scholar
  22. 22.
    Waterer, GW, ElBahlawan L, Quasney MW, et al (2003) Heat shock protein 70−2+1267 AA homozygotes have an increased risk of septic shock in adults with community-acquired pneumonia. Crit Care Med 31:1367–1372PubMedCrossRefGoogle Scholar
  23. 23.
    Temple SE, Lim E, Cheong KY (2003) Alleles carried at positions −819 and −592 of the IL10 promoter affect transcription following stimulation of peripheral blood cells with Streptococcus pneumoniae. Immunogenetics. 55:629–632PubMedCrossRefGoogle Scholar
  24. 24.
    Schaaf B, Boehmke F, Esnaashari H, et al (2003) Pneumococcal septic shock is associated with the interleukin-10-1082 gene promoter polymorphism. Am J Respir Crit Care Med 168:476–480PubMedCrossRefGoogle Scholar
  25. 25.
    Avery OT, Dubos R (1931) The protective action of a specific enzyme against type III pneu-mococcus infection in mice. J Exp Med 54:73–89CrossRefPubMedGoogle Scholar
  26. 26.
    Brueggemann AB, Griffiths DT, Meats E, Peto T, Crook DW, Spratt BG (2003) Clonal relationships between invasive and carriage Streptococcus pneumoniae and serotype and clone-specific differences in invasive potential. J Infect Dis 187:1424–1432PubMedCrossRefGoogle Scholar
  27. 27.
    Henriques B, Kalin M, Ortqvist A, et al (2000) Molecular epidemiology of Streptococcus pneumoniae causing invasive disease in 5 countries. J Infect Dis 182: 833–839PubMedCrossRefGoogle Scholar
  28. 28.
    Sjostrom K, Spindler C, Ortquist A, et al (2006) Clonal and capsular types decide whether pneumococci will act as a primary or opportunistic pathogen. Clin infect Dis 42:451–459PubMedCrossRefGoogle Scholar
  29. 29.
    Berry AM, Paton JC (2000) Additive attenuation of virulence of Streptococcus pneumoniae by mutation of the genes encoding pneumolysin and other putative pneumococcal virulence proteins. Infect Immun 68:133–140PubMedGoogle Scholar
  30. 30.
    Houldsworth SP, Andrew W, Mitchell TJ (1994) Pneumolysin stimulates production of tumor necrosis factor alpha and interleukin 1-beta by human mononuclear phagocytes. Infect Immunol 62:1501–1503Google Scholar
  31. 31.
    Rubins, JB, Janoff EN (1998) Pneumolysin: a multifunctional pneumococcal virulence factor. J Lab Clin Med 131:21–27PubMedCrossRefGoogle Scholar
  32. 32.
    Rayner CFJ, Jackson AD, Rutman A (1995) Interaction of pneumolysin-sufficient and-deficient isogenic variants of Streptococcus pneumoniae with human respiratory mucosa. Infect Immun 63:422–427Google Scholar
  33. 33.
    Witzenrath M, Gutbier B, Hocke AC, et al (2006) Role of pneumolysin for the development of acute lung injury in pneumococcal pneumonia. Crit Care Med 34:1947–1954PubMedCrossRefGoogle Scholar
  34. 34.
    Crain MJ, Waltmann WD Turner JS, et al (1990) Pneumococcal surface protein A is serologically highly variable and is expressed by all clinically important capsular serotypes of Streptococcus pneumoniae. Infect Immun 58:3293–3299PubMedGoogle Scholar
  35. 35.
    Hammerschmidt S, Bethe G, Remane PH, Chhatwal GS (1999) Identification of pneumococcal surface protein A as a lactoferrin-binding protein of Streptococcus pneumoniae. Infect Immun 67:1683–1687PubMedGoogle Scholar
  36. 36.
    Yother J, White JM (1994) Novel surface attachment mechanism of the Streptococcus pneumoniae protein PspA. J Bacteriol 176:2976–2985PubMedGoogle Scholar
  37. 37.
    Briles DE, Hollingshead SK, Swiatlo E, et al (1997) PspA and PspC: their potential for use as pneumococcal vaccines. Microb Drug Resist 3:401–408PubMedGoogle Scholar
  38. 38.
    Rogers HJ, Perkins HR, Ward JB (1980) Formation of cell wall polymers, In: Nombela C (ed) Microbial Cell Wall and Membranes. Chapman & Hall, Ltd., London, pp 437–460Google Scholar
  39. 39.
    Manco S, Hernon F, Yesilkaya H, et al (2006) Pneumococcal neuraminidases A and B both have essential roles during infection of the respiratory tract and sepsis. Infect Immun 74:4014–4020PubMedCrossRefGoogle Scholar
  40. 40.
    Magnusdottir AB, Hermansson A, Melhus A (2000) Experimental study of the virulence of Streptococcus pneumoniae with reduced susceptibility to penicillin. Int J Pediatr Otorhinolaryngol 55:1–9PubMedCrossRefGoogle Scholar
  41. 41.
    Aspa J, Rajas O, Rodriguez de Castro F, et al (2004) Drug-resistant pneumococcal pneumonia: clinically relevant and related factors. Clin Infect Dis 38: 787–798PubMedCrossRefGoogle Scholar
  42. 42.
    Jacobs MR, Koornhof HJ, Robins-Browne RM, et al (1978) Emergency of multiply resistant pneumococci. N Engl J Med 299:735–740PubMedCrossRefGoogle Scholar
  43. 43.
    Ewig S, Ruiz M, Torres A, et al (1999) Pneumonia acquired in the community through drug-resistant Streptococcus pneumoniae. Am J Respir Crit Care Med 159:1835–1842PubMedGoogle Scholar
  44. 44.
    Musher DM, Bartlett JG, Doern GV (2001) A fresh look at the definition of susceptibility of Streptococcus pneumoniae to beta-lactam antibiotics. Arch Intern Med 161:2538–2544PubMedCrossRefGoogle Scholar
  45. 45.
    Feikin DR, Schuchat A, Kolczak M, et al (2000) Mortality from invasive pneumococcal pneumonia in the era of antibiotic resistance, 1995–1997. Am J Public Health 90:223–229PubMedCrossRefGoogle Scholar
  46. 46.
    National Committee for Clinical Laboratory Standards (2002) Performance standards for antimicrobial susceptibility testing. Twelfth informational supplement. Document M100-S12. National Committee for Clinical Laboratory Standards, WayneGoogle Scholar
  47. 47.
    Yu VL, Chiou CC, Feldman C, et al (2003) An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome. Clin Infect Dis 37:230–237PubMedCrossRefGoogle Scholar
  48. 48.
    Lonks JR, Garau J, Gomez L, et al (2002) Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae. Clin Infect Dis 35:556–564PubMedCrossRefGoogle Scholar
  49. 49.
    Davidson R, Cavalcanti R, Brunton JL (2002) Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N Engl J Med 346:747–750PubMedCrossRefGoogle Scholar
  50. 50.
    Mufson MA, Stanek RJ (1999) Bacteremic pneumococcal pneumonia in one American City: a 20-year longitudinal study, 1978–1997. Am J Med 107:34S–43SPubMedCrossRefGoogle Scholar
  51. 51.
    Waterer G, Somes GW, Wunderink R (2001) Monotherapy may be suboptimal for severe bacteremic pneumococcal pneumonia. Arch Intern Med 161:1837–1842PubMedCrossRefGoogle Scholar
  52. 52.
    Martinez JA, Horcajada, JP, Almela M, et al (2003) Addition of a macrolide to a betalactam-based empirical antibiotic regimen is associated with lower in-hospital mortality for patients with bacteremic pneumococcal pneumonia. Clin Infect Dis 36:389–385PubMedCrossRefGoogle Scholar
  53. 53.
    Baddour LM, Yu VL, Klugman KP, et al (2004) Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia. Am J Respir Crit Care Med 170:440–444PubMedCrossRefGoogle Scholar
  54. 54.
    Harbarth S, Garbino J, Pugin J, et al (2005) Lack of effect of combination antibiotic therapy on mortality in patients with pneumococcal sepsis. Eur J Clin Microbiol Infect Dis 24:688–690PubMedCrossRefGoogle Scholar
  55. 55.
    Dwyer R, Ortqvist A, Aufwerber E, et al (2006) Addition of a macrolide to a ss-lactam in bacteremic pneumococcal pneumonia. Eur J Clin Microbiol Infect Dis 25:518–521PubMedCrossRefGoogle Scholar
  56. 56.
    Finch R, Schurmann D, Collins O, et al (2002) Randomized controlled trial of sequential intravenous (i.v.) and oral moxifloxacin compared with sequential i.v. and oral co-amoxiclav with or without clarithromycin in patients with community-acquired pneumonia requiring initial parenteral treatment. Antimicrob Agents Chemother 46:1746–1754PubMedCrossRefGoogle Scholar
  57. 57.
    Frank E, Liu J, Kinasewitz G, et al (2002) A multicenter, open-label, randomized comparison of levofloxacin and azithromycin plus ceftriaxone in hospitalized adults with moderate to severe community-acquired pneumonia. Clin Ther 24:1292–308PubMedCrossRefGoogle Scholar
  58. 58.
    Lujan M, Gallego M, Rello J (2006) Optimal therapy for severe pneumococcal community-acquired pneumonia. Intensive Care Med 32:971–980PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media Inc. 2007

Authors and Affiliations

  • M. Luján
    • 1
  • C. Muñoz-Almagro
    • 2
  • J. Rello
    • 3
  1. 1.Pulmonary DepartmentInstitut Universitari Parc TauliSabadellSpain
  2. 2.Microbiology DepartmentHospital Sant Joan de DeuEsplugues BarcelonaSpain
  3. 3.Department of Intensive CareJoan XXIII University HospitalTarragonaSpain

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