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Invasive pneumococcal (Streptococcus pneumoniae) infections and bacteremia

Daniel J Sexton, MD
Section Editor
John G Bartlett, MD
Deputy Editor
Sheila Bond, MD


Invasive pneumococcal disease is defined as an infection confirmed by the isolation of Streptococcus pneumoniae from a normally sterile site (eg, blood or cerebrospinal fluid but not sputum). S. pneumoniae (the pneumococcus) is an important and well-known cause of bacteremia in both immunocompetent and immunosuppressed patients. Pneumococcal bacteremia can occur as a result of pneumococcal pneumonia or in its absence. When bacteremia is present, secondary complications, such as arthritis, meningitis, and/or endocarditis, may occur.

This topic review will focus on the epidemiology, clinical manifestations, diagnosis, and treatment of pneumococcal bacteremia and selected aspects of other forms of invasive pneumococcal infections, such as meningitis, endocarditis, peritonitis, and various focal infections. The clinical features, epidemiology, and treatment of pneumococcal pneumonia and meningitis as well as vaccination against S. pneumoniae and the microbiology and pathogenesis of S. pneumoniae are discussed separately. (See "Pneumococcal pneumonia in adults" and "Pneumococcal vaccination in adults" and "Microbiology and pathogenesis of Streptococcus pneumoniae".)


The incidence of invasive pneumococcal disease in any population is affected by geographic location, time of year, serotype prevalence, age, comorbidities, and vaccination status. The highest incidence of invasive pneumococcal disease occurs in adults ≥65 years of age, in children <2 years of age, and in those with certain underlying conditions, such as HIV infection. According to the United States Active Bacterial Core surveillance (ABCs) database of the Emerging Infections Program Network, in 2010 the incidence of invasive pneumococcal disease in individuals ≥65 years of age was 36.4 cases per 100,000 population and, in infants <1 year, the incidence was 34.2 cases per 100,000 population, compared with 3.8 cases per 100,000 population in individuals between 18 and 34 years of age (table 1) [1]. However, some subgroups have markedly higher risks. For example, in adults aged 18 to 64 years of age with a hematologic malignancy, the incidence was 186 per 100,000 population and, for individuals with HIV infection, the incidence was 173 per 100,000 population in 2010 [2].

Impact of childhood vaccination — The overall incidence of invasive pneumococcal disease in the United States declined following the introduction and widespread use of the 7-valent pneumococcal conjugate vaccine (PCV7) in children, beginning in 2000 [3-9]. This reduction was due to declines in the incidence of invasive pneumococcal disease in the vaccinated population (children) and in adults presumably due to indirect effects on pneumococcal transmission via herd immunity. However, simultaneous increases in the proportion of cases of pneumococcal infections and nasopharyngeal colonization due to pneumococcal serotypes not included in the PCV7 vaccine (so-called replacement strains) were observed [4-7].

Following the introduction of PCV7, reductions in pneumococcal meningitis and hospitalizations for all-cause pneumonia were observed in both children and adults [10,11]. In a population-based study in one county in Minnesota, reductions in case-fatality and mortality rates were also observed [12]. The largest reductions in case-fatality rates were observed in adults ≥65 years of age and in patients with invasive pneumonia. Declines in invasive pneumococcal disease have also been reported in Europe. As an example, there was a substantial decline in pneumococcal meningitis among adults in the Netherlands following the introduction of pneumococcal conjugate vaccination in children [13]. However, the timing and extent of these changes vary in different countries because of differences in immunization policies and herd immunity.

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Literature review current through: Nov 2017. | This topic last updated: Mar 07, 2017.
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  1. Centers for Disease Control and Prevention. Active Bacterial Core Surveillance (ABCs) Report Emerging Infections Program Network: Streptococcus pneumoniae, 2010 (ORIG). http://www.cdc.gov/abcs/reports-findings/survreports/spneu10-orig.pdf (Accessed on March 21, 2013).
  2. Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2012; 61:816.
  3. Talbot TR, Poehling KA, Hartert TV, et al. Reduction in high rates of antibiotic-nonsusceptible invasive pneumococcal disease in tennessee after introduction of the pneumococcal conjugate vaccine. Clin Infect Dis 2004; 39:641.
  4. Centers for Disease Control and Prevention. Active Bacterial Core surveillance (ABCs). http://www.cdc.gov/abcs/index.html (Accessed on February 01, 2012).
  5. Centers for Disease Control and Prevention (CDC). Direct and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease--United States, 1998-2003. MMWR Morb Mortal Wkly Rep 2005; 54:893.
  6. Shah SS, Ratner AJ. Trends in invasive pneumococcal disease-associated hospitalizations. Clin Infect Dis 2006; 42:e1.
  7. Lexau CA, Lynfield R, Danila R, et al. Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine. JAMA 2005; 294:2043.
  8. Albrich WC, Baughman W, Schmotzer B, Farley MM. Changing characteristics of invasive pneumococcal disease in Metropolitan Atlanta, Georgia, after introduction of a 7-valent pneumococcal conjugate vaccine. Clin Infect Dis 2007; 44:1569.
  9. Pingali SC, Warren JL, Mead AM, et al. Association Between Local Pediatric Vaccination Rates and Patterns of Pneumococcal Disease in Adults. J Infect Dis 2016; 213:509.
  10. Hsu HE, Shutt KA, Moore MR, et al. Effect of pneumococcal conjugate vaccine on pneumococcal meningitis. N Engl J Med 2009; 360:244.
  11. Griffin MR, Zhu Y, Moore MR, et al. U.S. hospitalizations for pneumonia after a decade of pneumococcal vaccination. N Engl J Med 2013; 369:155.
  12. Tsigrelis C, Tleyjeh IM, Lahr BD, et al. Decreases in case-fatality and mortality rates for invasive pneumococcal disease in Olmsted County, Minnesota, during 1995-2007: a population-based study. Clin Infect Dis 2008; 47:1367.
  13. Bijlsma MW, Brouwer MC, Kasanmoentalib ES, et al. Community-acquired bacterial meningitis in adults in the Netherlands, 2006-14: a prospective cohort study. Lancet Infect Dis 2016; 16:339.
  14. Miller E, Andrews NJ, Waight PA, et al. Herd immunity and serotype replacement 4 years after seven-valent pneumococcal conjugate vaccination in England and Wales: an observational cohort study. Lancet Infect Dis 2011; 11:760.
  15. Moore MR, Link-Gelles R, Schaffner W, et al. Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance. Lancet Infect Dis 2015; 15:301.
  16. Hampton LM, Farley MM, Schaffner W, et al. Prevention of antibiotic-nonsusceptible Streptococcus pneumoniae with conjugate vaccines. J Infect Dis 2012; 205:401.
  17. Kaplan SL, Barson WJ, Lin PL, et al. Early trends for invasive pneumococcal infections in children after the introduction of the 13-valent pneumococcal conjugate vaccine. Pediatr Infect Dis J 2013; 32:203.
  18. Tomczyk S, Lynfield R, Schaffner W, et al. Prevention of Antibiotic-Nonsusceptible Invasive Pneumococcal Disease With the 13-Valent Pneumococcal Conjugate Vaccine. Clin Infect Dis 2016; 62:1119.
  19. Brueggemann AB, Peto TE, Crook DW, et al. Temporal and geographic stability of the serogroup-specific invasive disease potential of Streptococcus pneumoniae in children. J Infect Dis 2004; 190:1203.
  20. Østergaard C, Brandt C, Konradsen HB, Samuelsson S. Differences in survival, brain damage, and cerebrospinal fluid cytokine kinetics due to meningitis caused by 3 different Streptococcus pneumoniae serotypes: evaluation in humans and in 2 experimental models. J Infect Dis 2004; 190:1212.
  21. Hausdorff WP, Feikin DR, Klugman KP. Epidemiological differences among pneumococcal serotypes. Lancet Infect Dis 2005; 5:83.
  22. Alanee SR, McGee L, Jackson D, et al. Association of serotypes of Streptococcus pneumoniae with disease severity and outcome in adults: an international study. Clin Infect Dis 2007; 45:46.
  23. Garau J, Calbo E. Capsular types and predicting patient outcomes in pneumococcal bacteremia. Clin Infect Dis 2007; 45:52.
  24. Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1997; 46:1.
  25. Centers for Disease Control and Prevention (CDC). Advisory Committee on Immunization Practices. Pneumococcal vaccination for cochlear implant candidates and recipients: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2003; 52:739.
  26. Gentile JH, Sparo MD, Mercapide ME, Luna CM. Adult bacteremic pneumococcal pneumonia acquired in the community. A prospective study on 101 patients. Medicina (B Aires) 2003; 63:9.
  27. Laupland KB, Gregson DB, Zygun DA, et al. Severe bloodstream infections: a population-based assessment. Crit Care Med 2004; 32:992.
  28. Talbot TR, Hartert TV, Mitchel E, et al. Asthma as a risk factor for invasive pneumococcal disease. N Engl J Med 2005; 352:2082.
  29. Hargreaves RM, Lea JR, Griffiths H, et al. Immunological factors and risk of infection in plateau phase myeloma. J Clin Pathol 1995; 48:260.
  30. Twomey JJ. Infections complicating multiple myeloma and chronic lymphocytic leukemia. Arch Intern Med 1973; 132:562.
  31. Chi RC, Jackson LA, Neuzil KM. Characteristics and outcomes of older adults with community-acquired pneumococcal bacteremia. J Am Geriatr Soc 2006; 54:115.
  32. Romney MG, Hull MW, Gustafson R, et al. Large community outbreak of Streptococcus pneumoniae serotype 5 invasive infection in an impoverished, urban population. Clin Infect Dis 2008; 47:768.
  33. Nuorti JP, Butler JC, Farley MM, et al. Cigarette smoking and invasive pneumococcal disease. Active Bacterial Core Surveillance Team. N Engl J Med 2000; 342:681.
  34. Lipsky BA, Boyko EJ, Inui TS, Koepsell TD. Risk factors for acquiring pneumococcal infections. Arch Intern Med 1986; 146:2179.
  35. Cruickshank HC, Jefferies JM, Clarke SC. Lifestyle risk factors for invasive pneumococcal disease: a systematic review. BMJ Open 2014; 4:e005224.
  36. Kantsø B, Simonsen J, Hoffmann S, et al. Inflammatory Bowel Disease Patients Are at Increased Risk of Invasive Pneumococcal Disease: A Nationwide Danish Cohort Study 1977-2013. Am J Gastroenterol 2015; 110:1582.
  37. Shigayeva A, Rudnick W, Green K, et al. Invasive Pneumococcal Disease Among Immunocompromised Persons: Implications for Vaccination Programs. Clin Infect Dis 2016; 62:139.
  38. de St Maurice A, Schaffner W, Griffin MR, et al. Persistent Sex Disparities in Invasive Pneumococcal Diseases in the Conjugate Vaccine Era. J Infect Dis 2016; 214:792.
  39. Tuomanen EI, Austrian R, Masure HR. Pathogenesis of pneumococcal infection. N Engl J Med 1995; 332:1280.
  40. Ampofo K, Bender J, Sheng X, et al. Seasonal invasive pneumococcal disease in children: role of preceding respiratory viral infection. Pediatrics 2008; 122:229.
  41. Burgos J, Larrosa MN, Martinez A, et al. Impact of influenza season and environmental factors on the clinical presentation and outcome of invasive pneumococcal disease. Eur J Clin Microbiol Infect Dis 2015; 34:177.
  42. Talbot TR, Poehling KA, Hartert TV, et al. Seasonality of invasive pneumococcal disease: temporal relation to documented influenza and respiratory syncytial viral circulation. Am J Med 2005; 118:285.
  43. French N, Gordon SB, Mwalukomo T, et al. A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N Engl J Med 2010; 362:812.
  44. Munier AL, de Lastours V, Porcher R, et al. Risk factors for invasive pneumococcal disease in HIV-infected adults in France in the highly active antiretroviral therapy era. Int J STD AIDS 2014; 25:1022.
  45. Thornhill J, Sivaramakrishnan A, Orkin C. Pneumococcal vaccination in people living with HIV. Vaccine 2015; 33:3159.
  46. Marcus JL, Baxter R, Leyden WA, et al. Invasive Pneumococcal Disease Among HIV-Infected and HIV-Uninfected Adults in a Large Integrated Healthcare System. AIDS Patient Care STDS 2016; 30:463.
  47. McEllistrem MC, Mendelsohn AB, Pass MA, et al. Recurrent invasive pneumococcal disease in individuals with human immunodeficiency virus infection. J Infect Dis 2002; 185:1364.
  48. Schuchat A, Broome CV, Hightower A, et al. Use of surveillance for invasive pneumococcal disease to estimate the size of the immunosuppressed HIV-infected population. JAMA 1991; 265:3275.
  49. Jacobs MR, Good CE, Bajaksouzian S, Windau AR. Emergence of Streptococcus pneumoniae serotypes 19A, 6C, and 22F and serogroup 15 in Cleveland, Ohio, in relation to introduction of the protein-conjugated pneumococcal vaccine. Clin Infect Dis 2008; 47:1388.
  50. Mwenya DM, Charalambous BM, Phillips PP, et al. Impact of cotrimoxazole on carriage and antibiotic resistance of Streptococcus pneumoniae and Haemophilus influenzae in HIV-infected children in Zambia. Antimicrob Agents Chemother 2010; 54:3756.
  51. Schuchat A, Robinson K, Wenger JD, et al. Bacterial meningitis in the United States in 1995. Active Surveillance Team. N Engl J Med 1997; 337:970.
  52. Aronin SI, Peduzzi P, Quagliarello VJ. Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing. Ann Intern Med 1998; 129:862.
  53. Durand ML, Calderwood SB, Weber DJ, et al. Acute bacterial meningitis in adults. A review of 493 episodes. N Engl J Med 1993; 328:21.
  54. Fowler R. Primary peritonitis: changing aspects 1956-1970. Aust Paediatr J 1971; 7:73.
  55. AUSTRIAN R. Pneumococcal endocarditis, meningitis, and rupture of the aortic valve. AMA Arch Intern Med 1957; 99:539.
  56. Gransden WR, Eykyn SJ, Phillips I. Pneumococcal bacteraemia: 325 episodes diagnosed at St Thomas's Hospital. Br Med J (Clin Res Ed) 1985; 290:505.
  57. Aronin SI, Mukherjee SK, West JC, Cooney EL. Review of pneumococcal endocarditis in adults in the penicillin era. Clin Infect Dis 1998; 26:165.
  58. Petti CA, Ignatius Ou SH, Sexton DJ. Acute terminal ileitis associated with pneumococcal bacteremia: case report and review of pneumococcal gastrointestinal diseases. Clin Infect Dis 2002; 34:E50.
  59. Heltberg O, Korner B, Schouenborg P. Six cases of acute appendicitis with secondary peritonitis caused by Streptococcus pneumoniae. Eur J Clin Microbiol 1984; 3:141.
  60. Astagneau P, Goldstein FW, Francoual S, et al. Appendicitis due to both Streptococcus pneumoniae and Haemophilus influenzae. Eur J Clin Microbiol Infect Dis 1992; 11:559.
  61. Ross JJ, Saltzman CL, Carling P, Shapiro DS. Pneumococcal septic arthritis: review of 190 cases. Clin Infect Dis 2003; 36:319.
  62. Ryczak M, Sands M, Brown RB, Sklar JH. Pneumococcal arthritis in a prosthetic knee. A case report and review of the literature. Clin Orthop Relat Res 1987; :224.
  63. Turner DP, Weston VC, Ispahani P. Streptococcus pneumoniae spinal infection in Nottingham, United Kingdom: not a rare event. Clin Infect Dis 1999; 28:873.
  64. Grigoriadis E, Gold WL. Pyogenic brain abscess caused by Streptococcus pneumoniae: case report and review. Clin Infect Dis 1997; 25:1108.
  65. Taylor SN, Sanders CV. Unusual manifestations of invasive pneumococcal infection. Am J Med 1999; 107:12S.
  66. Musher DM, Alexandraki I, Graviss EA, et al. Bacteremic and nonbacteremic pneumococcal pneumonia. A prospective study. Medicine (Baltimore) 2000; 79:210.
  67. Ma JS, Chen PY, Mak SC, et al. Clinical outcome of invasive pneumococcal infection in children: a 10-year retrospective analysis. J Microbiol Immunol Infect 2002; 35:23.
  68. Baggett HC, Rhodes J, Dejsirilert S, et al. Pneumococcal antigen testing of blood culture broth to enhance the detection of Streptococcus pneumoniae bacteremia. Eur J Clin Microbiol Infect Dis 2012; 31:753.
  69. Petti CA, Woods CW, Reller LB. Streptococcus pneumoniae antigen test using positive blood culture bottles as an alternative method to diagnose pneumococcal bacteremia. J Clin Microbiol 2005; 43:2510.
  70. Appelbaum PC, Bhamjee A, Scragg JN, et al. Streptococcus pneumoniae resistant to penicillin and chloramphenicol. Lancet 1977; 2:995.
  71. Jacobs MR, Koornhof HJ, Robins-Browne RM, et al. Emergence of multiply resistant pneumococci. N Engl J Med 1978; 299:735.
  72. Kaplan SL, Mason EO Jr, Barson WJ, et al. Three-year multicenter surveillance of systemic pneumococcal infections in children. Pediatrics 1998; 102:538.
  73. Choi EH, Lee HJ. Clinical outcome of invasive infections by penicillin-resistant Streptococcus pneumoniae in Korean children. Clin Infect Dis 1998; 26:1346.
  74. Turett GS, Blum S, Fazal BA, et al. Penicillin resistance and other predictors of mortality in pneumococcal bacteremia in a population with high human immunodeficiency virus seroprevalence. Clin Infect Dis 1999; 29:321.
  75. Feikin DR, Schuchat A, Kolczak M, et al. Mortality from invasive pneumococcal pneumonia in the era of antibiotic resistance, 1995-1997. Am J Public Health 2000; 90:223.
  76. Yu VL, Chiou CC, Feldman C, et al. An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome. Clin Infect Dis 2003; 37:230.
  77. Hicks LA, Chien YW, Taylor TH Jr, et al. Outpatient antibiotic prescribing and nonsusceptible Streptococcus pneumoniae in the United States, 1996-2003. Clin Infect Dis 2011; 53:631.
  78. Marrie TJ, Tyrrell GJ, Garg S, Vanderkooi OG. Factors predicting mortality in invasive pneumococcal disease in adults in Alberta. Medicine (Baltimore) 2011; 90:171.
  79. Verhaegen J, Flamaing J, De Backer W, et al. Epidemiology and outcome of invasive pneumococcal disease among adults in Belgium, 2009-2011. Euro Surveill 2014; 19:14.