- Author: Claudia Antonieta Nieves Prado, MD; Chief Editor: John L Brusch, MD, FACP more...
Pneumococcal infections are caused by Streptococcus pneumoniae, a gram-positive, catalase-negative organism commonly referred to as pneumococcus. S pneumoniae is the most common cause of community-acquired pneumonia (CAP), bacterial meningitis, bacteremia, and otitis media, as well as an important cause of sinusitis, septic arthritis, osteomyelitis, peritonitis, and endocarditis. Complications of each of these diagnoses are common. See the image below. Clinical signs and symptoms and physical examination findings alone cannot distinguish S pneumoniae disease from infections caused by other pathogens.
S pneumoniae can cause a wide variety of clinical symptoms owing to its ability to cause disease by either direct extension from the nasopharynx into surrounding anatomic structures or vascular invasion with hematogenous spread. Features that should prompt the clinician to consider pneumococcal infection include the following:
High-risk age groups (children younger than 5 years, particularly aged 2 years or younger; adults older than 55-65 years)
Conditions that cause immune deficits (eg, HIV infection, malignancy, or diabetes mellitus)
Conditions associated with decreased pulmonary clearance functions (eg, asthma, chronic bronchitis, or chronic obstructive pulmonary disease [COPD])
Presentation from late fall to early spring
Conditions that may develop by direct extension of S pneumoniae from the nasopharynx include the following:
Acute exacerbations of chronic bronchitis (AECB)
Pneumonia (which may be complicated by purulent pericarditis)
Conditions that may result from vascular invasion and hematogenous spread of S pneumoniae include the following:
Bacteremia (most common manifestation of invasive pneumococcal disease)
Joint and bone infections (osteomyelitis and septic arthritis)
Soft tissue infections (eg, myositis, periorbital cellulitis, abscess)
Cardiac infections (eg, endocarditis)
See Clinical Presentation for more detail.
If a pneumococcal infection is suspected or considered, Gram stain and culture of appropriate specimens should be obtained, when possible. Potential specimens may include 1 or more of the following:
Pleural fluid or lung aspirate
Other abscess or tissue specimens
All S pneumoniae isolates, regardless of the isolation site, should be tested for susceptibility to penicillin and cefotaxime or ceftriaxone. Susceptibilities based on the type of specimen (CSF versus other) were defined by the Clinical and Laboratory Institute (CLSI) in 2008.[1, 2]
Nonspecific laboratory tests that may support the diagnosis include the following:
Complete blood count and differential
Erythrocyte sedimentation rate (ESR)
C-reactive protein (CRP)
Imaging studies that may be helpful include the following:
Ultrasonography of the chest
Computed tomography (CT) of the chest, sinuses, face, or affected bones or joints
Magnetic resonance imaging (MRI) of the brain (in meningitis) or affected bones and joints
Other modalities that may help define the extent of infection include the following:
Middle-ear fluid aspiration
Pleural fluid aspiration
Chest tube thoracostomy or catheter placement
Video-assisted thoracoscopy (VATS) or pleural decortication
Joint fluid aspiration
Biopsy of bone, soft tissue, or muscle
See Workup for more detail.
Antibiotics are the mainstay of therapy. Treatments for specific infections may include the following:
Otitis media: In most cases, amoxicillin 80-90 mg/kg/day; if there is no improvement within 48-72 hours, amoxicillin-clavulanate or a second- or third-generation oral cephalosporin (or parenteral ceftriaxone for highly resistant pneumococci)
Sinusitis: Initial recommendations as for otitis media; in adult penicillin-allergic patients and patients who do not respond to initial therapy, switching to fluoroquinolones (not approved for children in this clinical situation) may be considered
Pneumonia: For penicillin-sensitive S pneumoniae (minimum inhibitory concentration [MIC] <2 μg/mL), penicillin G or amoxicillin is considered first-line therapy; for penicillin-resistant S pneumoniae infection (MIC ≥2 μg/mL), the choice of antimicrobial agent should be directed by susceptibility testing 
Meningitis: In children, a beta-lactam (penicillin, ceftriaxone, or cefotaxime) with or without vancomycin pending susceptibility testing; children with hypersensitivity to beta-lactams should receive vancomycin plus rifampin; meropenem and chloramphenicol have also been used; for adults with penicillin-sensitive S pneumoniae infection (MIC ≤ 0.06 μg/mL), intravenous penicillin G or ampicillin is first-line therapy; for penicillin-resistant pneumococcus (MIC ≥0.12 μg/mL), treatment with a third-generation cephalosporin (if ceftriaxone or cefotaxime MIC <1 μg/mL) or a third-generation cephalosporin plus vancomycin (if cefotaxime or ceftriaxone MIC ≥1 μg/mL) is recommended
Additional treatment measures that may be helpful for particular conditions are as follows:
Complicated pneumonia: Chest tube placement for drainage of pleural fluid; in more severe cases, VATS or decortication
Suspected septic arthritis or osteomyelitis: Collection of appropriate specimens for Gram stain, cell count, histology, or culture
Recurrent or chronic otitis media, periorbital or orbital cellulitis, or facial cellulitis: Surgical intervention
Measures for preventing pneumococcal infection include the following:
Behavior modification and risk factor reduction
Antimicrobial prophylaxis (in selected patients) with recurrent otitis media.
S pneumoniae is a gram-positive, catalase-negative coccus that has remained an extremely important human bacterial pathogen since its initial recognition in the late 1800s. The term pneumococcus gained widespread use by the late 1880s, when it was recognized as the most common cause of bacterial lobar pneumonia.
Worldwide, S pneumoniae remains the most common bacterial cause of community-acquired pneumonia (CAP). However, a recent study involving state-of-the-art diagnostic techniques for bacterial, viral, and fungal infections indicated that a specific pathogen was detected in only 38% of CAP cases. Of these cases, one or more viruses were retrieved in 23% of cases and bacteria in 11%. A combination of bacterial and viral pathogens was seen in 3%. Fungal and mycobacterial organisms accounted for 1%. Human rhinoviruses were isolated in 9% of cases and influenza virus in 6%. S pneumoniae remained the most common cause of bacterial CAP, at 5% of patients.
S pneumoniae is a common cause of bacterial meningitis, bacteremia, and otitis media. S pneumoniae infection is also an important cause of sinusitis, septic arthritis, osteomyelitis, peritonitis, and endocarditis. Worldwide in 2000, 14.5 million estimated episodes of invasive pneumococcal disease were reported in children younger than 5 years, which correlates to more than 800,000 estimated deaths (11% of all deaths in this age group).
Pneumococcal vaccination, particularly routine childhood pneumococcal conjugate vaccine (PCV; introduced in the United States in 2000), has led to decreased rates of invasive pneumococcal infections (>90%) caused by pneumococcal serotypes covered by the vaccine, as well as overall decreased rates of invasive disease (45% overall; 75% in children < 5 years). In addition, herd immunity has led to decreased rates of disease in older children and adults.[6, 7, 8]
Surveillance data following introduction and widespread uptake of 7-valent PCV (PCV7) immunization showed an astounding reduction in invasive disease of 100% in children younger than 5 years in the United States (94% in all ages) when considering disease caused by serotypes contained in PCV7.
Many subsequent studies have shown increased rates of invasive and noninvasive disease caused by serotypes not covered by the vaccine, including serotypes 15, 19A, and 33F. An analysis of over 700 cases of invasive disease in completely immunized children (PCV7) showed that 96% were due to nonvaccine serotypes. An additional 6 serotypes accounted for almost two thirds of invasive infections in this age group.
An analysis of 653 invasive pneumococcal infections in the Spanish population before and after the implementation of PCV7 immunization showed an increased incidence of invasive disease in the postvaccine period, which was primarily due to nonvaccine serotypes and was associated with higher rates of complications, such as septic shock. Similar studies in the United States and other European countries have shown similar results, introducing the concept of replacement disease and its effects.
Serotype 19A has received the most attention, not only because of increased disease rates associated with this serotype, but also owing to its association with increased drug resistance. Increased rates of invasive disease with such serotypes caused the overall rates of invasive disease to remain somewhat steady starting in 2002, although these rates remain greatly reduced from rates prior to introduction of the conjugate vaccine.
For these reasons, work on the development of a vaccine containing additional serotypes continued. A 13-valent PCV (PCV13) was approved by the US Food and Drug Administration (FDA) on February 24, 2010 with the hope that its induced T-cell–dependent immune response would have increased efficacy in children and elderly persons. This potential benefit has yet to be demonstrated in elderly individuals.[6, 9, 10, 11, 12, 13, 14, 15, 8, 16, 17, 18, 5, 19, 20]
The 23-valent polysaccharide vaccine is more effective in decreasing pneumococcal bacteremia than pneumonia. As a result, mortality rates have decreased. Ongoing surveillance will help determine the effects of widespread routine immunization with PCV13 and its expanded serotype coverage on pneumococcal disease in children and adults.
In January 2013, the FDA approved PCV13 for the prevention of invasive pneumococcal disease in children and adolescents between 6 and 17 years of age. In February 2013, the CDC's Advisory Committee on Immunization Practices (ACIP) voted for the use of the vaccine in children with immunodeficiencies. The panel recommends routine use of a single dose of PCV13 for children aged 6-18 years who have an immunocompromising condition (eg, sickle cell disease or HIV infection) and have not previously received the vaccine.
Despite an overall decreased incidence of otitis media caused by serotypes covered by vaccination since the introduction of the conjugate pneumococcal vaccine, an increase in rates of disease caused by serotypes not covered by the vaccine has occurred, as well as an increase in rates of diseases caused by vaccine-covered serotypes in incompletely immunized children. The incidence of otitis media caused by serotype 19F has remained steady. Overall health care utilization for otitis media has decreased, as has the incidence of recurrent otitis media in some populations and studies.[7, 23, 24, 25]
The capsule is composed of polysaccharides that cover the cell wall, which is made up of peptidoglycan and teichoic acid, characterizing the classic gram positive structure; It acts as the principal antiphagocytic and protective element that prevents access of the leukocytes to the underlying cell wall elements. The capsular polysaccharides have served as means of serotyping and identifying these organisms. The Quellung reaction is the criterion standard method for pneumococcal capsular serotyping. More than 9 serotypes of S pneumoniae have been identified; currently, serotypes 6, 14, 18, 19, and 23 are the most prevalent agents that cause infections. Serotyping provides important epidemiological information, especially with the widespread use of vaccination, but rarely provides timely clinical information.
The virulence of each organism is determined in part by two distinct states: opaque and transparent colony types that influence the capacity to evade host defenses. The nasopharynx is predominantly colonized by the transparent phenotype. Conversely, the opaque type predominates in lung, CNS, and bloodstream infections; it has increased capsular polysaccharide and produces more biofilm. In addition, in vitro and in vivo studies of clinical isolates have shown that pneumococci have the ability to obtain DNA from other pneumococci (or other bacteria) via transformation, allowing them to switch to serotypically distinct capsular type.
Adherence and Invasion
S pneumoniae is an extracellular bacterial pathogen that can adhere avidly to the respiratory epithelium and mucus. It exhibits different surface proteins that recognize and attach to human cells. Pneumococcal surface protein C (PspC) binds to the poly-Ig receptor on epithelial cells, pneumococcal surface antigen A (PsaA) binds to E-cadherin on epithelial cells, pneumococcal adhesion and virulence factor A (PavA) binds to fibronectin, and enolase (Eno) binds to plasminogen that may bridge binding to host cells. Phospho-cholines interact with the receptor for platelet-activating on activated epithelial cells. Capsule, pneumolysin, and the ABC transporter Ami have also been implicated in adherence. S pneumoniae produces biofilm after binding to host cells. Biofilm production is regulated by external factors, such as temperature.
Invasion is promoted by phospho-cholines. After interacting with the PAF receptor, it is inserted into the host cell via endocytosis, causing translocation of bacteria through the endothelium. This is particularly important for translocation over the blood-brain barrier during meningitis development. Bacteria surface coat is changed via gene expression to avoid host defenses and complete translocation. Invasion is also mediated by adhesins and pneumolysin; pneumolysin is a cytotoxin that induces apoptosis of epithelial cells by membrane pore formation, resulting in access to subendothelium. Intraalveolar replication of pneumococci, penetration into the interstitium, and dissemination into the bloodstream are among other functions of pneumolysin.
Much of the clinical severity of pneumococcal disease results from the activation of the complement pathways and cytokine release, which induce a significant inflammatory response. S pneumoniae cell wall components, along with the pneumococcal capsule, activate the alternative complement pathway; antibodies to the cell wall polysaccharides activate the classic complement pathway. Cell wall proteins, autolysin, and DNA released from bacterial breakdown all contribute to the production of cytokines, inducing further inflammation.
S pneumoniae remains an important pathogen in large part because of its ability to first colonize the nasopharynx efficiently. Studies performed in the United States prior to universal vaccination recommendations have shown average carriage rates of 40%-50% in healthy children and 20%-30% in healthy adults. Factors such as age, daycare attendance, composition of household, immune status, antibiotic use, and others obviously affect these numbers.[29, 30, 31] With the implementation of childhood vaccination with the heptavalent conjugate vaccine for S pneumoniae, the colonization rates have decreased in children receiving the vaccine and in adults and other children in their household because of the phenomenon of herd immunity.
Most individuals who are colonized with S pneumoniae carry only a single serotype at any given time; the duration of colonization varies and depends on specific serotype and host characteristics. Invasive disease is usually related to recent acquisition of a new serotype. However, in most healthy hosts, colonization is not associated with symptoms or disease but allows for the continued presence of S pneumoniae within the population, allowing for prolonged low-level transmission among contacts.
S pneumoniae infection is the most common cause of CAP, bacterial meningitis, bacteremia, and otitis media in the United States. There is a clear seasonality, with infections peaking in the fall and winter months.
Pneumococcal colonization allows for spread of organisms into the adjacent paranasal sinuses, middle ear, and/or tracheobronchial tree down to the lower respiratory tract. This spread results in specific clinical syndromes (sinusitis, otitis media, bronchitis, pneumonia) related to the noninvasive spread of the organisms.
Worldwide, the most common cause of death due to pneumococcal disease is pneumonia. In adults admitted to the hospital in the United States for pneumonia treatment, S pneumoniae remains the most common organism isolated. Until 2000, 100,000-135,000 patients were hospitalized for pneumonia proven to be caused by S pneumoniae infection in the United States annually. These numbers are likely a gross underestimate, as a definite cause is not determined in most cases of pneumonia treated each year. In addition, the actual rates are also likely decreasing owing to implementation of pneumococcal conjugate vaccination.
S pneumoniae infection is an important cause of bacterial co-infection in patients with influenza and can increase the morbidity and mortality in these patients. This has been emphasized recently by the increased number of cases of invasive pneumococcal disease seen in association with increased rates of hospitalizations for influenza during the 2009 H1N1 influenza A pandemic. Postmortem lung specimens from patients who died of H1N1 influenza A from May to August of 2009 were examined for evidence of concomitant bacterial infection. Twenty-nine percent of the specimens showed evidence of bacterial co-infection, with almost half of these being S pneumoniae.
S pneumoniae infection is estimated to cause over 6-7 million cases of otitis media annually in the United States. These numbers have likely decreased somewhat with the advent of universal vaccinations; however, S pneumoniae infection remains the most common cause of otitis media.[36, 31]
Statistics regarding invasive pneumococcal disease in the United States are based on active surveillance using the Centers for Disease Control and Prevention (CDC) Active Bacterial Core Surveillance (ABC) system. Calculations for 2010 estimated 39,750 (12.9 cases per 100,000 population) cases of invasive disease nationally, with 4,000 (1.3 cases per 100,000 population) estimated deaths. (Comparable 2008 data showed 44,000 (14.5 cases per 100,000 population) episodes of invasive disease with 4,500 (1.5 cases per 100,000 population) deaths.
Children younger than 5 years and adults older than 65 years are 2 identified age groups in whom rates of disease and death are increased. In 2010, rates of pneumococcal invasive disease in these groups were estimated to be 19 per 100,000 population and 36 per 100,000 population, respectively. This compares with rates of 20.2 and 40.4 in 2008, 21.8 and 39.2 in 2007, and 23.2 and 43.3 in 2002, respectively. More than half of deaths due to invasive pneumococcal disease occur in adults with specific risk factors (age, immunosuppression) for severe disease. Such risk factors are an indication for vaccination.[6, 37]
Despite the worldwide importance of disease due to S pneumoniae infection, very little information is available on the extent of pneumococcal disease in developing countries. A review of the available literature does show an increase in reports of incidence, prevalence, complications, and vaccine effects in many areas of Europe, Asia, and Australia.
In developing countries, pneumococcus remains the most common and important disease-causing organism in infants. Although exact numbers are difficult to obtain, it is estimated that pneumococcal infections are responsible for more than one million of the 2.6 million annual deaths due to acute respiratory infection in children younger than 5 years. Case fatality rates associated with invasive disease vary widely but can approach and surpass 50% and are greatest in patients with meningitis; one quarter to more than one half of those who survive develop long-term sequelae of infection.[36, 38]
Estimates of pneumococcal disease in Gambian children show high rates of infection in the first year of life (≥500 per 100,000 children). Latin American studies also show a particularly high risk in infants younger than 6 months, and children in southern India have higher rates of colonization at younger ages compared with US children, according to US clinical studies. Some particular populations, such as indigenous Australians and minority Israeli persons, also have disproportionately higher rates of disease, similar to the native Alaskan and native Indian populations in the United States, although determining the role of socioeconomic factors in the higher incidence of disease in these populations is difficult.
In Europe, children younger than 2 years constitute the population most at risk for pneumococcal infection, with rates decreasing with age. The overall incidence of invasive disease is estimated to be somewhat lower in Europe (14 per 100,000 persons in Germany vs 35.8 per 100,000 persons in England vs 45.3 per 100,000 persons in Finland vs 90 per 100,000 persons in Spain vs 235 per 100,000 persons in the United States), although many have postulated that this may be due in part to the more liberal blood-culture collection practices in the American health care system.[39, 36]
Even fewer data are available on the worldwide incidence of pneumococcal disease in adults. As in the United States, the most common cause of CAP in Europe is S pneumoniae infection, affecting approximately 100 per 100,000 adults each year. Overall rates of febrile bacteremia and meningitis are also similar, (15–19 per 100,000 adults and 1–2 per 100,000 adults, respectively), with the risk for these diseases increased in elderly and infant populations.
Because no population-based data on pneumococcal disease in adults in developing countries are available, estimates of disease burden are based on small clinical studies, vaccine trials, extrapolation from data in developed countries, and studies of persons at high risk for disease. The information gleaned from these sources suggests that the incidence of and mortality rates associated with pneumococcal disease are high, with HIV-positive populations exhibiting particularly high rates of infection. Further studies are greatly needed.[41, 36]
Although exact rates are difficult to determine, the World Health Organization (WHO) estimates that, worldwide, 1.6 million deaths were caused by pneumococcal disease in 2005, with 700,000 to 1 million of these occurring in children younger than 5 years. Even in patients in developed countries, invasive pneumococcal disease carries a high mortality rate—an average of 10-20% in adults with pneumococcal pneumonia, with much higher rates in those with risk factors for disease.[43, 44]
In the United States, invasive pneumococcal disease is more common in native Alaskans, Navajo and Apache Indians, and African Americans than in other ethnic groups. Some studies have shown this difference persists even when the results are controlled for socioeconomic factors, and the reasons for this discrepancy among certain populations are unclear.
Most clinical studies of pneumococcal disease show a slight male predilection for disease; the reason for this is unclear.
Children younger than 2 years carry the highest burden of S pneumoniae disease worldwide. In developed countries, the incidence is highest in those aged 6 months to 1 year, while, in developing countries, the disease is particularly common in children younger than 6 months.
Adults older than 55-65 years are the next most commonly affected age group worldwide.
Immunosuppressed persons of any age are at a higher risk for pneumococcal disease.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: 18th Informational Supplement. 2008.
Centers for Disease Control and Prevention. Effects of new penicillin susceptibility breakpoints for Streptococcus pneumoniae- United States, 2006-2007. 2008. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5750a2.htm.
[Guideline] 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 Mar 1. 44 Suppl 2:S27-72. [Medline].
Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015 Jul 30. 373 (5):415-27. [Medline].
O'Brien KL, Wolfson LJ, Watt JP, et al. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet. 2009 Sep 12. 374(9693):893-902. [Medline].
Active Bacterial Core Surveillance (ABCs) Report; Emerging Infections Program Network; Streptococcus pneumoniae. 2010;
Committee on Infectious Diseases; American Academy of Pediatrics. Pneumococcal Infections. Pickering LK, Baker CJ, Long SS, McMillan JA. Red Book 2009 Report of the Committee on Infectious Diseases. 28th. American Academy of Pediatrics; 2009. 525-335.
Centers for Disease Control and Prevention (CDC). Invasive pneumococcal disease in children 5 years after conjugate vaccine introduction--eight states, 1998-2005. MMWR Morb Mortal Wkly Rep. 2008 Feb 15. 57(6):144-8. [Medline]. [Full Text].
Hsu KK, Shea KM, Stevenson AE, Pelton SI,. Changing Serotypes Causing Childhood Invasive Pneumococcal Disease: Massachusetts, 2001-2007. Pediatr Infect Dis J. 2009 Nov 21. [Medline].
Singleton RJ, Hennessy TW, Bulkow LR, Hammitt LL, Zulz T, Hurlburt DA. Invasive pneumococcal disease caused by nonvaccine serotypes among alaska native children with high levels of 7-valent pneumococcal conjugate vaccine coverage. JAMA. 2007 Apr 25. 297(16):1784-92. [Medline].
Ongkasuwan J, Valdez TA, Hulten KG, Mason EO Jr, Kaplan SL. Pneumococcal mastoiditis in children and the emergence of multidrug-resistant serotype 19A isolates. Pediatrics. 2008 Jul. 122(1):34-9. [Medline]. [Full Text].
Eiland LS. Increasing Prevalence of Pneumococcal Serotype 19A Among US Children. Journal of Pharmacy Practice. 2008. 21(5):356-62.
Singleton RJ, Hennessy TW, Bulkow LR, Hammitt LL, Zulz T, Hurlburt DA, et al. Invasive pneumococcal disease caused by nonvaccine serotypes among alaska native children with high levels of 7-valent pneumococcal conjugate vaccine coverage. JAMA. 2007 Apr 25. 297(16):1784-92. [Medline].
McNeil JC, Hulten KG, Mason EO Jr, Kaplan SL. Serotype 19A is the Most Common Streptococcus pneumoniae Isolate in Children With Chronic Sinusitis. Pediatr Infect Dis J. 2009 Sep. 28(9):766-8. [Medline].
Pilishvili T, Lexau C, Farley MM, Hadler J, Harrison LH, Bennett NM, et al. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis. 201(1). 2010 Jan 1:32-41. [Medline].
Centers for Disease Control and Prevention (CDC). Invasive pneumococcal disease in young children before licensure of 13-valent pneumococcal conjugate vaccine - United States, 2007. MMWR Morb Mortal Wkly Rep. 2010 Mar 12. 59(9):253-7. [Medline]. [Full Text].
Centers for Disease Control and Prevention (CDC). Licensure of a 13-valent pneumococcal conjugate vaccine (PCV13) and recommendations for use among children - Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Morb Mortal Wkly Rep. 2010 Mar 12. 59(9):258-61. [Medline]. [Full Text].
American Academy of Pediatrics, Committee on Infectious Diseases. Recommendations for the Prevention of Streptococcus pneumoniae Infections in Infants and Children: Use of 13-Valent Pneumococcal Conjugate Vaccine (PCV13) and Pneumococcal Polysaccharide Vaccine (PPSV23). Pediatrics. July 1, 2010. 126:186 -190. [Full Text].
Burgos J, Falcó V, Borrego A, Sordé R, et al. Impact of the emergence of non-vaccine pneumococcal serotypes on the clinical presentation and outcome of adults with invasive pneumococcal pneumonia. Clin Microbiol Infect. 2012 Apr 16. [Medline].
Gubbins PO, Li C. The Influence of Influenza and Pneumococcal Vaccines on Community-Acquired Pneumonia (CAP) Outcomes Among Elderly Patients. Curr Infect Dis Rep. 2015 Dec. 17 (12):49. [Medline].
Hede K. FDA extends pneumococcal vaccine use to older children. Medscape Medical News. January 29, 2013. Available at http://www.medscape.com/viewarticle/778454. Accessed: February 11, 2013.
Tucker ME. CDC Panel Endorses PCV13 Use in Immunocompromised Children. Available at http://www.medscape.com/viewarticle/779664. Accessed: February 28, 2013.
McEllistrem MC, Adams JM, Patel K, Mendelsohn AB, Kaplan SL, Bradley JS, et al. Acute otitis media due to penicillin-nonsusceptible Streptococcus pneumoniae before and after the introduction of the pneumococcal conjugate vaccine. Clin Infect Dis. 2005 Jun 15. 40(12):1738-44. [Medline]. [Full Text].
Poehling KA, Szilagyi PG, Grijalva CG, Martin SW, LaFleur B, Mitchel E, et al. Reduction of frequent otitis media and pressure-equalizing tube insertions in children after introduction of pneumococcal conjugate vaccine. Pediatrics. 2007 Apr. 119(4):707-15. [Medline].
Poehling KA, Lafleur BJ, Szilagyi PG, Edwards KM, Mitchel E, Barth R, et al. Population-based impact of pneumococcal conjugate vaccine in young children. Pediatrics. 2004 Sep. 114(3):755-61. [Medline].
Henriques-Normark B, Tuomanen EI. The pneumococcus: epidemiology, microbiology, and pathogenesis. Cold Spring Harb Perspect Med. 2013 Jul 1. 3 (7):[Medline].
Kadioglu A, Weiser JN, Paton JC, Andrew PW. The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease. Nat Rev Microbiol. 2008 Apr. 6 (4):288-301. [Medline].
Rubins JB, Charboneau D, Paton JC, Mitchell TJ, Andrew PW, Janoff EN. Dual function of pneumolysin in the early pathogenesis of murine pneumococcal pneumonia. J Clin Invest. 1995 Jan. 95 (1):142-50. [Medline]. [Full Text].
Ghaffar F, Friedland IR, McCracken GH Jr. Dynamics of nasopharyngeal colonization by Streptococcus pneumoniae. Pediatr Infect Dis J. 1999 Jul. 18(7):638-46. [Medline].
Dagan R, Greenberg D, Jacobs MR. Pneumococcal Infections. Feigin RD, Cherry JD, Demmler GJ, Kaplan SL. Textbook of Pediatric Infectious Diseases. 5th. Philadelphia, Pennsylvania: Saunders (Elsevier Science); 2004. 1: 1204-1258/90.
Musher DM. Streptococcus pneumoniae. Mandell GL, Bennett JE, Dolin R. Principles and Practice of Infectious Diseases. 6th. Philadelphia, Pennsylvania: Elsevier, Churchill Livingstone; 2005. 2: 197.
Lynch JP 3rd, Zhanel GG. Streptococcus pneumoniae: epidemiology and risk factors, evolution of antimicrobial resistance, and impact of vaccines. Curr Opin Pulm Med. 2010 May. 16(3):217-25. [Medline].
CDC. Streptococcus pneumoniae Disease. CDC.gov. Available at http://www.cdc.gov/ncidod/dbmd/diseaseinfo/streppneum_t.htm. Accessed: December 5, 2009.
CDC. 2009 H1N1 Pandemic Update: Pneumococcal Vaccination Recommended to Help Prevent Secondary Infections. CDC. November 16, 2009. Available at http://www.cdc.gov/H1N1flu/HAN/111609.htm.
Centers for Disease Control and Prevention (CDC). Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1) - United States, May-August 2009. MMWR Morb Mortal Wkly Rep. 2009 Oct 2. 58(38):1071-4. [Medline]. [Full Text].
WHO Initiative for Vaccine Research Division. Acute Respiratory Infections, Streptococcus pneumoniae. World Health Organization (WHO). [Full Text].
National Center for Immunization and Respiratory Diseases / Division of Bacterial Diseases. ABCs Report: Streptococcus pneumoniae, PROVISIONAL 2008Active Bacterial Core Surveillance (ABCs): Emerging Infections Program Network. CDC. 1 September 2009. Available at http://www.cdc.gov/abcs/survreports/spneu08.htm.
Goetghebuer T, West TE, Wermenbol V, Cadbury AL, Milligan P, Lloyd-Evans N, et al. Outcome of meningitis caused by Streptococcus pneumoniae and Haemophilus influenzae type b in children in The Gambia. Trop Med Int Health. 2000 Mar. 5(3):207-13. [Medline]. [Full Text].
Eskola J, Black S, Shinefield H. Pneumococcal conjugate vaccines. Plotkin SA, Orenstein WA, eds. Vaccines. 4th ed. Philadelphia, PA: Elsevier Inc; 2004. 23.
Scott JA. The preventable burden of pneumococcal disease in the developing world. Vaccine. 2007 Mar 22. 25(13):2398-405. [Medline].
Fedson DS, Scott JA. The burden of pneumococcal disease among adults in developed and developing countries: what is and is not known. Vaccine. 1999 Jul 30. 17 Suppl 1:S11-8. [Medline].
World Health Organization. Weekly Epidemiological Record. March/2007. Available at http://www.who.int/wer.
WHO.INT; Immunization, Vaccines and Biologicals Division. Pneumococcal Vaccines. WHO.INT. Available at http://www.who.int/vaccines/en/pneumococcus.shtml. Accessed: April 2003.
Rudan I, Campbell H. The deadly toll of S pneumoniae and H influenzae type b. Lancet. 2009 Sep 12. 374(9693):854-6. [Medline].
[Guideline] Brunton S, Carmichael BP, Colgan R, Feeney AS, Fendrick AM, Quintiliani R, et al. Acute exacerbation of chronic bronchitis: a primary care consensus guideline. Am J Manag Care. 2004 Oct. 10(10):689-96. [Medline].
Peter G, Klein JO. Streptococcus pneumoniae. Long SS, Pickering LK, Prober CG, eds. Principles and Practices of Pediatric Infectious Diseases. 2nd ed. Philadelphia, PA: Churchill Livingstone (Elsevier); 2002. 739-746/131.
Worsoe L, Caye-Thomasen P, Brandt CT, Thomsen J, Ostergaard C. Factors associated with the occurrence of hearing loss after pneumococcal meningitis. Clin Infect Dis. 2010 Oct 15. 51(8):917-24. [Medline].
Stoll ML, Rubin LG. Incidence of occult bacteremia among highly febrile young children in the era of the pneumococcal conjugate vaccine: a study from a Children's Hospital Emergency Department and Urgent Care Center. Arch Pediatr Adolesc Med. 2004 Jul. 158(7):671-5. [Medline]. [Full Text].
Bradley JS, Kaplan SL, Tan TQ, Barson WJ, Arditi M, Schutze GE, et al. Pediatric pneumococcal bone and joint infections. The Pediatric Multicenter Pneumococcal Surveillance Study Group (PMPSSG). Pediatrics. 1998 Dec. 102(6):1376-82. [Medline].
American Academy of Pediatrics Subcommittee on Management of Acute Otitis Media. Clinical Practice Guideline: Diagnosis and management of acute otitis media. Pediatrics. 2004 May. 113(5):1451-65. [Medline]. [Full Text].
Anevlavis S, Petroglou N, Tzavaras A, Maltezos E, Pneumatikos I, Froudarakis M, et al. A prospective study of the diagnostic utility of sputum Gram stain in pneumonia. J Infect. 2009 Aug. 59(2):83-9. [Medline].
Casado Flores J, Nieto Moro M, Berrón S, Jiménez R, Casal J. Usefulness of pneumococcal antigen detection in pleural effusion for the rapid diagnosis of infection by Streptococcus pneumoniae. Eur J Pediatr. 2010 May. 169(5):581-4. [Medline].
Chavez MA, Shams N, Ellington LE, Naithani N, Gilman RH, Steinhoff MC, et al. Lung ultrasound for the diagnosis of pneumonia in adults: a systematic review and meta-analysis. Respir Res. 2014 Apr 23. 15:50. [Medline]. [Full Text].
Cunha BA. Pneumonia Essentials. 2nd ed. Sudbury, MA: Jones & Bartlett, Publishers; 2010.
Fung HB, Monteagudo-Chu MO. Community-acquired pneumonia in the elderly. Am J Geriatr Pharmacother. 2010 Feb. 8(1):47-62. [Medline].
Johnstone J. Review: pneumococcal vaccination is not effective for preventing pneumonia, bacteraemia, bronchitis, or mortality. Evid Based Med. 2009 Aug. 14(4):109. [Medline].
Johnstone J, Eurich DT, Minhas JK, Marrie TJ, Majumdar SR. Impact of the pneumococcal vaccine on long-term morbidity and mortality of adults at high risk for pneumonia. Clin Infect Dis. 2010 Jul 1. 51(1):15-22. [Medline].
Luján M, Gallego M, Belmonte Y, Fontanals D, Vallès J, Lisboa T, et al. Influence of pneumococcal serotype group on outcome in adults with bacteremic pneumonia. Eur Respir J. 2010 Feb 11. [Medline].
Donowitz GR, Mandell GL. Acute pneumonia. Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 5th ed. Philadelphia, Pa: Churchill Livingstone; 2000. 717-43.
Madeddu G, Fois AG, Pirina P, Mura MS. Pneumococcal pneumonia: clinical features, diagnosis and management in HIV-infected and HIV noninfected patients. Curr Opin Pulm Med. 2009 May. 15(3):236-42. [Medline].
Austrian R. Pneumococcal pneumonia. Diagnostic, epidemiologic, therapeutic and prophylactic considerations. 1986. Chest. 2009 Nov. 136(5 Suppl):e30. [Medline].
Clifford V, Tebruegge M, Vandeleur M, Curtis N. Question 3: can pneumonia caused by penicillin-resistant Streptococcus pneumoniae be treated with penicillin?. Arch Dis Child. 2010 Jan. 95(1):73-7. [Medline].
Cunha BA. Clinical relevance of penicillin-resistant Streptococcus pneumoniae. Semin Respir Infect. 2002 Sep. 17(3):204-14. [Medline].
Garnacho-Montero J, García-Cabrera E, Diaz-Martín A, Lepe-Jiménez JA, Iraurgi-Arcarazo P, Jiménez-Alvarez R, et al. Determinants of outcome in patients with bacteraemic pneumococcal pneumonia: importance of early adequate treatment. Scand J Infect Dis. 2010 Mar. 42(3):185-92. [Medline].
van der Poll T, Opal SM. Pathogenesis, treatment, and prevention of pneumococcal pneumonia. Lancet. 2009 Oct 31. 374(9700):1543-56. [Medline].
van de Beek D, de Gans J, McIntyre P, Prasad K. Steroids in adults with acute bacterial meningitis: a systematic review. Lancet Infect Dis. 2004 Mar. 4(3):139-43. [Medline].
Karlowsky JA, Thornsberry C, Jones ME, Evangelista AT, Critchley IA, Sahm DF. Factors associated with relative rates of antimicrobial resistance among Streptococcus pneumoniae in the United States: results from the TRUST Surveillance Program (1998-2002). Clin Infect Dis. 2003 Apr 15. 36(8):963-70. [Medline].
Whitney CG, Farley MM, Hadler J, Harrison LH, Lexau C, Reingold A, et al. Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States. N Engl J Med. 2000 Dec 28. 343(26):1917-24. [Medline].
Song JH, Jung SI, Ko KS, Kim NY, Son JS, Chang HH, et al. High prevalence of antimicrobial resistance among clinical Streptococcus pneumoniae isolates in Asia (an ANSORP study). Antimicrob Agents Chemother. 2004 Jun. 48(6):2101-7. [Medline].
Cunha BA. Effective antibiotic-resistance control strategies. Lancet. 2001 Apr 28. 357(9265):1307-8. [Medline].
Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011 Oct. 53(7):e25-76. [Medline].
Shea KW, Cunha BA, Ueno Y, Abumustafa F, Qadri SM. Doxycycline activity against Streptococcus pneumoniae. Chest. 1995 Dec. 108(6):1775-6. [Medline].
Postma DF, van Werkhoven CH, van Elden LJ, Thijsen SF, Hoepelman AI, Kluytmans JA, et al. Antibiotic treatment strategies for community-acquired pneumonia in adults. N Engl J Med. 2015 Apr 2. 372 (14):1312-23. [Medline]. [Full Text].
Jones RN, Sader HS, Mendes RE, Flamm RK. Update on antimicrobial susceptibility trends among Streptococcus pneumoniae in the United States: report of ceftaroline activity from the SENTRY Antimicrobial Surveillance Program (1998-2011). Diagn Microbiol Infect Dis. 2013 Jan. 75 (1):107-9. [Medline].
Jones RN, Jacobs MR, Sader HS. Evolving trends in Streptococcus pneumoniae resistance: implications for therapy of community-acquired bacterial pneumonia. Int J Antimicrob Agents. 2010 Sep. 36 (3):197-204. [Medline].
[Guideline] American Academy of Pediatrics Committee on Infectious Diseases. Recommendations for the prevention of Streptococcus pneumoniae infections in infants and children: use of 13-valent pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23). Pediatrics. 2010 Jul. 126(1):186-90. [Medline].
[Guideline] Advisory Committee on Immunization Practices (ACIP). Preventing pneumococcal disease among infants and young children. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2000 Oct 6. 49:1-35. [Medline]. [Full Text].
[Guideline] Centers for Disease Control and Prevention (CDC); Advisory Committee on Immunization Practices (ACIP). Updated recommendation from the Advisory Committee on Immunization Practices (ACIP) for use of 7-valent pneumococcal conjugate vaccine (PCV7) in children aged 24-59 months who are not completely vaccinated. MMWR Morb Mortal Wkly Rep. 2008 Apr 4. 57(13):343-4. [Medline]. [Full Text].
Domínguez A, Izquierdo C, Salleras L, Ruiz L, Sousa D, Bayas JM, et al. Effectiveness of the pneumococcal polysaccharide vaccine in Preventing Pneumonia in the elderly. Eur Respir J. 2010 Jan 14. [Medline].
Grijalva CG, Poehling KA, Nuorti JP, Zhu Y, Martin SW, Edwards KM, et al. National impact of universal childhood immunization with pneumococcal conjugate vaccine on outpatient medical care visits in the United States. Pediatrics. 2006 Sep. 118(3):865-73. [Medline].
Centers for Disease Control and Prevention (CDC); Advisory Committee on Immunization Practices. Updated recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent pneumococcal polysaccharide vaccine (PPSV23). MMWR Morb Mortal Wkly Rep. 2010 Sep 3. 59(34):1102-6. [Medline].
Rinta-Kokko H, Dagan R, Givon-Lavi N, Auranen K. Estimation of vaccine efficacy against acquisition of pneumococcal carriage. Vaccine. 2009 Jun 12. 27(29):3831-7. [Medline].
Centers for Disease Control and Prevention (CDC). Recommended Adult Immunization Schedule – United States, 2012 MMWR 2012 feb 3;61(4):66-72. [Full Text].
Nuorti JP, Whitney CG. Prevention of pneumococcal disease among infants and children - use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine - recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010 Dec 10. 59:1-18. [Medline]. [Full Text].
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 Oct 12. 61:816-9. [Medline]. [Full Text].
Hung IF, Leung AY, Chu DW, Leung D, Cheung T, Chan CK. Prevention of acute myocardial infarction and stroke among elderly persons by dual pneumococcal and influenza vaccination: a prospective cohort study. Clin Infect Dis. 2010 Nov 1. 51(9):1007-16. [Medline].
Black SB, Shinefield HR, Hansen J, Elvin L, Laufer D, Malinoski F. Postlicensure evaluation of the effectiveness of seven valent pneumococcal conjugate vaccine. Pediatr Infect Dis J. 2001 Dec. 20(12):1105-7. [Medline].
Kaplan SL, Mason EO Jr, Wald ER, Schutze GE, Bradley JS, Tan TQ, et al. Decrease of invasive pneumococcal infections in children among 8 children's hospitals in the United States after the introduction of the 7-valent pneumococcal conjugate vaccine. Pediatrics. 2004 Mar. 113(3 Pt 1):443-9. [Medline].
Reuters Health Information. U.S. advisory panel recommends Prevnar 13 vaccine for elderly. Medscape Medical News. August 14, 2014. [Full Text].
Bonten M, Bolkenbaas M, Huijts S, et al. Community Acquired Pneumonia Immunization Trial in Adults (CAPiTA). Abstract no. 0541. Pneumonia 2014;3:95. Available at https://pneumonia.org.au/public/journals/22/PublicFolder/ABSTRACTBOOKMASTERforwebupdated20-3-14.pdf.
Tomczyk S, Bennett NM, Stoecker C, Gierke R, Moore MR, Whitney CG, et al. Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine Among Adults Aged =65 Years: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2014 Sep 19. 63(37):822-5. [Medline]. [Full Text].
Mitchell AM, Mitchell TJ. Streptococcus pneumoniae: virulence factors and variation. Clin Microbiol Infect. 2010 May. 16(5):411-8. [Medline].
Hawser SP. Activity of tigecycline against Streptococcus pneumoniae, an important causative pathogen of community-acquired pneumonia (CAP). J Infect. 2010 Apr. 60(4):306-8. [Medline].
Grau I, Pallares R, Tubau F, Schulze MH, Llopis F, Podzamczer D, et al. Epidemiologic changes in bacteremic pneumococcal disease in patients with human immunodeficiency virus in the era of highly active antiretroviral therapy. Arch Intern Med. 2005 Jul 11. 165(13):1533-40. [Medline].
Park SY, Van Beneden CA, Pilishvili T, Martin M, Facklam RR, Whitney CG. Invasive pneumococcal infections among vaccinated children in the United States. J Pediatr. 2010 Mar. 156(3):478-483.e2. [Medline].
Pilishvili T, Lexau C, Farley MM, et al. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis. 2010 Jan 1. 201(1):32-41. [Medline].
Ray GT, Pelton SI, Klugman KP, Strutton DR, Moore MR. Cost-effectiveness of pneumococcal conjugate vaccine: an update after 7 years of use in the United States. Vaccine. 2009 Nov 5. 27(47):6483-94. [Medline].
Flamm RK, Sader HS, Farrell DJ, Jones RN. Antimicrobial activity of ceftaroline tested against drug-resistant subsets of Streptococcus pneumoniae from U.S. medical centers. Antimicrob Agents Chemother. 2014. 58 (4):2468-71. [Medline]. [Full Text].
- Table 1. Routine Vaccination With Pneumococcal Vaccines[84, 85, 82]
- Table 2. Vaccination of High-Risk Children Aged 2-18 Years With Pneumococcal Polyvalent Vaccine 23-Valent
- Table 3. Vaccination of High-Risk Adults Aged 19 Years or Older With Pneumococcal Vaccines
- Table 4. Recommended Schedule for Doses of PCV13, Including Catch-up Immunizations in Previously Unimmunized and Partially Immunized Children
|Children aged 6 weeks through 5 years: 0.5 mL IM; series of 4 doses at ages 2, 4, 6, and 12-15 months (catch-up schedule through age 5 y)||Pneumococcal conjugate vaccine 13-valent (Prevnar 13)|
|Adults ≥50 years*: 0.5 mL IM as a single dose||Pneumococcal conjugate vaccine 13-valent (Prevnar 13, PCV13)|
|Adults >65 years*†: 0.5 mL IM||Pneumococcal polyvalent vaccine 23-valent (PPSV23); 6-12 mo after PCV13|
|*Although PCV13 is licensed by the FDA for individuals aged ≥50 y, ACIP recommends routine vaccination with both PCV13 plus PPSV23 for individuals aged ≥65 y.
†Those who received PPSV23 before age 65 years for any indication should receive another dose of the vaccine at age 65 years or later if at least 5 years have passed since their previous dose.
|Pediatric Risk Group||Condition|
|Immunocompetent||Chronic heart disease (particularly cyanotic congenital heart disease and cardiac failure)
Chronic lung disease (including asthma if treated with high-dose corticosteroids)
Cerebrospinal fluid leaks
|Functional or anatomic asplenia||Sickle cell disease and other hemoglobinopathies
Congenital or acquired asplenia or splenic dysfunction
|Immunocompromising conditions||HIV infection
Chronic renal failure and nephrotic syndrome
Immunosuppressive drugs or radiation therapy, malignant neoplasms, leukemias, lymphomas, Hodgkin disease, solid organ transplantation
|Risk Group||Condition||PCV13||PPSV23||Revaccinate With PPSV23 5 Years After First Dose|
|Immunocompetent individuals||Chronic heart disease*|
|Chronic lung disease†|
|Cerebrospinal fluid leaks||x||x|
|Chronic liver disease, cirrhosis||x|
|Functional or anatomic asplenia||Sickle cell disease and other hemoglobinopathies||x||x||x|
|Congenital or acquired asplenia||x||x||x|
|Immunocompromised individuals||Congenital or acquired immunodeficiency||x||x||x|
|Chronic renal failure||x||x||x|
|Solid organ transplant||x||x||x|
|*Congestive heart failure and cardiomyopathies, excluding hypertension.
†Including chronic obstructive pulmonary disease, emphysema, and asthma.
‡Diseases requiring treatment with immunosuppressive drugs, including long-term systemic corticosteroids and radiation therapy.
|Age at Examination (mo)||Immunization History||Recommended Regimen*|
|2-6||0 doses||3 doses, 2 mo apart; fourth dose at age 12-15 mo|
|1 dose||2 doses, 2 mo apart; fourth dose at age 12-15 mo|
|2 doses||1 dose, 2 mo after the most recent dose; fourth dose at age 12-15 mo|
|7-11||0 doses||2 doses, 2 mo apart; third dose at age 12 mo|
|1 or 2 doses before age 7 mo||1 dose at age 7-11 mo, with another dose at age 12-15 mo (≥2 mo later)|
|12-23||0 doses||2 doses, ≥2 mo apart|
|1 dose at < 12 mo||2 doses, ≥2 mo apart|
|1 dose at ≥12 mo||1 dose, ≥2 mo after the most recent dose|
|2 or 3 doses at < 12 mo||1 dose, ≥2 mo after the most recent dose|
|Any incomplete schedule||1 dose, ≥2 mo after the most recent dose†|
|Children at high
risk‡ (24-71 mo)
|Any incomplete schedule of < 3 doses||2 doses, one ≥2 mo after the most recent dose and another dose ≥2 mo later|
|Any incomplete schedule of 3 doses||1 dose, ≥2 mo after the most recent dose|
|*In children immunized before age 12 mo, the minimum interval between doses is 4 weeks. Doses administered at age 12 months or later should be administered at least 8 weeks apart.
† Providers should administer a single dose to all healthy children aged 24-59 mo with any incomplete schedule.
‡Children with sickle cell disease, asplenia, chronic heart or lung disease, diabetes mellitus, CSF leak, cochlear implant, HIV infection, or another immunocompromising condition. PPV23 is also indicated (see below).