INTRODUCTION — Pneumococcal vaccination is an important preventive health care measure that substantially reduces the burden of pneumococcal disease in vaccinated individuals and in the population. Pneumococcal vaccination is indicated for adults with risk factors for pneumococcal disease or for severe adverse outcomes should disease occur. Pneumococcal vaccination is also a routine part of infant and childhood immunization schedules worldwide.

The indications for pneumococcal vaccination in adults, vaccine types, schedules, and the efficacy and safety of vaccination are reviewed here. (Related Pathway(s): Pneumococcal vaccination: Indications and administration in adults.)

Pneumococcal vaccination in children is discussed separately. (See "Pneumococcal vaccination in children".)

TYPES OF VACCINES — Two kinds of pneumococcal vaccines are available for clinical use: pneumococcal polysaccharide vaccine (PPSV) and pneumococcal conjugate vaccine (PCV) (table 1). Each type is composed of the pneumococcal polysaccharide antigens that most commonly cause invasive disease. The immune response elicited by each type of vaccine varies based on its formulation.

●Pneumococcal polysaccharide vaccine – PPSV is composed of partially purified pneumococcal capsular polysaccharides. PPSV23 (Pneumovax or Pnu-Immune) is the most widely available formulation and contains 23 pneumococcal polysaccharides (table 2). In the past, these serotypes caused approximately 85 to 90 percent of cases of pneumococcal disease [1] but now cause only about 50 to 60 percent of such cases in adults [2].

●Pneumococcal conjugate vaccine – PCV is composed of pneumococcal capsular polysaccharides covalently linked (conjugated) to a protein. Available formulations contain a varying number of capsular types conjugated to a nontoxic protein that is nearly identical to diphtheria toxin. Infants and very young children do not respond to polysaccharide antigens, but linkage to this protein enables the developing immune system to recognize and process polysaccharide antigens, leading to production of antibody. Thus, PCV is the appropriate formulation for infants and young children. With a much less well-established scientific basis, this vaccine is also used in adults at high risk for pneumococcal infection or its complications.

Conjugated polysaccharides also stimulate mucosal immunity, which eradicates nasopharyngeal carriage. Since infants and toddlers are the principal reservoir for pneumococci in the population, the widespread use of PCV in this population has led to a dramatic reduction in incidence of disease caused by vaccine serotypes in adults.

PCV13 (Prevnar13) contains 13 capsular types and is the most widely used formulation. PCV7 (Prevnar7), the first available formulation, contains 7 capsular types and is still used in some regions of the world. PCV20 (Prevnar 20) and PCV15 (Prevnar 15), which contain 20 and 15 capsular types respectively, were approved by the FDA in 2021 [3] (table 2). Indications for PCV15 and PCV20 have not yet been determined.

Overall, >90 serologically distinct pneumococcal capsular serotypes have been identified. Clearly, a single vaccine cannot contain this large number of components. Available vaccines select capsular polysaccharides from serotypes that most commonly cause disease. (See "Microbiology and pathogenesis of Streptococcus pneumoniae", section on 'Capsule'.)

IMPORTANCE OF VACCINATION — Streptococcus pneumoniae is the leading bacterial cause of pneumonia worldwide. Other manifestations of pneumococcal infection include meningitis, bacteremia of undetermined cause, and otitis media. These pneumococcal infections cause substantial morbidity and mortality [4]. Vaccination of adults with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) protects 50 to 85 percent of relatively healthy adult recipients against invasive pneumococcal disease [5-7]. Widespread use of the 7-valent pneumococcal conjugate vaccine (PCV7) has led to a >90 percent reduction in PCV7 serotype disease among children and older adults (figure 1) [8-11]. The subsequent introduction of 13-valent conjugate vaccine (PCV13) has led to continued, dramatic decline in carriage of and disease attributed to vaccine strains [12]. Studies in Kenya and the United States attributed the decline in cases in adults specifically to the indirect effect of vaccination of children [13,14]. Disease in adults caused by S. pneumoniae serotypes 3 and 19A have not been reduced, but this is because these two polysaccharides fail to induce good antibody responses (type 3) or persistent antibody responses (type 19A).

As expected, the reduction of PCV13-strain related illness in adults is primarily attributable to the overall reduction in circulation of PCV13- strain caused widespread vaccination in children, rather than vaccination of adults [13-16]. These findings raise the question as to whether adults need to receive PCV13.

INITIAL VACCINATION — Our recommendations for initial vaccination against pneumococcus are largely consistent with the Advisory Committee on Immunization Practices (ACIP) [17-20]. In contrast with the ACIP, we also recommend vaccinating adults who have a history of invasive pneumococcal disease because they have proven to be susceptible. The ACIP makes no specific statement about this population. (See 'Society guideline links' below.) (Related Pathway(s): Pneumococcal vaccination: Indications and administration in adults.)

Adults, ages 19 to 64 years

Healthy — Pneumococcal vaccination is not recommended for healthy adults under the age of 65 years.

Immunocompetent

Chronic conditions — A single dose of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) is indicated for adults (ages 19 to 64 years) who have conditions that increase the risk of pneumococcal infection or serious complications should infection occur (algorithm 1) [17-19,21]. Those conditions include:

●Chronic heart disease, such as heart failure and cardiomyopathy (excluding hypertension alone)

●Chronic lung disease, such as asthma and chronic obstructive pulmonary disease

●Chronic liver disease

●Poorly controlled diabetes mellitus

●Current cigarette smoking

●Alcohol use disorder

Because patients with chronic kidney disease can be hypogammaglobulinemic and are at increased risk for invasive pneumococcal disease, these patients are vaccinated according to the same schedule as immunocompromised patients. However, the degree to which chronic kidney disease confers risk for pneumococcal disease likely varies from patient to patient. For example, those with protein-losing nephropathies (eg, nephrotic syndrome) may be at greater risk than others. Thus, this is not a strict classification. (See 'Other immunocompromising conditions' below.)

The 13-valent pneumococcal conjugate vaccine (PCV13) is generally not indicated for these patients but can be considered on a case-by-case basis once the patient reaches age 65 years (see 'Adults, ages 65 years or older' below). Because immunity to PPSV23 wanes over time, we favor revaccination with PPSV23 at regular intervals. (See 'Revaccination' below.)

Additional discussion of risk factors for pneumococcal infection and its complications is provided separately. (See "Invasive pneumococcal (Streptococcus pneumoniae) infections and bacteremia", section on 'Risk factors for infection' and "Pneumococcal pneumonia in patients requiring hospitalization", section on 'Risk factors'.)

At risk for meningitis (cerebrospinal fluid leak, cochlear implant) — Vaccination with both PCV13 and PPSV23 is indicated for individuals who are at increased risk of meningitis due to structural abnormalities that allow communication with the subarachnoid space or who have previously had pneumococcal meningitis [17,22]. Major conditions in this category include [17,21]:

●Cochlear implant placement

●Cerebrospinal fluid leak

●History of pneumococcal meningitis

●Prior head injury and/or head, neck, or spinal surgery with resultant cranial defect or other potential communication to the subarachnoid space

We give a single dose of PCV13 followed by PPSV23 ≥8 weeks later for adults with these conditions who have not received either vaccine previously. For those who have received either vaccine previously, the dosing schedule and recommended intervals between vaccines vary (algorithm 2A-B). (See 'PCV13 and PPSV23 sequence and intervals' below.)

Because immunity to PPSV23 wanes over time, we favor revaccination with PPSV23 at regular intervals. (See 'Revaccination' below.)

History of invasive pneumococcal disease — We vaccinate individuals who have a history of invasive pneumococcal disease (eg, meningitis, bacteremia) with both PCV13 and PPSV23 because they have proven to be susceptible to pneumococcal infection and because infection with one serotype does not provide protection against other serotypes. However, the ACIP has not issued a statement on vaccination for this population.

As with other individuals, we give a single dose of PCV13 followed by PPSV23 ≥8 weeks later for adults with a history of these conditions who have not received either vaccine previously. For those who have received either vaccine previously, the dosing schedule and recommended intervals between vaccines vary (algorithm 2B).

In patients who have been treated for invasive pneumococcal disease and are likely to be compliant with medical recommendations, we give the first dose of vaccine two months after recovery from pneumococcal infection because of the possibility that the infection has caused transient immunosuppression. We vaccinate patients who are not likely to return at the time of hospital discharge.

Because immunity to PPSV23 wanes over time, we favor revaccination with PPSV23 at regular intervals. (See 'Revaccination' below.)

Immunocompromised

Impaired splenic function — Vaccination with both PCV13 and PPSV23 is indicated in individuals with impaired splenic function because, if pneumococcal infection occurs, it can be severe and rapidly fatal in this population (algorithm 2C) [17,18]. Patients with impaired splenic function include those with:

●Anatomic asplenia or hyposplenism (eg, due to splenectomy or congenital absence)

●Sickle cell disease or other hemoglobinopathy

●Functional asplenia or hyposplenism

We give a single dose of PCV13 followed by PPSV23 ≥8 weeks later for adults with impaired splenic functions who have not received either vaccine previously. For those who have received either vaccine previously, the dosing schedule and recommended intervals between vaccines vary (algorithm 2C) (see 'PCV13 and PPSV23 sequence and intervals' below). Repeated vaccination with PPSV23 at regular intervals is important because immunity to PPSV23 wanes with time. (See 'Revaccination' below.)

Details on other vaccinations and preventive health care measures for patients with impaired splenic function are provided separately. (See "Prevention of infection in patients with impaired splenic function".)

Other immunocompromising conditions — Vaccination with both PCV13 and PPSV23 is indicated in all immunocompromised individuals, including but not limited to those with the following conditions (algorithm 2D) [17,18,21]:

●HIV infection

●Chronic kidney disease (especially nephrotic syndrome and other protein-losing nephropathies)

●Hematologic malignancy (eg, leukemia, lymphoma, multiple myeloma)

●Generalized malignancy (eg, patients with solid tumors treated with chemotherapy and/or metastatic disease)

●Solid organ transplantation

●Hematopoietic stem cell transplantation

●Iatrogenic immunosuppression (including long-term systemic glucocorticoid use or radiation)

●Congenital or acquired immunodeficiency, including B or T lymphocyte deficiency, complement deficiencies (particularly C1, C2, C3, and C4 deficiencies), and phagocytic disorders (excluding chronic granulomatous disease)

We give a single dose of PCV13 followed by PPSV23 ≥8 weeks later for most immunocompromised patients who have not received either vaccine previously. For those who have received either vaccine previously, the dosing schedule and recommended intervals between vaccines vary (algorithm 2D) (see 'PCV13 and PPSV23 sequence and intervals' below). We generally favor repeat vaccination with PPSV23 at regular intervals as immunity to PPSV23 wanes with time. (See 'Revaccination' below.)

While there is evidence that many patients with immunocompromising conditions may not develop antibody following vaccination with PCV and PPSV, the benefits greatly outweigh the risks and the cost is regarded as appropriate for the benefit received.

Additional detail on vaccine efficacy and timing in specific immunocompromised patients is provided separately. (See "Pneumococcal immunization in adults with HIV" and "Immunizations in autoimmune inflammatory rheumatic disease in adults" and "Immunizations in adults with cancer" and "Immunizations in solid organ transplant candidates and recipients" and "Immunizations in hematopoietic cell transplant candidates and recipients".)

Adults, ages 65 years or older — Vaccination with PPSV23 is indicated for all adults because the overall incidence of pneumococcal disease rises greatly after this age (table 3) [18,20]. However, the incidence of pneumococcal disease specifically caused by PCV13 serotypes is low as a result of widespread childhood vaccination (figure 2) [8]; thus:

●We do not routinely vaccinate adults ≥65 years old with PCV13 unless they have another indication for PCV13 (ie, immunocompromise, asplenia, cerebrospinal fluid leak, cochlear implant, or history invasive pneumococcal disease) and have not previously received the vaccine.

●For adults with certain chronic conditions that place them at higher risk for pneumococcal disease (ie, chronic cardiac, lung, and/or liver disease, diabetes mellitus, smoking, and/or alcohol use disorder), we discuss risks and benefits of PCV13 on an individual basis when deciding to give this vaccine. For most persons in the United States, we consider the absolute risk of acquiring pneumococcal disease caused by a PCV13 serotype to be so low that the expected benefit is very small.

The ACIP has rescinded its prior recommendation to vaccinate all adults ≥65 years old with both PCV13 and PPSV23 [23]. The committee now recommends PPSV23 for all patients in this age group and advises clinicians to engage in shared decision-making to determine whether PCV13 should be given in addition to PPSV23 for patients who otherwise lack an indication for dual vaccination (eg, asplenia, cochlear implant) (table 4) [20]. The change in recommendation is based on the dramatic reduction in the incidence of infection with PCV13 serotypes that has resulted from universal childhood PCV13 vaccination [14]. Because the likelihood of infection with a PCV13 serotype is now so low, we generally find that the benefits of the additional vaccination with PCV13 do not outweigh its risk or costs.

REVACCINATION — We revaccinate at-risk individuals with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) at 5- to 10-year intervals because the antibody response to PPSV23 wanes over this time period [24,25]. However, the optimal timing and number of vaccine doses needed to prevent disease are unknown. Recommendations vary among experts and clinical practice guidelines [17,19,26].

●For individuals with impaired splenic function, cerebrospinal fluid (CSF) leaks, and cochlear implants, or other head, neck, or spinal defects that may result in communication with the subarachnoid space, we revaccinate with PPSV23 every 5 to 7 years because they are at particularly high risk for severe pneumococcal infection.

●For individuals with immunocompromising conditions (apart from impaired splenic function), we revaccinate every 5 to 10 years.

●For all other at-risk individuals (eg, those with chronic conditions that predispose to pneumococcal infection, those with a history of invasive pneumococcal disease, those ≥65 years old), we revaccinate every 10 years.

Revaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) is not recommended for any age or risk group [27].

Our approach to revaccination is based on studies that show that responses to PPSV23 wanes approximately 5 to 7 years postvaccination and reaches near prevaccination levels by 10 years [24,25]. Revaccinating before five years have elapsed can blunt the immune response [28]; this hyporesponsiveness is lost if more than five years have passed since the previous dose [24,29,30]. Injection site reactions are more common after revaccination than after primary vaccination, but, in most studies, such reactions have been mild or moderate and self-limited and have tended to occur when the time between vaccinations was less than five years [17,20,25,31-33]. One study showed no increase in medically attended adverse events among individuals who received three or more doses of PPSV23 compared with those who received one dose [34]. (See 'Adverse effects' below.)

This approach to revaccination differs from the Advisory Committee on Immunization Practices (ACIP), which recommends one PPSV23 revaccination dose (≥5 years after the first) for persons age 19 to 64 years with impaired splenic function and other immunocompromising conditions followed by a second revaccination dose once the individual reaches age 65 years (provided ≥5 years have elapse since the last). The ACIP does not recommend revaccination for any other at-risk population (eg, those >65 years or those with CSF leaks or cochlear implants).

Some organizations suggest checking pneumococcal antibodies to help guide the need for PPSV23 revaccination in high-risk patients [35]. However, we do not use this approach because meaningful protective antibody levels have not been established and likely vary from person to person. Although a serum concentration of 0.35 mcg/mL has been designated as protective for children, it is unclear if this is reliable [36].

VACCINE ADMINISTRATION

Dose and route — Both pneumococcal vaccines are administered as a 0.5 mL dose. The 13-valent pneumococcal conjugate vaccine (PCV13) should be given intramuscularly, whereas the 23-valent pneumococcal polysaccharide vaccine (PPSV23) can be given either intramuscularly or subcutaneously. Intradermal administration of either vaccine can cause severe local reactions and should be avoided.

PCV13 and PPSV23 sequence and intervals — For patients who need both pneumococcal vaccines, PCV13 is ideally given first, followed by PPSV. In patients who are at high risk for pneumococcal infection, we recommend waiting only eight weeks between doses; for all others, we recommend that PPSV23 be given one year after PCV.

●For adults who have received neither vaccine previously, PCV13 should be given before PPSV23.

•For adults between the ages of 19 and 64 years who require both vaccines, we give PCV13 first followed by PPSV23 ≥8 weeks later.

Although a ≥1-year interval is optimal for the development of protective antibody responses, patients who require both vaccines in this age group are generally at high risk for pneumococcal infection; thus, we abbreviate the interval. Additionally, for immunocompromised individuals, extending the interval between vaccinations is unlikely to augment antibody development.

•For patients whose primary indication for vaccination is age ≥65 years, we give PCV13 first followed by PPSV23 ≥1 year later. As noted above, PCV13 is no longer routinely recommended for patients aged ≥65 years but can be considered on a case-by-case basis. (See 'Adults, ages 65 years or older' above.)

●For adults who have received PPSV23 prior to PCV13, a ≥1-year interval is recommended between the two vaccines.

Giving a pneumococcal conjugate vaccine (eg, PCV13) prior to a polysaccharide vaccine (eg, PPSV23) has the potential to enhance the immune response to the polysaccharide vaccine by stimulating memory B cells and priming the immune system [37-40]. While this has theoretical appeal, a priming effect has not been consistently demonstrated in clinical studies. In two large observational studies, giving PCV13 followed one year later by PPSV23 led to higher antibody activity one month after PPSV23 administration [40,41]. In a smaller study, conjugate vaccine followed by PPSV23 led to higher antibody levels at one month but, by six months after receipt of PPSV23, antibody levels in booster recipients had fallen to their baseline [42]. Other studies have failed to show that a prime-boost regimen with a pneumococcal conjugate vaccine followed by a pneumococcal polysaccharide vaccine enhances immunogenicity [42-46].

In contrast, giving a polysaccharide vaccine closely followed by a conjugate vaccine suppresses immune responses. In a randomized trial, administration of PPSV23 six months prior to the 7-valent pneumococcal conjugate vaccine (PCV7) resulted in attenuated antibody concentrations compared with PCV7 alone [45].

Administration with other vaccines — Either formulation of pneumococcal vaccine may be given concomitantly with other nonpneumococcal vaccines [47,48]. When more than one vaccine is given, they should be administered with different syringes and at different injection sites.

Concurrent administration of PPSV23 with the influenza vaccine is safe and does not alter the effectiveness of either vaccine [49]. Coadministration of PPSV23 and the recombinant zoster vaccine probably does not alter the antibody response to PPSV23 [50] but may reduce the immunogenicity of the zoster vaccine [47,50,51]. In order to avoid introducing barriers to patients receiving indicated vaccines, the United States Centers for Disease Control and Prevention (CDC) recommends that PPSV23 and the zoster vaccine be administered at the same visit if the patient is eligible for both vaccines [52-54].

EFFICACY

Polysaccharide vaccine — The pneumococcal polysaccharide vaccine (PPSV) was introduced in the United States in 1977, an important milestone in preventive care. Several randomized trials have demonstrated the vaccine's efficacy in reducing invasive pneumococcal disease in otherwise healthy adults, particularly invasive disease caused by serotypes targeted by the vaccine [5].

In a meta-analysis of 18 randomized trials evaluating over 64,500 individuals, the following results were observed [5]:

●PPSV reduced the risk of invasive pneumococcal disease, defined as pneumococcal infection with isolation of S. pneumoniae from a normally sterile body site (odds ratio [OR] 0.26, 95% CI 0.14-0.45). This reduction was observed in otherwise healthy individuals of all ages in low-income countries (OR 0.14, 95% CI 0.03-0.61) and in otherwise healthy individuals (many of whom were older adults) in high-income countries (OR 0.20, 95% CI 0.10-0.39).

●The benefit of PPSV for preventing invasive pneumococcal disease was greater when the analysis was limited to trials that assessed the incidence of disease caused by serotypes included in the vaccine (OR 0.18, 95% CI 0.10-0.31).

●PPSV was associated with a substantial reduction in both invasive (OR 0.26, 95% CI 0.15-0.46) and noninvasive pneumococcal pneumonia (OR 0.46, 95% CI 0.25-0.84).

●PPSV was associated with a reduction in pneumonia of any cause in low-income countries (OR 0.54, 95% CI 0.43-0.67), presumably because S. pneumoniae remains the principal cause of pneumonia in such countries but not among individuals in high-income countries in either the general population or in adults with chronic illness.

Although we find the above result to be valid, the degree of protection provided by pneumococcal polysaccharide vaccines is still debated among experts and varies among studies. For example, some studies suggest that PPSV protects against invasive (ie, bacteremia, meningitis, bacteremic pneumonia) but not noninvasive pneumococcal disease [37,55-65] (a suggestion that we find biologically implausible). Other studies have failed to demonstrate efficacy for preventing either invasive or noninvasive disease [59,60,65-68] or for reducing mortality [5,69]. Possible reasons for the conflicting results include the rarity of the outcomes being assessed (leading to a small number of events in studies), difficulties in accurately diagnosing pneumococcal pneumonia, and use of nonvalidated diagnostic tests (which lead to false-positive results and reduce the apparent efficacy of the vaccine). As might be expected, studies with more specific endpoints (eg, invasive pneumococcal disease caused by specific vaccine serotypes) have been more likely to demonstrate vaccine efficacy than studies with less specific endpoints (eg, all-cause pneumonia, all-cause mortality) [37].

An unfortunate practical concern is that vaccine efficacy is diminished in those who are at greatest need for vaccination (eg, older and immunocompromised patients). In one case-control study evaluating >2000 patients, PPSV was 85 to 90 percent effective in preventing invasive pneumococcal disease in adults <55 years of age [57]. Efficacy declined as age increased as did the duration of any observed effect, such that no benefit was observed five years after vaccination among persons >80 years old. Among immunocompromised patients, vaccine efficacy varies with the degree and type of immunosuppression [70]. However, even among patients with significant humoral immune deficits (ie, asplenia), vaccination does appear to provide some protection, is safe, and, thus, is recommended [71].

Conjugate vaccine — The development of the pneumococcal conjugate vaccine (PCV) represented a major advance in preventive care. The success of the pneumococcal conjugate vaccine owes to its ability to directly prevent infection in immunized individuals and to indirectly induce immunity in the population by reducing nasopharyngeal colonization rates (termed "indirect effect" or "herd immunity").

In 2000, the 7-valent pneumococcal conjugate vaccine (PCV7) was shown to be highly effective in preventing invasive pneumococcal disease in infants and young children [72]. The Advisory Committee on Immunization Practices (ACIP) recommended it for routine use in this population. As use became widespread, the incidence of PCV7 serotypes declined across the population and a >90 percent reduction in PCV7 serotype disease was observed in children and older adults (figure 1) [8-11], illustrating the indirect effect of this vaccine.

The direct effect of vaccinating adults with PCV7 was assessed in the CAPiTA trial [6,73]. This trial compared the 13-valent pneumococcal conjugate vaccine (PCV13) with placebo in approximately 85,000 immunocompetent adults ≥65 years of age in the Netherlands who were enrolled between 2008 and 2010 and who had not received a pneumococcal vaccine previously or who had a prior history of pneumococcal disease [6]. The trial demonstrated 46 percent efficacy (95% CI 22 to 63 percent) of PCV13 against vaccine-type pneumococcal pneumonia, 45 percent efficacy (95% CI 14 to 65 percent) against vaccine-type nonbacteremic pneumococcal pneumonia, and 75 percent efficacy (95% CI 41 to 91 percent) against vaccine-type invasive pneumococcal disease. Efficacy persisted for the duration of the trial (mean follow-up four years).

However, the CAPiTA trial had several limitations, and it is uncertain whether PCV13 is more efficacious than the 23-valent pneumococcal polysaccharide vaccine (PPSV23) or whether giving PCV13 in addition to PPSV23 adds value for older adults. Specific limitations of the CAPiTA trial include:

●It did not have a comparative group that received PPV23, so it did not address the question of whether PCV13 provides better protection for adults than PPSV23 against the 13 serotypes contained within it [10].

●The trial specifically excluded subjects who were regarded as immunocompromised [6].

●Importantly, among subjects who developed an immunocompromising condition or who were placed on some immunosuppressive therapy during the period of the study, PCV13 exhibited no protective effect (22 cases of pneumococcal disease in vaccine recipients versus 24 cases in placebo recipients) [10].

●Because this trial began before PCV13 was used routinely in infants in the Netherlands, it does not answer the question of whether PCV13 is efficacious in countries that routinely administer conjugate vaccines to infants [10].

Given the dramatic reduction in invasive pneumococcal disease observed in adults following the routine use of PCV in children in the United States due to the herd effect (figure 1), the added benefit of vaccinating adults ≥65 years may be marginal. However, one case-control study suggests that there is added benefit [74]. Among 68 cases of pneumococcal pneumonia caused by PCV13 serotypes, 4.4 percent received PCV13 compared with 14.5 percent of controls, corresponding to a vaccine efficacy rate of approximately 71 percent.

While PCV13 is recommended for most immunocompromised patients because they are at increased risk of severe infection, efficacy data supporting this recommendation are limited. As noted above, in the CAPiTA trial, patients who became immunocompromised during the study were not protected by PCV7. The best-studied immunocompromised group has been HIV-infected patients in Africa, in whom PPSV was not effective [75] but in whom PCV demonstrated modest, albeit short-lived, efficacy [76]. (See "Pneumococcal immunization in adults with HIV", section on 'Efficacy and immunogenicity of pneumococcal vaccination'.)

An untoward effect of the widespread use of pneumococcal conjugate vaccines has been the emergence of "replacement strains," a term used to describe nonvaccine pneumococcal serotypes that have appeared as colonizers of the nasopharynx and as a cause of pneumococcal disease [77]. Reduction in nasal carriage of PCV serotypes appears to create an ecologic niche for nonvaccine serotypes [37]. As an example, S. pneumoniae type 19A (not included in PCV7) emerged as the most common cause of pneumococcal disease in children and adults a few years after universal vaccination with PCV7 began in the United States (figure 1) [9,78]. Several other serotypes have greatly increased in prevalence since the introduction of PCV13. (See "Impact of universal infant immunization with pneumococcal conjugate vaccines in the United States".)

SAFETY

Adverse effects — The immune response to pneumococcal vaccination can elicit a clinically apparent inflammatory response at the injection site and systemically. While most adverse effects associated with vaccination are not severe and are self-limited, all should be reported. In the United States, suspected adverse events should be reported to the Vaccine Adverse Event Reporting System (VAERS). VAERS can be contacted via the VAERS website or by telephone at 1-800-822-7967.

Injection site reactions — Injection site reactions are the most common adverse effects associated with pneumococcal vaccination in adults [47,79]. For the 23-valent pneumococcal polysaccharide vaccine (PPSV23), pain and tenderness at the injection site occur in over half of vaccinees, swelling and/or induration in approximately 20 percent, and redness in approximately 15 percent [47,79]. Rates are similar for pneumococcal conjugative vaccines [79]. In some, these symptoms limit arm movement.

Injection site reactions usually resolve spontaneously over three to four days. Nonsteroidal antiinflammatory drugs and warm compresses can help relieve pain.

Other adverse effects — Systemic symptoms (eg, fever, chills, fatigue, headache, myalgias, arthralgias) can also occur following vaccination [47,79]. While fever (temperature ≥38°C) occurs in less than 5 percent, other systemic symptoms occur frequently but are usually mild. Like injection site reactions, systemic symptoms following vaccination are self-limited.

Contraindications — Vaccination is contraindicated for patients who have a history of severe allergic reactions (eg, anaphylaxis) to either pneumococcal vaccine or any of its components (eg, diphtheria toxoid for pneumococcal conjugate vaccines).

COST-EFFECTIVENESS — A cost-effectiveness analysis has suggested that the use of the 13-valent pneumococcal conjugative vaccine (PCV13) in adults using the existing indications (ie, vaccination at age 65 years and at younger ages if comorbidities are present) would be more cost-effective than the 23-valent pneumococcal polysaccharide vaccine (PPSV23), provided that the effectiveness of PCV13 at preventing nonbacteremic pneumococcal pneumonia is high ($28,900 versus $34,600 per quality-adjusted life-year [QALY] gained, respectively) [80]. This study relied on a meta-analysis [65], which appeared to show that PPSV23 provides no protection against noninvasive pneumococcal infection. However, another meta-analysis showed equivalent protection against invasive and noninvasive disease [5]. Had data from the second analysis been used to assess cost-effectiveness, the benefit of vaccination would have been much greater. On the other hand, if the herd effect of PCV13 is as large as has been shown for the 7-valent pneumococcal conjugate vaccine (PCV7; and results to date in the United States, United Kingdom, and France suggest that it appears to be [81,82]), infection in adults due to strains contained in PCV13 will largely be eliminated, which will render the use of pneumococcal conjugative vaccines in adults irrelevant and will greatly increase the cost per QALY. Not surprisingly, therefore, a more recent cost analysis from the United Kingdom recognized the herd effect of conjugate vaccine, concluding that use of PCV13 in adults at risk for pneumococcal infection was not likely to be cost effective [83].

INVESTIGATIONAL APPROACHES — Existing pneumococcal vaccines utilize capsular polysaccharides as antigens. Vaccines cannot include all serotypes, replacement strains appear, and pneumococci readily acquire DNA from other microorganisms by transformation, giving them the ability to switch capsular serotypes. These facts have led to attempts to develop vaccines based on highly conserved proteins (eg, pneumolysin, histidine triad protein D, surface proteins A and C), some of which are surface expressed and one of which (pneumolysin) contributes substantially to the pathogenesis of pneumococcal disease. Several such vaccines are in development [10,37,84]. Data suggest that the best approach for new vaccines might be to target virulence factors other than the pneumococcal capsule [85].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pneumococcal vaccination in adults" and "Society guideline links: Immunizations in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Vaccines for adults (The Basics)" and "Patient education: What you should know about vaccines (The Basics)")

●Beyond the Basics topic (see "Patient education: Pneumonia prevention in adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Pneumococcal infections (eg, pneumonia, bacteremia, meningitis) are an important cause of morbidity and mortality in adults, especially among older adults (table 3) and those with certain conditions, including immunocompromising conditions and asplenia. (See 'Introduction' above and 'Importance of vaccination' above.)

●Two types of pneumococcal vaccines are approved and have defined indications for use in the United States (table 1) (see 'Types of vaccines' above):

•A pneumococcal polysaccharide vaccine (PPSV23; Pneumovax 23, Pnu-Immune) that includes 23 purified capsular polysaccharide antigens

•A pneumococcal protein-conjugate vaccine (PCV13; Prevnar 13) that includes capsular polysaccharide antigens covalently linked to a nontoxic protein that is nearly identical to diphtheria toxin

A 20-valent and 15-valent pneumococcal protein-conjugate vaccines (PCV20 and PCV15) have also been approved but indications for its use are not yet defined.

●We recommend pneumococcal vaccination for all adults ≥65 years old and adults <65 years old who are at risk for pneumococcal infection or severe complications from pneumococcal infection (Grade 1B). Whether both PCV13 and PPSV23 are indicated and whether revaccination with PPSV23 is indicated vary based on patient age and risk status (table 5). (See 'Initial vaccination' above.) (Related Pathway(s): Pneumococcal vaccination: Indications and administration in adults.)

•For adults ages 19 to 64 years with certain chronic conditions (eg, chronic heart, lung, or liver disease, diabetes mellitus, smoking, alcohol use disorder), we give a single dose of PPSV23 (algorithm 1). (See 'Chronic conditions' above.)

•For adults with higher risk conditions (ie, immunocompromise, asplenia, cerebrospinal fluid leak, cochlear implant, other head, neck, or spinal defects that may result in communication with the subarachnoid space, or history of invasive pneumococcal disease), we give both PCV13 and PPSV23 (algorithm 2A-D). (See 'Immunocompromised' above and 'At risk for meningitis (cerebrospinal fluid leak, cochlear implant)' above and 'History of invasive pneumococcal disease' above.)

•For adults ≥65 years, we give PPSV23. We generally do not give PCV13 unless they have another indication for PCV13 (eg, asplenia, immunocompromise) because the incidence of pneumococcal disease caused by PCV13 serotypes is very low. (See 'Adults, ages 65 years or older' above.)

●When both PCV13 and PPSV23 are indicated, they should be given at separate time points to help ensure that protective antibodies to each vaccine develop. When possible, PCV13 should be given before PPSV23. (See 'PCV13 and PPSV23 sequence and intervals' above.)

•For adults who have not received any pneumococcal vaccine previously, PCV13 should be given before PPSV23. If the primary indication for vaccination is age ≥65 years, PPSV23 should be given ≥1 year after PCV13. For adults between ages 19 and 64 years who require both vaccines, PPSV23 can be given ≥8 weeks after PCV13.

•For adults who have already received PPSV23, PCV13 should be given ≥1 year following PPSV23.

●Revaccination with PPSV23 is recommended for selected patients because immunity to polysaccharide vaccines wanes over time. Data supporting best practice are limited, and recommendations on revaccination vary among experts and clinical practice guidelines. Most authorities agree that at least one revaccination PPSV23 dose should be given to immunocompromised and asplenic individuals ages 19 to 64 years. Revaccination with PCV13 is not indicated for any age or risk group. (See 'Revaccination' above.)

●Injection site reactions (tenderness, redness, swelling at site) are the most common adverse effects associated with pneumococcal vaccination in adults and are typically mild. Most are self-limited and resolve within a few days of vaccination. Warm compresses and nonsteroidal antiinflammatory drugs can help with symptom relief. (See 'Adverse effects' above.)

●Vaccination is contraindicated for patients who have a history of a severe allergic reactions (eg, anaphylaxis) to either pneumococcal vaccine or any of its components (eg, diphtheria toxoid for pneumococcal conjugate vaccines). (See 'Contraindications' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Elaine Tuomanen, MD and Patricia Hibberd, MD, PhD who contributed to earlier versions of this topic review.

We are saddened by the death of John G Bartlett, MD, who passed away in January 2021. UpToDate gratefully acknowledges his tenure as the founding Editor-in-Chief for UpToDate in Infectious Diseases and his dedicated and longstanding involvement with the UpToDate program.