US Pharm. 2021;46(4):32-35.

ABSTRACT: Infections caused by Streptococcus pneumoniae represent a significant public-health concern. Invasive pneumococcal disease, including pneumonia, meningitis, and bacteremia, are more common in high-risk populations, including young children, older adults, and the immunocompromised. PPSV23 (Pneumovax 23) and PCV13 (Prevnar 13) are two vaccines included as part of routine immunization schedules and are recommended for use in those with high-risk comorbidities. Pharmacists play an important role in improving immunization rates and reducing missed opportunities for pneumococcal vaccinations.

Infections caused by Streptococcus pneumoniae are a global health concern. In the United States, CDC estimates indicate that 150,000 hospitalizations due to pneumococcal pneumonia occur each year.¹ Worldwide, S pneumoniae is the leading cause of pneumonia-related death.²

S pneumoniae is a Gram-positive bacterium that commonly colonizes the respiratory tract. Pneumococcal infections range from otitis media and sinusitis to more severe infections, known as invasive pneumococcal disease (IPD).¹ IPD includes pneumonia, meningitis, and bacteremia, with case-fatality rates approaching 18%.³

For many adults considered high-risk for pneumococcal disease, prior hospitalizations and other encounters within the healthcare system represent missed opportunities for pneumococcal vaccination.⁴ These interactions should be leveraged to reduce the burden of this vaccine-preventable illness, and pharmacists can play an important role in identifying at-risk patients and facilitating pneumococcal vaccinations.

Pneumococcal Vaccines

While there are more than 80 pneumococcal serotypes, only a few of them cause IPD.⁴ There are two vaccines currently available in the U.S. to help protect patients from pneumococcal disease: pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23).¹

Pneumococcal Polysaccharide Vaccine (PPSV23)

S pneumoniae is covered by a polysaccharide capsule, which protects it from the human immune system.² The pneumococcal polysaccharide vaccine contains a part of the capsule from 23 different serotypes. These 23 serotypes make up 85% to 90% of the disease-causing pneumococcal serotypes in the U.S. The six serotypes that most frequently cause invasive, drug-resistant pneumococcal infections in the U.S. (6B, 9V, 14, 19A, 19F, and 23F) are represented in the 23-valent vaccine, which is about 60% to 70% effective at preventing invasive disease caused by these serotypes.¹ These vaccines elicit their immune response by stimulating B-cells without helper T-cells. Within 2 to 3 weeks, healthy adults develop antibodies against the PPSV23 serotypes.¹   

While pneumococcal disease is common in children aged <2 years, their immature immune system does not allow them to respond consistently to polysaccharide vaccines. Therefore, PPSV23 is not recommended in children aged <2 years.¹

PPSV23 is only available on the market in the U.S. as Pneumovax 23.⁵ It is available as a 0.5-mL SC or IM injection.⁵ It is contraindicated in patients who have a history of anaphylaxis to any component of the vaccine.⁵ The most common side effects are injection-site soreness (60%), injection-site swelling (20.3%), headache (17.6%), injection-site erythema (16.4%), fatigue (13.2%), and myalgia (11.9%).⁵ Any adverse reaction should be reported to the healthcare provider, who should then report the event to the Vaccine Adverse Event Reporting System (VAERS).⁵

PPSV23 or PCV13 may be administered at the same time as influenza vaccines.⁶ One randomized, controlled trial found that the coadministration of PPSV23 and zoster vaccine (ZV) produced a decreased immune response to ZV compared with individuals who received them 4 weeks apart.⁷ However, this study compared PPSV23 to Zostavax, the live zoster vaccine, which was removed from the market by the FDA in November 2020.⁸ Recombinant zoster vaccine (RZV), Shingrix, is the only vaccine currently on the market for herpes zoster, and it is safe to administer concomitantly with PPSV23.⁹

Pneumococcal Conjugate Vaccine (PCV13)

Researchers discovered that covalently binding a carrier protein to the pneumococcal polysaccharide complex elicited a positive immune response, especially in children aged <2 years. This technology was utilized to create the pneumococcal conjugate vaccine, which works by inducing a T-cell–dependent immune response. The B-cells mature after receiving the signals from the protein carrier-specific T-cells. The main serotypes in PCV13 are targeted towards those that most commonly cause disease in U.S. children aged <6 years: 4, 6B, 9V, 14, 18C, 19F, and 23F.¹⁰

PCV13 replaced the previously commercially available pneumococcal conjugate vaccine, PCV7, in 2010.¹¹ The only commercially available PCV13 vaccine in the U.S. is Prevnar 13.¹² It is supplied as a 0.5-mL prefilled syringe and should be given as an IM injection. It is contraindicated in any patient who has had a severe allergic reaction to any component of PCV13 or any diphtheria toxoid–containing vaccine. Side-effect types and frequencies vary by age group and include irritability, fatigue, injection-site tenderness/redness/swelling, decreased appetite, increased or decreased sleep, and fever.¹² Apnea has been reported after administration of IM vaccines in premature infants. The decision to administer any IM vaccine should take into consideration the patient’s medical status, as well as the risks and benefits of the vaccine.¹² 

PCV13 can be coadministered with most other pediatric vaccines. Patients who require the quadrivalent meningococcal conjugate vaccine, Menactra, should not receive PCV13 at the same time. Instead, the two vaccines should be given at least 4 weeks apart.⁶

Pneumococcal Vaccine Indications

PCV13 is recommended as a four-shot series for children aged <2 years and should be given at 2 months, 4 months, and 6 months, with a booster dose given at 12 to 15 months. The first dose may be given as early as 6 weeks, but there are limited data in infants aged <6 weeks. If a dose of the vaccine is missed, the number of subsequent doses is based upon current age and the age at which the first PCV13 vaccine was administered. Children aged 2 to 4 years who did not receive the pneumococcal series or did not complete the series should receive one dose of PCV13. More guidance on the routine immunization and catch-up schedules may be found on the CDC website at https://www.cdc.gov/vaccines/schedules/.

In children aged 2 to 5 years who are unvaccinated or those who received fewer than three doses of PCV13 and who also have chronic heart and lung disease, diabetes, cerebrospinal fluid (CSF) leak, cochlear implant, sickle cell disease and other hemoglobinopathies, functional or anatomic asplenia, HIV infection, or an immunocompromising condition resulting from disease or treatment of a disease should receive two doses of PCV13 separated by 8 weeks. Patients who meet the above criteria but received three doses of PCV13 before the age of 12 months only need one additional dose of PCV13.  After the PCV13 series is completed, these patients should receive one dose of PPSV23 at 8 weeks after their last PCV13.¹ In children with sickle cell disease and other hemoglobinopathies, functional or anatomic asplenia, HIV infection, or immunocompromising conditions resulting from disease or treatment of a disease, an additional dose of PPSV23 (two total) should be given at least 5 years apart.¹

Children aged 6 to 18 years who have not received a dose of PPSV23 or PCV13 and have CSF leaks, cochlear implant, or an immunocompromising condition should receive one dose of PCV13, followed by PPSV23 at least 8 weeks later. Patients with an immunocompromising condition should receive an additional PPSV23 dose at least 5 years after the first dose.¹ Children aged 6 to 18 years who have not received a PPSV23 vaccine and who have chronic heart, liver, or lung disease, diabetes, or alcoholism should receive one dose of PPSV23.¹

Based on the Advisory Committee for Immunization Practice (ACIP) guidance, a single dose of PPSV23 is recommended by the CDC for adults aged 19 to 64 years who have a chronic condition that puts them at an increased risk of pneumococcal disease. These conditions include chronic heart disease (excluding hypertension), diabetes, lung or liver disease, alcoholism, or cigarette smoking.¹

Patients aged 19 to 64 years with cochlear implants or CSF leaks should receive one dose of PCV13, followed by a dose of PPSV23 at least 8 weeks later. Adults aged 19 to 64 years with immunocompromising conditions (asplenia, HIV, malignancies, etc.) should receive a dose of PCV13 followed by two doses of PPSV23. The PCV13 should be given first, followed 8 weeks later by the first dose of PPSV23, and then the second PPSV23 vaccine 5 years after the first PPSV23 dose.¹

From 2000 to 2014, the rates of IPD in adults aged ³65 years decreased ninefold. The decrease correlated with the introduction of the pneumococcal vaccination program in children in 2000 (first with PCV7 in 2000 and then with PCV13 in 2010).¹¹ In 2014, the ACIP recommended that PCV13 be used in series with PPSV23 in patients aged ³65 years.

As of 2018, 62% of patients > age 65 years had received any pneumococcal vaccine; 47% had received PCV13 alone; 45% had received PPSV23 alone; and 30% had received both PCV13 and PPSV23. However, from 2014 to 2017, the change in the incidence of IPD in this population was minimal; it remained steady at around five in 100,000 persons. In addition, two independent economic models were less favorable towards the continued use of PCV13 in series with PPSV23 compared to PPSV23 alone.¹¹

As of June 2019, the ACIP recommends that patients aged 65 years and older without immunocompromising conditions, CSF leaks, or cochlear implant receive a single dose of PPSV23 at least 5 years after they receive any previous PPSV23 vaccination.¹¹

While the indirect effects of the pediatric PCV13 vaccination recommendations have led to a decreased risk of IPD in older adults, some persons may still have an increased risk of IPD. In these instances, the ACIP recommends that the decision to receive PCV13 in patients older than age 65 years be a shared decision between the healthcare provider and the patient. Those who are at an increased risk of exposure to PCV13 serotypes include:

• Patients residing in a nursing home or long-term care facility

• Patients residing in an area with low uptake of PCV13 or no PCV13 pediatric program.

In addition, there was no difference found in the incidence in IPD in patients older than age 65 years with chronic heart, lung, or liver disease; with diabetes; with chronic alcoholism; or who smoke. These patient populations are more susceptible to negative residual effects of IPD and may also consider receiving a dose of PCV13.¹¹

In adults aged 65 years and older with an immunocompromising condition, cochlear implant, or CSF leak who have not received a dose of PCV13, one dose of PCV13 should be given, followed by a single dose of PPSV23 8 weeks later.¹

If a patient and provider decide that a dose of PCV13 is appropriate for the patient, the PCV13 dose should be given first, followed by a single PPSV23 dose at least 1 year following the PCV13 dose. If that patient already received a dose of PPSV23 after age 65 years, he or she could still receive one dose of PCV13 at least 1 year following the PPSV23 dose.¹

Tools for Providers

The CDC has created an app called PneumoRecs VaxAdvisor for providers to help determine when and which pneumococcal vaccine may be due for a specific patient. The provider inputs into the app the patient’s age, prior pneumococcal vaccination history, and underlying medical conditions. Patient-specific recommendations based on the ACIP schedule will be provided. The app is available on iOS, Android, or desktop.¹³ Additional information, including tables and algorithms for specific pneumococcal vaccine recommendations, can be found at https://www.cdc.gov/vaccines/vpd/pneumo/downloads/pneumo-vaccine-timing.pdf.

Conclusion

Vaccination against S pneumoniae continues to be an important public-health initiative and is included in the Healthy People 2030 goals to encourage vaccination and reduce the burden of noninvasive and invasive pneumococcal illness, namely pneumonia, among older adults.¹⁴ Pharmacists play a key role in immunization delivery by advocating for vaccinations, identifying patients who are candidates for immunizations, administering vaccinations, and mitigating missed opportunities.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

REFERENCES

1. CDC. Epidemiology and Prevention of Vaccine-Preventable Diseases. Hamborsky J, Kroger A, Wolfe S, eds. 13th ed. Washington D.C.: Public Health Foundation, 2015. www.cdc.gov/vaccines/pubs/pinkbook/index.html.
2. CDC. Global pneumococcal disease and vaccine. www.cdc.gov/
pneumococcal/global.html. Accessed January 30, 2021.
3. Demirdal T, Sen P, Emir B. Predictors of mortality in invasive pneumococcal disease: a meta-analysis. Expert Rev Anti-infect Ther. 2020:1-18.
4. Olasupo O, Segal R, Brown J. Missed opportunities for pneumococcal vaccinations in high-risk and older adults in the United States. J Infect Public Health. 2020;13(1):101-103.
5. Pneumovax 23 (pneumococcal vaccine polyvalent) [package insert]. Whitehouse Station, NJ: Merck & Co., Inc; March 2013. www.merck.com/product/usa/pi_circulars/p/pneumovax_23/pneumovax_pi.pdf.
6. CDC. Timing and spacing of immunobiologics. www.cdc.gov/
vaccines/hcp/acip-recs/general-recs/timing.html. Accessed January 30, 2021.
7. MacIntyre CR, Egerton T, McCaughey M, et al. Concomitant administration of zoster and pneumococcal vaccines in adults ³60 years old. Hum Vaccin. 2010;6(11):894-902.
8. CDC. What everyone should know about Zostavax. www.cdc.gov/vaccines/vpd/shingles/public/zostavax/index.html. Accessed January 23, 2021.
9. Marechal C, Lal H, Poder A, et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine co-administered with the 23-valent pneumococcal polysaccharide vaccine in adults ³50 years of age: a randomized trial. Vaccine. 2018;36(29):4278-4286.
10. Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1997;46(RR-08):1-24.
11. Matanock A, Lee G, Gierke R, et al. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged ³65 years: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68(46):1069-1075.
12. Prevnar 13 (pneumococcal 13-valent conjugate vaccine) [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals (Pfizer); January 2014. http://labeling.pfizer.com/showlabeling.aspx?id=501. Accessed January 30, 2021.
13. CDC. PneumoRecs VaxAdvisor Mobile App for Vaccine Providers. https://www.cdc.gov/vaccines/vpd/pneumo/hcp/pneumoapp.html. Accessed January 30, 2021.
14. United States Department of Health and Human Services Office of Disease Prevention and Health Promotion. Healthy People 2030. https://health.gov/healthypeople. Accessed January 30, 2021.

To comment on this article, contact rdavidson@uspharmacist.com.