Meta-Analysis: Pneumococcal Vaccination Reduces Hospitalization, Mortality in Older Adults

Results from a new meta-analysis and systematic review published in Human Vaccines & Immunotherapeutics affirm the efficacy of pneumococcal vaccination in reducing all-cause hospitalization and mortality. Specific benefits were seen in patients aged 75 and older and those receiving mixed pneumococcal polysaccharide vaccine (PPSV) and conjugate vaccine (PCV).¹

Importance of Pneumococcal Vaccination

Pneumococcal vaccines are a proven cornerstone of public health and have been for decades. Contracting Streptococcus pneumoniae is a major concern for many, especially older adults who are disproportionately affected due to comorbidities and age-related immune weakness. Pneumococcal pneumonia, a serious manifestation of the Streptococcus pneumoniae bacteria, constitutes a scourge on older adults globally; complications can include long hospital stays, sepsis, and respiratory failure.^1,3

Given the immense burdens posed by the bacteria, vaccination is a critical tool pharmacists can use to protect high-risk patients. A series of pneumococcal vaccines are recommended by the Advisory Committee on Immunization Practices (ACIP) , with vaccine choices stratified across populations. For adults aged 50 and older, ACIP recommends routine vaccination with 15-valent PCV, 20-valent PCV, or 21-valent PCV, with additional PPSV vaccination recommended if PCV15 was used.^1,4

Existing meta-analyses have tackled evaluations of the broader effectiveness of pneumococcal vaccines, but they often focused on the general population or general outcomes rather than specifically analyzing the impact on older adults and associated hospitalization and mortality. These outcomes are especially salient to investigate as they are the biggest contributors to high economic and clinical burden. Therefore, the current investigators sought to systematically evaluate the effect of pneumococcal vaccination on mortality and hospitalization in older adults.¹

Meta-Analysis Affirms Effectiveness But Reports Inconsistencies

A comprehensive search of electronic databases was conducted up until March 2025. Studies were included if they enrolled older adults, had a pneumococcal vaccine administered or considered as an intervention, featured a comparator arm, reported outcomes such as hospitalization or mortality, and followed a randomized study design. In total, 35 publications were included.¹

Interestingly, pneumococcal vaccination was initially not associated with a reduction in pneumonia-associated hospitalization (odds ratio [OR]: 0.83 [95% CI, 0.60—1.15]; P = .27) compared with unvaccinated individuals. Similar results were seen in a subgroup analysis of patients administered PPSV23 (OR: 0.75 [95% CI, 0.56—1.03]; P = .07) or PCV13 (OR: 2.88 [95% CI, 0.41—20]; P = .29). There was, however, a major reduction among patients receiving mixed PPSV23 or PCV13 (OR: 0.49 [95% CI, 0.35—0.69]; P < .0001) compared with unvaccinated individuals.¹

A subgroup analysis based on the duration of follow-up time demonstrated significant reductions in pneumonia-associated hospitalization at 1 year (OR: 0.63 [95% CI, 0.42—0.95]; P = .03) and 1-to-5 years (OR: 0.76 [95% CI, 0.61—0.94]; P = .010). Notably, this association was not significant after 5 years.¹

Furthermore, the investigators observed major reductions in hospitalization and mortality among adults aged older than 75 (OR: 0.71 [95% CI, 0.54—0.94]; P = .02), although this was not similarly observed among adults aged 60 through 74 years.¹

Once again, when shifting towards the effectiveness of pneumococcal vaccination on pneumonia-related mortality, the most significant reductions were observed in patients that received mixed PCV13 or PPSV23 vaccination, intermediate follow-up of 1-to-5 years, older adults aged 60 through 75 years, and adults aged older than 75. There were no significant mortality benefits among patients who received PPSV23 alone, had less than 1 year of follow-up, or had chronic and non-chronic comorbidities. Similar indications were found when evaluating all-cause mortality.¹

Addressing Limitations

Although this review highlights the effectiveness of pneumococcal vaccines in preventing hospitalization and reducing mortality, there were mixed results that showcase inconsistencies. The investigators said these inconsistencies are due to limitations in outcome ascertainment and unmeasured confounding, causing variability in the observations. Despite this, the majority of studies agree that pneumococcal vaccination is a valuable tool, especially in patients who utilize other preventive measures.¹

“Large, high‑quality randomized trials are needed to confirm the effectiveness of pneumococcal vaccination in [older adults],” the study authors concluded.¹

REFERENCES

1. Bulkhi A, Khadawardi HA, Dairi MS, et al. Effectiveness of pneumococcal vaccination in reducing hospitalization and mortality among the elderly: A systematic review and meta-analysis. Hum Vac Immuno. 2025;21(1). doi:10.1080/21645515.2025.2561315

2. Kruckow KL, Zhao K, Bowdish DM, Orihuela CJ. Acute organ injury and long-term sequelae of severe pneumococcal infections. Pneumonia (Nathan). 2023;15(1). doi:10.1186/s41479-023-00110-y

3. Darkwah S, Kotey FCN, Ahenkorah J, et al. Sepsis-related lung injury and the complication of extrapulmonary pneumococcal pneumonia. Diseases. 2024;12(4):72. doi:10.3390/diseases12040072

4. Pneumococcal—Pneumococcal vaccine recommendations. CDC. Updated October 26, 2024. Accessed October 3, 2025. https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/index.html