Antibiotic Resistance in Pneumococcal Disease Falls as Vaccine Serotypes Recede

Streptococcus pneumoniae remains a leading cause of invasive disease worldwide, with a 30-day case fatality risk ranging from 8% to 30%. Researchers analyzed data from Switzerland's national invasive pneumococcal disease (IPD) surveillance system, which requires laboratories to send sterile-site pneumococcal isolates to the Swiss National Reference Center for Invasive Pneumococci for serotyping and susceptibility testing. The study, published in Pneumonia, examined how the 2011 introduction of the pediatric PCV13 program and the COVID-19 pandemic affected antibiotic resistance patterns.¹

“There are 2 types of pneumococcal vaccines: pneumococcal conjugate vaccines (PCV15, PCV20, and PCV21) and a pneumococcal polysaccharide vaccine (PPSV23). Each of these vaccines is approved to prevent pneumococcal disease and protect against specific strains of pneumococcal bacteria,” Gretchen K. Garofoli, PharmD, BCACP, CTTS, FAPhA, clinical professor at the West Virginia University School of Pharmacy, said.²

Of 8747 total IPD cases identified between 2012 and 2022, 7833 had a reported antibiogram. Investigators found that the proportion of isolates nonsusceptible to erythromycin and cotrimoxazole significantly declined across the study period (incidence rate ratio [IRR], 0.9; P < .001 for both), and penicillin nonsusceptibility held roughly steady overall, falling from 9.2% in 2012 to 4.7% in 2022.¹

Ceftriaxone resistance was rare throughout, and levofloxacin nonsusceptibility was detected in just 11 cases over the entire 11-year period. Notably, resistance did not rise during the early pandemic years, in contrast to reports from several other European countries during that period.¹

Vaccine and Nonvaccine Serotypes Both Drive Resistance

Using multivariate logistic regression, the researchers linked specific serotypes to nonsusceptibility across 4 antibiotic classes. Among PCV13 serotypes, 6B, 9V, 14, 19A, and 19F were significantly associated with penicillin nonsusceptibility, and serotypes 14, 19A, and 19F were also linked to ceftriaxone nonsusceptibility. These same 5 PCV13 serotypes were significantly associated with nonsusceptibility to 3 antibiotic classes—penicillin, erythromycin, and cotrimoxazole—across the full study period.¹

Resistance was not limited to vaccine-covered strains, however. Among serotypes not covered by the 20-valent vaccine (PCV20), 15A, 23B, 24/F, and 6C were each associated with nonsusceptibility to at least 2 antibiotic groups. Serotype 23B, for example, showed strong associations with both penicillin (odds ratio [OR], 11.1) and cotrimoxazole (OR, 4.1) nonsusceptibility. Serotype 33F stood out for its association exclusively with erythromycin nonsusceptibility (OR, 11.1). The 2 most frequently detected serotypes overall, 3 and 8, were susceptible to all antibiotics tested.¹

The authors noted that this serotype-resistance relationship is well established, with several resistant serotypes, including 6A, 6B, 9V, 14, 19A, 19F, and 23F, being documented years before PCVs were introduced and being part of the rationale for including them in the original 7-valent vaccine. Because the more resistant serotypes tend to be vaccine-covered while nonvaccine serotypes such as 3 and 22F remain comparatively susceptible, the declining prevalence of vaccine-type disease is likely the primary driver of the overall resistance reduction observed in Switzerland. Similar declines following PCV13 introduction have been reported in South Africa, Spain, and Belgium.¹

Clinical and Demographic Associations

Antibiotic nonsusceptibility was more common in patients aged 0 to 16 years, particularly for penicillin and cotrimoxazole, and proportions were comparable between adults aged 17 to 64 years and those 65 years and older. Splenectomy was significantly associated with both penicillin (OR, 2.2) and erythromycin (OR, 2.3) nonsusceptibility, and cotrimoxazole nonsusceptibility was linked to immunosuppression, nephrotic syndrome, and other risk factors. The authors suggested this cotrimoxazole association likely reflects the frequent use of the drug as prophylaxis against Pneumocystis jirovecii in immunosuppressed and nephrotic patients, and the splenectomy-erythromycin link may reflect chronic macrolide use for infection prevention in asplenic patients.¹

Importantly, meningitis was significantly associated with penicillin nonsusceptibility, a finding the authors said echoes recent French data linking pediatric meningitis increases to the penicillin-resistant serotype 24F. Despite this, overall antibiotic nonsusceptibility was not significantly associated with death. Instead, mortality risk was tied to older age, bacteremia without focus, meningitis, and underlying conditions such as immunosuppression, functional asplenia, and chronic kidney disease or diabetes. The authors attributed the lack of a resistance-mortality link to generally low resistance rates and the ability to overcome low-level penicillin resistance with adequate beta-lactam dosing.¹

Why This Matters for Pharmacists

The findings carry direct implications for antimicrobial stewardship and vaccine counseling in practice. Pneumococcal disease remains a substantial clinical burden, with the Centers for Disease Control and Prevention (CDC) estimating that pneumococcal bacteria causing IPD are nonsusceptible to at least 1 antibiotic class in more than 40% of cases, and pneumococcal pneumonia alone causes an estimated 150,000 hospitalizations annually in the United States. Drug-resistant S pneumoniae was linked to roughly 900,000 US infections and 3600 deaths as of 2018, according to CDC estimates.^3,4

Pharmacists are increasingly positioned to help close remaining immunization gaps. In June 2024, the FDA approved a 21-valent pneumococcal conjugate vaccine (Capvaxive), the first PCV designed specifically for adults, covering serotypes responsible for approximately 84% of IPD in adults 50 years and older, compared with roughly half that coverage for PCV20.^5,6

“One other interesting thing to consider when choosing a PCV for a patient is that there are different strains in each of the vaccines. Serotype 4 is a strain that is often pointed out as it is in PCV20 but not in PCV21,” Garofoli said.² “In certain populations, specifically in the Western US as well as in the unhoused population, this serotype is more prevalent. When determining which product to utilize, not only the individual patient risk but also where they live and their lifestyle factors should be considered. In this population, you would recommend PCV20 to ensure coverage for serotype 4.”

The Advisory Committee on Immunization Practices subsequently lowered the routine PCV recommendation age to 50 years for all adults, expanding the population eligible for pharmacist-administered vaccination.⁴ The Swiss study's authors noted that adult pneumococcal vaccination coverage remains low even where recommended, creating an ongoing opportunity for community and health-system pharmacists to identify and vaccinate eligible patients, particularly those with the splenectomy, immunosuppression, and chronic kidney or lung disease risk factors flagged in the study as linked to both resistance and mortality.¹

The authors cautioned that as newer, broader-coverage vaccines continue to reshape which serotypes circulate, continued resistance surveillance will be essential to track whether currently uncommon but resistant nonvaccine serotypes expand to fill the gap left by vaccine-type strains.¹

REFERENCES

1. Just N, Casanova C, Baty F, Albrich WC, Hilty M. Antibiotic non-susceptibility associated serotypes of invasive pneumococcal disease - a nationwide population study from Switzerland, 2012–2022. Pneumonia. 2026;18:15. doi:10.1186/s41479-026-00203-4

2. Nowosielski B, Garofoli G. FAQ: How a Variety of Pneumococcal Vaccines Protect Patient Populations. Drug Topics. May 12, 2026. Accessed July 7, 2026. https://www.drugtopics.com/view/how-a-variety-of-pneumococcal-vaccines-protect-patient-populations

3. Pneumococcal disease surveillance and trends. Centers for Disease Control and Prevention. Updated February 25, 2026. Accessed July 7, 2026. https://www.cdc.gov/pneumococcal/php/surveillance/index.html

4. Chapter 11: Pneumococcal. Manual for the Surveillance of Vaccine-Preventable Diseases. Centers for Disease Control and Prevention. Updated February 20, 2026. Accessed July 7, 2026. https://www.cdc.gov/surv-manual/php/table-of-contents/chapter-11-pneumococcal.html

5. Kobayashi M, Farrar JL, Gierke R, et al. Use of 21-valent pneumococcal conjugate vaccine among U.S. adults: recommendations of the Advisory Committee on Immunization Practices — United States, 2024. MMWR Morb Mortal Wkly Rep. 2024;73(36):793-798. https://www.cdc.gov/mmwr/volumes/73/wr/mm7336a3.htm

6. U.S. FDA approves Capvaxive (pneumococcal 21-valent conjugate vaccine) for prevention of invasive pneumococcal disease and pneumococcal pneumonia in adults. News release. Merck & Co. June 17, 2024. Accessed July 7, 2026. https://www.merck.com/news/u-s-fda-approves-capvaxive-pneumococcal-21-valent-conjugate-vaccine-for-prevention-of-invasive-pneumococcal-disease-and-pneumococcal-pneumonia-in-adults/