BackgroundIn 2014, pneumococcal conjugate (PCV13) and polysaccharide (PPSV23) vaccines were recommended in series for all US adults ≥65 years. We conducted a case–control study to evaluate risk factors for invasive pneumococcal disease (IPD) among adults ≥65 years old.MethodsIPD cases (isolation of pneumococcus from sterile sites) were identified through Active Bacterial Core surveillance during 2015–2018. Isolates were serotyped using whole genome sequencing. Four controls, identified through a commercial database, were matched per case by age and zip code. We obtained vaccination and medical histories from providers, vaccine registries and participant interviews. A functional status score was calculated based on participant interview. We calculated IPD odds ratios using multivariable conditional logistic regression.ResultsWe enrolled 328 IPD cases and 1,280 matched controls. Fifty percent of case-patients and 55% of controls received a dose of PCV13. Case-patients were more likely than controls to have a chronic condition (heart, liver, or lung disease, diabetes, cochlear implant, alcohol abuse, smoking; 82% vs. 59%), immunosuppression (60% vs. 32%), poor functional status (score of ≥ 3; 71% vs. 50%), annual household income <$30,000 (38% vs. 25%) and education level of high school or less (36% vs. 25%). In a multivariable model, case-patients were more likely than controls to have a chronic condition (OR 2.48, 95% CI 1.72, 3.58), immunosuppression (OR 2.56, 95% CI 1.92,3.42), poor functional status (OR 3.66, 95% CI 2.42, 5.54), and primary or secondary smoking exposure (OR 3.09, 95% CI 1.32, 7.2). In analysis limited to PCV13-type cases and matched controls, adjusting for PCV13 receipt, measures of association were no longer significant for chronic conditions (OR 1.45, 95% 0.71, 2.95), immunosuppression (OR 1.51, 95% CI 0.83, 2.74), or poor functional status (OR 1.98, 95% CI 0.91, 4.3).ConclusionChronic and immunosuppressive conditions remain IPD risk factors for adults in the era of PCV13 use; poor functional status was also identified as a risk factor. Targeted evaluation of adults with poor functional status could inform IPD prevention strategies. PCV13 may reduce the risk of PCV13-type IPD associated with chronic conditions and poor functional status.Disclosures W. Schaffner, Merck: Member, Data Safety Monitoring Board, Consulting fee; Pfizer: Member, Data Safety Monitoring Board, Consulting feeDynavax: Consultant, Consulting fee; Seqirus: Consultant, Consulting fee; SutroVax: Consultant, Consulting fee; Shionogi: Consultant, Consulting fee.