title: Risk stacking of pneumococcal vaccination indications increases mortality in unvaccinated adults with Streptococcus pneumoniae infections.
abstract: Several chronic disease states have been identified as pneumococcal vaccination indications due to their ability to increase pneumococcal disease development and subsequent mortality. However, the risk of mortality according to the number of these disease states present is unknown. We sought to determine the impact of concomitant, multiple risk factors (stacked risks) for pneumococcal disease on 30-day mortality in adults.
  
  
  
  This was a national case-control study of unvaccinated older Veterans (≥50years of age) admitted to Veterans Affairs medical centers from 2002 to 2011 with serious pneumococcal infections (pneumonia, bacteremia, meningitis) based on positive S. pneumoniae blood, cerebrospinal fluid, or respiratory cultures, respectively. Cases were those not alive 30days following culture, while controls were alive. Using logistic regression, we quantified risk of 30-day mortality among patients with stacked risk factors, including age ≥65years, alcohol abuse, chronic heart disease, chronic liver disease, chronic respiratory disease, diabetes mellitus, immunodeficiency, and smoking.
  
  
  
  We identified 9730 serious pneumococcal infections, with an overall 30-day mortality rate of 18.6% (1764 cases, 7966 controls). Infection types included pneumonia (62%), bacteremia (26%), and bacteremic pneumonia (11%). Along with eight individual risk factors, we assessed 247 combinations of risk factors. Most cases (85%) and controls (74%) had at least two risk factors. Mortality increased as risks were stacked, up to six risk factors (one: OR 1.5, CI 1.08-2.07; two: OR 2.01, CI 1.47-2.75; three: OR 2.71, CI 1.99-3.69; four: OR 3.27, CI 2.39-4.47; five: OR 3.63, CI 2.60-5.07; six: OR 4.23, CI 2.69-6.65), with each additional risk factor increasing mortality an average of 55% (±13%).
  
  
  
  Among adults ≥50years with serious pneumococcal disease, mortality risk increased approximately 55% as vaccination indications present increased. Mortality with six stacked indications was double that of two indications.
authors.affiliation: Veterans Affairs Medical Center, Infectious Diseases Research Program and Center of Innovation in Long Term Services and Supports, Providence, RI, United States; University of Rhode Island, Department of Pharmacy Practice, College of Pharmacy, Kingston, RI, United States.
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Morton
authors.affiliation: Veterans Affairs Medical Center, Infectious Diseases Research Program and Center of Innovation in Long Term Services and Supports, Providence, RI, United States; University of Rhode Island, Department of Pharmacy Practice, College of Pharmacy, Kingston, RI, United States.
authors.forename: Haley J
authors.initials: HJ
authors.lastname: Morrill
authors.affiliation: Veterans Affairs Medical Center, Infectious Diseases Research Program and Center of Innovation in Long Term Services and Supports, Providence, RI, United States; University of Rhode Island, Department of Pharmacy Practice, College of Pharmacy, Kingston, RI, United States; Warren Alpert Medical School of Brown University, Division of Infectious Diseases, Providence, RI, United States.
authors.forename: Kerry L
authors.initials: KL
authors.lastname: LaPlante
authors.affiliation: Veterans Affairs Medical Center, Infectious Diseases Research Program and Center of Innovation in Long Term Services and Supports, Providence, RI, United States; University of Rhode Island, Department of Pharmacy Practice, College of Pharmacy, Kingston, RI, United States; Brown University School of Public Health, Providence, RI, United States. Electronic address: Aisling_Caffrey@uri.edu.
authors.forename: Aisling R
authors.initials: AR
authors.lastname: Caffrey
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D011008:Pneumococcal Infections / Q000401:mortality*; D018570:Risk Assessment; D016019:Survival Analysis; D014728:Veterans
keywords: Mortality; Pneumococcal vaccination; Risk stacking; Streptococcus pneumoniae