Risk stacking of pneumococcal vaccination indications increases mortality in unvaccinated adults with Streptococcus pneumoniae infections

Abstract

Background

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.

Methods

This was a national case-control study of unvaccinated older Veterans (≥50 years 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 30 days following culture, while controls were alive. Using logistic regression, we quantified risk of 30-day mortality among patients with stacked risk factors, including age ≥65 years, alcohol abuse, chronic heart disease, chronic liver disease, chronic respiratory disease, diabetes mellitus, immunodeficiency, and smoking.

Results

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%).

Conclusions

Among adults ≥50 years 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.

Introduction

Serious Streptococcus pneumoniae infections, including pneumonia, bacteremia, and meningitis, are a major cause of morbidity and mortality among older adults [1], [2], [3]. Since the 1980s, vaccines to prevent pneumococcal disease have been used on a global scale to mitigate the risks associated with these bacterial infections [4]. The Advisory Committee on Immunization Practices (ACIP) recommends administration of the pneumococcal vaccination to adults with certain risk factors for pneumococcal disease, including age ≥ 65 years, alcoholism, heart disease and heart failure, chronic respiratory disease, hepatic dysfunction, immunodeficiency, and smoking, in an effort to prevent invasive pneumococcal disease (IPD) and subsequent poor outcomes [3].

Recent research has revealed that the presence of multiple, concomitant risk factors (risk stacking), particularly those conditions identified by ACIP as indications for pneumococcal vaccination, increases the likelihood of developing pneumococcal disease beyond the risk posed by individual risk factors alone [5], [6]. As our population ages, it is becoming more common for patients to have two or more risk factors [6]. However, the impact of risk stacking on outcomes, namely mortality, of adults who end up developing pneumococcal disease remains unknown. Furthermore, current data on risk stacking are limited in that there is no information regarding the impact of risk stacking “at-risk” conditions (e.g., alcoholism, heart disease, liver disease, cigarette smoking) with “high-risk” conditions (e.g., immunodeficiency) [5], [6], [7]. As such, the purpose of this study was to quantify the impact of stacking risk factors for developing pneumococcal disease on 30-day mortality among unvaccinated older adults.