Host Factors and Biomarkers Associated with Poor Outcomes in Adults with Invasive Pneumococcal Disease

Abstract

Background: Invasive pneumococcal disease (IPD) causes considerable morbidity and mortality. We aimed to identify host factors and biomarkers associated with poor outcomes in adult patients with IPD in Japan, which has a rapidly-aging population.

Methods: In a large-scale surveillance study of 506 Japanese adults with IPD, we investigated the role of host factors, disease severity, biomarkers based on clinical laboratory data, treatment regimens, and bacterial factors on 28-day mortality.

Results: Overall mortality was 24.1%, and the mortality rate increased from 10.0% in patients aged ˂50 years to 33.1% in patients aged ≥80 years. Disease severity also increased 28-day mortality, from 12.5% among patients with bacteraemia without sepsis to 35.0% in patients with severe sepsis and 56.9% with septic shock. The death rate within 48 hours after admission was high at 54.9%. Risk factors for mortality identified by multivariate analysis were as follows: white blood cell (WBC) count <4000 cells/μL (odds ratio [OR], 6.9; 95% confidence interval [CI], 3.7-12.8, p < .001); age ≥80 years (OR, 6.5; 95% CI, 2.0-21.6, p = .002); serum creatinine ≥2.0 mg/dL (OR, 4.5; 95% CI, 2.5-8.1, p < .001); underlying liver disease (OR, 3.5; 95% CI, 1.6-7.8, p = .002); mechanical ventilation (OR, 3.0; 95% CI, 1.7-5.6, p < .001); and lactate dehydrogenase ≥300 IU/L (OR, 2.4; 95% CI, 1.4-4.0, p = .001). Pneumococcal serotype and drug resistance were not associated with poor outcomes.

Conclusions: Host factors, disease severity, and biomarkers, especially WBC counts and serum creatinine, were more important determinants of mortality than bacterial factors.

Fig 1. Case fatality rates by age groups and disease severity.

Fig 2. Distribution of deaths in patients with invasive pneumococcal disease in relation to the time elapsed after admission to the hospital.

Fig 3. Kaplan-Meier estimate of the probability of 28-day survival.

(A) Patients with leukopenia on admission had a higher risk for death, compared to patients without leukopenia. The majority of deaths occurred within the first 5 days after admission to the hospital (p < .001 by the log-rank test). WBC, white blood cell count. (B) Patients with severe sepsis or septic shock compared to patients with bacteraemia without sepsis or sepsis on admission. Mortality increased with severity of sepsis (p < .001 by the log-rank test).