The Roles of the Charlson Comorbidity Index and Time to First Antibiotic Dose as Predictors of Outcome in Pneumococcal Community-Acquired Pneumonia.

PURPOSE: In this retrospective study, we aimed to investigate the role of comorbidities using the Charlson comorbidity index (CCI) and time to first antibiotic dose (TFAD) in patients with pneumococcal community-acquired pneumonia (PCAP). METHODS: All consecutive ER admissions with PCAP who were hospitalized in the University Hospital, Zurich between 2006 and 2012 were included. The primary outcome was to determine possible determinants of all-cause in-hospital mortality (ACIHM). The second endpoint was to detect risk factors for adverse events (AEs) and determinants of length of stay (LOS). RESULTS: 108 subjects (mean age 57.6 years) were included. The median (IQR) CCI was 4 (1, 8). The median (IQR) TFAD was 210 (150, 280) min. ACIHM was 6.5 % (7/108), and median (IQR) LOS was 9 (6, 14) days. PCAP-related AEs were observed in 57 cases (52.8 %). In the multivariable analysis, neither CCI nor TFAD was associated with the outcome measures. Pneumonia severity index (PSI) was the only statistically significant predictor of ACIHM (HR 1.31/10 point increase, 95 % CI 1.12-1.53, p = 0.001) and AE rate (OR 1.31, 95 % CI 1.15-1.50, p < 0.001). CONCLUSIONS: In this study including comparatively young patients with rather mild disease severity, we found no strong evidence supporting that CCI or TFAD influenced short-term outcome measures of PCAP. Yet, pneumonia severity appears to be the most important factor for the outcome.

Host genetic variants associated with susceptibility and severity of pneumococcal pneumonia in adult patients.

BACKGROUND: Pneumococcal community-acquired pneumonia (P-CAP) is a major cause of morbidity and hospitalization. Several host genetics factors influencing risk of pneumococcal disease have been identified, with less information about its association with P-CAP. The aim of the study was to assess the influence of single nucleotide polymorphisms (SNP) within key genes involved in the innate immune response on the susceptibility to P-CAP and to study whether these polymorphic variants were associated with the severity and outcome of the episodes in a cohort of adult Caucasian patients. METHODS: Seventeen SNPs from 7 genes (IL-R1, IL-4, IL-10, IL-12B, NFKBIA, NFKBIE, NFKBIZ) were analyzed. For susceptibility, a case-control study including a cohort of 57 adult with P-CAP, and 280 ethnically matched controls was performed. Genetic influence on clinical severity and outcome was evaluated in a prospective observational study including all consecutive adult P-CAP patients from November 2015 to May 2017. RESULTS: The NFKBIA polymorphism rs696 and a haplotype combination were associated with susceptibility to P-CAP (OR = 0.62, p = 0.005 and OR = 0.63, p = 0.008, respectively). The SNP IL4 rs2227284 was associated with severe P-CAP (OR = 2.17, p = 0.04). IL-R1 (rs3917267) and IL-10 (rs3024509) variants were related with respiratory failure (OR = 3.31, p = 0.001 and OR = 0.18, p = 0.003, respectively) as well as several haplotype combinations in NFKBIA, NFKBIZ, IL-R1 and IL-10 (p = 0,02, p = 0,01, p = 0,001, p = 0,03, respectively). CURB-65 values were associated with the IL-10 rs3024509 variant (beta = - 0.4, p = 0.04), and with haplotype combinations of NFKBIZ and IL-10 (p = 0.05, p = 0.04, respectively). Genetic variants in IL-10 (rs3024509) and in IL-12B (rs730691) were associated with PSI values (beta = - 0.54, p = 0.01, and beta = - 0.28, p = 0.04, respectively), as were allelic combinations in IL-R1 (p = 0.02) and IL-10 (p = 0.01). Finally, several polymorphisms in the IL-R1 gene (rs13020778, rs2160227, & rs3917267) were associated with the time elapsed until clinical stability (beta = - 0.83, p = 0.03; beta = - 1, p = 0.02 and beta = 1.07, p = 0.008, respectively). CONCLUSIONS: A genetic variant in NFKBIA was associated with susceptibility to P-CAP in adult Caucasian patients and genetic variants from key cytokines of the innate immune response (Il-4, IL-10, IL-R1 and IL-12B) and NF-κB inhibitors were associated with different phenotypes of severe P-CAP. If validated, these SNPs may help to identify people at risk of P-CAP or severe P-CAP on which preventive measures could be applied.