RESUMEN
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.
Asunto(s)
Infecciones Comunitarias Adquiridas/mortalidad , Comorbilidad , Neumonía Neumocócica/mortalidad , Índice de Severidad de la Enfermedad , Tiempo de Tratamiento , Adulto , Anciano , Antibacterianos/administración & dosificación , Infecciones Comunitarias Adquiridas/complicaciones , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Neumonía Neumocócica/complicaciones , Neumonía Neumocócica/tratamiento farmacológico , Factores de Riesgo , Suiza/epidemiologíaRESUMEN
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.