ABSTRACT
Studies have established that diabetic patients with community-acquired pneumonia (CAP) may have increased mortality. The primary objective of this study was to investigate if time to first appropriate antibiotic in the emergency department (ED) was associated with in-hospital mortality of CAP in patients with diabetes mellitus (DM). This was a retrospective cohort study of adult diabetic patients who were admitted with CAP. Patients were stratified into two groups: those who received first dose of appropriate antibiotic within 8 hours of triage and those who received it later than 8 hours. A multiple logistic regression analysis was performed. Two hundred six patients were included in the study. Fifty-nine patients (28.6%) had complications of CAP on admission and 31 patients (16%) died. In-hospital mortality was higher in patients who received their initial appropriate antibiotic after 8 hours of triage than those who received it within 8 hours [18 (35.3%), 15 (9.7%), p < 0.0001]. Time to first appropriate antibiotic later than 8 hours of triage was associated with increased in-hospital mortality (OR 4, 95% CI 1.2-13.1, p = 0.02). Antibiotic administration later than 8 hours of triage in the ED was associated with increased in-hospital mortality of CAP among patients with DM.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Community-Acquired Infections/drug therapy , Diabetes Complications , Drug Therapy/methods , Emergency Medical Services/methods , Pneumonia, Bacterial/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Community-Acquired Infections/mortality , Female , Humans , Male , Middle Aged , Pneumonia, Bacterial/mortality , Retrospective Studies , Time Factors , Treatment Outcome , Young AdultABSTRACT
Inflammation may influence response to pharmacotherapy. We investigated the effect of inflammation on response to sotalol, a beta-adrenergic receptor and potassium channel antagonist. Racemic sotalol (40 mg kg(-1)) was administered to healthy, acutely (interferonalpha 2a-induced) and chronically (Mycobacterium butyricum-induced adjuvant arthritis) inflamed male Sprague-Dawley rats (n=4 - 6/group). Another group of interferon-treated rats received 3 mg kg(-1) of anti-TNF antibody infliximab. Electrocardiogram (ECG) recorded and plasma sotalol concentration monitored for 6 h. The study was repeated in acutely inflamed rats following administration of stereochemically pure individual sotalol enantiomers [40 mg kg(-1) S (potassium channel blocker) or 20 mg kg(-1) R (beta-adrenergic/potassium channel blocker)]. Chronic arthritis was readily evident. Acute arthritis was associated with elevated segmented neutrophils and increased plasma nitrite and tumour necrosis factor (TNF) concentrations. Sotalol affected ECG in all rats. In both inflamed groups, however, response to sotalol in prolongation of QT interval (potassium channel sensitivity) was reduced. The effect of PR interval (beta-adrenergic activity) was also reduced following administration of the racemate and R-enantiomer. No significant differences in pharmacokinetics were observed between control and inflamed rats. Infliximab reduced nitrite and TNF concentrations and reversed the effect of acute inflammation on both PR and QT intervals. The reduced electrocardiographic responses to sotalol is likely due to the influence of inflammation on the action of the drug on both beta-adrenergic and potassium channel receptors secondary to over-expression of pro-inflammatory cytokines and/or nitric oxide. Our observation may have therapeutic consequences in all conditions where inflammatory mediators are increased.
