allopurinol and Pneumonia--Bacterial

Community-acquired pneumonia (CAP) has high morbidity and mortality among adults. Several clinical guidelines recommend prompt administration of combined antimicrobial therapy. However, the association between guidelines concordance and mortality in patients with severe pneumonia remains unclear. The present study aimed to examine the impact of guidelines-concordant empiric antimicrobial therapy on 7-day mortality in patients with extremely severe pneumonia who required mechanical ventilation at admission, using a nationwide inpatient database in Japan.. Data of CAP patients aged over 20 years who required mechanical ventilation at admission between April 2012 and March 2014 were retrospectively analyzed. Multivariable logistic regression analysis was performed to examine the association between guidelines-concordant empiric antimicrobial therapy and all-cause 7-day mortality, with adjustment for patient backgrounds and pneumonia severity.. There were a total of 3719 eligible patients, 836 (22.5%) of whom received guidelines-concordant combination therapy. Overall, 7-day mortality was 29.5%. Higher 7-day mortality was associated with advanced age, confusion, lower systolic blood pressure, malignant tumor or immunocompromised state, and C-reactive protein ≥20mg/dl or infiltration occupying two-thirds of one lung on chest radiography. After adjustment for these variables, guidelines-concordant combined antimicrobial therapy was associated with significantly lower 7-day mortality (odds ratio: 0.78; 95% confidence interval: 0.65-0.95; P=0.013).. Adherence to initial empiric treatment as recommended by the guidelines was associated with better short-term prognosis in patients with extremely severe pneumonia who required mechanical ventilation on hospital admission.

Topics: Aged; Aged, 80 and over; Allopurinol; Anti-Bacterial Agents; Community-Acquired Infections; Databases, Factual; Female; Humans; Immunocompromised Host; Japan; Logistic Models; Male; Pneumonia, Bacterial; Practice Guidelines as Topic; Respiration, Artificial; Retrospective Studies; Severity of Illness Index; Time Factors

In the Pseudomonas aeruginosa-induced rodent pneumonia model, it is thought that free radicals are significantly associated with the disease pathogenesis. However, until now there has been no direct evidence of free radical generation in vivo. Here we used electron spin resonance (ESR) and in vivo spin trapping with α-(4-pyridyl-1-oxide)-N-tert-butylnitrone to investigate free radical production in a murine model. We detected and identified generation of lipid-derived free radicals in vivo (a(N) =14.86 ± 0.03 G and a(H)(β) =2.48 ± 0.09 G). To further investigate the mechanism of lipid radical production, we used modulating agents and knockout mice. We found that with GdCl(3) (phagocytic toxicant), NADPH-oxidase knockout mice (Nox2(-)/(-)), allopurinol (xanthine-oxidase inhibitor) and Desferal (metal chelator), generation of lipid radicals was decreased; histopathological and biological markers of acute lung injury were noticeably improved. Our study demonstrates that lipid-derived free radical formation is mediated by NADPH-oxidase and xanthine-oxidase activation and that metal-catalysed hydroxyl radical-like species play important roles in lung injury caused by Pseudomonas aeruginosa.

Topics: Allopurinol; Animals; Deferoxamine; Electron Spin Resonance Spectroscopy; Free Radicals; Lung; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NADPH Oxidases; Oxidation-Reduction; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Spin Trapping; Xanthine Oxidase

The effects of Qing Fei Tang (Sei-hai To in Japanese), a Chinese traditional medical mixture, on aspiration pneumonia were studied using mice inoculated with both Streptococcus pneumoniae and gastric juice as aspiration pneumoniae models. Daily (4 weeks) oral usage of Qing Fei Tang before inoculation reduced remarkably the mortality rate of mice. In this aspiration pneumonia model, xanthine oxidase (XO) activity in the lung tissues was elevated, but this elevation was remarkably decreased by use of Qing Fei Tang. These results suggest that Qing Fei Tang pretreatment can reduce oxygen radical production in inflammed lungs and may reduce the mortality for aspiration pneumonia.

Topics: Animals; Antioxidants; Colony Count, Microbial; Drugs, Chinese Herbal; Humans; Leukocyte Count; Lung; Male; Mice; Neutrophils; Pneumonia, Aspiration; Pneumonia, Bacterial; Streptococcus pneumoniae; Superoxide Dismutase; Xanthine Oxidase