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There is clinical evidence suggesting that glucocorticoids may be useful in severe pneumonia, but the pathogenic mechanisms explaining these beneficial effects are unknown.The aim of the present study was to determine the effects of adding glucocorticoids to antibiotic treatment in an experimental model of severe pneumonia.In total, 15 Lagerwhite-Landrace piglets were ventilated for 96 h. After intubation, a 75 mL solution containing Pseudomonas aeruginosa (10 6 cfu?mL -1 ) was bronchoscopically inoculated.The animals were randomised into three groups 12 h after inoculation: 1) untreated; 2) treated with ciprofloxacin; and 3) treated with ciprofloxacin plus methylprednisolone. Physiological and laboratory parameters were monitored throughout the study. Pro-inflammatory cytokines were measured in serum and bronchoalveolar lavage (BAL). Histopathology of the lungs and cultures from blood, BAL and lungs were performed. At the end of the study, piglets receiving the antibiotic plus glucocorticoids showed: 1) a decrease in the concentration of interleukin-6 in BAL; and 2) a decrease in the global bacterial burden both in BAL and lung tissue.In conclusion, in this experimental model of pneumonia, the association of glucocorticoids with antibiotics attenuates local inflammatory response and decreases bacterial burden in the lung.

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The present multicenter study reports the results of a clinical trial, designed on the basis of a pharmacodynamic study published previously (Bantar et al., J. Chemother 2000; 12: 223-227) to assess the efficacy of amoxicillin/sulbactam (875 mg/125 mg), given orally twice-a-day for 7 days in the treatment of patients with community-acquired pneumonia (CAP). Eighty-four evaluable subjects older than 19 years with clinical symptoms and features suggestive of CAP, consulting from June 2000 to March 2002 and meeting the PORT risk class I through III, were enrolled in the study. Mean age (y +/- standard deviation) was 46.7 +/- 16.3 and 62% of the patients had some co-morbidity predisposing for CAP. Several individuals (77.4%) fell into a low-risk class (i.e. PORT I or II) and 22.6% of patients belonged to a moderate-risk class at the start of treatment. Six patients (6.45%) had pneumococcal bacteremia. Streptococcus pneumoniae was the organism most frequently isolated (61.9% of all the patients in whom an etiologic diagnosis was made), followed by Haemophilus influenzae. Clinical success was observed in 97.6% of the patients (confidence interval 95%, 94.3%-100%). Almost all the individuals with clinical success became afebrile within the first 3 days of therapy. Ten patients (11.8%) reported mild or moderate adverse events (especially diarrhea) possibly related to the antimicrobial therapy, but this did not lead to withdrawal from the trial. The results of this study suggest that amoxicillin/sulbactam (875 mg/125 mg) is an efficacious and well tolerated option for treating patients with CAP belonging to a low-moderate risk class and support the use of a short, oral (7-day) b.i.d. regimen.