A randomized controlled trial of nebulized gentamicin in non-cystic fibrosis bronchiectasis.

RATIONALE: Bronchiectasis is a chronic debilitating disease with few evidence-based long-term treatments. OBJECTIVES: A randomized controlled trial assessing the efficacy of nebulized gentamicin therapy over 1 year in patients with non-cystic fibrosis bronchiectasis. METHODS: Sixty-five patients were randomized to either twice-daily nebulized gentamicin, 80 mg, or nebulized 0.9% saline, for 12 months. All were reviewed at three-monthly intervals during treatment and at 3 months' follow-up. MEASUREMENTS AND MAIN RESULTS: At each review the following were assessed: quantitative and qualitative sputum bacteriology; sputum purulence and 24-hour volume; FEV(1), FVC, and forced expiratory flow, midexpiratory phase; exercise capacity; Leicester Cough Questionnaire and St. George's Respiratory Questionnaire; and exacerbation frequency. Fifty-seven patients completed the study. At the end of 12 months' treatment, compared with the saline group, in the gentamicin group there was reduced sputum bacterial density with 30.8% eradication in those infected with Pseudomonas aeruginosa and 92.8% eradication in those infected with other pathogens; less sputum purulence (8.7% vs. 38.5%; P < 0.0001); greater exercise capacity (510 [350-690] m vs. 415 [267.5-530] m; P = 0.03); and fewer exacerbations (0 [0-1] vs. 1.5 [1-2]; P < 0.0001) with increased time to first exacerbation (120 [87-161.5] d vs. 61.5 [20.7-122.7] d; P = 0.02). The gentamicin group had greater improvements in Leicester Cough Questionnaire (81.4% vs. 20%; P < 0.01) and St. George's Respiratory Questionnaire (87.5% vs. 19.2%; P < 0.004) score. No differences were seen in 24-hour sputum volume, FEV(1), FVC, or forced expiratory flow, midexpiratory phase. No P. aeruginosa isolates developed resistance to gentamicin. At follow-up, all outcome measures were similar to baseline. CONCLUSIONS: Regular, long-term nebulized gentamicin is of significant benefit in non-cystic fibrosis bronchiectasis but treatment needs to be continuous for its ongoing efficacy. Clinical trial registered with www.clinicaltrials.gov (NCT 00749866).

Outcomes of a standardized triple-drug regimen for the treatment of nontuberculous mycobacterial pulmonary infection.

The treatment of fibrocavitatory pulmonary infection due to Mycobacterium avium complex and Mycobacterium malmoense poses a challenge. This study assessed microbial, inflammatory, radiographic, and clinical outcomes for a standardized 24-month triple-drug regime. Following treatment completion, all patients had fewer symptoms, experienced a reduction in systemic inflammation, and had negative sputum mycobacterial culture results.

Do processing time and storage of sputum influence quantitative bacteriology in bronchiectasis?

This study aimed to establish whether the bacterial density of spontaneous sputum is affected by the time and mode of sample storage. Ten patients with bronchiectasis collected all sputum expectorated over 45 min. The samples were aliquoted and processed at 25 degrees C for qualitative and quantitative bacteriology at 1, 2, 4 and 6 h from expectoration. Further aliquots were stored at 25 degrees C, 4 degrees C and -20 degrees C for 24 and 48 h prior to processing. The species present was identified and median (interquartile range) sputum log(10) bacterial density (c.f.u. ml(-1)) calculated. All samples cultured grew Pseudomonas aeruginosa and for two patients Staphylococcus aureus additionally grew for all samples. There was no significant difference in P. aeruginosa density in samples processed at 1, 2, 4 and 6 h following expectoration [8.2 (7.8-8.3) c.f.u. ml(-1), 8.0 (7.8-8.3) c.f.u. ml(-1), 8.0 (7.9-8.2) c.f.u. ml(-1), 8.1 (7.9-8.2) c.f.u. ml(-1), respectively, P=0.392]. Storage for 24 and 48 h at 4 degrees C did not significantly change the bacterial load compared with processing at 1 h [8.03 (7.6-8.2) c.f.u. ml(-1), P=0.07, and 7.96 (7.49-8.22) c.f.u. ml(-1), P=0.09, respectively]. Storage for 24 and 48 h at -20 degrees C significantly reduced P. aeruginosa density [7.1 (6.1-7.7) c.f.u. ml(-1), P=0.005, and 6.9 (6.2-7.6) c.f.u. ml(-1), P=0.008, respectively]. Storage at 25 degrees C for 24 and 48 h was associated with a significant increase in bacterial load [8.3 (8.1-8.6) c.f.u. ml(-1), P=0.009, and 8.4 (8.1-8.5) c.f.u. ml(-1), P=0.03, respectively]. Bacterial density was not affected by storage for up to 6 h following expectoration at 25 degrees C; beyond this, storage at 4 degrees C is preferred.

Prior statin use is associated with improved outcomes in community-acquired pneumonia.

BACKGROUND: Statins have potent anti-inflammatory effects in laboratory studies of pulmonary inflammation. We investigated whether statin users had improved outcome when admitted with community-acquired pneumonia. METHODS: We carried out a prospective observational study of patients admitted to the hospital with community-acquired pneumonia between January 2005 and November 2007. The use of statins, angiotensin-converting enzyme inhibitors, beta-blockers, and aspirin were recorded. The outcomes of interest were 30-day mortality, need for mechanical ventilation or inotropic support, and the development of complicated pneumonia. RESULTS: On multivariate logistic regression, statin use was associated with significantly lower 30-day mortality (adjusted odds ratio [AOR] 0.46, 95% confidence interval [CI], 0.25-0.85, P=.01) and development of complicated pneumonia (AOR 0.44, 95% CI, 0.25-0.79, P=.006). There was no effect on requirement of mechanical ventilation or inotropic support (AOR 0.93, 95% CI, 0.49-1.76, P=.8). Patients prescribed statins had more severe pneumonia (median Pneumonia Severity Index 4, interquartile range [IQR] 3-4) compared with patients not prescribed cardiovascular drugs (median Pneumonia Severity Index 3, IQR 2-4, P < .0001). Despite this, C-reactive protein levels on admission were significantly lower in patients prescribed statins (median 119 mg/L, IQR 46-215) compared with patients prescribed no cardiovascular drugs (182 mg/L, IQR 66-326, P < .0001). On multivariate logistic regression, statin use was independently protective against a C-reactive protein that failed to fall by 50% or more at day 4 (AOR 0.50, 95% CI 0.27-0.92, P=.02). CONCLUSIONS: Statin use is associated with reduced markers of systemic inflammation and improved outcomes in patients admitted with community-acquired pneumonia.