Antibiotics in Addition to Systemic Corticosteroids for Acute Exacerbations of Chronic Obstructive Pulmonary Disease

• Published in: American journal of respiratory and critical care medicine Vol. 181; no. 2; pp. 150 - 157
• Main Authors: Daniels, Johannes M. A, Snijders, Dominic, de Graaff, Casper S, Vlaspolder, Fer, Jansen, Henk M, Boersma, Wim G
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 15-01-2010; American Thoracic Society
• Subjects: Acute Disease; Adrenal Cortex Hormones - therapeutic use; Aged; Aged, 80 and over; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anti-Bacterial Agents - therapeutic use; Antibiotics; Bacterial infections; Bacterial Infections - drug therapy; Bacterial Infections - microbiology; Bacterial Infections - mortality; Biological and medical sciences; Bronchodilator Agents - therapeutic use; C-Reactive Protein - metabolism; Chronic obstructive pulmonary disease; Chronic obstructive pulmonary disease, asthma; Confidence intervals; Double-Blind Method; Doxycycline - therapeutic use; Drug Administration Schedule; Drug Therapy, Combination; Dyspnea; Enrollments; Female; Humans; Infections; Intensive care medicine; Male; Medical sciences; Middle Aged; Pathogens; Pneumology; Pneumonia; Prednisolone - therapeutic use; Prednisone - therapeutic use; Proteins; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - microbiology; Pulmonary Disease, Chronic Obstructive - mortality; Steroids; Success; Survival Rate; Netherlands; Infection; Corticosteroid; Lung disease; Antibiotic; Intensive care; Respiratory disease; pulmonary disease; antibacterial agents; Bronchus disease; Chronic obstructive pulmonary disease; Antibacterial agent; Resuscitation
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200906-0837OC

The role of antibiotics in acute exacerbations is controversial and their efficacy when added to systemic corticosteroids is unknown.
We conducted a randomized, placebo-controlled trial to determine the effects of doxycycline in addition to corticosteroids on clinical outcome, microbiological outcome, lung function, and systemic inflammation in patients hospitalized with an acute exacerbation of chronic obstructive pulmonary disease.
Of 223 patients, we enrolled 265 exacerbations defined on the basis of increased dyspnea and increased sputum volume with or without increased sputum purulence. Patients received 200 mg of oral doxycycline or matching placebo for 7 days in addition to systemic corticosteroids. Clinical and microbiological response, time to treatment failure, lung function, symptom scores, and serum C-reactive protein were assessed.
On Day 30, clinical success was similar in intention-to-treat patients (odds ratio, 1.3; 95% confidence interval, 0.8 to 2.0) and per-protocol patients. Doxycycline showed superiority over placebo in terms of clinical success on Day 10 in intention-to-treat patients (odds ratio, 1.9; 95% confidence interval, 1.1 to 3.2), but not in per-protocol patients. Doxycycline was also superior in terms of clinical cure on Day 10, microbiological outcome, use of open label antibiotics, and symptoms. There was no interaction between the treatment effect and any of the subgroup variables (lung function, type of exacerbation, serum C-reactive protein, and bacterial presence).
Although equivalent to placebo in terms of clinical success on Day 30, doxycycline showed superiority in terms of clinical success and clinical cure on Day 10, microbiological success, the use of open label antibiotics, and symptoms. Clinical trial registered with www.clinicaltrials.gov (NCT00170222).