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

Department of Pulmonary Diseases, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 10/2009; 181(2):150-7. DOI: 10.1164/rccm.200906-0837OC
Source: PubMed


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 (NCT00170222).

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    • "In the current environment, where cost is so fundamental to appropriate delivery of care, the increased expenditure from unnecessary treatments is unacceptable. Improving the cost-effectiveness of treatment of COPD exacerbations is vital to further enhance COPD services overall.6,17,18 "
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    ABSTRACT: To determine the efficacy and usefulness of a chronic obstructive pulmonary disease (COPD) care bundle designed for the initial management of acute exacerbations of COPD and to assess whether it improves quality of care and provides better outcomes. The level of care provided in the emergency department (ED) for COPD exacerbations varies greatly, and there is a need for a more systematic, consistent, evidence-based quality improvement approach to improve outcomes and costs. A prospective before and after study was carried out in a university teaching hospital. Fifty consecutive patients were identified in the ED with COPD exacerbations and their management was reviewed. Following the education of ED staff and the implementation of a COPD care bundle, the outcome for 51 consecutive patients was analyzed. This COPD care bundle consisted of ten elements considered essential to the management of COPD exacerbations and was scored 0-10 according to the number of items on the checklist implemented correctly. Following implementation, the mean bundle score out of 10 improved from 4.6 to 7 (P<0.001). There was a significant decrease in the unnecessary use of intravenous corticosteroids from 60% to 32% (P=0.003) and also a marked improvement in the use of oxygen therapy, with appropriate treatment increasing from 76% to 96% (P=0.003). Prophylaxis for venous thromboembolism also improved from 54% to 73% (P=0.054). The 30-day readmission rate did not significantly improve. The use of a bundle improves the delivery of care for COPD exacerbations in the ED. There is more appropriate use of therapeutic interventions, especially oxygen therapy and intravenous corticosteroids.
    International Journal of COPD 11/2013; 8:605-611. DOI:10.2147/COPD.S52883 · 3.14 Impact Factor
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    • "Patients with a type I exacerbation receiving antibiotics had a higher success rate compared to placebo (62.9% vs 43%, P = 0.01) but no benefit was seen for patients with type II (70% vs 60%) and type III (74% vs 70%) exacerbations. However in the study by Daniels et al the treatment effect did not differ significantly between the Anthonisen groups.120 A meta-analysis of ten trials including 1557 patients by Puhan et al reported that the effects of treatment varied according to the severity of exacerbations. "
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory condition in adults and is characterized by progressive airflow limitation that is not fully reversible. The main etiological agents linked with COPD are cigarette smoking and biomass exposure but respiratory infection is believed to play a major role in the pathogenesis of both stable COPD and in acute exacerbations. Acute exacerbations are associated with more rapid decline in lung function and impaired quality of life and are the major causes of morbidity and mortality in COPD. Preventing exacerbations is a major therapeutic goal but currently available treatments for exacerbations are not very effective. Historically, bacteria were considered the main infective cause of exacerbations but with the development of new diagnostic techniques, respiratory viruses are also frequently detected in COPD exacerbations. This article aims to provide a state-of-the art review of current knowledge regarding the role of infection in COPD, highlight the areas of ongoing debate and controversy, and outline emerging technologies and therapies that will influence future diagnostic and therapeutic pathways in COPD.
    International Journal of COPD 08/2012; 7:555-69. DOI:10.2147/COPD.S28286 · 3.14 Impact Factor
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    • "Furthermore, moxifloxacin-treated patients were significantly less likely than those treated with a comparator to experience treatment failure, a new exacerbation or require any further antibiotic treatment within 5 months of the end of treatment. A number of other clinical trials and meta-analyses have also shown improved outcomes for alternative versus first-line treatments [12, 37, 47, 48]. Among these, two studies identified quinolones as effective therapy options in terms of increasing treatment success versus first-line therapies [12] and reducing relapse rates [48]. "
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    ABSTRACT: Bacterial infections causing acute exacerbations of chronic obstructive pulmonary disease (AECOPD) frequently require antibacterial treatment. More evidence is needed to guide antibiotic choice. The Moxifloxacin in Acute Exacerbations of Chronic Bronchitis TriaL (MAESTRAL) was a multiregional, randomised, double-blind non-inferiority outpatient study. Patients were aged ≥60 yrs, with an Anthonisen type I exacerbation, a forced expiratory volume in 1 s <60% predicted and two or more exacerbations in the last year. Following stratification by steroid use patients received moxifloxacin 400 mg p.o. q.d. (5 days) or amoxicillin/clavulanic acid 875/125 mg p.o. b.i.d. (7 days). The primary end-point was clinical failure 8 weeks post-therapy in the per protocol population. Moxifloxacin was noninferior to amoxicillin/clavulanic acid at the primary end-point (111 (20.6%) out of 538, versus 114 (22.0%) out of 518, respectively; 95% CI -5.89–3.83%). In patients with confirmed bacterial AECOPD, moxifloxacin led to significantly lower clinical failure rates than amoxicillin/clavulanic acid (in the intent-to-treat with pathogens, 62 (19.0%) out of 327 versus 85 (25.4%) out of 335, respectively; p=0.016). Confirmed bacterial eradication at end of therapy was associated with higher clinical cure rates at 8 weeks post-therapy overall (p=0.0014) and for moxifloxacin (p=0.003). Patients treated with oral corticosteroids had more severe disease and higher failure rates. The MAESTRAL study showed that moxifloxacin was as effective as amoxicillin/clavulanic acid in the treatment of outpatients with AECOPD. Both therapies were well tolerated.
    European Respiratory Journal 12/2011; 40(1):17-27. DOI:10.1183/09031936.00090311 · 7.64 Impact Factor
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