Antibiotic Treatment and Baseline Severity of Disease in Acute Exacerbations of Chronic Bronchitis: A Re-evaluation of Previously Published Data of a Placebo-controlled Randomized Study

doi:10.1006/pupt.2001.0289

Pulmonary Pharmacology & Therapeutics

Volume 14, Issue 2, March 2001, Pages 149-155

https://doi.org/10.1006/pupt.2001.0289 Get rights and content

Abstract

The study was designed to extend retrospectively the analysis of a previously reported study on chronic bronchitis patients with acute exacerbations treated with amoxicillin–clavulanic acid or matched placebo. We retrospectively re-clustered patients on the basis of severity of baseline lung function: Cluster 1 (104 patients) mean screening FEV₁32.67±6.83 (SD); Cluster 2 (109 patients) mean screening FEV₁54.12±5.56; Cluster 3 (122 patients) mean screening FEV₁71.54±5.51. The success rate in the antibiotic group was significantly greater compared to the placebo group (P<0.001). When clinical improvement was analysed on the basis of patient re-clustering, 31.4% of Cluster 1 (severe COPD) patients treated with amoxicillin/clavulanate showed clinical improvement, whereas success was recorded in 58.8%. Conversely, 13.2% of Cluster 1 patients receiving placebo improved and 17% successfully recovered (P<0.001). Mild and moderate COPD patients (Clusters 2 and 3) were grouped together. In these two groups, 31.2% and 53.6% of patients receiving antibiotic treatment showed improvement or recovery, respectively, compared to 29.2% improvements and 30.2% successful recoveries among placebo-treated patients (P<0.001). In placebo-treated patients the improvement/success vs. failure rate was significantly different in Cluster 1 patients compared to Cluster 2+3 subjects (P<0.01, ²test). The differences in final FEV₁values in the treatment group and placebo group were significantly different (P<0.01) in favour of the active treatment group. Among more severe patients (Cluster 1), the comparison between screening and follow up FEV₁values showed an improvement following antibiotic treatment and worsening after placebo (P<0.01). In Clusters 2 and 3 the difference between screening and follow up FEV₁values was not significant for both treatment groups. Our patients with severe functional impairment and higher number of exacerbations per year are those who derive the greatest benefit from antibiotic treatment.

References (12)

J Eller et al.
Infective exacerbations of chronic bronchitis. Relation between bacteriologic etiology and lung function
Chest
(1998)
JT MacFarlane et al.
Prospective study of aetiology and outcome of adult lower-respiratory tract infections in the community
Lancet
(1993)
P Ball et al.
Acute exacerbations of chronic bronchitis: An international comparison
Chest
(1998)
RF Grossman
The value of antibiotics and the outcomes of antibiotic therapy in exacerbations of COPD
Chest
(1998)
American Thoracic Society
Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease
Am J Respir Crit Care Med
(1995)
NR Anthonisen et al.
Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease
Ann Intern Med
(1987)

There are more references available in the full text version of this article.

Cited by (86)

Antibiotics for treatment and prevention ofexacerbations of chronic obstructive pulmonary disease
2013, Journal of Infection
Acute exacerbations (AE) can be recurrent problems for patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) increasing morbidity and mortality. Evidence suggests that ≥50% of acute exacerbations involve bacteria requiring treatment with an antibiotic which should have high activity against the causative pathogens. However, sputum analysis is not a pre-requisite for antibiotic prescription in outpatients as results are delayed and patients are likely to be colonised with bacteria in the stable state. Clinicians rely on the clinical symptoms, sputum appearance and the patient's medical history to decide if an AE-COPD should be treated with antibiotics. This article reviews the available data of antibiotic trials in AE-COPD. Management of frequent exacerbators is particularly challenging for physicians. This may include antibiotic prophylaxis, especially macrolides because of anti-inflammatory properties; though successful in reducing exacerbations, concerns about resistance development remain. Inhalation of antibiotics achieves high local concentrations and minimal systemic exposure; therefore, it may represent an attractive alternative for antibiotic prophylaxis in certain COPD patients. Inhaled antibiotic prophylaxis has been successfully used in other respiratory conditions such as non-cystic fibrosis bronchiectasis which itself might be present in COPD patients who have chronic bacterial infection, particularly with Pseudomonas aeruginosa.
Prulifloxacin versus levofloxacin in the treatment of severe COPD patients with acute exacerbations of chronic bronchitis
2013, Pulmonary Pharmacology and Therapeutics
Citation Excerpt :
The primary parameter to test the efficacy of the study medication was the clinical assessment at the TOC visit (7–10 days after the end of treatment) of signs and symptoms of AECB, namely sputum purulence, sputum volume, dyspnoea, cough and body temperature. A clinical score was calculated according to the following semi-quantitative scales [11–13]: Sputum was recorded for appearance and according to a colorimetric range, namely 0 = mucoid (white to grey), 1 = mucopurulent (yellow), 2 = purulent (green), 3 severe grade of purulence (brown).
Antimicrobial therapy of chronic bronchitis exacerbations in patients with severe chronic obstructive pulmonary disease (COPD) is based on empiric antibiotic treatment.
To evaluate the efficacy of prulifloxacin versus levofloxacin therapy in severe COPD patients with exacerbations of chronic bronchitis.
This study involved a multicenter, parallel, double-blind, randomized clinical trial. Patients aged 40 years or older, smokers, or ex-smokers (>10 pack-years) with spirometrically confirmed severe COPD (FEV₁ ≤ 50% predicted and FEV₁/FVC ratio < 0.7) and diagnosed with an acute exacerbation of chronic bronchitis were enrolled in the study. Patients were randomized to receive prulifloxacin 600 mg once a day or levofloxacin 500 mg once a day for 7 days.
The primary outcome measure was clinical assessment at the TOC visit (7–10 days after the end of treatment) of signs and symptoms of exacerbation, namely sputum purulence, sputum volume, dyspnoea, cough and body temperature assessed through semi-quantitative scales. The ITT population included 346 (174 prulifloxacin, 172 levofloxacin) out of 351 treated subjects. A total of 161 patients with prulifloxacin (92.5%) and 166 with levofloxacin (96.5%) were considered cured at TOC (the difference in the percentage of cured patients was −3.98 with 95%CI of −8.76; 0.79). At the 6-month follow-up, the rates of patients with no relapse of AECB were higher than 95% in both the prulifloxacin and levofloxacin groups.
Both prulifloxacin and levofloxacin showed efficacy rates higher than 90% in the treatment of severe COPD patients with exacerbations of chronic bronchitis, with no statistically significant differences between the two antibiotics. The long-term follow-up confirmed a very low incidence of relapse, endorsing the appropriateness of this therapeutic approach.
EUDRACT no. 2006-004167-56.
Antibiotics
2009, Asthma and COPD
This chapter describes the optimal approach to antibiotic treatment of exacerbations recognizing these limitations. Such an approach relies upon an accurate diagnosis of an exacerbation, including judicious application of diagnostic tests. Determining the severity of an exacerbation follows this. If antibiotics are indicated, then a risk stratification approach is described to choose an appropriate antibiotic. An increase in airway inflammation from the baseline level in a patient appears central to the pathogenesis of most acute exacerbations. Airway inflammation measured in induced or expectorated sputum, bronchoalveolar lavage or bronchial biopsy has revealed that increased inflammation accompanies exacerbations and resolves with treatment. Potential pathogens in chronic obstructive pulmonary disease (COPD) exacerbations include typical respiratory bacterial pathogens, respiratory viruses, and atypical bacteria. The current model of bacterial exacerbation pathogenesis involves both host and pathogen factors. Acquisition of strains of bacterial pathogens that are new to the host from the environment is the primary event that puts the patient with COPD at risk for an exacerbation. The traditional aims of treatment of an exacerbation are improvement in clinical status and the prevention of complications. The role of antibiotics in the treatment of COPD exacerbations has been a matter of controversy. Even more contentious has been the issue whether antibiotic choice is relevant to clinical outcome of exacerbations. Recommendations for antibiotic use among published guidelines are inconsistent.
Antibiotics
2008, Asthma and COPD: Basic Mechanisms and Clinical Management
This chapter describes the optimal approach to antibiotic treatment of exacerbations recognizing these limitations. Such an approach relies upon an accurate diagnosis of an exacerbation, including judicious application of diagnostic tests. Determining the severity of an exacerbation follows this. If antibiotics are indicated, then a risk stratification approach is described to choose an appropriate antibiotic. An increase in airway inflammation from the baseline level in a patient appears central to the pathogenesis of most acute exacerbations. Airway inflammation measured in induced or expectorated sputum, bronchoalveolar lavage or bronchial biopsy has revealed that increased inflammation accompanies exacerbations and resolves with treatment. Potential pathogens in chronic obstructive pulmonary disease (COPD) exacerbations include typical respiratory bacterial pathogens, respiratory viruses, and atypical bacteria. The current model of bacterial exacerbation pathogenesis involves both host and pathogen factors. Acquisition of strains of bacterial pathogens that are new to the host from the environment is the primary event that puts the patient with COPD at risk for an exacerbation. The traditional aims of treatment of an exacerbation are improvement in clinical status and the prevention of complications. The role of antibiotics in the treatment of COPD exacerbations has been a matter of controversy. Even more contentious has been the issue whether antibiotic choice is relevant to clinical outcome of exacerbations. Recommendations for antibiotic use among published guidelines are inconsistent.
Mapping the evidence about the natural history of acute infections commonly seen in primary care and managed with antibiotics: a scoping review
2023, Research Square
A systematic review and Bayesian meta-analysis of the antibiotic treatment courses in AECOPD
2023, Frontiers in Pharmacology

View all citing articles on Scopus

^☆: Author for correspondence: Francesco Blasi, MD, PhD, Instituto di Tisiologia e Malattie dell»Apparato Respiratorio, Università degli Studi di Milano, Pad. Litta, IRCCS Ospedale Maggiore di Milano. via F. Sforza, 35 I-20122 Milano-ITALY. Fax: +39 02 55190332. E-mail: [email protected]

View full text

Regular ArticleAntibiotic Treatment and Baseline Severity of Disease in Acute Exacerbations of Chronic Bronchitis: A Re-evaluation of Previously Published Data of a Placebo-controlled Randomized Study☆

Abstract

Chest

Lancet

Chest

Chest

Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease

Am J Respir Crit Care Med

Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease

Ann Intern Med

Regular Article
Antibiotic Treatment and Baseline Severity of Disease in Acute Exacerbations of Chronic Bronchitis: A Re-evaluation of Previously Published Data of a Placebo-controlled Randomized Study☆