Macrolide antibiotics for cystic fibrosis.

Nov 2012

Southern KW, Barker PM, Solis-Moya A, Patel L.

Source

Institute of Child Health, University of Liverpool, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, Merseyside, UK, L12 2AP.

Abstract

BACKGROUND:

Macrolide antibiotics may have a modifying role in diseases which involve airway infection and inflammation, like cystic fibrosis.

OBJECTIVES:

To test the hypotheses that, in people with cystic fibrosis, macrolide antibiotics: 1. improve clinical status compared to placebo or another antibiotic; 2. do not have unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, dose and duration of macrolide therapy.

SEARCH METHODS:

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.We contacted investigators known to work in the field, previous authors and pharmaceutical companies manufacturing macrolide antibiotics for unpublished or follow-up data (May 2010).Latest search of the Group's Cystic Fibrosis Trials Register: 29 February 2012.

SELECTION CRITERIA:

Randomised controlled trials of macrolide antibiotics compared to: placebo; another class of antibiotic; another macrolide antibiotic; or the same macrolide antibiotic at a different dose.

DATA COLLECTION AND ANALYSIS:

Two authors independently extracted data and assessed risk of bias. Seven groups were contacted and provided additional data which were incorporated into the review.

MAIN RESULTS:

Ten of 31 studies identified were included (959 patients). Five studies with a low risk of bias examined azithromycin versus placebo and demonstrated consistent improvement in forced expiratory volume in one second over six months (mean difference at six months 3.97% (95% confidence interval 1.74% to 6.19%; n = 549, from four studies)). Patients treated with azithromycin were approximately twice as likely to be free of pulmonary exacerbation at six months, odds ratio 1.96 (95% confidence interval 1.15 to 3.33). With respect to secondary outcomes, there was a significant reduction in need for oral antibiotics and greater weight gain in those taking azithromycin. Adverse events were uncommon and not obviously associated with azithromycin, although a once-weekly high dose regimen was associated with more frequent gastrointestinal adverse events. Treatment with azithromycin was associated with reduced identification of Staphylococcus aureus on respiratory culture, but also a significant increase in macrolide resistance.

AUTHORS' CONCLUSIONS:

This review provides evidence of improved respiratory function after six months of azithromycin. Data beyond six months were less clear, although reduction in pulmonary exacerbation was sustained. Treatment appeared safe over a six-month period; however, emergence of macrolide resistance was a concern. A multi-centre trial examining long-term effects of this antibiotic treatment is needed, especially for infants recognised through newborn screening.

PubMed

Antibiotic treatment for Burkholderia cepacia complex in people with cystic fibrosis experiencing a pulmonary exacerbation.

Oct 2012

Horsley A, Jones AM.

Source

School of Translational Medicine, University Hospital of South Manchester, Southmoor Road, Manchester, UK, M23 9LT.

Abstract

BACKGROUND:

Chronic pulmonary infection is one of the hallmarks of lung disease in cystic fibrosis. Infections dominated by organisms of the Burkholderia cepacia complex, a group of at least 17 closely-related species of gram-negative bacteria, are particularly difficult to treat. These infections may be associated with a fulminant necrotising pneumonia, and are greatly feared by patients. Burkholderia cepacia bacteria are innately resistant to many common antibiotics and able to acquire resistance against many more. Since strict patient segregation was introduced to cystic fibrosis medical care, the incidence of the more virulent epidemic strains has fallen, and new infections are more likely to be with environmentally-acquired strains which seem to exhibit less virulence. Nonetheless, exacerbations of respiratory symptoms require effective therapy directed against the dominant bacterial species. Although evidence-based guidelines exist for the treatment of respiratory exacerbations involving Pseudomonas aeruginosa, the most common chronic infection in cystic fibrosis, these cannot be directly extended to Burkholderia cepacia complex infections. The aim of this review is to assess the available trial evidence for choice and application of treatments for Burkholderia cepacia complex infections.

OBJECTIVES:

To assess the effectiveness and safety of different antibiotic regimens in people with cystic fibrosis experiencing an exacerbation, who are chronically infected with organisms of the Burkholderia cepacia complex.

SEARCH METHODS:

We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of latest search: 29 November 2011.

SELECTION CRITERIA:

Randomised and quasi-randomised controlled trials of treatments for exacerbations of pulmonary symptoms in cystic fibrosis patients chronically infected with organisms of the Burkholderia cepacia complex.

DATA COLLECTION AND ANALYSIS: No trials were included in this review.

MAIN RESULTS: No trials were included in this review.

AUTHORS' CONCLUSIONS:

Burkholderia cepacia complex infections present a significant challenge for cystic fibrosis clinicians and patients alike. The incidence is likely to increase as the cystic fibrosis population ages and the problem of how to manage and treat these infections becomes more important. There is a lack of trial evidence to guide decision making and no conclusions can be drawn from this review about the optimal antibiotic regimens for cystic fibrosis patients with chronic Burkholderia cepacia complex infections. Clinicians must continue to assess each patient individually, taking into account in vitro antibiotic susceptibility data, previous clinical responses and their own experience. There is a clear need for multi-centre randomised clinical trials to assess the effectiveness of different antibiotic regimens in cystic fibrosis patients infected with organisms of the Burkholderia cepacia complex.

PubMed

Update on antibiotics for infection control in cystic fibrosis.

Update on antibiotics for infection control in

cystic fibrosis.

Expert Rev Anti Infect Ther. 2009 Oct

Kirkby S, Novak K, McCoy K.

Section of Pulmonary Medicine, Nationwide Children's Hospital, Ohio State University Medical Center, Columbus, OH 43205, USA. stephen.kirkby@nationwidechildrens.org

Cystic fibrosis pulmonary disease is characterized by chronic and recurrent infection, airway inflammation, bronchiectasis and progressive obstructive lung physiology. Advances in the treatment of common airway pathogens such as Pseudomonas aeruginosa have led to a marked improvement in overall survival. However, antibiotic treatment options are often limited by multidrug resistance, potential toxicities and treatment burden to individual patients. While appropriate anti-infective therapy reduces bacterial density in the airways and may result in clinical improvement, true eradication of airway infection is seldom achieved except for early-stage infections. This review summarizes current approaches for acute and chronic anti-infective therapy in cystic fibrosis.

Expert Reviews