Manejo Nutricional De Niños Y Adolescentes Con Fq

Chronic Respiratory Disease 2005; 2: 85–98
www.CRDjournal.com

REVIEW SERIES: practical management of cystic fibrosis

Macrolides in cystic fibrosis
SC Bell,1,2 SL Senini3 and JG McCormack3
1

Adult Cystic Fibrosis Unit, Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia;
2
Department of Medicine, University of Queensland, The Prince Charles Hospital,Brisbane Australia; and
3
Department of Medicine and Infectious Diseases, University of Queensland,
Mater Adult Hospital, Brisbane, Australia

Macrolide antibiotics have been licensed since the 1950s and have an important role in the treatment of
a diverse range of infectious diseases. Macrolide antibiotics have antibacterial activity against grampositive bacteria, some gram-negative bacteria andintracellular pathogens. The spectrum of
antibacterial activity combined with excellent intracellular and tissue penetration has led to the
extensive use of this class of drugs in respiratory disease. Macrolide antibiotics also have demonstrated
anti-inflammatory properties in various in vitro and in vivo model systems. Novel antimicrobial and
anti-inflammatory properties of macrolide mayresult in clinical benefits, particularly in conditions
where the infectious agent is inherently resistant to macrolides. Three randomized control trials have
demonstrated improved lung function in patients treated with the macrolide antibiotic, azithromycin.
Azithromycin was generally well tolerated and resulted in reduction in the inflammatory response
which may be due to an immunomodulatory role.Short term studies (three to six months) have not
demonstrated the development of increased bacterial resistance or the emergence of new pathogens
following azithromycin. Chronic Respiratory Disease 2005; 2: 85 – 98
Key words: azithromycin; cystic fibrosis; diffuse pan bronchiolitis; inflammation; macrolides

Introduction
Three randomized control trials have recently been
published which havestudied the effect of the
macrolide antibiotic, azithromycin, in patients with
cystic fibrosis (CF).1 – 3 This review examines the
history of macrolide development, antimicrobial indications for macrolides, potential immunomodulatory
effects of macrolides and evidence for the role of
macrolides in lung diseases, including CF.

History of macrolide antibiotics
Early macrolide antibioticswere licensed as antimicrobials in the 1950s, and have continued to have an
important role in the treatment of infectious disease.4,5
In the 1970s, several studies reported improvement
in stability of severe steroid-dependent asthma in
patients treated with macrolides.6 – 8 Subsequently,
erythromycin was shown to reduce bronchial
Correspondence: Dr Scott C Bell, Director of Cystic Fibrosis,Department of
Thoracic Medicine, The Prince Charles Hospital, Rode Road, Chermside,
Q 4032, Australia
Email: scott_bell@health.qld.gov.au
# 2005 Edward Arnold (Publishers) Ltd

hyper-responsiveness in patients with asthma.9 – 11 In
the 1980s erythromycin was found to be an effective
therapy for treatment of diffuse panbronchiolitis (DPB),
a disease with many similarities to CF.12 Thiseventually led to the investigation of a possible role
of macrolides in the treatment of CF.

Structure of macrolide antibiotics
Macrolides are classified into three groups (14membered, 15-membered or 16-membered macrolides), depending on chemical structure (Table 1).
Fourteen-membered macrolides (e.g., erythromycin,
clarithromycin, roxithromycin, dirithromycin) have a
lactone ring structurewhich contains oxygen and
carbon, and has a monobasic charge (Figure 1).
Azithromycin is a 15-membered macrolide, which is
strictly an azalide: a novel macrolide subclass. Its ring
A recent study has provided further evidence of an anti-inflammatory effect
of azithromycin. Tsai et al. using a murine model of pseudomonas infection
demonstrated dramatic reduction in lung cellular infiltrates and...