The Effect Of Chronic Macrolide Therapy In Cystic Fibrosis Individuals

Infected With Pseudomonas Aeruginosa

Natalie E. West, MDPostdoctoral Fellow

Pulmonary and Critical Care MedicineJuly 23, 2010

Pulmonary infections are the main complication in Cystic Fibrosis

• Cystic Fibrosis (CF) is characterized by– chronic pulmonary infection – intermittent acute pulmonary exacerbations

• Most CF exacerbations:– Identified by increased symptoms & decreased

lung function (FEV1)

• Severe exacerbations require hospitalization and IV antibiotics

38% of CF patients have a severe exacerbation each year

CF Foundation Registry Report 2007

Acute pulmonary exacerbations decrease lung function in Cystic Fibrosis

CF Foundation Registry Report 2007

Advancement in therapy has increased survival

CF Foundation Registry Report 2007

Pseudomonas aeruginosa is pathogenic in Cystic Fibrosis

CF Foundation Registry Report 2007

Azithromycin therapy has been shown to be beneficial in Pseudomonas treatment

• Design: Randomized, placebo-controlled, multicenter trial

• Participants: -CF individuals with P. aeruginosa-Age >6, Weight >25kg

• Exposure Azithromycin M/W/F• Primary Outcome Change in FEV1

• Results Azithromycin compared to control:Increase in FEV1 by 6.2% f (p=0.009)

Decreased exacerbations (p=0.03)0.7kg weight gain (p=0.02)

Saiman, L. JAMA. 2003; 290 (13):1749-56.

Azithromycin decreased exacerbations

Saiman, L. JAMA. 2003; 290 (13):1749-56.

Large scale long term follow-up studies are needed

CF Foundation Registry Report 2007

Rate of Macrolide use per CF center

Our study: Does chronic macrolide therapy improve outcomes?

• HypothesisChronic macrolide therapy in CF patients with P.

aeruginosa results in decreased rates of pulmonary exacerbations requiring hospitalization, compared to those not treated

• Specific AimTo evaluate the long term effects of chronic

macrolide use in individuals with CF and P. aeruginosa infection, by looking at rates of pulmonary exacerbations requiring hospitalization

Long term study using the CF Registry• Design: Longitudinal, 3 year study using

the CF Foundation registry

• Participants: -CF individuals with P. aeruginosa-Age >6, Weight >25kg

• Exposure Macrolide use• Exposure Assessment Patient report

• Primary Outcome Exacerbations → hospitalizations• Outcome Assessment Chart Review

Statistical Analysis

• Multiple Poisson regression for repeated measures

• Adjusted for:– FEV1

– Inhaled Tobramycin (TOBI), pulmozyme , hypertonic saline

– methicillin-resistant Staphylococcus aureus (MRSA), Burkholderia cepacia.

• Incidence rate ratio (IE/IO) calculated

Study population similar to general CF population

Variable

Age (± SD) 22.4 ± 10.4 years

Gender (% female) 47.2

Mean FEV1 % predicted (± SD) 72.3 ± 24.3

Inhaled Tobramycin (TOBI) (%) 79.6

Pulmozyme (%) 85.0

Hypertonic Saline (%) 57.4

MRSA (%) 31.0

Burkholderia cepaciae (%) 4.6

Macrolide therapy led to a decreased exacerbation rate

IRR SE P-value 95% CI

Macrolide therapy 0.85 0.07 0.043 0.73-0.99

FEV1 0.71 0.03 0.000 0.66-0.76

Tobramycin (TOBI) 1.20 0.71 0.002 1.07-1.35

Pulmozyme 1.14 0.09 0.080 0.98-1.32

Hypertonic Saline 1.23 0.07 0.000 1.11-1.37

Methicillin-Resistant Staphylococcus Aureus (MRSA)

1.32 0.08 0.000 1.16-1.49

Burkholderia cepacia 1.43 0.21 0.01 1.08-1.91

Strengths and Limitations• Strengths– Long term longitudinal

data– Aligns RCT and current

guidelines

• Limitations– Data collected at

individual centers, may increase risk of misclassification bias

Conclusion• We have shown that macrolide therapy

improves outcomes in individuals with CF and P.aeruginosa

• We recommend that macrolide therapy should be implemented widely in this population

Significance

• Large scale, long term study• Potential for improved patient

adherence• Potential for improved survival

Acknowledgements

• My Mentor– Noah Lechtzin, MD

• Co-Mentors– Michael Boyle, MD– Christian Merlo, MD

• Co-Authors – above plus…– Elliott Dasenbrook, MD– Patrick Sosnay, MD