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Treatments of CF Infection Have Similar Efficacy

  • Authors: News Author: Laurie Barclay, MD
    CME Author: Désirée Lie, MD, MSEd
  • CME Released: 9/12/2011
  • Valid for credit through: 9/12/2012
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Target Audience and Goal Statement

This article is intended for primary care clinicians, pulmonologists, and other specialists who care for children with cystic fibrosis.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  1. Compare the efficacy of cycled vs culture-based therapy on pulmonary exacerbation of cystic fibrosis in children.
  2. Compare the efficacy of ciprofloxacin vs no ciprofloxacin in cycled or culture-based therapy for children with cystic fibrosis.


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  • Laurie Barclay, MD

    Freelance writer and reviewer, Medscape, LLC


    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.


  • Brande Nicole Martin

    CME Clinical Editor, Medscape, LLC


    Disclosure: Brande Nicole Martin has disclosed no relevant financial relationships.

CME Author(s)

  • Désirée Lie, MD, MSEd

    Clinical Professor; Director of Research and Faculty Development, Department of Family Medicine, University of California, Irvine at Orange


    Disclosure: Désirée Lie, MD, MSEd, has disclosed the following relevant financial relationship:
    Served as a nonproduct speaker for: "Topics in Health" for Merck Speaker Services

CME Reviewer(s)

  • Sarah Fleischman

    CME Program Manager, Medscape, LLC


    Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.

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Treatments of CF Infection Have Similar Efficacy

Authors: News Author: Laurie Barclay, MD CME Author: Désirée Lie, MD, MSEdFaculty and Disclosures

CME Released: 9/12/2011

Valid for credit through: 9/12/2012


Clinical Context

According to the current study by Treggiari and colleagues, Pseudomonas aeruginosa is the predominant organism associated with cystic fibrosis (CF) and results in rapid decline in lung function, increased hospitalizations, and increased mortality rates. Inhaled antibiotics (tobramycin or colistin) may reduce the frequency of colonization or acquisition. However, it is unclear whether the addition of antibiotics or the use of cycled vs culture-based therapy would improve pulmonary and other outcomes in children with CF.

This 18-month randomized controlled trial examines if 4 different regimens are associated with different outcomes of pulmonary exacerbation (PE) and P aeruginosa colonization among children with CF.

Study Synopsis and Perspective

In children with CF, there is no difference in the rate of exacerbation or prevalence of P aeruginosa positivity between cycled and culture-based therapies, with or without ciprofloxacin, according to the results of a randomized controlled trial reported in the September issue of the Archives of Pediatrics & Adolescent Medicine.

"It remains unclear whether clearance of P aeruginosa from airway cultures has any impact on other health indicators such as exacerbation of respiratory symptoms (pulmonary exacerbation [PE]), lung function, hospitalization, and growth," write Miriam M. Treggiari, MD, PhD, MPH, and colleagues from the Early Pseudomonas Infection Control Investigators. "While there is potential to benefit from early intervention, concerns remain regarding the risks of long-term antibiotic exposure and selection of resistant bacterial pathogens. We compared the clinical and microbiological effectiveness as well as the safety of 4 antibiotic treatment strategies for newly identified P aeruginosa infection isolated from respiratory cultures in children with CF."

In this multicenter US trial, 304 children 1 to 12 years old with CF were randomly assigned within 6 months of P aeruginosa detection to receive 1 of 4 antibiotic regimens. Between December 2004 and June 2009, these treatments were administered for 18 months (six 12-week quarters). Cycled therapy consisted of tobramycin inhalation solution (300 mg twice a day) for 28 days, with oral ciprofloxacin (15 - 20 mg/kg twice a day) or oral placebo for 14 days every quarter. Culture-based therapy consisted of the same treatments only during quarters with positive P aeruginosa culture results.

Analysis was by intent-to-treat, with main study outcomes of time to PE requiring intravenous antibiotics, and proportion of P aeruginosa–positive culture results. No interaction among treatments was detected.

The cycled and culture-based groups did not differ significantly in exacerbation rates (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.54 - 1.66), nor did ciprofloxacin and placebo (HR, 1.45; 95% CI, 0.82 - 2.54).

Comparing the cycled vs the culture-based therapy group, the odds ratio (OR) of a P aeruginosa–positive culture result was 0.78 (95% CI, 0.49 - 1.23). For ciprofloxacin vs placebo, the OR was 1.10 (95% CI, 0.71 - 1.71). Both groups had similar adverse events.

"No difference in the rate of exacerbation or prevalence of P aeruginosa positivity was detected between cycled and culture-based therapies," the study authors write. "Adding ciprofloxacin produced no benefits."

Limitations of this study were that only 47% of study children were able to perform pulmonary function testing, and only 6% of children were able to expectorate sputum.

"These data also indicate that young children recently acquiring P aeruginosa have a high likelihood of eradication with antibiotic therapy and a prolonged period until reemergence of the pathogen," the study authors conclude.

In an accompanying editorial, Lisa Saiman, MD, MPH, from Columbia University and New York-Presbyterian Hospital in New York, NY, and Mitchell B. Cohen, MD, from Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio, note that this study lacked a placebo group.

"Early treatment to eradicate P aeruginosa is now a well-accepted treatment paradigm for infants and children with CF," Drs. Saiman and Cohen write. "Evidence from the current study combined with data from a prior trial demonstrating efficacy of a 28-day course of therapy in eradicating P aeruginosa leads us to concur with the conclusion of the investigators that judicious use of tobramycin inhalation solution with close microbiologic monitoring of airway cultures is recommended based on current evidence."

The Cystic Fibrosis Foundation; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; and the National Center for Research Resources supported this study. Study drugs and devices were supplied free of charge by Novartis Pharmaceutical Corp, Bayer Healthcare AG, and PARI Respiratory Equipment Inc. One of the study authors (Barbara A. Chatfield, MD) has received research grants or contracts from Gilead Pharmaceuticals, Vertex Pharmaceuticals, and the Cystic Fibrosis Foundation. Drs. Saiman and Cohen have disclosed no relevant financial relationships.

Arch Pediatr Adolesc Med. 2011;165:847-856, 867-868.

Study Highlights

  • The study involved 55 CF centers in the United States.
  • Included were children aged 1 to 12 years with a CF diagnosis and a documented respiratory culture result positive for P aeruginosa within 6 months that was either new or observed after a 2-year absence from infection.
  • Children were randomly assigned to one of 4 regimens: (1) scheduled cycled tobramycin inhalation with ciprofloxacin every 3 months; (2) scheduled cycled therapy with placebo instead of ciprofloxacin every 3 months; (3) culture-based therapy with inhaled tobramycin and oral ciprofloxacin every quarter when culture results were positive; and (4) culture-based therapy with ciprofloxacin substituted with placebo when culture results were positive.
  • Tobramycin was administered at 300 mg twice daily for 28 days during cycles. Ciprofloxacin was administered at 15 to 20 mg/kg/dose twice daily up to 750 mg/dose twice daily for 14 days.
  • Treatment continued for 18 months.
  • Anthropometric measurements, nutritional assessments, and lung function were assessed.
  • Adverse effects were monitored, including audiometric testing.
  • Study visits occurred at baseline, at 3 weeks, and then quarterly for 18 months.
  • The primary endpoint was time to first PE requiring intravenous antibiotics or hospital admission.
  • The primary microbiologic endpoint was the proportion of positive culture results among quarterly cultures obtained after the initial treatment cycle.
  • Secondary endpoints included time to PE requiring any treatment and anthropometric measures.
  • 304 children were randomly selected, 76 to each of the 4 treatment regimens.
  • 3 to 4 children withdrew from each group, and adherence rate was 90% or greater for medication intake during the 18-month period.
  • Mean age of the children was 5.5 years, 51% were girls, more than 90% were white, and mean height was 110 cm.
  • There were no significant differences between the cycled and culture-based treatment groups for rates of PE or time to PE.
  • Overall, the proportion of children with positive P aeruginosa culture results was less than 20%.
  • 46% in the cycled group and 54% in the culture-based group had a PE requiring intravenous antibiotics or hospital admission (difference not significant).
  • 19% in the ciprofloxacin group and 14% in the placebo group experienced a PE requiring hospital admission or intravenous antibiotics (difference not significantly different).
  • There was no significant difference on colonization or infection with P aeruginosa between the ciprofloxacin group and placebo group.
  • The emergence of tobramycin or ciprofloxacin resistance was low at 0% to 4% and was not significantly different across treatment groups.
  • There were no differences in rate of change in height or weight across the 4 groups.
  • Rates of adverse effects were similar across the 4 groups except for the ciprofloxacin group, which had a higher rate of cough.
  • The authors concluded that use of a cyclic regimen vs culture-based treatment was not associated with improved outcomes of PE or culture-positive respiratory tract infection among children with CF.

Clinical Implications

  • Use of cycled vs culture-based treatment of P aeruginosa infection is not associated with a reduced rate of PE in children with CF.
  • The addition of ciprofloxacin to either a cycled or culture-based regimen is not associated with a reduced rate of PE or positive respiratory culture results in children with CF.

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