Use of a Biofilm Antimicrobial Susceptibility Assay to Guide Antibiotic Therapy

NCT ID: NCT00786513

Last Updated: 2014-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 134 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2014-03-31

Brief Summary

The purpose of this study is to determine whether choosing antibiotics based on a biofilm antimicrobial susceptibility assay rather than a conventional planktonic antimicrobial susceptibility assay to treat CF patients with chronic P. aeruginosa infection with an acute pulmonary exacerbation is a safe intervention that will result in improved microbiological and clinical outcomes and decrease markers of pulmonary inflammation.

Detailed Description

Cystic fibrosis (CF) is the most common fatal genetic condition in the Caucasian population and affects over 3,000 Canadians. Respiratory failure caused by chronic pulmonary infection is the primary cause of death in CF patients. The improved life expectancy of CF patients in the past several decades is due in part to the more aggressive use of antibiotics in the treatment of respiratory infections. However, there is currently no antimicrobial susceptibility assay that can predict which antibiotics will result in improved patient outcomes. Since Pseudomonas aeruginosa is known to grow as a resistant biofilm in the CF lung, antimicrobial susceptibility testing based on biofilm growth of P. aeruginosa may lead to different antibiotic choices that significantly decrease the pulmonary bacterial density of P. aeruginosa. A biofilm antimicrobial susceptibility assay thus has the ability to change the way antibiotics are chosen to treat CF patients and result in improved lung function and longer lives for all CF patients.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Control Arm

Group Type: ACTIVE_COMPARATOR

Conventional antimicrobial susceptibility testing

Intervention Type: OTHER

Subjects in this arm will be prescribed 14 days of an intravenous 2 drug antibiotic combination based on conventional planktonic antimicrobial susceptibility testing results.

Intervention Arm

Group Type: EXPERIMENTAL

Biofilm antimicrobial susceptibility testing

Intervention Type: OTHER

Subjects in this arm will be prescribed 14 days of an intravenous 2 drug antibiotic combination based on biofilm antimicrobial susceptibility testing results.

Interventions

Conventional antimicrobial susceptibility testing

Subjects in this arm will be prescribed 14 days of an intravenous 2 drug antibiotic combination based on conventional planktonic antimicrobial susceptibility testing results.

Intervention Type: OTHER

Biofilm antimicrobial susceptibility testing

Subjects in this arm will be prescribed 14 days of an intravenous 2 drug antibiotic combination based on biofilm antimicrobial susceptibility testing results.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Diagnosis of CF based on the following: sweat chloride > 60 mEq/L or genotype with 2 identifiable mutations consistent with CF; and one or more clinical features consistent with CF
• Chronically infected with P. aeruginosa (>50% of respiratory specimens positive for P. aeruginosa in the 24 months prior to screening)
• Able to produce sputum (expectorated or induced)
• Able to reproducibility perform pulmonary function testing
• Written informed consent provided

Exclusion Criteria

• Sputum culture negative for P. aeruginosa or with a density of less that 10^5 CFU/g at screening
• Sputum culture positive for Burkholderia cepacia at screening
• History of B. cepacia positive respiratory culture within 24 months prior to screening
• Use of antibiotics other than those prescribed by the principal investigator
• History of allergy (urticarial rash, diffuse erythroderma, serum sickness) to more than two groups of antibiotics (aminoglycosides, penicillins, cephalosporins, monobactams, macrolides, or quinolones) that are a therapeutic option
• History of anaphylaxis or other life threatening complication to any antibiotic in the six groups that are a therapeutic option
• Post lung transplantation or listed for lung transplantation
• Pregnancy
• A septic or clinically unstable patient
• Presence of a condition or abnormality that in the opinion of an investigator would compromise the safety of the patient or the quality of the data

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Valerie Waters

Staff Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Valerie Waters, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Yvonne Yau, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Locations

BC Children's Hospital

Vancouver, British Columbia, Canada

St. Paul's Hospital

Vancouver, British Columbia, Canada

Hamilton Health Sciences

Hamilton, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

Canada

References

Yau YC, Ratjen F, Tullis E, Wilcox P, Freitag A, Chilvers M, Grasemann H, Zlosnik J, Speert D, Corey M, Stanojevic S, Matukas L, Leahy TR, Shih S, Waters V. Randomized controlled trial of biofilm antimicrobial susceptibility testing in cystic fibrosis patients. J Cyst Fibros. 2015 Mar;14(2):262-6. doi: 10.1016/j.jcf.2014.09.013. Epub 2014 Oct 30.

Reference Type: DERIVED

PMID: 25453872 (View on PubMed)

Other Identifiers

1000011132

Identifier Type: -

Identifier Source: org_study_id