Use of a Biofilm Antimicrobial Susceptibility Assay to Guide Antibiotic Therapy

The Hospital for Sick Children

Status and phase

Completed

Phase 2

Conditions

Cystic Fibrosis

Treatments

Other: Conventional antimicrobial susceptibility testing

Other: Biofilm antimicrobial susceptibility testing

Study type

Interventional

Funder types

Other

Identifiers

NCT00786513

1000011132

Details and patient eligibility

About

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.

Full 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.

Enrollment

134 patients

Sex

All

Volunteers

No Healthy Volunteers

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