Standard vs. Biofilm Susceptibility Testing in Cystic Fibrosis (CF)

Patients were screened to determine eligibility and to obtain a sputum culture. Eligible patients were randomized to either the standard or biofilm study arm. Antibiotic selection was performed centrally according to a standard algorithm using the susceptibility test results of the assigned study arm. On Day 0, patients were started on a 14-day course of two antibiotics as selected per protocol. Antibiotics were administered intravenously (IV) and/or orally. A follow-up phone call or visit occurred on Day 7. An end of treatment visit was conducted after completion of antibiotic therapy. A total of 39 patients were randomized. Many screened patients were ineligible for randomization based on microbiology results.

Inclusion criteria

• Diagnosis of CF based on the following: sweat chloride > 60 mEq/L (by quantitative pilocarpine iontophoresis), or genotype with 2 identifiable mutations consistent with CF; and one or more clinical features consistent with CF.
• Age ≥ 14 years (changed from ≥ 18 years by protocol amendment).
• Able to expectorate sputum at screening.
• History of persistent positivity for P. aeruginosa on respiratory culture (at least three positive oropharyngeal (OP), sputum and/or bronchoscopy cultures in the 24 months prior to screening).
• Able to reproducibly perform pulmonary function testing.
• Clinically stable at screening, with no evidence of pulmonary exacerbation.
• Written informed consent provided.

Exclusion criteria

• Sputum culture negative for P. aeruginosa or density less than 10E5 CFU/gm at screening.
• Sputum culture positive for B. cepacia at screening.
• Presence of P. aeruginosa in sputum with off-scale resistance to all antibiotics by either method of susceptibility testing at screening. (changed from multiply-resistant P. aeruginosa by protocol amendment)
• History of B. cepacia positive respiratory culture within 24 months prior to screening.
• Hospitalization or treatment for a pulmonary exacerbation within 2 months prior to screening.
• Administration of parenteral anti-pseudomonal antibiotics within 2 months prior to screening.
• Treatment with oral or inhaled anti-pseudomonal antibiotics, or azithromycin or other macrolides within 14 days prior to screening.
• 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.
• History of abnormal renal function (serum creatinine > 1.5 x upper limit of normal) within one year of enrollment.
• History of abnormal liver function tests (> 2.5 x upper limit of normal) within one year of enrollment.
• Clinically documented hearing loss that precludes treatment with aminoglycosides.
• Post lung transplantation.
• Positive pregnancy test or female who is lactating or is not practicing an acceptable method of birth control.
• 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.
• Administration of any investigational agent within 30 days prior to screening.