Category: Cystic Fibrosis - Part 3

Use of Aerosolized Antibiotics in Patients With Cystic Fibrosis: Rationale for Aerosolized Antibiotic DosageRationale for Aerosolized Antibiotic Dosage
Various factors, including sputum penetration, sputum components such as glycoproteins that antagonize antibiotic bioactivity, and the patient-to-patient differences in glycoprotein concentration, impact on the activity of antibiotics within the lung. These factors make estimating dosages difficult and are summarized below. asthma inhaler

Sputum Penetration of IV Administered Antibiotics Is Poor: Studies with (3-lactam agents have indicated that at most, 10 to 20% of the maximum serum concentration can be quantitated in the sputum. Virtually all these studies have used bioassays that may not detect antagonism of (3-lactam action by sputum components. …Read the rest of this article

3.    Aerosolized preservative-free tobramycin might be considered for bacterial suppression in other patients. For example, a logical extrapolation of these data suggests that this therapy may also be efficacious in patients < 6 years of age, patients with FEV1 < 25% or > 75% predicted, and patients colonized with other pathogens susceptible to tobramycin. However, to our knowledge, there are no data to support these extrapolations (consensus grade III). …Read the rest of this article

Use of Aerosolized Antibiotics in Patients With Cystic Fibrosis: Recommendations for the Use of Aerosolized Antibiotics in CFConclusion
Evidence-based recommendations for aerosolized antibiotic use in CF are possible only regarding their use as suppressive therapy. Although aminoglycosides, semisynthetic penicillins, and Coly-Mycin have demonstrated a variable clinical benefit, adequately powered trials have not been performed, with the exception of studies of preservative-free 300-mg per dose tobramycin. This preparation has undergone the most extensive clinical, safety, and pharmacokinetic testing. …Read the rest of this article

In a nonrandomized trial, 20 CF patients awaiting lung transplantation were begun on a regimen of aerosolized colistin 75 mg twice daily when a multiply antibiotic-resistant P aeruginosa was cultured from their sputum. Ten other patients with multiply resistant P aeruginosa were not offered colistin treatment. The mean FEV1 percent predicted was not significantly different between the treated and untreated patients, but treated patients were more likely to develop sensitive organisms (p < 0.05) more rapidly (p = 0.007) than untreated patients. Such a strategy merits a randomized, placebo-controlled trial. …Read the rest of this article

Use of Aerosolized Antibiotics in Patients With Cystic Fibrosis: Studies Using PolymyxinsTobramycin significantly improved pulmonary function, decreased sputum P aeruginosa bacterial density, reduced hospitalizations, and reduced the use of other antipseudomonal antibiotics. The tobramycin treatment effect on FEV1 percent predicted in both trials was approximately 12%. antibiotics buy

In all subgroups analyzed, stratified by age, gender, disease severity, and concurrent use of rhDNase (Pulmozyme; Genentech; South San Francisco, CA), tobramycin-treated patients had greater improvements in pulmonary function test (PFT) results and greater reductions in P aeruginosa sputum bacterial density than patients receiving standard therapy without tobramycin. …Read the rest of this article

A multicenter trial of aerosolized tobramycin (Lederle Laboratories; Wayne, NJ) was designed to overcome some of the limitations of previous stud-ies. Seventy-one CF patients with stable pulmonary status were enrolled in a multicenter, doubleblind, placebo-controlled, taste-masked, crossover design study of tobramycin, 600 mg tid, delivered by ultrasonic nebulizer (Ultraneb 100/99; Sunrise Medical HHG; Somerset, PA). This dose effectively achieves sputum tobramycin concentrations > 10 times the minimal inhibitory concentration (MIC*) of all tobramycin-susceptible P aeruginosa, a concentration shown necessary to overcome competitive binding of tobramycin by CF sputum. …Read the rest of this article

Use of Aerosolized Antibiotics in Patients With Cystic Fibrosis: Background Review of EfficacyBackground Review of Efficacy
Investigators have primarily examined the efficacy of aerosolized antibiotics in reducing morbidity in patients in stable condition (suppression therapy), a few studies have examined the role of aerosol antibiotics as adjunctive therapy for acute exacerbations of pulmonary disease (treatment), and several have examined their role in delaying chronicPseudomonas aeruginosa infection/colonization* (prevention). Aerosolized aminoglycosides, (3-lactams, and polymyxins have been studied. …Read the rest of this article