Use of Aerosolized Antibiotics in Patients With Cystic Fibrosis: Studies Using fi-Lactam Antibiotics
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.
Therapy Designed To Delay Chronic Infection With P aeruginosa: Three studies have evaluated the efficacy of oral ciprofloxacin (Miles Inc; West Haven, CT) used with aerosolized colistin alone or with aerosolized colistin and tobramycin together to delay chronic P aeruginosa infection. Because historical controls were used and oral ciprofloxacin was administered concomitantly, the effect of aerosolized colistin is difficult to determine from these trials. there
These preliminary studies suggest that aerosolized polymyxins may have a therapeutic role alone or in combination with other aerosolized or oral antibiotics. To our knowledge, however, no published studies have examined the biological activity or particle size distribution of polymyxins in aerosol form or measured sputum drug concentrations. Coly-Mycin. the most commonly prescribed polymyxin for aero-solization in CF, is a pro-drug that must be hydrolyzed to the bioactive form, colistin, and the rate of hydrolysis in airway secretions is unknown. Furthermore, studies of prophylactic polymyxin for the prevention of Gram-negative bacillary pneumonia in the ICU raised serious concerns about overgrowth by bacterial species inherently resistant to polymyxins such as B cepacia and Serratia marcescens. To date, though, overgrowth of B cepacia has not been a practical problem with long-term use of aerosolized polymyxins in England.
Studies Using fi-Lactam Antibiotics
Studies examining aerosolized β-lactams are limited. Hodson et al carried out a crossover study of aerosolized carbenicillin and gentamicin administered for 6 months and found significant improvement in pulmonary function and a trend toward decreased hospitalizations. Of note, carbenicillin and gentamicin are incompatible in solution as inactivation of the gentamicin may occur. Nolan and colleagues examined the efficacy of aerosolized cephaloridine in patients with mild-to-moderate lung disease and found no beneficial effects,