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Microbiological and immunologic considerations with aerosolized drug delivery
1Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA. jlipuma@umich.edu
Chest
|September 14, 2001
Summary
Inhaled tobramycin for cystic fibrosis (CF) showed a temporary increase in Pseudomonas aeruginosa resistance, but pulmonary function improved. Resistance levels decreased after drug holidays, though this effect diminished over time.
Area of Science:
- Pulmonary Medicine
- Microbiology
- Pharmacology
Background:
- Long-term inhaled antibiotics for cystic fibrosis (CF) raise concerns about drug resistance.
- Pseudomonas aeruginosa (PA) is a common pathogen in CF patients.
Purpose of the Study:
- To evaluate the impact of inhaled tobramycin on PA resistance and clinical outcomes in CF patients.
- To assess microbiological parameters including minimal inhibitory concentrations (MICs) and prevalence of resistant strains.
Main Methods:
- A randomized, placebo-controlled, double-blind study comparing inhaled tobramycin with standard CF care.
- Microbiological parameters were monitored over 24 months, including MICs, MIC50, MIC90, and prevalence of resistant PA strains.
- Pulmonary function and superinfections were also assessed.
Main Results:
- A transient increase in tobramycin-resistant PA (MIC > 16 microg/mL) was observed during on-drug cycles, but resistance decreased after off-drug periods.
- No significant changes in MIC50 or MIC90 were observed.
- Pulmonary function improved in all groups, even in patients with high MICs.
- Increases in Stenotrophomonas maltophilia were noted but similar in both groups.
Conclusions:
- Inhaled tobramycin can be used in CF patients with improved pulmonary function, despite temporary increases in PA resistance.
- Resistance appears to be related to increased drug impermeability and is partially reversible after drug cessation.
- Long-term resistance trends require further investigation, and Stenotrophomonas maltophilia increases may be unrelated to tobramycin therapy.