Aminoglycoside-resistance mechanisms for cystic fibrosis Pseudomonas aeruginosa isolates are unchanged by long-term, intermittent, inhaled tobramycintreatment

Aminoglycoside-resistance mechanisms were characterized in Pseudomonas aeru ginosa isolates from cystic fibrosis (CF) patients during a recent clinical trial of inhaled tobramycin, Impermeability, in which bacteria have reduce d susceptibility to all aminoglycosides, was the predominant mode of resist ance in isolates obtained both before and after 6 months of cyclic treatmen t with tobramycin or placebo administered by aerosol, Enzymatic resistance mechanisms were found in fewer than 10% of resistant isolates. P. aeruginos a from individual patients could be grouped on the basis of genetic related ness. When enzymatic resistance was involved, all isolates in a group had e levated tobramycin MICs, When impermeability occurred, MICs of a genotypic group varied from susceptible to resistant. These findings suggest that imp ermeability resistance occurs in only a fraction of the P. aeruginosa popul ation in lungs of persons with CF and that this form of resistance arises b y a process involving multiple small changes in MIC.