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.