MECHANISM OF AMIKACIN RESISTANCE IN PSEUDOMONAS-AERUGINOSA ISOLATES FROM PATIENTS WITH CYSTIC-FIBROSIS

We studied 27 amikacin-resisiant isolates of Pseudomonas aeruginosa from patients with cystic fibrosis to determine the mechanism of antibiotic resistance. The absence of aminoglycoside-modifying enzymes (AMEs) in these isolates was inferred from the failure of DNA probes for 16 candidate AMEs to hybridize with DNA harvested from these isolates and, in addition, the uniform reduction in susceptibility to a panel of aminoglycosides. In eight of the 27 isolates that were resistant to amikacin at high levels (minimum inhibitory concentration greater than or equal to 250 mu g/ml), plasmids were not detected. The ribosomes of these isolates were sensitive to amikacin in studies of protein synthesis by cell ''ghosts.'' These data suggest that impermeability is the mechanism of amikacin resistance in isolates of P. aeruginosa from patients with cystic fibrosis. Recognition of this mode of resistance may be difficult, as some isolates appeared to be borderline susceptible when tested against aminoglycosides other than amikacin, or had zone diameters that overlapped those obtained with amikacin-susceptible isolates.