Aminoglycoside adaptive resistance.

Aminoglycoside adaptive resistance is defined as reduced antimicrobial killing in originally susceptible bacterial populations after initial incubation with aminoglycoside. It is observed in vitro and in vivo, most commonly with Pseudomonas aeruginosa. It appears to correlate with a marked reduction in intracellular aminoglycoside accumulation, although its specific mechanism and the cellular structures responsible remain unknown in P. aeruginosa. Recent work suggests that adaptive resistance develops coincident with cytoplasmic membranes protein changes and regulated expression of genes in the anaerobic respiratory pathway of the organism. It is clinically most relevant in immunocompromised patients and in those with serious infections, especially infections due to gram-negative rods. Treatment of these patients by targeting high peak concentration:minimum inhibitory concentration ratios with once-daily dosing may result in the best outcome. A major unresolved issue concerns the effect of combination therapy on the development of aminoglycoside adaptive resistance.