INFLUENCE OF PH ON ADAPTIVE RESISTANCE OF PSEUDOMONAS-AERUGINOSA TO AMINOGLYCOSIDES AND THEIR POSTANTIBIOTIC EFFECTS

Adaptive resistance to aminoglycosides in Pseudomonas aeruginosa and o ther gram-negative bacilli is usually induced by the initial exposure to the drug. We investigated the influence of pH on the adaptive resis tance of a clinical P. aeruginosa strain to aminoglycosides in vitro a nd on their postantibiotic effects, For adaptive resistance, the first -exposure concentrations of both amikacin and netilmicin were one, two , four, and eight times the MIC of each drug and the second-exposure c oncentrations were two times the MIC of each drug, Adaptive resistance was greater and more prolonged with higher initial aminoglycoside con centrations, and the bactericidal effects of the aminoglycosides were concentration dependent at pH 7.4, At pH 6.5, the killing rates of ami kacin and netilmicin were far lower than those observed at pH 7.4, At pH 5.5, amikacin and netilmicin exerted practically no bactericidal ef fect on the P. aeruginosa strain used, However, with media at pH 5.5 a nd 6.5, adaptive resistance of P, aeruginosa preexposed to amikacin an d netilmicin was also clearly exhibited, with the degree of adaptive r esistance depending on the bactericidal effects of both drugs on nonpr eexposed controls, Maximal adaptive resistance occurred between 0 and 4 h after preexposure. The postantibiotic effects of amikacin and neti lmicin against the P, aeruginosa strain were shown to be concentration dependent and were reduced at acidic pHs, No changes in outer and inn er membrane proteins occurred during the adaptive-resistance interval.