BETA-LACTAM ENHANCEMENT OF AMINOGLYCOSIDE ACTIVITY UNDER CONDITIONS OF REDUCED PH AND OXYGEN-TENSION THAT MAY EXIST IN INFECTED-TISSUES

Aminoglycoside activity is suppressed under conditions of low pH and oxygen tension that are likely to occur in infected tissues; the suppressive effects of these conditions are additive. Under aerobic conditions, the MIC of amikacin for 10 isolates of Escherichia coli was 4.8 +/- 0.7-mu-g/ml at pH 7.2 and increased to 40.0 +/- 8.2-mu-g/ml at pH 6.0. Under anaerobic conditions, the MIC of amikacin for E. coli was 30.0 +/- 1.5-mu-g/ml at pH 7.2 and > 50.0-mu-g/ml at pH 6.0. In vitro and in vivo studies of amikacin activity in an acidic and hypoxic milieu containing beta-lactamase demonstrated substantially enhanced bactericidal activity when amikacin and beta-lactams were used together. Under conditions of reduced pH and oxygen tension, cefotaxime enhanced [H-3]tobramycin uptake by E. coli 14-fold and [H-3]amikacin uptake 7-fold and appeared to overcome the suppressive effect of those conditions on uptake of aminoglycosides by bacteria.