Beta-lactam enhancement of aminoglycoside activity under conditions of reduced pH and oxygen tension that may exist in infected tissues.

Abstract

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 micrograms/ml at pH 7.2 and increased to 40.0 +/- 8.2 micrograms/ml at pH 6.0. Under anaerobic conditions, the MIC of amikacin for E. coli was 30.0 +/- 1.5 micrograms/ml at pH 7.2 and greater than 50.0 micrograms/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 [3H]-tobramycin uptake by E. coli 14-fold and [3H]amikacin uptake 7-fold and appeared to overcome the suppressive effect of those conditions on uptake of aminoglycosides by bacteria.