title: 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.
authors.affiliation: Department of Medicine, School of Medicine, Oregon Health Sciences University, Portland 97201.
authors.forename: R E
authors.initials: RE
authors.lastname: Bryant
authors.forename: K
authors.initials: K
authors.lastname: Fox
authors.forename: G
authors.initials: G
authors.lastname: Oh
authors.forename: V H
authors.initials: VH
authors.lastname: Morthland
mesh_terms: D000038:Abscess / Q000188:drug therapy*; D000332:Aerobiosis; D000583:Amikacin / Q000494:pharmacology / Q000627:therapeutic use; D000693:Anaerobiosis; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001441:Bacteroides fragilis / Q000187:drug effects; D002439:Cefotaxime / Q000494:pharmacology / Q000627:therapeutic use; D004357:Drug Synergism; D004755:Enterobacteriaceae / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D010100:Oxygen / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013982:Ticarcillin / Q000494:pharmacology; D014031:Tobramycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000583:Amikacin; D013982:Ticarcillin; D002439:Cefotaxime; D010100:Oxygen; D014031:Tobramycin