TY - JOUR
T1 - ß-Lactam Enhancement of Aminoglycoside Activity under Conditions of Reduced pH and Oxygen Tension That May Exist in Infected Tissues
AU - Bryant, Richard E.
AU - Fox, Kaye
AU - Oh, George
AU - Morthland, Virginia H.
PY - 1992/4/1
Y1 - 1992/4/1
N2 - 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 ± O.7 µg/ml at pH 7.2 and increased to 40.0 ± 8.2 µg/ml at pH 6.0. Under anaerobic conditions, the MIC of amikacin for E. coli was 30.0 ±1.5 µg/ml at pH 7.2 and >50.0 µg/ml at pH 6.0. In vitro and in vivo studies of amikacin activity in an acidic and hypoxic milieu containing, 8-lactamase demonstrated substantially enhanced bactericidal activity when amikacin and ß-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.
AB - 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 ± O.7 µg/ml at pH 7.2 and increased to 40.0 ± 8.2 µg/ml at pH 6.0. Under anaerobic conditions, the MIC of amikacin for E. coli was 30.0 ±1.5 µg/ml at pH 7.2 and >50.0 µg/ml at pH 6.0. In vitro and in vivo studies of amikacin activity in an acidic and hypoxic milieu containing, 8-lactamase demonstrated substantially enhanced bactericidal activity when amikacin and ß-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.
UR - http://www.scopus.com/inward/record.url?scp=0026735946&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026735946&partnerID=8YFLogxK
U2 - 10.1093/infdis/165.4.676
DO - 10.1093/infdis/165.4.676
M3 - Article
C2 - 1552196
AN - SCOPUS:0026735946
SN - 0022-1899
VL - 165
SP - 676
EP - 682
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -