In-vitro synergy between aminoglycosides deployed against Staphylococcus spp. harbouring a 6'-aminoglycoside acetyltransferase, 2"-aminoglycoside phosphotransferase enzyme.
In-vitro synergistic effects between commercial aminoglycosides are described for gentamicin resistant Staphylococcus strains harbouring 6'-aminoglycoside acetyltransferase activity. Seventy eight strains were studied using the double-disc test and synergy was observed with combinations in which at least one of the components has a garosamine-like 6'-aminosugar. These results were confirmed in chequerboard titrations (sigma FIC < or = 0.5) carried out on Staphylococcus epidermidis strains RYC13036 and RYC4904. Additionally, a clear reduction in tobramycin acetylating activity was observed in the presence of gentamicin or netilmicin in crude extracts of these strains. These experiments suggest that the observed synergy is due to inhibition of the aminoglycoside-modifying enzyme by aminoglycosides with a garosamine like 6'-aminosugar component.
Culebras
E
E
Departamento de Microbiología, Hospital Ramón y Cajal, Madrid, Spain.
Perez-Diaz
J C
JC
Blazquez
J
J
Alonso
R
R
Baquero
F
F
D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000328:Adult; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001711:Biotransformation; D004357:Drug Synergism; D006801:Humans; D019868:Kanamycin Kinase; D007700:Kinetics; D008297:Male; D008826:Microbial Sensitivity Tests; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013210:Staphylococcus / Q000187:drug effects* / Q000201:enzymology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000123:Acetyltransferases; C056532:aminoglycoside N(6')-acetyltransferase; D017853:Phosphotransferases (Alcohol Group Acceptor); D019868:Kanamycin Kinase