ROLES OF DIVALENT-CATIONS AND PH IN MECHANISM OF ACTION OF NITROXOLINE AGAINST ESCHERICHIA-COLI STRAINS

The antibacterial activity of nitroxoline (NIT), an antibiotic used in the treatment of acute or recurrent urinary tract infections caused b y Escherichia coli, is decreased in the presence of Mg2+ and Mn2+ but not Ca2+, In order to elucidate the interaction between this drug and the divalent cations, spectrophotometric studies based on the natural absorption of the nitroxoline moiety were conducted, In the presence o f the divalent metal ions, a shift in the NIT A(448) suggested the for mation of drug-ion complexes, for which the stability followed the ord er Mn2+ > Mg2+ > Ca2+, A clear correlation was found between the chela ting property and antibacterial activity of NIT; both were pH dependen t, A convenient colorimetric method for the determination of NIT uptak e by bacterial cells was also developed, Uptake was energy independent and showed biphasic kinetics: a rapid association with cells and then a slower increase in cell-associated NIT which reached a plateau, NIT uptake was reduced in the presence of magnesium, The implications of metal ion complexation and pH on the clinical efficacy of NIT are disc ussed.