Chemotherapy 2001 May;47(3):170-176
Department of Bacteriology, School of Medicine, Juntendo University, Tokyo,
Japan.
We evaluated a series of novel cephem antibiotics, N-alkylpyridinium (alkyl
group), N-carboxyethylpyridinium (carboxylic group), N-sulfoethylpyridinium
(sulfonic group) and N-alkylquaternary ammonium salts (ammonioethyl group),
N-alkyl-aromatic-quaternary ammonium salts and N-alkyl-heterocyclic
quaternary ammonium salts (cyclic group) as vinylthio pyridinium
derivatives at the C-3 position and hydroxyiminoaminothiazol at the C-7
position, for their activity against methicillin-resistant Staphylococcus
aureus (MRSA) and their solubility, by measuring the minimum inhibitory
concentrations (MICs) and the dissolving test in phosphate buffer. All
tested compounds, except for the alkyl group, showed good solubility (>10%)
in 1/15 M phosphate buffer (pH 7.2). The concentrations required to inhibit
80% of the bacterial strains (MIC(80)s) of the alkyl group, carboxylic
group, sulfonic group, ammonioethyl group and cyclic group against MRSA
were 1.56, 12.5-25, 6.25, 1.56 and 1.56 ?g/ml, respectively. These results
indicated that the ammonioethyl and cyclic groups yield the maximum
anti-MRSA and anti-Enterococcus faecalis activity, and also good water
solubility.