In Vitro Antimicrobial Activity of Pyridonecarboxylic Acids against Fish Pathogens

New pyridonecarboxylic acids (PCAs) were evaluated for in vitro antibacterial activity against Pasteurella piscicida, Vibrio anguillarum, Edwardsiella tarda, and Streptococcus sp., which were pathogens isolated from diseased fish in Japan. The minimal inhibitory concentrations of 11 PCAs, nalidixic acid, oxolinic acid, piromidic acid, pipemidic acid, miloxacin, flumequine, enoxacin, ofloxacin, norfloxacin, ciprofloxacin, and FR77040, were determined with the serial twofold agar dilution method. Newer PCAs, enoxacin, ofloxacin, norfloxacin, ciprofloxacin, and FR77040, showed the strongest antibacterial activity against all the fish pathogens. Oxolinic acid, miloxacin, and flumequine were highly active against the tested fish pathogens except Streptococcus sp. The remaining PCAs, nalidixic, piromidic, and pipemidic acids, were also effective against gram-negative pathogens, but the level of activity was even lower than that of the previous three. The frequency of spontaneous mutation of the pathogens that resulted in resistance to ofloxacin, norfloxacin, ciprofloxacin, and FR77040 was as low as that of pathogens resistant to oxolinic and nalidixic acids. Although cross-resistance of bacteria to the PCAs occurred, the new PCAs were active against bacteria resistant to nalidixic, piromidic, and pipemidic acids. Our results suggest that the new PCAs are potentially effective drugs for the treatment of bacterial diseases offish.