The Response of Escherichia coli to Nalidixic Acid

The response of Escherichia coli to nalidixic acid was investigated by continuous turbidimetric monitoring of cultures exposed to the drug. Two distinct types of turbidimetric response were detected when dense populations of E. coli were exposed to nalidixic acid in a static system, but this difference was not found in low-inoculum experiments, nor in experiments in which initially dense inocula of E. coli were exposed to the drug in conditions similar to those encountered in the treatment of bacterial cystitis. Stable resistance to nalidixic acid was readily induced in cultures of E. coli. Such resistance emerged by a step-wise process and cultures could easily be converted to resistance to at least 64 μg nalidixic acid per millilitre by sequential transfer. Resistance to drug levels greater than 64 μg/ml was more difficult to induce and such variants were unstably resistant to the higher drug levels. ‘Wild’ nalidixic-acid-resistant E. coli were correspondingly found to be partially susceptible to concentrations of nalidixic acid exceeding 64 μg/ml. Nalidixic acid resistance was even easier to induce in an in vitro model of the treatment of bacterial cystitis than in the static system, in that a single cycle of exposure to a ‘dose’ of the drug allowed the emergence of a population exhibiting a relatively high level of resistance. It is suggested that the therapeutic efficiency of nalidixic acid resides in a highly effective initial onslaught, and that, if infection is not controlled at this stage, the emergence of resistance is likely to be a cause of therapeutic failure.