Resistance to ten different fluoroquinolone antibiotics following in vitro exposures to nalidixic acid
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The in vitro activities of five quinolinecarboxylic acids against two laboratory strains of Chlamydia trachomatis were compared. The minimal inhibitory concentrations of nalidixic acid, cinoxacin, and pipemidic acid were all greater than or equal to 50 micrograms/ml; the activity of norfloxacin was intermediate (minimal inhibitory concentration, 8 to 16 micrograms/ml). Ciprofloxacin was the most active of these drugs (minimal inhibitory concentration, 0.5 to 1 microgram/ml).
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To validate the screening of low-level fluoroquinolone resistance in typhoid salmonellae by using nalidixic acid (30 mg) disk providing an acceptable zone of inhibition.Quasi-experimental study.The Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan from July 2002 to June 2003.Antimicrobial susceptibility of 225 clinical isolates of S. typhi (n=126) and S. paratyphi A (n=99) against nalidixic acid and ciprofloxacin was determined by the modified Kirby-Bauer disk diffusion and agar dilution techniques of NCCLS. The relationship between the zone sizes and the MICs of the two quinolones was plotted in the form of scattergrams and nalidixic acid MICs and zone of inhibition sizes were correlated with those of ciprofloxacin by regression analysis.One hundred and ninety-five isolates were nalidixic acid-susceptible (MIC <16 microg/mL) and approximately 30 were nalidixic acid-resistant (MIC >32 microg/mL). All the nalidixic acid-susceptible isolates had ciprofloxacin MIC of <0.064 microg/mL. Among the nalidixic acid-resistant isolates approximately 20 had ciprofloxacin MIC > or =0.125 microg/mL and approximately 10 had ciprofloxacin MIC < or =0.03-0.064 microg/mL. The diameter of inhibition zone around a 30 mg nalidixic acid disk of nalidixic acid-resistant isolates was < or =13 mm (range 6-16 mm, mean 10.3 mm + SD 3.5 mm), while among nalidixic acid-susceptible isolates it ranged from 14 to 30 mm (mean 23.8 mm + SD 2.2 mm). The diameter of inhibition zone around a 5mg ciprofloxacin disk of nalidixic acid-resistant isolates ranged from 26 to 35 mm (mean 29.8 mm + SD 3.1 mm), while in nalidixic acid-susceptible isolates it ranged from 32 to 42 mm (mean 36.6 mm + SD 1.9 mm). With ciprofloxacin MIC > or =0.125 microg/mL taken as a breakpoint, a zone of
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Oxolinic acid
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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.
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The susceptibility of 49 strains of Aeromonas hydrophila and 77 strains of Enterobacteriaceae towards nalidixic acid was compared by tube dilution and agar diffusion methods. A higher susceptibility was exhibited by Aerom. hydrophila and no overlap in MICs was found for strains of the two groups of microorganisms. Discs containing 0.25 microgram of nalidixic acid produced measurable zones of growth inhibition with Aerom. hydrophila and no zones with the Enterobacteriaceae. The use of a disc with 0.25 microgram of nalidixic acid for the primary differentiation of strains of Aerom. hydrophila from those of the Enterobacteriaceae with similar biochemical properties is suggested.
Enterobacteriaceae Infections
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Background: Fluoroquinolones are the drugs of choice for the treatment of typhoid fever. But the recent increase in minimum inhibitory concentration (MIC) values of ciprofloxacin in Salmonella Typhi may result in delayed response and serious complications. Nalidixic acid resistance has been used as an indirect evidence of increased minimum inhibitory concentration for ciprofloxacin in Salmonella Typhi. Methods: We evaluated the isolates received at the National Salmonella and Escherichia Centre for nalidixic acid and ciprofloxacin susceptibility using standard methods. Minimum inhibitory concentrations have also been evaluated. Results: Ninety-six percent of the isolates were found to be nalidixic acid resistant while all isolates were found to be ciprofloxacin sensitive. The difference between minimum inhibitory concentration values of ciprofloxacin for nalidixic acid resistant and nalidixic acid sensitive isolates was found to be statistically significant. Conclusion: The study may be helpful in revising treatment strategies for the infections caused by nalidixic acid resistant Salmonella Typhi in the country.
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The antibacterial activity of quinolones and fluoroquinolones was evaluated against several strains of enterobacteria growing in Mueller-Hinton broth and in urine at different pH. The data obtained in alkaline urine and in Mueller-Hinton broth indicate that the MIC values of the fluoroquinolones are about 16-32 times inferior to those found in urine at pH 6. On the other hand, the activity of nalidixic acid and more particularly that of cinoxacin in urine appears to be optimum at this lower pH, showing MIC values only 2-4 times higher than those obtained in Mueller-Hinton media. Although the fluoroquinolones appear to have the highest degree of activity, a better MBC/MIC ratio was observed for cinoxacin and for nalidixic and oxolinic acids.
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