In-vitro and in-vivo selection of Staphylococcus aureus mutants resistant to ciprofloxacin

Abstract

Staphylococcus aureus mutants resistant to ciprofloxacin were selected both in vitro and in vivo. In-vitro selection was achieved by incubating two strains of S. aureus (MICs of ciprofloxacin of 0.5 and 4 mg/L respectively) in the presence of ciprofloxacin in concentrations equivalent to 1/2 x MIC for 24 h and isolating the mutants on agar containing the quinolone at 1, 2 or 5 x MIC. Stably-resistant mutants of both strains were isolated, although the frequency of mutation of the susceptible strain was higher than that of the resistant strain. A murine subcutaneous abscess model was used for in-vivo selection. Mice which had been infected with a ciprofloxacin-susceptible strain of S. aureus were treated for 24 h with ciprofloxacin in a dosage which yielded concentrations in the abscess cavity equivalent to 1/2 or 1 x MIC for the pathogen. Additional groups of infected mice received ciprofloxacin for varying periods in a dosage which produced concentrations at the site of infection equivalent to 1/2 x MIC. Stably-resistant mutants were isolated from the abscesses, the number of mice from which mutants were isolated and the mutational frequency being inversely proportional to the dosage of ciprofloxacin administered and the duration of treatment. The results of this study confirm that, in the treatment of patients with infections caused by S. aureus, the dosage of ciprofloxacin should be adequate to ensure inhibitory concentrations at the site of infection.

In vitro Analysis of the Change in Resistance of <i>Chlamydia trachomatis</i> under Exposure to sub-MIC Levofloxacin for a Therapeutic Term

“…In addition, strains of the organism resistant to sulfisoxazole, which is the antimicrobial recommended as an alternative agent for its treatment [4], were isolated by a stepwise procedure [5]. In in vitro and in vivo studies on bacteria, mutant resistant Staphylococcus aureus were able to be selected with exposure to a sub-MIC of ciprofloxacin [10]. These studies offered important information, because some C. trachomatis strains may have the potential to develop resistance to fluoroquinolone when they are exposed to fluoroquinolone in the clinical setting.…”

Changes in Susceptibility of <i>Pseudomonas aeruginosa</i> to Gatifloxacin andCarbapenem in an in vitro Urinary BladderModel

“…Doss et al [4] reported that resistant mutants, which persisted even after treatment was discontinued, were selected in their study, which was designed to obtain subinhibitory concentrations of ciprofloxacin in subcutaneous abscess cavities. Thus, it is justified to speculate that the failure of an empirical therapy for UTI may partly depend on a situation in Takahashi/Hirose/Sano/Nishimura/ Matsukawa/Mikami/Tsukamoto which the less susceptible strains were selected and multiplied under the conditions of sub-MIC antibacterial exposure.…”

In-vitro investigation of the antibacterial activity of agents which may be used for the oral treatment of lung infections in CF patients

“…Ciprofloxacin-, trimethoprim-and sulphonamide-resistant mutants were selected according to the method used by Doss et al 5 Each of the study strains was inoculated into Iso-sensitest broth containing ciprofloxacin, trimethoprim, sulphadiazine and sulphamethoxazole alone or in combination at concentrations equivalent to 0.5 MIC. After 24 h, 0.1 mL aliquots were subcultured on to Iso-sensitest agar containing either no antibacterial or antibacterials, singly or in combination, at concentrations equivalent to 1, 2 or 5 MIC for each strain.…”

“…Fluoroquinolones initially provided effective therapy with patient convenience but became limited with use because of rapidly increasing bacterial resistance. [3][4][5][6] The aim of the present investigation was to determine the in-vitro effectiveness of an oral therapy consisting of a combination of ciprofloxacin with trimethoprim and…”