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In-vitro and in-vivo selection of Staphylococcus aureus mutants resistant to ciprofloxacin
S A Doss1, G S Tillotson, N L Barg
1Department of Medical Microbiology, Medical School, University of Edinburgh, UK.
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.
Insights
Emerging ciprofloxacin resistance in Staphylococcus aureus can be selected both in vitro and in vivo. Adequate ciprofloxacin dosage is crucial to prevent resistance development during treatment.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Staphylococcus aureus is a common pathogen causing various infections.
- Ciprofloxacin is a fluoroquinolone antibiotic frequently used to treat S. aureus infections.
- Antibiotic resistance, including to ciprofloxacin, is a growing public health concern.
Purpose of the Study:
- To investigate the selection of ciprofloxacin-resistant Staphylococcus aureus mutants.
- To compare in vitro and in vivo selection of resistant strains.
- To determine the impact of antibiotic dosage and duration on resistance development.
Main Methods:
- In vitro selection involved incubating S. aureus strains with sub-inhibitory concentrations of ciprofloxacin.
- In vivo selection utilized a murine subcutaneous abscess model with ciprofloxacin treatment.
- Mutant isolation and frequency determination were performed under varying antibiotic concentrations and treatment durations.
Main Results:
- Stably-resistant S. aureus mutants were successfully selected both in vitro and in vivo.
- The frequency of mutation was higher in susceptible strains compared to resistant strains in vitro.
- In vivo, the number of resistant mutants and mutational frequency were inversely proportional to ciprofloxacin dosage and treatment duration.
Conclusions:
- Sub-optimal ciprofloxacin concentrations can lead to the selection of resistant S. aureus strains.
- Adequate dosing and sufficient treatment duration are essential to prevent resistance.
- Clinical treatment strategies for S. aureus infections should ensure inhibitory concentrations at the infection site.