The production of virulence factors by various bacteria can be influenced by sub-inhibitory concentrations of antibiotics. The effect of six antibiotics on the production of representative extracellular enzymes and toxins produced by Staphylococcus aureus was investigated. The production of the virulence determinants coagulase, protein A, alpha and delta haemolysin was monitored in the presence of ciprofloxacin, enoxacin, chloramphenicol, gentamicin, tetracycline and methicillin. The protein synthesis inhibitors reduced the production of coagulase and protein A, and almost completely inhibited the production of the haemolysins. Haemolysin production was also reduced by ciprofloxacin and enoxacin, but these antibiotics had little effect on the production of coagulase and protein A. Methicillin stimulated the production of alpha and delta haemolysins but had no effect on the production of coagulase and protein A.

No abstract

No abstract

No 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.