الفهرس 
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Abstract
The aim of the present work was to study the antimicrobial activity of fusidic acid, a relatively old antibiotic which is internationally revisited, in term of mechanism of action, possible mechanisms of resistance and combination therapy.
One hundred bacterial isolates obtained from different sources were used in this study. These isolates were identified, by macroscopical examination of the colony morphology, the classical microscopical and some important biochemical tests, as S. aureus (82%) and non S. aureus (18%).
The bacteriostatic activity of fusidic acid against the Staphylococcal clinical isolates was investigated through determination of MIC using the agar dilution technique. The MICs ranged between 0.2 and > 1000 μg/mL. All tested isolates under investigation were considered sensitive at MIC ≤ 1 μg/mL following EUCAST and BSAC guidelines.
Out of the 100 collected isolates, more than 50% of the tested strains were resistant to β-lactams, gentamicin, tetracycline and erythromycin. In general, most of the tested Staphylococcal isolates showed multidrug resistance with fifteen different resistance patterns observed, in total. The presence of different resistance patterns indicated some degree of strain heterogeneity among the isolates.
The bactericidal activity of fusidic acid was further investigated by the viable count technique against ten Staphylococcal clinical isolates using three concentrations of fusidic acid, which are ½ x MIC, 1 x MIC and 2 x MIC. Fusidic acid was bactericidal in a concentration dependent manner. Significant declines in bacterial bioburden were observed after 6 h in most of the tested Staphylococcal clinical strains at 2 x MIC of fusidic acid, except highly resistant isolates. In general, the bactericidal activity of fusidic acid was more remarkable against sensitive isolates than the resistant ones.
Heteroresistance was investigated in five isolates and none of the selected cells survived in more than 2 x MIC, which indicated homogeneous populations. However, induction of resistance by passing the cells in ½ x MIC of fusidic acid allowed strains S208 and S412 to grow on plates containing 4 x MIC of fusidic acid.
In the present study, the direct application of fusidic acid cream was assessed in-vitro using viable count technique against eight isolates. A good response was observed in a count reduction for sensitive isolates, induced-resistance isolates and resistant isolates. However, highly resistant isolates remained viable throughout the experiment even after 6 h of contact.