Abstract
BackgroundIvermectin is an endectocide against many parasites. Though being a macrocyclic lactone, its activity against bacteria has been less known, possibly due to the fact that micromolar concentrations at tissue levels are required to achieve a therapeutic effect. Among pathogenic bacteria of major medical significance, Staphylococcus aureus cause a number of diseases in a wide variety of hosts including humans and animals. It has been attributed as one of the most pathogenic organisms. The emergence of methicillin resistance has made the treatment of S. aureus even more difficult as it is now resistant to most of the available antibiotics. Thus, search for alternate anti-staphylococcal agents requires immediate attention.MethodsTwenty-one clinical isolates of S. aureus were isolated from bovine milk collected from Lahore and Faisalabad Pakistan. Different anthelmintics including levamisole, albendazole and ivermectin were tested against S. aureus to determine their minimum inhibitory concentrations. This was followed-up by growth curve analysis, spot assay and time-kill kinetics.ResultsThe results showed that ivermectin but not levamisole or albendazole exhibited a potent anti-staphylococcal activity at the concentrations of 6.25 and 12.5 μg/ml against two isolates. Interestingly, one of the isolate was sensitive while the other was resistant to methicillin/cefoxitin.ConclusionsOur novel findings indicate that ivermectin has an anti-bacterial effect against certain S. aureus isolates. However, to comprehend why ivermectin did not inhibit the growth of all Staphylococci needs further investigation. Nevertheless, we have extended the broad range of known pharmacological effects of ivermectin. As pharmacology and toxicology of ivermectin are well known, its further development as an anti-staphylococcal agent is potentially appealing.
Highlights
Ivermectin is an endectocide against many parasites
Time kill-kinetics For further confirmation of the above results, bacterial suspension of 0.5 McFarland was prepared for both isolates from freshly prepared overnight cultures as described above. 0.5 McFarland culture for both S. aureus
Inhibition of S. aureus growth by IVM as evidenced by growth curves The growth curve analysis demonstrated that ALB, LEV, and dimethyl sulfoxide (DMSO) did not have any effect on the growth of both S. aureus isolates (Fig. 1a, b), whereas IVM reduced the Inhibition of S. aureus growth by IVM as shown in the spot assay and time-kill kinetics The spot assay showed no growth in both isolates beyond their Minimum Inhibitory Concentration (MIC) representing absence of any bacterial spots at concentration of 12.5 μg/ml for the O9 (MSSA) and 25 μg/ml for the P22 (MRSA) isolates (Fig. 2c, d)
Summary
Ivermectin is an endectocide against many parasites. Though being a macrocyclic lactone, its activity against bacteria has been less known, possibly due to the fact that micromolar concentrations at tissue levels are required to achieve a therapeutic effect. Among pathogenic bacteria of major medical significance, Staphylococcus aureus cause a number of diseases in a wide variety of hosts including humans and animals. It has been attributed as one of the most pathogenic organisms. The major classes of broad spectrum anthelmintics include benzimidazoles (BZ) (e.g. albendazole (ALB)), imidathiozoles (e.g. levamisole (LEV)), tetrahydropyrimidines (e.g. pyrantel), and macrocyclic lactones (MLs) (e.g. ivermectin (IVM)). These four classes of anthelmintics have different modes of action. Imidathiozoles and tetrahydropyrimidines target the nicotinic receptors i.e. they bind to acetylcholine-gated cation channels as agonists at
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