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      Is Open Access

      Zolav ®: a new antibiotic for the treatment of acne

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          Abstract

          Background

          Acne is a prominent skin condition affecting >80% of teenagers and young adults and ~650 million people globally. Isotretinoin, a vitamin A derivative, is currently the standard of care for treatment. However, it has a well-established teratogenic activity, a reason for the development of novel and low-risk treatment options for acne.

          Objective

          To investigate the effectiveness of Zolav ®, a novel antibiotic as a treatment for acne vulgaris.

          Materials and methods

          Minimum inhibitory concentration of Zolav ® against Propionibacterium acnes was determined by following a standard protocol using Mueller-Hinton broth and serial dilutions in a 96-well plate. Cytotoxicity effects on human umbilical vein endothelial cells and lung cells in the presence of Zolav ® were investigated by determining the growth inhibition (GI 50) concentration, total growth inhibition concentration, and the lethal concentration of 50% (LC 50). The tryptophan auxotrophic mutant of Escherichia coli strain, WP2 uvrA (ATCC 49979), was used for the AMES assay with the addition of Zolav ® tested for its ability to reverse the mutation and induce bacterial growth. The in vivo effectiveness of Zolav ® was tested in a P. acnes mouse intradermal model where the skin at the infection site was removed, homogenized, and subjected to colony-forming unit (CFU) counts.

          Results

          Susceptibility testing of Zolav ® against P. acnes showed a minimum inhibitory concentration of 2 µg/mL against three strains with no cytotoxicity and no mutagenicity observed at the highest concentrations tested, 30 µM and 1,500 µg/plate, respectively. The use of Zolav ® at a concentration of 50 µg/mL (q8h) elicited a two-log difference in CFU/g between the treatment group and the control.

          Conclusion

          This study demonstrates the potential of Zolav ® as a novel treatment for acne vulgaris.

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          Most cited references 9

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          Acne vulgaris.

          Acne is a chronic inflammatory disease of the pilosebaceous unit resulting from androgen-induced increased sebum production, altered keratinisation, inflammation, and bacterial colonisation of hair follicles on the face, neck, chest, and back by Propionibacterium acnes. Although early colonisation with P acnes and family history might have important roles in the disease, exactly what triggers acne and how treatment affects the course of the disease remain unclear. Other factors such as diet have been implicated, but not proven. Facial scarring due to acne affects up to 20% of teenagers. Acne can persist into adulthood, with detrimental effects on self-esteem. There is no ideal treatment for acne, although a suitable regimen for reducing lesions can be found for most patients. Good quality evidence on comparative effectiveness of common topical and systemic acne therapies is scarce. Topical therapies including benzoyl peroxide, retinoids, and antibiotics when used in combination usually improve control of mild to moderate acne. Treatment with combined oral contraceptives can help women with acne. Patients with more severe inflammatory acne usually need oral antibiotics combined with topical benzoyl peroxide to decrease antibiotic-resistant organisms. Oral isotretinoin is the most effective therapy and is used early in severe disease, although its use is limited by teratogenicity and other side-effects. Availability, adverse effects, and cost, limit the use of photodynamic therapy. New research is needed into the therapeutic comparative effectiveness and safety of the many products available, and to better understand the natural history, subtypes, and triggers of acne. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Guidelines of care for acne vulgaris management.

            Adherence to these guidelines will not ensure successful treatment in every situation. Furthermore, these guidelines should not be deemed inclusive of all proper methods of care or exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient.
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              Is Open Access

              A new antibiotic with potent activity targets MscL

              The growing problem of antibiotic-resistant bacteria is a major threat to human health. Paradoxically, new antibiotic discovery is declining, with most of the recently approved antibiotics corresponding to new uses for old antibiotics or structurally similar derivatives of known antibiotics. We used an in silico approach to design a new class of nontoxic antimicrobials for the bacteria-specific mechanosensitive ion channel of large conductance, MscL. One antimicrobial of this class, compound 10, is effective against methicillin-resistant Staphylococcus aureus with no cytotoxicity in human cell lines at the therapeutic concentrations. As predicted from in silico modeling, we show that the mechanism of action of compound 10 is at least partly dependent on interactions with MscL. Moreover we show that compound 10 cured a methicillin-resistant S. aureus infection in the model nematode Caenorhabditis elegans. Our work shows that compound 10, and other drugs that target MscL, are potentially important therapeutics against antibiotic-resistant bacterial infections.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2016
                22 March 2016
                : 10
                : 1235-1242
                Affiliations
                [1 ]AXD Pty Ltd, Semaphore Park, Flinders University, Bedford Park, SA, Australia
                [2 ]School of Chemical and Physical Sciences, Flinders University, Bedford Park, SA, Australia
                [3 ]Boulos & Cooper Pharmaceuticals Pty Ltd, Port Adelaide, SA, Australia
                Author notes
                Correspondence: Ramiz A Boulos, Boulos & Cooper Pharmaceuticals Pty Ltd, 6 Todd Street, Port Adelaide, SA 5015, Australia, Tel +61 8 8440 2494, Email ceo@ 123456bouloscooper.com
                Article
                dddt-10-1235
                10.2147/DDDT.S106462
                4809335
                27042015
                © 2016 Dinant and Boulos. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

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