1. The Antimicrobial Activity of Omiganan Alone and In Combination against Candida Isolated from Vulvovaginal Candidiasis and Bloodstream Infections
Wojciech Kamysz, Damian Neubauer, Maciej Jaśkiewicz, Paulina Czechowicz, Joanna Nowicka, Andrzej Wajda, Dawid Żyrek Antibiotics (Basel) . 2021 Aug 19;10(8):1001. doi: 10.3390/antibiotics10081001.
Fungi from theCandidagenus are widespread commensals and, at the same time, are the leading cause of fungal infections worldwide. For instance, vulvovaginal candidiasis (VVC) affects approximately 75% of women at least once in their lifetime, remaining the second most common gynecological infection. On the contrary, hospital-acquired fungal bloodstream infections (BSIs), although less frequent, are characterized by a high mortality rate. Undoubtedly, the main reason for this situation are virulence factors that these yeast-like fungi can produce, and the ability to form a biofilm is one of the most important of them. Due to the low effectiveness of classic antimycotics againstCandidabiofilms, an intense search for new drugs capable of eradicating this structure is highly demanded. One of the most promising groups of compounds exhibiting such properties are antimicrobial peptides (AMPs). This study focuses on a comparison of the efficacy of Omiganan and fluconazole alone and in combination againstCandidastrains isolated from BSIs. The obtained results are consistent with our previous reports on the effectiveness of Omiganan against clinical strains isolated from VVC. This is also the first report on the combinatory application of Omiganan in the context of fungal BSI. The majority of combinations with fluconazole showed an additive effect, as well as a synergistic effect in the range of certain concentrations. Importantly, such effects are visible at concentrations much lower than for those compounds used individually. Potentially, this entails the possibility of limiting the adverse effects (e.g., toxicity) of Omiganan and fluconazole applied in vivo, thus improving the safety profile of this particular antifungal therapy.
2. Omiganan Enhances Imiquimod-Induced Inflammatory Responses in Skin of Healthy Volunteers
Errol P Prens, Thomas P Buters, Robert Rissmann, Matthijs Moerland, Jacobus Burggraaf, Erica S Klaassen, Edwin Florencia, Tessa Niemeyer-van der Kolk, Martijn B A van Doorn, Gary Feiss, Melanie Rijsbergen, Salma Assil Clin Transl Sci . 2020 May;13(3):573-579. doi: 10.1111/cts.12741.
Omiganan (OMN; a synthetic cationic peptide) and imiquimod (IMQ; a TLR7 agonist) have synergistic effects on interferon responses in vitro. The objective of this study was to translate this to a human model for proof-of-concept, and to explore the potential of OMN add-on treatment for viral skin diseases. Sixteen healthy volunteers received topical IMQ, OMN, or a combination of both for up to 4 days on tape-stripped skin. Skin inflammation was quantified by laser speckle contrast imaging and 2D photography, and molecular and cellular responses were analyzed in biopsies. IMQ treatment induced an inflammatory response of the skin. Co-treatment with OMN enhanced this inflammatory response to IMQ, with increases in perfusion (+17.1%; 95% confidence interval (CI) 5.6%-30%; P < 0.01) and erythema (+1.5; 95% CI 0.25%-2.83; P = 0.02). Interferon regulatory factor-driven and NFκB-driven responses following TLR7 stimulation were enhanced by OMN (increases in IL-6, IL-10, MXA, and IFNɣ), and more immune cell infiltration was observed (in particular CD4+, CD8+, and CD14+ cells). These findings are in line with the earlier mechanistic in vitro data, and support evaluation of imiquimod/OMN combination therapy in human papillomavirus-induced skin diseases.
3. Omiganan pentahydrochloride in the front line of clinical applications of antimicrobial peptides
Miguel A R B Castanho, Manuel N Melo, Dominique Dugourd Recent Pat Antiinfect Drug Discov . 2006 Jun;1(2):201-7. doi: 10.2174/157489106777452638.
Ribosomally synthesized antimicrobial peptides have very wide killing spectra and bacterial resistance to these peptides seems to be a rare phenomenon. Indolicidin is a ribosomally synthesized antimicrobial peptide that served as a template to omiganan, which is in development for the prevention of catheter-related bloodstream infections; clinical trials also proved its efficiency against acne vulgaris. Omiganan is the most advanced molecule in the front line of clinical applications of antimicrobial peptides. The mode and site of action of omiganan are not yet settled although its interaction with membranes is known to play a fundamental role. The biochemical and biophysical foundations for the action of indolicidin and its analogues are reviewed in this paper, as well as the clinical application of omiganan. The in vitro efficiency tests and the outcome of clinical trials are addressed. Altogether, despite the very specific use of omiganan as a topical antibiotic, it has the potential of being a pioneer of a new generation of antibiotics that carry the promise of ending the multi-resistance problem.
