ArticleThe Journal of infectious diseases2013
Tacrolimus enhances the potency of posaconazole against Rhizopus oryzae in vitro and in an experimental model of mucormycosis.
Article in The Journal of infectious diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 64 citations in OpenAlex.
- Commemorating the Landmark Advances in Our Understanding of Mucormycosis by Dimitrios P. Kontoyiannis.Journal of fungi (Basel, Switzerland) · 2025Article
- Structure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Combinations of posaconazole and tacrolimus are effective against infections with azole-resistantFrontiers in cellular and infection microbiology · 2025Article
- Calcineurin activity in Fonsecaea pedrosoi: tacrolimus and cyclosporine A inhibited conidia growth, filamentation and showed synergism with itraconazole.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2024Article
- The Impact of Dimitrios P. Kontoyiannis on Mucormycosis Research.Journal of fungi (Basel, Switzerland) · 2024Article
- Development of a Combat-Relevant Murine Model of Wound Mucormycosis: A Platform for the Pre-Clinical Investigation of Novel Therapeutics for Wound-Invasive Fungal Diseases.Journal of fungi (Basel, Switzerland) · 2024Article
- Molecular mechanisms that govern infection and antifungal resistance in Mucorales.Microbiology and molecular biology reviews : MMBR · 2024Review
- Experimental Models to Study the Pathogenesis and Treatment of Mucormycosis.Journal of fungi (Basel, Switzerland) · 2024Review
- AlternativeFrontiers in cellular and infection microbiology · 2024Review
- Hyphae ofJournal of fungi (Basel, Switzerland) · 2023Article
- Epidemiology, Modern Diagnostics, and the Management of Mucorales Infections.Journal of fungi (Basel, Switzerland) · 2023Review
- Current Treatment Options for COVID-19 Associated Mucormycosis: Present Status and Future Perspectives.Journal of clinical medicine · 2022Review
- IFN-γ Mediated Signaling Improves Fungal Clearance in Experimental Pulmonary Mucormycosis.Mycopathologia · 2022Article
- Article
- Dental and Oral Manifestations of COVID-19 Related Mucormycosis: Diagnoses, Management Strategies and Outcomes.Journal of fungi (Basel, Switzerland) · 2021Review
- Mucormycosis associated with COVID-19 in two kidney transplant patients.Transplant infectious disease : an official journal of the Transplantation Society · 2021Article
- Donor-derived renal allograft mucormycosis in a combined liver and kidney transplantation: Case report and review of the literature.Transplant infectious disease : an official journal of the Transplantation Society · 2021Review
- In Vitro Interaction between Isavuconazole and Tacrolimus, Cyclosporin A, or Sirolimus againstJournal of fungi (Basel, Switzerland) · 2020Article
- Article
- Calcium-Calmodulin-Calcineurin Signaling: A Globally Conserved Virulence Cascade in Eukaryotic Microbial Pathogens.Cell host & microbe · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundWe hypothesized that tacrolimus, an inhibitor of the calcineurin pathway, would enhance the in vivo activity of posaconazole against Rhizopus oryzae, the Mucorales species most commonly associated with mucormycosis.
methodsWe examined patterns of growth inhibition and fungicidal activity of posaconazole and tacrolimus, alone and in combination, against R. oryzae in vitro, using multiple methods (ie, hyphal metabolic and fluorescent vital dye reduction assays and measurement of chitin concentrations), and in vivo, using 2 mucormycosis models: an invertebrate model (Drosophila) and a nonlethal murine model of cutaneous mucormycosis.
resultsCombinations of posaconazole and tacrolimus were synergistic in checkerboard assays for 4 clinical isolates of R. oryzae (48-hour fractional inhibitory concentration index, 0.187-0.281). Pharmacodynamic analysis of the combination revealed that the 90% effective concentration threshold of posaconazole activity against R. oryzae could be achieved with 2-fold lower drug concentrations (0.5-1 mg/L) when administered with tacrolimus (0.007-2 mg/L). In vivo, combination therapy was associated with improved survival in the fly model of mucormycosis (65% vs 57% posaconazole alone) and with significant reductions in cutaneous lesions and R. oryzae fungal burden, compared with animals that received posaconazole monotherapy, in the cutaneous model of mucormycosis.
conclusionsCombination posaconazole-tacrolimus therapy displays synergism in vitro and improved antifungal efficacy in vivo in 2 phylogenetically distinct models of mucormycosis.
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