Statin Concentrations Below the Minimum Inhibitory Concentration Attenuate the Virulence of<i>Rhizopus oryzae</i>

Bellanger, Anne Pauline; Tatara, Alexander M.; Shirazi, Fazal; Gebremariam, Teclegiorgis; Albert, Nathaniel D.; Lewis, Russell E.; Ibrahim, Ashraf S.; Kontoyiannis, Dimitrios P.

doi:10.1093/infdis/jiw090

Cited by 35 publications

(33 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…63 Another class of drugs with possible antifungal properties are the statins. A previous study 65 found a synergistic antifungal effect of lovastatin with azoles in vitro, whereas a recent experimental study 66 found that use of statins significantly affected various biologic functions of R oryzae and affected its virulence. Because statins are frequently prescribed agents, the clinical result of their use in combination with antifungal agents should be sought.…”

Section: Implications and Future Directionsmentioning

confidence: 95%

Recent Advances in the Pathogenesis of Mucormycoses

Petrikkos

Tsioutis

2018

Clinical Therapeutics

View full text Add to dashboard Cite

Section: Implications and Future Directionsmentioning

confidence: 95%

Recent Advances in the Pathogenesis of Mucormycoses

Petrikkos

Tsioutis

2018

Clinical Therapeutics

View full text Add to dashboard Cite

“…Granulocyte transfusions have also been tested with unclear success but with some risk for inflammatory lung injury [ 110 ]. Statins have shown in vitro and in vivo activity against Rhizopus spp., but reliable clinical data are lacking [ 111 , 112 ]. In a recent case report, an immunosuppressed, trauma patient with intractable mucormycosis was successfully treated with combination of interferon-γ and nivolumab [ 113 ], a monoclonal antibody that decreases programmed death-1 (PD-1) expression on T-cells.…”

Section: Treatmentmentioning

confidence: 99%

Therapy of Mucormycosis

Sipsas

Gamaletsou

Anastasopoulou

et al. 2018

JoF

Self Cite

164

150

View full text Add to dashboard Cite

Despite the recent introduction of mold-active agents (posaconazole and isavuconazole), in addition to amphotericin B products, to our armamentarium against mucormycosis, many uncertainties remain for the management of this uncommon opportunistic infection, as there are no data from prospective randomized clinical trials to guide therapy. In this mini-review, we present the current status of treatment options. In view of the heterogeneity of the disease (different types of affected hosts, sites of infection, and infecting Mucorales), mucormycosis management requires an individualized management plan that takes into account the net state of immunosuppression of the host, including comorbidities, certainty of diagnosis, site of infection, and antifungal pharmacological properties.

show abstract

“…After a lag time of 3 to 4 days, mice were immunocompromised with cortisone acetate combined to cyclophosphamide. This combination was commonly used in mucormycosis animal models (15,(31)(32)(33)(34)(35). Corticosteroids are used to suppress pulmonary alveolar macrophage function.…”

Section: Methodsmentioning

confidence: 99%

“…Cortisone acetate (Sigma) was dissolved in PBS containing 0.01% Tween 20 (Sigma) to obtain a 50 mg/ml solution, and cyclophosphamide (Sigma) was dissolved in PBS (40 mg/ml). Both drugs were administered intraperitoneally (IP) every 5 days at 500 mg/kg and 200 mg/kg, respectively (15,(31)(32)(33)(34)(35). All immunosuppressive drugs were prepared at the day of use.…”

Section: Methodsmentioning

confidence: 99%

Lichtheimia corymbifera Colonization Leading to Pulmonary Infection Can Be Prevented with Liposomal Amphotericin B in a New Murine Model

Brunet

Jouvion

et al. 2019

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The incidence of pulmonary mucormycosis is constantly increasing, especially in hematological patients staying in high-efficiency particulate air-filtered rooms. Pulmonary inhalation of spores may occur outside the hospital, leading to invasive disease once patients received chemotherapies. We developed a new pulmonary mucormycosis mouse model mimicking the expected pathophysiology in human to study antifungal drugs. Naive mice were inoculated intratracheally with Lichtheimia corymbifera spores. After 3 days, mice received corticosteroids and cyclophosphamide and secondarily developed the disease, while only 5% of the initial inoculum was present in the lungs at day 3. Lung colonization with L. corymbifera spores in immunocompetent mice can last at least 44 days. Antifungal drug was administered the day of immunosuppression. Injection of a single 15 mg/kg of body weight dose of liposomal amphotericin B significantly improved survival and pulmonary fungal burden compared with controls, whereas 80 mg/kg oral posaconazole did not. These results show that a unique dose of liposomal amphotericin B offers a real potential decolonization treatment to prevent infection in our mouse model of L. corymbifera lung colonization followed by lung infection.

show abstract

Statin Concentrations Below the Minimum Inhibitory Concentration Attenuate the Virulence ofRhizopus oryzae

Abstract: Exposure of R. oryzae to statins at concentrations below their MICs decreased virulence both in vitro and in vivo. Further investigation is warranted into the use of statins as adjunctive therapy in mucormycosis.

Cited by 35 publications

References 26 publications

Recent Advances in the Pathogenesis of Mucormycoses

Recent Advances in the Pathogenesis of Mucormycoses

Therapy of Mucormycosis

Lichtheimia corymbifera Colonization Leading to Pulmonary Infection Can Be Prevented with Liposomal Amphotericin B in a New Murine Model

Contact Info

Product

Resources

About