Pentamidine Is Active in a Neutropenic Murine Model of Acute Invasive Pulmonary Fusariosis

Lionakis, Michail S.; Chamilos, Georgios; Lewis, Russell E.; Wiederhold, Nathan P.; Raad, Issam; Samonis, George; Kontoyiannis, Dimitrios P.

doi:10.1128/aac.50.1.294-297.2006

Cited by 10 publications

(6 citation statements)

References 12 publications

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“…Activity of pentamidine (in vitro studies and animal models) against Fusarium spp. has also been described (89,90). The mechanistic explanations and the clinical relevance supporting these potential synergisms are unclear.…”

Section: Efficacy Of Antifungals In Vivomentioning

confidence: 99%

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Therapeutic Challenges of Non- Aspergillus Invasive Mold Infections in Immunosuppressed Patients

Lamoth

Kontoyiannis

2019

Antimicrob Agents Chemother

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While Aspergillus spp. remain the major cause of invasive mold infections in hematologic cancer patients and transplant recipients, other opportunistic molds, such as Mucorales, Fusarium, and Scedosporium spp. are increasingly encountered in an expanding population of patients with severe and prolonged immunosuppression. High potential for tissue invasion and dissemination, resistance to multiple antifungals and high mortality rates are hallmarks of these non-Aspergillus invasive mold infections (NAIMIs). Assessment of drug efficacy is particularly difficult in the complex treatment scenarios of NAIMIs. Specifically, correlation between in vitro susceptibility and in vivo responses to antifungals is hard to assess, in view of the multiple, frequently interrelated factors influencing outcomes, such as pharmacokinetic/pharmacodynamic parameters determining drug availability at the site of infection, the net state of immune suppression, delay in diagnosis, or surgical debulking of infectious foci. Our current therapeutic approach of NAIMIs should evolve toward a better integration of the dynamic interactions between the pathogen, the drug and the host. Innovative concepts of experimental research may consist in manipulating the host immune system to induce a specific antifungal response or targeted drug delivery. In this review, we discuss the challenges in the management of NAIMIs and provide an update about the latest advances in diagnostic and therapeutic approaches.

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Section: Efficacy Of Antifungals In Vivomentioning

confidence: 99%

“…Another antiprotozoal agent, pentamidine, also demonstrated in vitro activity and efficacy in murine models against Fusarium spp. (89,90). In addition, colistin has been shown to display modest in vitro and in vivo fungicidal activity against Mucorales (112).…”

Section: Novel Antifungal Agentsmentioning

confidence: 99%

Therapeutic Challenges of Non- Aspergillus Invasive Mold Infections in Immunosuppressed Patients

Lamoth

Kontoyiannis

2019

Antimicrob Agents Chemother

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“…A percutaneous needle biopsy specimen of the lung grew the same mold that had been isolated from the bronchoalveolar lavage fluid. A trial treatment using intravenous pentamidine, based on its activity in murine models of fusariosis (20), resulted in transiently altered mental status. Lung and chest wall biopsy specimens showed numerous hyphae ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Aspergillus tanneri sp. nov., a New Pathogen That Causes Invasive Disease Refractory to Antifungal Therapy

et al. 2012

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The most common cause of invasive aspergillosis (IA) in patients with chronic granulomatous disease (CGD) is Aspergillus fumigatus followed by A. nidulans; other aspergilli rarely cause the disease. Here we review two clinical cases of fatal IA in CGD patients and describe a new etiologic agent of IA refractory to antifungal therapy. Unlike typical IA caused by A. fumigatus, the disease caused by the new species was chronic and spread from the lung to multiple adjacent organs. Mycological characteristics and the phylogenetic relationship with other aspergilli based on the sequence analysis of Mcm7, RPB2, and Tsr1 indicated that the new species, which we named as A. tanneri, belongs to Aspergillus section Circumdati. The species has a higher amphotericin B, voriconazole, and itraconazole MIC and causes more chronic infection in CGD mice than A. fumigatus. This is the first report documenting IA in CGD patients caused by a species belonging to the Aspergillus section Circumdati that is inherently resistant to azoles and amphotericin B. Unlike the results seen with many members of Aspergillus section Circumdati, ochratoxin was not detected in filtrates of cultures grown in various media. Our phenotypic and genetic characterization of the new species and the case reports will assist future diagnosis of infection caused by A. tanneri and lead to more appropriate patient management.

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“…In addition, T-2307 has been reported to be well-tolerated in immunocompetent and neutropenic murine models of invasive fungal infections at doses of up to 6 mg/kg/day [ 12 , 14 , 20 , 21 , 22 , 23 ]. In contrast, pentamidine, which is structurally similar to T-2307, is known to cause numerous adverse effects/toxicities in both animals and humans, including serious endocrine/metabolic, cardiovascular, and renal toxicities when administered systemically [ 29 , 30 , 31 , 32 ]. T-2307 pharmacokinetic data are not available in the literature, and it is also unknown what formulations may be available for the treatment of patients.…”

Section: Tolerability Safety and Clinical Datamentioning

confidence: 99%

Review of T-2307, an Investigational Agent That Causes Collapse of Fungal Mitochondrial Membrane Potential

Wiederhold

2021

JoF

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Invasive infections caused by Candida that are resistant to clinically available antifungals are of increasing concern. Increasing rates of fluconazole resistance in non-albicans Candida species have been documented in multiple countries on several continents. This situation has been further exacerbated over the last several years by Candida auris, as isolates of this emerging pathogen that are often resistant to multiple antifungals. T-2307 is an aromatic diamidine currently in development for the treatment of invasive fungal infections. This agent has been shown to selectively cause the collapse of the mitochondrial membrane potential in yeasts when compared to mammalian cells. In vitro activity has been demonstrated against Candida species, including C. albicans, C. glabrata, and C. auris strains, which are resistant to azole and echinocandin antifungals. Activity has also been reported against Cryptococcus species, and this has translated into in vivo efficacy in experimental models of invasive candidiasis and cryptococcosis. However, little is known regarding the clinical efficacy and safety of this agent, as published data from studies involving humans are not currently available.

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Pentamidine Is Active in a Neutropenic Murine Model of Acute Invasive Pulmonary Fusariosis

Cited by 10 publications

References 12 publications

Therapeutic Challenges of Non- Aspergillus Invasive Mold Infections in Immunosuppressed Patients

Therapeutic Challenges of Non- Aspergillus Invasive Mold Infections in Immunosuppressed Patients

Aspergillus tanneri sp. nov., a New Pathogen That Causes Invasive Disease Refractory to Antifungal Therapy

Review of T-2307, an Investigational Agent That Causes Collapse of Fungal Mitochondrial Membrane Potential

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