Vulnerable immunocompromised individuals are at risk of opportunistic infections by invasive molds, and available antifungal treatments for these invasive infections are currently restricted. Therefore, a combination of therapies has been proposed as a potential strategy to enhance the effectiveness of treatment outcomes. Prof. Mahmoud Ghannoum (Case Western Reserve University and University Hospitals Cleveland Medical Centre, Cleveland, OH, USA) discusses an early phase study evaluating the effect of ibrexafungerp alone and in combination with amphotericin B or posaconazole against Rhizopus and Cunnighamella sp. using time-kill and scanning electron microscopy.
Interviews in this series:
Ibrexafungerp against Mucor strains using time-kill and scanning electron microscopy
Antifungal resistance – biofilms, tolerance phenomena, treatment and diagnostics
ECCMID 2023 highlights in fungal infections
The abstract ‘Evaluate the effect of ibrexafungerp alone and in combination with amphotericin B or posaconazole against Mucor strains using time kill kinetics and scanning electron microscopy‘ (Abstract number: P2020) was presented at ECCMID 2023, 15-18 April, 2023, Copenhagen, Denmark.
Questions
- What challenges do invasive molds hold for vulnerable immunocompromised populations?
- What are the aims and design of the study?
- What were the key findings from the study?
- What questions remain unanswered and what future studies are planned?
Disclosures: Mahmoud Ghannoum is a consultant for Ortho Dermatologics.
Support: Interview and filming supported by Touch Medical Media Ltd. Interview conducted by Katey Gabrysch.
Filmed in coverage of the 33rd European Congress of Clinical Microbiology & Infectious Diseases
Click here for more content on fungal infections & for further ECCMID 2023 highlights visit here.
Transcript
I’m Mahmoud Ghannoum. I am the Director of the Center for Medical mycology and integrated microbiome core at Case Western Reserve University and University Hospitals in Cleveland, Ohio.
What challenges do invasive molds hold for vulnerable immunocompromised populations?
Mold infections are quite serious problem for immunocompromised patients, particularly with Aspergillus as well as daily infections, and really the challenge is that we don’t have many, many drugs that can treat them. And because of this, we always are trying to discover new antifungals to try to deal with them. The good news is there are some new antifungals coming into the market where they will be. They have been shown to be actually effective, at least in clinical trials that are not yet approved by the European Union, regulatory bodies or the FDA. But they are really showing great promise in order to deal with these infections.
What are the aims and design of the study?
The aim of the study was to try to see can we find a combination therapy to treat three invasive fungal infections, and as I alluded to earlier, we really don’t have great drugs at the moment to deal with some fungal infections. The study concept starts by thinking of using combination therapy, compare combination of two different drugs from different classes of antifungals which could be the way forward. This is a big issue, because in the antifungal field, we tend not to apply combination therapies, because in a study many years ago, that combined fluconazole and amphotericin B – the outcome was negative, so the whole medical community and medical mycology community shield away from this method of treatment. To me, it’s about time for us to start thinking how can we use this combination therapy? And by having a new classes of compounds, which were not here when we did fluconazole and amphotericin b were being studied. So, to me, this is a very important approach that we should try to exploit and this promise to treat this invasive fungal infections. The purpose of this study was to evaluate a new antifungal which was recently approved for DVC vulvovaginal candidiasis to see does it work more or in combination with amphotericin B or cortisone? And that’s exactly what we did. We evaluated the effect of the fungus alone and then combined with these two agents and we showed and improved the ability of these drugs to kill the aspergillus, for example, as well as a resource.
What were the key findings from the study?
The key finding of the study is that using ibrexafungerp with either amphotericin B or posaconazoleis is to increase the efficacy of both drugs. Nnumber one, we showed that we increased kill magnitude significantly. But also, when we looked at scanning electron microscopy to see when you put the two drugs, how can they break the fungal cells? It shows great morphological changes where the cell collapsed and we saw a lot of cytoplasmic material being produced, indicating that the cell had disrupted and died.
What questions remain unanswered and what future studies are planned?
The study was in vitro, and the good news is there were also other studies in vivo showing similar results. So the next step is to really start doing clinical trials to see whether this also can be translated into the patients. And I understand that these trials are being designed and it’s going to be really coming soon.
Subtitles and transcript are autogenerated.
