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Resistance to amphotericin B does not emerge during treatment for invasive aspergillosis
Mahomed-Yunus S Moosa1, George J Alangaden, Elias Manavathu
1Division of Infectious Diseases, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Abstract:
Emergence of resistance to antifungal drugs during therapy for invasive aspergillosis has received scant attention. We recovered Aspergillus isolates from six patients with invasive aspergillosis, who were receiving amphotericin B before fungal isolation. Although isolates were susceptible to amphotericin B in vitro, none of the patients survived. The MIC of amphotericin B for isolates was similar to that for isolates from 35 patients with no prior exposure to amphotericin B. Laboratory attempts to produce amphotericin B resistance in Aspergillus were unsuccessful. These data indicate that emergence of resistance to amphotericin B is uncommon during therapy for invasive aspergillosis.
Insights
Emergence of antifungal resistance during invasive aspergillosis therapy is rare. Studies show amphotericin B resistance did not develop in Aspergillus isolates from patients who did not survive invasive aspergillosis.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Pharmacology
Background:
- Invasive aspergillosis is a serious fungal infection.
- Antifungal drug resistance is a growing concern in treating such infections.
- Amphotericin B is a key antifungal medication.
Purpose of the Study:
- To investigate the emergence of resistance to amphotericin B during invasive aspergillosis treatment.
- To determine if Aspergillus isolates develop resistance to amphotericin B under therapy.
Main Methods:
- Collected Aspergillus isolates from six patients undergoing amphotericin B therapy for invasive aspergillosis.
- Performed in vitro susceptibility testing of isolates against amphotericin B.
- Compared Minimum Inhibitory Concentrations (MICs) with isolates from patients without prior amphotericin B exposure.
- Attempted to induce amphotericin B resistance in Aspergillus in laboratory settings.
Main Results:
- All six patient isolates were susceptible to amphotericin B in vitro.
- None of the six patients receiving amphotericin B therapy survived.
- Isolate MICs were comparable to those from amphotericin B-naive patients.
- Laboratory induction of amphotericin B resistance in Aspergillus proved unsuccessful.
Conclusions:
- Emergence of amphotericin B resistance during invasive aspergillosis therapy appears uncommon.
- Further research is needed to understand treatment failures in invasive aspergillosis despite in vitro susceptibility.