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Posaconazole prophylaxis in experimental azole-resistant invasive pulmonary aspergillosis

Seyedmojtaba Seyedmousavi1, Johan W Mouton1, Willem J G Melchers2

  • 1Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, the Netherlands.

Antimicrobial Agents and Chemotherapy
|December 24, 2014
PubMed

Insights

Posaconazole prophylaxis effectively prevented invasive aspergillosis in mice infected with azole-resistant Aspergillus fumigatus strains having low posaconazole minimum inhibitory concentrations (MICs). Higher MICs, however, led to breakthrough infections, indicating resistance limitations.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Pharmacology

Background:

  • Invasive aspergillosis is a serious fungal infection.
  • Azole resistance in Aspergillus fumigatus is an emerging clinical concern.
  • Posaconazole is a key antifungal agent for prophylaxis.

Purpose of the Study:

  • To evaluate the efficacy of posaconazole prophylaxis against azole-resistant Aspergillus fumigatus.
  • To determine the relationship between posaconazole MICs and treatment outcomes.

Main Methods:

  • A neutropenic murine model of pulmonary infection was utilized.
  • Four isogenic clinical isolates of Aspergillus fumigatus with varying posaconazole MICs were tested.
  • Posaconazole prophylaxis efficacy was assessed based on survival rates.

Main Results:

  • Posaconazole prophylaxis achieved 100% survival in mice infected with isolates having posaconazole MICs of ≤0.5 mg/liter.
  • Breakthrough infections occurred in mice infected with an isolate exhibiting a posaconazole MIC >16 mg/liter.
  • Isolates with F219I mutation and TR34/L98H mutation (MIC 0.5 mg/liter) were susceptible to prophylaxis.

Conclusions:

  • Posaconazole prophylaxis is effective against Aspergillus fumigatus with posaconazole MICs up to 0.5 mg/liter.
  • Higher posaconazole MICs (>16 mg/liter) in Aspergillus fumigatus isolates can lead to prophylaxis failure.
  • Antifungal resistance monitoring is crucial for effective invasive aspergillosis prevention.

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