Introduction.
Signal transducer and activator of transcription 3 (STAT3) deficiency is a rare primary immunodeficiency associated with increased susceptibility to bacterial and
fungal infections, notably
pulmonary aspergillosis.Aim. We describe the emergence of
azole-resistant Aspergillus fumigatus
infections in STAT3-deficient patients.Methodology. During a retrospective study of 13
pulmonary aspergillosis cases in STAT3-deficient patients conducted in France, we identified patients infected with
azole-resistant A. fumigatus isolates.Results. Two out of the 13 STAT3-deficient patients with
aspergillosis had
azole-resistant A. fumigatus
infection, indicating an unexpectedly high prevalence of resistance. The first patient with STAT3 deficiency presented several flares of
allergic bronchopulmonary aspergillosis-like episodes. He was chronically infected with two
azole-resistant A. fumigatus isolates (TR34/L98). Despite prolonged antifungal treatment, including
caspofungin and
amphotericin B, the patient was not able to clear the
azole-resistant A. fumigatus. The second patient had chronic cavitary
pulmonary aspergillosis (CCPA). The A. fumigatus isolate was initially
azole susceptible but harboured three F46Y, M172V and E427K point mutations. Despite prolonged antifungal
therapies, lesions worsened and the isolate became resistant to all
azoles. Surgery and
caspofungin treatments were then required to cure CCPA. Resistance was probably acquired from the environment (TR34/L98) in the first case whereas resistance developed under antifungal treatments in the second case. These
infections required long-term antifungal treatments and surgery.Conclusions. The emergence of
azole-resistant A. fumigatus
infections in STAT3-deficiency dramatically impacts both curative and prophylactic antifungal strategies. Physicians following patients with
primary immune-deficiencies should be aware of this emerging problem as it complicates management of the patient.