Present address: Unite de Neuropathologie expérimentale, Institut Pasteur, Paris, France.
Aspergillus Unit, Institut Pasteur, Paris, France.
J Med Microbiol. 2020 Jun;69(6):844-849. doi: 10.1099/jmm.0.001200.
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. We describe the emergence of azole-resistant infections in STAT3-deficient patients. During a retrospective study of 13 pulmonary aspergillosis cases in STAT3-deficient patients conducted in France, we identified patients infected with azole-resistant isolates. Two out of the 13 STAT3-deficient patients with aspergillosis had azole-resistant 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 isolates (TR/L98). Despite prolonged antifungal treatment, including caspofungin and amphotericin B, the patient was not able to clear the azole-resistant . The second patient had chronic cavitary pulmonary aspergillosis (CCPA). The 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 (TR/L98) in the first case whereas resistance developed under antifungal treatments in the second case. These infections required long-term antifungal treatments and surgery. The emergence of azole-resistant 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.
信号转导子和转录激活子 3（STAT3）缺陷是一种罕见的原发性免疫缺陷，与对细菌和真菌感染（尤其是肺曲霉病）的易感性增加有关。我们描述了 STAT3 缺陷患者中唑类耐药感染的出现。在法国进行的一项针对 STAT3 缺陷患者中 13 例肺曲霉病病例的回顾性研究中，我们发现了唑类耐药分离株感染的患者。在这 13 例 STAT3 缺陷肺曲霉病患者中，有 2 例出现唑类耐药感染，表明耐药率出乎意料地高。第一例 STAT3 缺陷患者出现了数次变应性支气管肺曲霉病样发作。他被两种唑类耐药的感染（TR/L98）慢性感染。尽管进行了包括卡泊芬净和两性霉素 B 在内的长期抗真菌治疗，但患者仍未能清除唑类耐药。第二例患者患有慢性空洞性肺曲霉病（CCPA）。最初分离株对唑类敏感，但存在三个 F46Y、M172V 和 E427K 点突变。尽管进行了长期抗真菌治疗，但病变恶化，分离株对所有唑类药物均产生耐药性。随后需要手术和卡泊芬净治疗来治愈 CCPA。在第一种情况下，耐药性可能是从环境中获得的（TR/L98），而在第二种情况下，耐药性是在抗真菌治疗下发展起来的。这些感染需要长期的抗真菌治疗和手术。唑类耐药感染在 STAT3 缺陷中的出现，对治愈和预防抗真菌策略都产生了重大影响。治疗原发性免疫缺陷患者的医生应该意识到这个新出现的问题，因为它会使患者的管理复杂化。
