Successful Treatment of Mucormycosis and Azole-Resistant Aspergillus Coinfection in a Diabetic Patient: A Case Report

Tingting Zhao,1 Yuan Fang,1 Qiuhui Wu,2 Minke Shi,3 Yueyan Ni,1 Ruyi Zou,1 Mengying Liu,1 Weiwei Wu,4 Xin Su1 1Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, People’s Republic of China; 2Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, People’s Republic of China; 3Department of Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, People’s Republic of China; 4Dinfectome Inc., Nanjing, Jiansu, 210000, People’s Republic of ChinaCorrespondence: Xin Su, Email [email protected]: To report a case of coinfection with mucormycosis and azole-resistant Aspergillus fumigatus in a patient with poorly controlled type 2 diabetes, highlighting successfully treated with high-dose posaconazole combined with liposomal amphotericin B and lobectomy.Methods: A 52-year-old man who presented to our hospital with a 1-month history of fever accompanied by productive cough and sputum. He had type 2 diabetes with poor control of glucose level. Chest computed tomography (CT) showed rapidly progressive multiple cavities and consolidation in the lungs. Sputum culture showed azole-resistant Aspergillus fumigatus, confirmed by whole genome sequencing, which revealed mutations in non-azole target genes (eg, CYP51A was wild-type). Targeted next-generation sequencing (tNGS) of bronchoalveolar lavage fluid (BALF) at admission detected Aspergillus fumigatus and Rhizopus microsporus, while histopathology of right upper lobe necrotic material on day 18 confirmed mucormycosis. The patients had previously received intravenous voriconazole (400 mg/d) combined with inhaled amphotericin B (10 mg twice daily) for 2 weeks without improvement. Upon admission, initial treatment with isavuconazole, liposomal amphotericin B, and caspofungin was also ineffective. Subsequently, high-dose posaconazole (600 mg/d) combined with liposomal amphotericin B was administered.Results: Following the initiation of high-dose posaconazole and liposomal amphotericin B, the patient’s temperature normalized, and pulmonary exudates significantly improved. Therapeutic drug monitoring (TDM) showed that posaconazole trough concentrations were maintained at 3– 4 mg/L without significant hepatic or renal toxicity. The main adverse effects observed were hypokalemia and anorexia. After 102 days of antifungal therapy, the patient underwent successful lobectomy, leading to complete resolution of symptoms.Conclusion: This case demonstrated the good efficacy and safety of high-dose posaconazole combined with liposomal amphotericin B in the treatment of azole-resistant Aspergillus and mucormycosis.Keywords: invasive pulmonary aspergillosis, mucormycosis, azole-resistant Aspergillus fumigatus, high-dose posaconazole, combination therapy