A 48-year-old Northern African man affected by Crohn's disease, protein-energy malnutrition and lymphopenia presented with fever, cough and respiratory failure in March 2018. He had received therapy with infliximab in December 2017. He received the last dose one month before the development of symptoms. His baseline Mantoux tested negative. At admission, a high resolution computed tomography (HRCT) showed bilateral pleural effusion, large parenchymal consolidation on the upper-right lobe, bilateral nodular consolidations, multiple mediastinic lymphadenopathies. We performed bronchoalveolar lavage (BAL) that showed positivity for M. tuberculosis PCR (XPert MTB/RIF ). QuantiFERON -TB Gold Plus test resulted indeterminate. We than started antitubercular therapy with rifampicin 600 mg, isoniazid 300 mg, ethambutol 1200 mg and pyrazinamide 1500 mg plus pyridoxine 300 mg 3 times per week. He was also on treatment with dexamethasone 8 mg twice daily and on total parenteral nutrition due to the poor clinical condition.
At admission he had WBC 2,300/uL, lymphocytes 440/uL, CD4 + 250/uL, hemoglobin 9.9 g/dL, C-reactive protein (CRP) 2.68 mg/dL (upper normal value 0.5). He reported penicillin allergy. The ECG on admission showed sinus rhythm with a QTc interval of 390 ms. Three days later, he developed atrial fibrillation that was successfully cardioverted with amiodarone. He remained apyretic for the following 7 days and the steroid dosage was slowly tapered to 4 mg of dexamethasone per day. Over the next two days he developed fever with chills and progressive worsening of dyspnea. All the blood cultures resulted negative.
Five days later, he developed respiratory failure, and another HRCT showed worsening of the pleural effusion and of the parenchymal lesions, with the appearance of new areas of consolidation. CRP was 12.7 mg/dL. Empiric therapy with linezolid and meropenem was added. In addition, we performed a second bronchoscopy and a thoracentesis. The Gene XPert MTB/RIF  test resulted negative both on BAL fluid (BALF) and on pleural fluid. BALF culture resulted positive for extended-spectrum beta-lactamase producer (ESBL) Klebsiella pneumonia and methicillin-resistant Staphylococcus aureus (MRSA). Moreover, galactomannan determination on BALF resulted strongly positive and, therefore, liposomal amphotericin B (L-AmB) therapy was started at 3 mg/kg/day.
Despite a slight improvement during the first days of antimicrobial therapy, ten days after the BAL he developed again respiratory failure (PaO2/FiO2 ratio: 129). We performed another HRCT that showed worsening of the bilateral pleural effusion that required left chest drainage tube placement. Oxygen therapy and dexamethasone (8 mg I.V. BID) were reintroduced. After that, he became apyretic and CRP levels declined (from 13.9 mg/dL to 1.4 mg/dL during the next ten days). Antibiotics were interrupted after 21 days. In the meantime, steroidal therapy was progressively tapered. He stopped ethambutol and pyrazinamide after 8 weeks of treatment and he continued with TB maintenance therapy; chest drainage tube was removed after 27 days. During L-AmB therapy hypokalemia occurred, with daily need for potassium supplementation.
After 8 weeks of antifungal therapy, L-AmB was interrupted, rifampin was substituted with moxifloxacin 400 mg per day and isavuconazole was started at 200 mg every 8 h for the first 48 h, followed by 200 mg daily, along with daily ECG monitoring. No significant alterations in sinus rhythm and QTc interval were seen during therapy with isavuconazole compared to baseline ECG on admission. After the withdrawal of L-AmB, potassium levels returned normal. He was discharged after 83 days of hospitalization in good clinical conditions on maintenance therapy with isavuconazole 200 mg daily, moxifloxacin 400 mg daily and isoniazid 300 mg daily.
After discharge, no alteration in sinus rhythm and QTc interval was noticed at weekly follow-up. On follow-up chest HRCTs performed one and three months later, pulmonary lesions and pleural effusion were significantly reduced.
He received a total of 24 weeks of antitubercular and antifungal therapy.