A 54-year-old male, HIV-infected, undergoing antiretroviral therapy, with a history of pulmonary TB, was admitted to the infectious diseases department for dyspnoea, fever and asthenia. Two months previously, he had completed a 6-month course of anti-TB drugs with poor compliance. Clinical symptoms date back to these 2 months: persistent cough, low-grade fever, night sweats, fatigability and weight loss of 5 kg. On admission, the physical examination revealed mucocutaneous pallor, dyspnoea with decreased breath sounds in both lungs, fever (38.5-39  C) and a weight of 47 kg.
Laboratory investigations showed anaemia (haemoglobin: 10.5 g dl-1), leucopenia (1.38 109 l-1), neutropenia (0.96 109 l-1) and lymphopenia (0.32 109 l-1). The CD4+ T-cell and CD8+ T-cell counts were 140 cells microl-1 and 180 cells microl-1 respectively, and the CD4+/CD8+ cell ratio was 0.78. The CRP level was high (171 mg l-1). A chest CT scan with maximal intensity projection showed scattered nodular consolidation with a tree-in-bud pattern predominantly in the upper lobe (Fig. 1). Testing for mycobacteria (Ziehl-Neelsen stain and GeneXpert), routine bacterial cultures and screening for respiratory viruses using the FilmArray respiratory panel with multiplex PCR were negative. The RT-PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and blood cultures were also negative. The patient was treated as a likely miliary TB and placed on empirical anti-TB drugs. He also received a combination of third-generation cephalosporin with aminoglycoside without significant clinical improvement. On day 15 of admission, a chest CT scan showed the appearance of a pleural effusion and worsening of consolidation (Fig. 1). A bronchoscopy with bronchoalveolar lavage (BAL) was performed. At this time, the patient had a fever of 40  C, respiratory distress and an increased CRP level of 243 mg l-1. Antibiotic therapy was changed to a combination of imipinem and aminoglycoside, together with trimethoprim/sulfamethoxazole and fluconazole (FLC) (200 mg/day). Direct examination of BAL fluid showed septate hyphae and annelloconidia (Fig. 2). The smears obtained by cytocentrifugation of BAL fluid were stained using the May-Grunwald-Giemsa method and examined under a light microscope with x40 and x100 objectives, ruling out Pneumocystis pneumonia.
Culture on Sabouraud media showed the growth of cream-coloured, dry, cottony and circular colonies after 48 h of incubation at 35  C (Fig. 3). Lactophenol cotton blue preparation showed true hyphae with rectangular arthroconidia without blastoconidia (Fig. 4). Identification was done by the VITEK-2 System (bioMerieux, France) using a YST card with a probable value of 99 %. Species confirmation was carried out using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Bruker Daltonik, Bremen, Germany). The FLC treatment was continued.
The susceptibility testing was performed using Fungitest (BioRad, France). The strain was sensitive to amphotericin B (AMB) and 5-flucytosine (5-FC) with a minimum inhibitory concentration (MIC) <2 mug ml-1 each, with intermediate susceptibility to FLC (8 mug ml-1 <MIC<64 mug ml-1). A second BAL was performed 1 day later and revealed similar results. Galactomannan antigenemia and blood cultures were negative.
On day 20 of hospitalization, day 4 of FLC therapy, the patient was switched to AMB. However, the patient's clinical condition deteriorated rapidly, and he died due to septic shock. The patient was neutropenic with an absolute neutrophil count of 0.93 109 l-1 upon admission and 0.86 109 l-1 on the day of death. No autopsy was conducted.