A 79-year-old woman presented to our infection division with hyperpyrexia. She had nephrotic syndrome and diabetes and had been treated with traditional Chinese medicine, hormones and insulin for a long time. Two weeks prior (day 0), she was referred to a local hospital for fever with shivering. A chest computed tomography (CT) scan revealed inflammatory lesions in both lungs. She was treated with cefazolin and levofloxacin, which were changed to imipenem combined with moxifloxacin on day 7 after her blood culture results indicated an Escherichia coli infection; however, her symptoms persisted after 1 week of treatment.
The patient was subsequently admitted to our infection division for further treatment. At the time of admission (day 15), her physical examination results were temperature, 38.2 C; blood pressure, 124/56 mmHg; heart rate, 99 beats/minute; and respiratory rate, 18 breaths/minute. The patient was lethargic and dispirited. Her laboratory examination results were white blood cells, 36,300/microL with 92.2% neutrophils; C-reactive protein, 105 microg/mL; procalcitonin, 0.5205 ng/mL; and interleukin, 60.042 ng/mL. During her hospitalization, her temperature continued to increase to 40 C (day 21). Her blood, sputum and cerebral spinal fluid (CSF) specimens were sent to our department for microbiological examinations. The CrAg LFA yielded a negative result for the serum (IMMY Inc., Norman, OK, USA) and a positive result for the CSF. India ink staining and CSF culture results were both negative. Parenteral voriconazole was initiated as empiric treatment pending diagnostic testing (day 21).
After 4 days and 16 hours (day 24) of blood culturing using an automated blood culture system (BACTEC FX,BD Becton, Dickinson and Company), pathogens were detected microscopically from two aerobic blood culture bottles. Microscopically, the pathogens were gram-positive, budding, round conidia, suggesting Cryptococcus spp. India ink staining of the fluid in the positive blood culture bottles revealed the pathogenic capsules. Microscopically, the pathogens appeared as rounded cells with thick halos (Figure 1A). The strains were isolated from Sabouraud dextrose agar after 24 hours of aerobic incubation and appeared as beige mucoid yeast colonies (Figure 1B). Identification using the VITEK 2 compact automated system (BioMerieux, France) yielded a positive result for C. neoformans. With confirmation of disseminated cryptococcosis, the initial negative serum LFA test result was questioned. Per the manufacturer's instructions, we serially diluted the serum and processed it using the CrAg LFA test kit. Increasing dilutions showed that the 1:5 dilution was negative, 1:10 and 1:20 were weakly positive, and 1:40 was positive.
Antimicrobial susceptibility tests were performed via the microdilution broth method using ATB FUNGUS 3 (BioMerieux). In vitro antimicrobial susceptibility testing showed that the minimal inhibitory concentrations for the C. neoformans were 5-fluorouracil (5-FC) 4 microg/mL, amphotericin B (AMB) 0.5 microg/mL, fluconazole (FLU) 1 microg/mL, voriconazole (VOR) 0.125 microg/mL, and itraconazole (ITR) 0.06 microg/mL. As per previous studies, the epidemiological cut-off values for C. neoformans were 8 microg/mL for 5-FC and FLU, 0.25 microg/mL for ITR and VOR, and 1 microg/mL for AMB. Thus, the patient's antibiotics were changed to AMB plus 5-FC on day 26. After 1 week of treatment, her infection was controlled, and she was transferred to a local hospital for rehabilitation.