An 81-year-old Caucasian male presented to the emergency department with shortness of breath and hemoptysis. Over the previous one to two months, the patient experienced fatigue and increasing shortness of breath. Episodes of hemoptysis were two to four times per day. His past medical history included ureteral and bladder cancer, recurrence of papillary tumor and prostatic urethra status after right nephroureterectomy and chemotherapy, deep vein thrombosis, hypertension, type 2 diabetes mellitus, and hypothyroidism. Regarding social history, the patient farmed full-time in his retirement, and he had recently cleaned out his chicken coop, which contained several months of built-up feces and straw bedding.
Upon admission, initial laboratory values included sodium 143 mEq/L, potassium 4.2 mEq/L, chloride 106 mEq/L, blood urea nitrogen 58 mg/L, creatinine 4.29 mg/dL, glucose 118 mg/dL, white blood cell count 9.7 x 103/mm3, hemoglobin 6.4 g/dL, and platelet count 169 x 103/mm3. Liver function test values were alanine aminotransferase 6 U/L, aspartate aminotransferase 13 U/L, and alkaline phosphatase 55 U/L. The patient was on warfarin for deep vein thrombosis, and anticoagulation results indicated prothrombin time (PT) 108.2 seconds, international normalized ratio (INR) 9.6, and activated partial thromboplastin time (aPTT) 49 seconds.
Numerous other laboratory tests were completed, including cytoplasmic anti-neutrophil cytoplasmic antibodies (c-ANCA), perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA), glomerular basement membrane antibody IgG, urine Histoplasma/Legionella/Streptococcus pneumoniae antigens, QuantiFERON tuberculosis gold, and beta-glucan. All of these tests were negative. Of note, beta-glucan test does not reliably detect Cryptococcus, Zygomycetes, or Blastomyces dermatitidis. Abnormal laboratory values included c-reactive protein 8.9 mg/dL, automated sedimentation rate >120 mm/hr, N-terminal pro-brain natriuretic peptide (NT-proBNP) 9,789 pg/mL, and troponin T 0.106 ng/mL.
The initial differential diagnosis and assessment included inflammatory pneumonitis, infection, and immunologic pathology. The patient was initiated on ceftriaxone and azithromycin, and a respiratory culture was obtained. Throughout the initial hospital course, his oxygen saturation dropped on a nonrebreather mask, and the patient was agreeable to elective intubation with bronchoscopy. Antibiotics were broadened to levofloxacin, piperacillin/tazobactam, and vancomycin, and corticosteroids were added. Cystogram was completed per urology which showed reflux with nonobstructive hydronephrosis, and nephrology was consulted to rule out other causes of the patient's acute kidney injury, none of which were definitive diagnoses. On hospital day 19, the patient's blood cultures were positive for yeast, which was presumed to be Cryptococcus neoformans, and liposomal amphotericin B 300 mg (3.1 mg/kg actual body weight) daily was initiated. On hospital day 23, Cryptococcus neoformans was identified in the blood via matrix assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry and confirmed via a biochemical method (API 20C strip). A lumbar puncture was completed which also grew Cryptococcus neoformans. Flucytosine was initiated on day five of liposomal amphotericin B treatment (hospital day 23).
As the patient was receiving intermittent hemodialysis at the time of flucytosine initiation, a dose of 2,500 mg (25.8 mg/kg actual body weight) every Tuesday, Thursday, and Saturday after dialysis sessions was chosen. See Table 2 for a schedule of the hemodialysis sessions the patient received. On hospital day 27, the patient was initiated on continuous renal replacement therapy due to hemodynamic instability with the addition of multiple vasopressors (norepinephrine, phenylephrine, and vasopressin). The patient remained intubated, sedated, and paralyzed for facilitation of mechanical ventilation. Continuous venovenous hemofiltration (CVVH) was initiated (with citrate for anticoagulation) as the primary mode of dialysis and was maintained on the following settings: total replacement fluid rate, 2,500 mL/hr; blood flow rate, 300 mL/min; preblood pump rate (PBP) (citrate flow rate), 450 mL/hr; and ultrafiltration rate, 100-400 mL/hr. Our institution utilizes the Gambro PrismaSATE system with the PrismaSATE HF 1400 polyarylethersulfone filter. Due to inability to ultrafiltrate with CRRT at all times, the average fluid removal rate was 265 mL/day (11 mL/hr) over 3 days (hospital days 27-29).
As a result of the dialysis change to CVVH, the flucytosine dose was increased to 2,500 mg (25.8 mg/kg actual body weight) by mouth every 12 hours. Of note, this flucytosine dose was significantly conservative, as it utilized a total daily dose of 50 mg/kg/day, as compared to some literature that recommends up to 150 mg/kg/day divided. The choice for conservative flucytosine dosing was made based on the patient's baseline thrombocytopenia; the patient's platelet count was 39 x 103/mm3 the day CVVH was initiated. Over the 3 days of CVVH, the patient had a mean urine output of approximately 0.21 mL/kg/day, classified as nonoliguric renal failure.
Flucytosine was discontinued on hospital day 29 due to thrombocytopenia, and high dose fluconazole was added. Liposomal amphotericin was replaced with conventional amphotericin on hospital day 37. The patient had negative blood cultures on hospital days 32 and 34.
The patient passed away on hospital day 47 from refractory hypoxemic respiratory failure, as life prolonging efforts were withdrawn per family request.