Cryptococcal infection in renal transplant: two case reports and a literature review

Abstract

The first case was a 64-year-old woman with chronic kidney failure secondary to nephroangiosclerosis and nonsteroidal anti-inflammatory drug use, who received a kidney transplant in July 2017. Immunosuppressive therapy included prednisone, tacrolimus, and mycophenolate. In October 2018, the patient was admitted for a two-week history of progressive cephalea, diplopia and occasional speech problems, although the patient remained afebrile. Routine serum chemistry was normal, except for creatinine 2.75 mg/dL and a glomerular filtration (GF) of 18 mL/min. Brain CT scan was normal. Findings in cerebrospinal fluid (CSF) were consistent with lymphocytic meningoencephalitis (Table 1). Bacterial and fungal culture was negative, as were nucleic-acid amplification tests (NAATs) for bacteria, mycobacteria, virus, and fungi. Empirical treatment with acyclovir (350 mg/24 h, IV), ceftriaxone (2 g/12 h IV), and antituberculous drugs was started. Mycophenolate was suspended, whereas tacrolimus and prednisone were maintained at previous doses. After a week, the patient developed neurological deterioration. A new lumbar puncture was performed and NAAT was positive for Cryptococcus neoformans/gatti. A yeast was isolated from culture and identified as C. neoformans by mass spectrometry (MALDI-TOF). Antifungal therapy with liposomal amphotericin B (250 mg/24h IV) and fluconazole (200 mg/12 h IV) was initiated and neurologic function of the patient improved significantly. Simultaneously, tacrolimus was suspended. After 10 days of antifungal treatment, the viral load of CMV progressively increased, and ganciclovir (115 mg/24 h) was added. Tacrolimus at low doses (1mg/day) was restarted at 14 days. India-ink staining of CSF obtained by control lumbar punctures performed weekly was persistently positive and C. neoformans was isolated again from culture. Four weeks after diagnosis, the patient developed pancytopenia, which was probably linked to drug toxicity and ganciclovir was withdrawn. After this finding, the patient had fever, dyspnea, and rapid progressive general deterioration resulting in death 34 days after admission. Streptococcus pneumoniae was isolated in blood culture.

Cryptococcemia in pancreas-kidney transplant patient

“…Furthermore, the study revealed high acute high mortality rates in cryptococcemia patients with more than 10% of the patients dying before the availability of culture results [ 6 ]. Few case reports have described cryptococcemia in solid organ transplant patients [ 7 , 8 ].…”

“…In solid organ transplant patients, Cryptococcus neoformans infection usually occurs in the late post-transplantation period, typically over 12 months after the transplantation. Primary acquisition upon transplantation or reactivation of a dormant infection are two possible causes of this infection [ 8 , 9 ]. In our case, the infection appeared five years after transplantation.…”

“…However, glucocorticoids also reduce cellular immunity, increasing the risk of Cryptococcus neoformans infection. On the other hand, mycophenolate and tacrolimus have reported to have activity against Cryptococcus neoformans [ 8 , 10 ]. Our patient was on prednisone, tacrolimus, and mycophenolate.…”