DISSEMINATED CRYPTOCOCCUS NEOFORMANS IN A RENAL TRANSPLANT RECIPIENT: AN OVERWHELMING INFECTION IN THE SETTING OF AN UNDERWHELMING PRESENTATION

Case Presentation: AH is a 74-year-old male with end stage renal disease, who received a living donor renal transplant in 6/2013. Following transplant AH had immediate graft function. His maintenance immunosuppression was tacrolimus and prednisone. Post transplant course was notable for the development of glomerulopathy, resulting in CKD III, complicated by chronic hyperkalemia, in part treated with fludrocortisone.  
AH initially presented to the ED on 1/10/2018 (day 1), at the referral of his PCP. Twelve days prior to ED presentation, the patient reported subjective fevers/chills, malaise, nasal congestion, and nausea. The PCP treated AH with azithromycin x5 days, but follow up with the PCP was concerning for profound dehydration, at which time AH was referred to the ED. In the ED, AH complained of persistent nausea, poor oral intake, and an unintentional 10 lbs weight loss since the onset of symptoms. Admission labs were notable for AKI, and CT Chest showing a left lung homogenous pleural mass consistent with fluid density.

AH was admitted to the hospital, and aggressively resuscitated with IVF with improvement in his symptoms and AKI. During the admission, AH did not receive any antibiotics. On day 3, AH reported feeling “fine”, and he was discharged. However, shortly following discharge, blood cultures from day 1 became positive for yeast at 60 hours, and AH returned to the hospital for re-admission on 1/13/18 (day 4).
 
On re-admission (day 4), AH was started on empiric micafungin for fungemia, and immunosuppression was dose reduced. On day 6, AH developed progressive encephalopathy, and blood cultures grew Cryptococcal species, at which time AH was switched to liposomal amphotericin B (AmB) 3 mg/kg/day. MRI Brain on day 7 showed leptomeningeal enhancement without hydrocephalus or crytococcomas. On day 8, lumbar puncture showed an opening pressure of 35 cm H2O, and CSF fungal stain with yeast. Liposomal AmB was increased to 5 mg/kg/day, which was continued through the remainder of the admission. AH continued to have serial lumbar punctures with persistently elevated opening pressures. Blood and CSF cultures speciated with Cryptococcus neoformans. AH developed shock, hypoxic respiratory failure requiring intubation, and allograft failure requiring continuous renal replacement therapy. Blood cultures cleared on day 12, but CSF cultures never cleared. AH died on 1/26/18 (day 17) from disseminated Cryptococcus neoformans.

Discussion: AH initially presented with URI symptoms, for which he saw his PCP. Twelve days after the onset of symptoms, AH was admitted with dehydration. After IVF resuscitation, AH was discharged. Following discharge, AH was found to have fungemia. In addition to transplant specific immunosuppression (tacrolimus, prednisone), AH was additionally taking fludrocortisone for hyperkalemia management, which further predisposed him to opportunistic infection. CT Chest on admission showed a focal pleural fluid collection. It is possible that this focal effusion, resulted from pulmonary Cryptococcal infection, which subsequently disseminated. Despite risk factors and known fungemia, AH was initially treated with micafungin, which does not have in vivo activity against Cryptoccous. Six days following the initial admission, AH was eventually started on appropriate therapy.

Conclusions: Given the often atypical and diverse presentation of Cryptococcal infection in renal transplant recipients, appropriate diagnosis and treatment requires a high level of clinical suspicion.