Peripherally-inserted central catheter-related fungemia due to hansenula polymorpha in a patient with pancreatic cancer.

The methylotrophic yeast Hansenula polymorpha, used mainly as an industrial agent in the production of pharmaceuticals, has rarely been reported to cause disease. The case of a 47-year old Pilipino male with pancreatic cancer presented here is the second reported in the literature. Major risk factors for this infection included underlying malignancy, abdominal surgery and the use of a peripherally-inserted central catheter for total parenteral nutrition. He was successfully treated with a two-week's course of voriconazole.

Infection with the methylotrophic, ascomycetous yeast species (e.g. Hansenula polymorpha) has only been reported in a patient with chronic granulomatous disease of childhood over 3 decades ago.[1] H. polymorpha is a single-celled yeast, described as a “versatile protein machinery”[2] with excellent characteristics for the production of insulin, hirudin, hepatitis B vaccines, interferon a-2a and industrial enzymes.[3] Its superior characteristics for the synthesis of pharmaceuticals, growth in industrial-scale fermentations, lack of pyrogens, pathogens and viral inclusions are some of the several key advantages this organism has over other yeast expression technologies. It is mainly used as an important cell factory for the production of vaccines, other pharmaceutical products[4] and also in biologic research.[5]

As a cell factory, H. polymorpha is thermotolerant and grows at high temperatures of up to 48°C, and also able to tolerate a broad range of pH values. It belongs to the group of organisms giving the “Generally Recognized As Safe” (GRAS) status as it was not known to contain or release pyrogens to cause any significant infection. Infections with fungi are rarely encountered in immunocompetent individuals. To the best of my knowledge, this is the second report of infection with H. polymorpha in the literature after the case mentioned above.[1]

A 47-year-old Pilipino male with no previous illness presented to the Emergency Department (ED) with upper abdominal pain. The only significant finding was for a palpable mass at the right upper quadrant of the abdomen. Computerized tomography (CT) scan of the abdomen revealed a large hypervascular mass (9cm × 13.5cm × 13.5cm) arising from the head of the pancreas. The patient underwent laparatomy for resection of the tumor, right hemi-colectomy, and splenectomy.

His hospital course was complicated by severe intra-abdominal bleeding that required massive transfusions of blood and blood products. He had multiple ICU admissions with intubation and mechanical ventilation. Additional complications included septic shock and disseminated intravascular coagulopathy (DIC) and entero-cutaneous fistula. He had multiple abdominal explorations to control bleeding and seal anastomotic leaks. To improve his nutrition and accelerate recovery, a peripherally-inserted central catheter (PICC) line was inserted on various occasions for total parenteral nutrition (TPN). During his hospital stay, he developed a high grade fever (39°C) with septic shock that required ICU admission, intubation, and inotropic support.

Blood cultures from the PICC line and peripheral blood yielded H. polymorpha from both the erobic and anerobic vials at 32.95 hours and 33.52 hours, respectively. The isolate was sensitive to all antifungals tested. His management included removal of the PICC line and a 14-days course of voriconazole from the last positive blood culture with good clinical response. Repeat blood culture within 48 hours of therapy was negative.

Prior exposure to multiple antimicrobials, his background immuno-suppression and TPN, and other reasons not fully understood might have predisposed him to acquiring an infection with this fungus that was very rarely associated with human disease.