Fungemia With Wickerhamomyces anomalus: A Case Report and Literature Review

We report the case of an 84-year-old man with a history of IgG4-related sclerosing cholangitis who was diagnosed with advanced esophageal cancer and underwent radiation and chemotherapy. An implantable central venous access port was placed for chemotherapy and total parenteral nutrition. The patient presented with a fever and received antimicrobial therapy for acute cholangitis but remained febrile, and subsequently, yeast was detected in the aerobic bottle of blood culture obtained from the central venous line. The yeast was identified as Wickerhamomyces anomalus. Liposomal amphotericin B was administered, and the central line access port was removed. After confirmation of negative blood cultures and 14 days post treatment, he underwent reinsertion of the central line access port. Due to persistent pain at the insertion site, fluconazole was added for an additional 14 days, and the patient was discharged and transferred to another hospital. Wickerhamomyces anomalus is a rare fungal infection with other synonyms including Pichia anomala, Hansenula anomala, and Candida pelliculosa. A literature review of 53 case reports of Wickerhamomyces anomalus, Pichia anomala, Hansenula anomala, and Candida pelliculosa was conducted, with a total of 211 cases reviewed. Fungemia was reported in 94% of cases, with central venous catheterization, parental feeding, low birth weight, and immunocompromised status identified as major risk factors. The majority of cases were pediatric, particularly neonatal, and there were reports of nosocomial infections causing outbreaks, with some cases involving the eye such as endophthalmitis or keratitis.


Introduction
Wickerhamomyces anomalus, also classified as Hansenula anomala, is a yeast described initially by Hansen in 1891.Interestingly, this pathogen has other synonyms, including Candida pelliculosa and Pichia anomala.It colonizes the throat and gastrointestinal tract of humans, although this microorganism has also been isolated from the soil, pigeon droppings, plants, and fruits [1][2][3].It is an emerging pathogen found mainly in immunocompromised patients, and little is known about its pathogenicity [4].
Here, we report a case in which Wickerhamomyces anomalus was identified in a patient with esophageal cancer who was receiving total parenteral nutrition, due to a bloodstream infection from the implantable central venous access port.

Case Presentation
We present an 84-year-old male with a medical history of IgG4-related sclerosing cholangitis and a bile duct stent.He was diagnosed with advanced esophageal cancer during a stent exchange in April, which occurred six months prior to his current admission.Following the diagnosis, he began radiation and chemotherapy therapy in June, four months before his admission.In August, an implantable central venous access port was placed for the administration of chemotherapy and total parenteral nutrition, two months before his admission.During the course of his treatment, he developed acute cholangitis, characterized by fever, leukocytosis, and abnormal liver function test results compared to his usual values (as shown in Figure 1), which led to his admission.Ampicillin/sulbactam was empirically started which accomplished defervescence.On day 8 of his hospitalization, percutaneous transhepatic biliary drainage (PTBD) was performed.After PTBD, he became febrile again accompanied by increasing abdominal pain.Retrograde cholangitis from PTBD was suspected, and therefore, antimicrobial therapy was switched from ampicillin/sulbactam to cefepime on day 14.His abdominal pain got better; however, he continued to be febrile.On day 18, blood culture was obtained due to suspected refractory cholangitis not responding to antimicrobials.Twenty-one hours later, yeast (Figure 2, Figure 3, and Figure 4) was detected from the aerobic bottle of the blood culture obtained from the central venous access port, which became positive 11 hours earlier than the culture obtained from the peripheral vein.Analysis with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry revealed that the yeast was Wickerhamomyces anomalus.The minimum inhibitory concentration (MIC) indicated that most of the antifungals might be effective (Table 1), but we opted for treatment with amphotericin B due to case reports of successful outcomes.Additionally, at this point, we were uncertain about the involvement of other organs, such as the eyes and urinary tract; therefore, we chose amphotericin B.  Liposomal amphotericin B was started at 3 mg/kg.On the next day (day 20), he underwent emergent removal of the implantable central venous access port, and the port itself was also sent for culture.The repeat blood culture, as well as the culture from the port, turned out to be positive for Wickerhamomyces anomalus as well.

Antifungals
Since the nature of this pathogen was similar to that of Candida spp., we sought ophthalmologic consultation to rule out endophthalmitis, which was not found.Blood culture was obtained every 48 hours, and the one obtained on day 23 confirmed a negative result.Liposomal amphotericin B was administered for 17 days, 14 days after the confirmation of negative blood culture.His fever and inflammatory markers improved.However, he complained of continuing pain at the central venous access port site, and upon discussion with the primary team, we decided to extend his antifungal treatment with fluconazole for 14 days and discharge him thereafter.

Discussion
This was a case of Wickerhamomyces anomalus catheter-related bloodstream infection in a patient undergoing radiation and chemotherapy for his esophageal cancer.He was successfully treated with liposomal amphotericin B, which achieved prompt negative blood culture.
Most patients were treated with either amphotericin B or fluconazole, which seemed to result in the clearance of fungemia and cure.In terms of susceptibility to antifungals, since there are no defined cutoffs in the Clinical and Laboratory Standards Institut (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines, we adopted the susceptibility profile from da Matta et al.
[56], specifying amphotericin B ≤ 1 mcg/mL, fluconazole ≤ 8 mcg/mL, itraconazole ≤ 0.12 mcg/mL, voriconazole ≤ 1 mcg/mL, and caspofungin ≤ 1 mcg/mL.Among the extensively used antifungals, which include amphotericin B and fluconazole, caution is advised in the selection of antifungals since some isolates appear to have a higher MIC to fluconazole, potentially leading to treatment failure.In this context, amphotericin B generally appears susceptible and may be preferable when susceptibility is unknown.However, even with amphotericin B, clinical failures have been documented [31], so one should closely monitor its response to treatment.
It is important to highlight an incident in which a pathogen triggered an outbreak of 379 fungemia cases within the pediatric ward of a hospital [25].Given the vulnerability of the affected individuals, a case-control study of this incident revealed a case fatality rate of 42%, which is alarming.Rapid infection control measures should be implemented, and early treatment should be initiated.If appropriate measures are not taken, this case report of an outbreak demonstrates that disastrous results can occur.
In our case, Wickerhamomyces anomalus fungemia occurred in an elderly patient with cancer, who was receiving total parenteral nutrition through an implantable central venous port.The risk factors included being an immunocompromised host, the use of a central venous line, and, finally, parenteral nutrition, which increased the risk for this pathogen.These factors are similar to the risks associated with candidemia.The MIC for amphotericin B was 0.5 mcg/mL, indicating excellent susceptibility.Similarly, susceptibility to fluconazole was measured at 2 mcg/mL, suggesting it would be effective if used initially.
Based on the results of the susceptibility testing, we confidently switched to oral fluconazole for extended treatment.Echinocandins also showed high susceptibility.However, due to the poor distribution of echinocandins to the eyes and urinary tract, and with the potential for eye and urinary involvement which was unknown at the time of detection, we opted for either amphotericin B or fluconazole.
Our investigation mainly focused on this specific mycotic species, Wickerhamomyces anomalus, due to its relative obscurity and infrequency in clinical encounters.This necessitates a deeper understanding and refined management strategies among healthcare providers.Although this fungus is rare, its repeated occurrence in past literature emphasizes the importance of this organism.By offering a detailed summary of this lesser-known fungal infection, this paper aims to provide direction for future clinical practice.One should be aware of this pathogen in low birth weight neonates and immunosuppressed patients, especially those receiving total parenteral nutrition through a central venous catheter.Broad-spectrum antibiotics also appear to predispose to Wickerhamomyces anomalus infection.When blood cultures indicate the presence of Wickerhamomyces anomalus, initiating treatment with amphotericin B or fluconazole is recommended.As Wickerhamomyces anomalus is similar to Candida spp., we should adopt the same treatment strategy until further differences are elucidated.Although Wickerhamomyces anomalus is uncommon, its likelihood increases in healthcare environments housing a considerable number of immunocompromised individuals, thereby potentially leading to outbreaks.Hence, it is of paramount importance for healthcare providers to maintain vigilance and implement stringent hygiene practices.

Conclusions
This study focuses on Wickerhamomyces anomalus, a rare fungus that causes infections mainly in pediatric and immunocompromised patients.Central venous catheters and immunocompromised conditions such as leukemia could be risk factors for this infection.Effective treatments include amphotericin B and fluconazole.The findings highlight the need for increased awareness and strict hygiene in healthcare settings to prevent outbreaks, especially among vulnerable patient groups.