Invasive Malassezia pachydermatis Infection in an 8-Year-Old Child on Lipid Parenteral Nutrition

Invasive disease due to Malassezia pachydermatis infection is uncommon but increasingly recognized in children, especially neonates on parenteral nutrition or immunocompromised children. We describe a case of Malassezia pachydermatis fungemia in a demographically distinct patient and discuss the workup and current strategies for managing this infection in the setting of a central venous catheter.


Introduction
e genus Malassezia (class Malasseziomycetes, subphylum Ustilaginomycotina, phylum Basidiomycota) comprises a group of lipid-dependent yeasts that are part of the human population skin mycobiome [1]. ough they are typically associated with common skin disorders, they are increasingly recognized as causes of invasive infections in children. ree species of Malassezia, Malassezia furfur, Malassezia pachydermatis, and Malassezia sympodalis, have been implicated in invasive infections found in humans [2].
M. pachydermatis is a zoophilic species that is part of the normal skin flora of dogs and cats [3] but has been implicated in human cases of catheter-related bloodstream infection, meningitis, and death [2,[4][5][6]. Pediatric cases are almost exclusively reported in premature infants on parenteral nutrition or immunocompromised children [2]. We describe an unusual case of invasive M. pachydermatis infection in a patient who is demographically unique compared with other pediatric cases.

Case Description
An 8-year-old girl with a history of short gut syndrome secondary to gastroschisis presented with fevers and fatigue. She received enteral feeds but was dependent on parenteral lipid nutrition (provided by the four-oil emulsion Smoflipid®) through a central venous catheter (CVC). She denied any new rashes, skin changes, or gastrointestinal symptoms including abdominal pain, diarrhea, or intolerance to enteral feeds. Her exposure history was notable for a 6-year-old pitbull at home.
On presentation, she was febrile to 100.6°F, but her remaining vital signs were within normal limits for her age. Her physical examination, including inspection of her CVC site, was unremarkable. e results of a complete blood count and C-reactive protein were within normal limits. Blood cultures (BacT/Alert®) obtained from the CVC subsequently flagged positive after 28 hours of incubation. A direct Gram-stained smear revealed yeast-like cells (Figure 1) that were approximately 3 × 5 μm with collarettes, making Candida species unlikely.
Slow growth was demonstrated on Sabouraud-dextrose agar (SDA) with and without long-chain fatty acid supplementation although more robust growth occurred with fatty acid supplementation over time ( Figure 2). e isolate was subsequently identified as M. pachydermatis using mass spectrometry time of flight (MALDI-TOF) (Bio-MerieuxVitek ® MS) with 99.9% confidence. e patient was started on intravenous fluconazole (12 mg/kg/day) when the Gram-stained smear was reported, and an Infectious Diseases consultation was sought upon organism identification. e primary team attempted a line salvage strategy with intravenous antifungals alone as her nutritional requirements prevented discontinuation of parenteral lipid nutrition and instillation of antifungal locks. However, growth of yeast was documented on daily blood cultures obtained from the CVC for the following 5 days.
Transthoracic echocardiogram and ophthalmologic funduscopic exam did not reveal evidence of cardiac or ocular involvement.
e CVC was ultimately removed and replaced with a peripherally inserted central catheter (PICC) on day 8, after which she had no further positive cultures. Results of

Discussion
e majority of case reports describing invasive disease due to M. pachydermatis involved neonates on parenteral nutrition or immunocompromised children [2]. Our patient was demographically distinct from these children and was an unexpected case of invasive disease due to M. pachydermatis.
e major risk factor contributing to our patient's infection was likely the receipt of parenteral lipid nutrition and the use of a CVC. Parenteral lipid nutrition is commonly reported as a risk factor, mainly in neonatal infections, due to the lipid dependence of Malassezia species [2]. M. pachydermatis was traditionally considered the only species within the genus not to be strictly lipid dependent [1,6].
is idea came from the observation that M. pachydermatis can grow on SDA without fatty acid supplementation. However, M. pachydermatis was recently discovered to lack the gene encoding for fatty acid synthase, as with all other Malassezia species. Its growth on nonsupplemented SDA was explained by the discovery that commercial peptone used to prepare SDA contains small amounts of fatty acids [1]. In a completely lipid-free media, the growth of M. pachydermatis does not occur. e dog exposure reported by our patient is worth discussing as M. pachydermatis is a known animal skin commensal with zoonotic potential given that dog owners are at increased rates of M. pachydermatis carriage [7]. During an outbreak investigation of 15 cases of M. pachydermatis in a neonatal intensive care unit, M. pachydermatis was also isolated from the skin of a healthcare worker and several dogs owned by different healthcare workers [4]. ese isolates had similar genetic signatures based on genotyping studies, implicating dogowning healthcare workers as potential vectors that allowed colonization of infants with M. pachydermatis. In our case, there were no cultures performed from the patient's dog to prove this association. Still, we suspect that the contact with the dog gave origin to the infection.
is case also illustrates the challenges with diagnosis and management of disease due to Malassezia species including M. pachydermatis. Cases of infection caused by Malassezia species may be underdetected because fatty acid supplementation is not routinely performed when culturing yeast on solid media. Fatty acid supplementation is also important for M. pachydermatis which can grow on some commercial lipid-free media, but the growth is more vigorous in the presence of fatty acids. Supplementation should be considered, especially if Gram-stain smears indicate the presence of yeast-like cells but growth is slow or lacking on solid media, as seen in our case.
Treatment of infections with Malassezia species is guided primarily by anecdotal experience in the absence of comparative studies and lack of standardized susceptibility testing [8,9]. Amphotericin B or fluconazole are commonly utilized as empiric therapy [8] although in vitro resistance to fluconazole has been reported, especially for M. pachydermatis [10][11][12][13]. In regards to our case, we replaced fluconazole with posaconazole after susceptibility test results were made available, though at that time, the infection appeared under control. e switch to another antifungal agent was made prudentially since the very low MIC suggested a higher effectiveness of posaconazole. e apparent discrepancy between the high MIC and clinical effectiveness of fluconazole may be explained by the high dosage employed, which may have allowed reaching therapeutic blood levels. Another explanation is that the removal of the CVC contributed to the success of the fluconazole treatment.
In addition to removal of CVCs, other key aspects in managing Malassezia fungemia include reducing or eliminating lipid parenteral nutrition [8,14]. Although CVC salvage may be desired, Malassezia species are known to form biofilms in a capacity similar to Candida species which may make this strategy ineffective [15,16]. e efficacy of antifungal lock therapy for salvage of CVC-associated infections is unknown, but its successful use has been reported in one instance [17]. Not surprisingly, our patient failed catheter salvage with persistent growth of M. pachydermatis despite a week of antifungal therapy.
In conclusion, invasive disease due to M. pachydermatis is an uncommon, opportunistic infection and should also be considered for children on lipid parenteral nutrition irrespective of age or immune status. e incidence of invasive M. pachydermatis in older, immunocompetent children is likely underrecognized, and clear communication of a suspicion or risk of any Malassezia species can help the microbiology laboratory consider fatty acid supplementation of solid media culture.

Data Availability
All underlying data used to support the findings of this study are included within the article.

Conflicts of Interest
e authors declare no conflicts of interest.