Dear Editor,

Candida vulturna is a new member of the Candida haemulonii species complex (CHSC), which includes Candida haemulonii, Candida duobushaemulonii, and Candida haemulonii var. vulnera [1, 2]. Since C. vulturna was first detected in 2016 on an unspecified flower in the Philippines and in the blood of a patient who died of aspiration pneumonia in Malaysia [1], the organism has been isolated from cultures of blood or other clinical specimens, mostly in Southeast Asia and South America [2^-4]. However, no detailed clinical data have been reported, except for one case of catheter-related fungemia in an elderly hospitalized patient [3]. Therefore, the full human infection potential of C. vulturna is unknown. We describe the first case of C. vulturna fungemia in an infant with congenital megacolon. Given the retrospective nature of the study, the Ethics Committee of Chonnam National University Hospital (CNUH), Gwangju, Korea, waived the need for informed parental consent (CNUH-2017-130).

A 4-month-old male infant was directly transferred from the Philippines to the pediatric intensive care unit (PICU) of CNUH, Korea, for further treatment of enterocolitis. The infant was born in the Philippines with Apgar score 8 or 9. After the 25th day after birth, he had been hospitalized four times because of recurrent fever, bloody diarrhea, and abdominal distention. While repeatedly being hospitalized for 8 to 22 days in the Philippines, he was treated with antibiotics, transfusions, and rectal lavages. At admission to CNUH, his systolic/diastolic blood pressure was 70/40 mmHg, leukocyte count 4.3×10⁹/L, and C-reactive protein level 2,019 nmol/L. He was treated with mechanical ventilation, a central venous catheter, total parenteral nutrition, and systemic antibiotics in the PICU.

Two blood cultures obtained on hospital day (HD) 1 and 5 yielded C. vulturna (Table 1). The isolates were misidentified as C. duobushaemulonii or Candida pseudohaemulonii by the VITEK2 YST card (bioMérieux, Marcy l’Étoile, France) and VITEK MS (bioMérieux) method or matrix-associated laser desorption/ionization time-of-flight mass spectrometry (Biotyper; Bruker Daltonics, Billerica, MA, USA) and the ASTA MicroIDSys system (ASTA, Suwon, Korea). The final identification was confirmed by sequence analysis of both the internal transcribed spacer (ITS) and the D1/D2 regions of the 26S rRNA gene. Antifungal susceptibility testing using the CLSI M27-ED4 broth microdilution method or the Etest (amphotericin B [AMB] only; bioMérieux) revealed the following minimum inhibitory concentrations (MICs): AMB, 8-12 μg/mL; fluconazole, 4 μg/mL; voriconazole, 0.25 μg/mL; caspofungin, 0.5 μg/mL; and micafungin, 0.5 μg/mL. Two stool cultures obtained on HD 1 and 7 showed no growth of bacterial pathogens. The patient received fluconazole therapy (oral, 12 mg/kg/day) starting on HD 7. The patient’s general condition improved, and follow-up blood cultures were negative. As a colon study was highly suggestive of a congenital megacolon, he was transferred to another hospital for surgical intervention on HD 14.

Table 1 . Result of identification and antifungal susceptibility testing of two Candida isolates from a pediatric patient with congenital megacolon

Test method	Isolate 1	Isolate 2
Identification
Vitek2 YST card (bioMérieux, Marcy-l’Étoile, France)	Candida duobushaemulonii	C. duobushaemulonii
MALDI-TOF VITEK MS (bioMérieux)	C. duobushaemulonii	C. duobushaemulonii
MALDI-TOF MS, Biotyper (Biotyper; Bruker Daltonics, Billerica, MA, USA)	Candida pseudohaemulonii	C. pseudohaemulonii
MALDI-TOF MS, ASTA MicroIDSys (ASTA, Suwon, Korea)	C. pseudohaemulonii	C. pseudohaemulonii
ITS sequence analysis (identical rate to reference GenBank No.)	Candida vulturna (100% [438/438 bp] identity to MN330068.1)	C. vulturna (100% [438/438 bp] identity to MN330068.1)
	C. pseudohaemulonii (95% [417/441 bp] identity to NR_163771.1)	C. pseudohaemulonii (95% [417/441 bp] identity to NR_16 3771.1)
D1/D2 domain sequence analysis (identical rate to reference GenBank No.)	C. vulturna (100% [482/482 bp] identity to MN197921.1)	C. vulturna (100% [482/482 bp] identity to MN197921.1)
	C. pseudohaemulonii (96% [464/484 bp] identity to EF177490.1)	C. pseudohaemulonii (96% [464/484 bp] identity to EF177490.1)
Antifungal susceptibility (MIC, μg/mL)
Amphotericin B (Etest)	8	12
Fluconazole (CLSI M27-ED4)	4	4
Voriconazole (CLSI M27-ED4)	0.25	0.25
Micafungin (CLSI M27-ED4)	0.5	0.5
Caspofungin (CLSI M27-ED4)	0.5	0.5

Abbreviations: MALDI-TOF MS, matrix-associated laser desorption/ionization time-of-flight mass spectrometry; ITS, internal transcribed spacer region; D1/D2 domain, D1/D2 regions of the 26S rRNA gene; MIC, minimum inhibitory concentration; CLSI M27-ED4, CLSI M27-ED4 broth microdilution method.

As C. vulturna has been newly isolated/defined, it is not included in the databases of commercial identification systems and therefore is likely to be misidentified as a member of the known CHSC or closely related species, such as Candida auris and C. pseudohaemulonii [3^-5]. Failed identification of C. vulturna using CHROMagar Candida has been reported [4]. At present, direct sequencing of the ITS and/or D1/D2 regions of 26S rRNA gene is best used for correct identification. Initial drug of choice for the treatment of infection caused by CHSC or closely related species would be echinocandins because CHSC isolates often have high MICs for fluconazole and AMB [6, 7]. Although CLSI clinical breakpoints are not available for this species, the isolates in this study had relatively low MICs against fluconazole (4 μg/mL), in agreement with previous findings [2, 3], and the patient improved after fluconazole therapy.

Pediatric candidemia is most prevalent in children under 1 year of age; the risk factors differ from those of adults [8]. Although a vascular catheter was not placed on admission to CNUH, the patient had been repeatedly admitted to hospitals and treated with antibiotics and rectal lavages in the Philippines. The portal of entry of the organism remains unknown, but it most likely entered via an invasive procedure, such as rectal lavage. The organism may have colonized and permeated the weakened intestinal wall of the patient with suspicious congenital megacolon to produce a bloodstream infection [9, 10]. As the first positive blood culture of the patient was obtained within 24 hours of CNUH admission and C. vulturna has been rarely isolated from clinical specimens in non-tropical countries, the present case of C. vulturna fungemia suggests that antifungal-resistant Candida species can be imported given the increase in immigration and travel.

None.

Oh YB, Lim HJ, and Lee SY curated the data; Byun SA and Choi MJ performed the experiments; Oh YB, Lim HJ, Lee SY, and Shin JH wrote and edited the manuscript; Lee SY, Choi HJ, and Shin MG participated in the review and discussion; Shin JH designed and supervised the study. All authors have accepted their responsibility for the entire content of this manuscript and approved the submission.

None declared.

This research was supported by the Basic Science Research Program through the National Research Foundation, funded by the Korean Ministry of Education (grant No. NRF-2022R1A2B5B0100322).