Background

Kodamaea ohmeri, a fungal micro-organism which belongs to the Ascomycetae class and the Saccharomycetaceae family, is the teleomorphic form of Candida guilliermondii [1]. The genus Kodamaea includes five species (K. anthrophila, K. kakaduensis, K. laetipori, K. nitidulidarum and K. ohmeri); K. ohmeri being the only species that can grow under 37⁰C and infect humans [2]. It is believed that K. ohmeri, formerly considered as a contaminant, was first isolated from a patient’s blood in 1998, and some decades later, it has become an emerging human pathogen that has witnessed a rise in severe infections as well as high mortality rates, especially in immunocompromised patients. Human infections due to K. ohmeri have been reported worldwide, predominantly cutaneous infection, endocarditis, fungemia and catheter-related bloodstream infections [3]. Neonates are predisposed to systemic fungal infections due to prematurity, immunocompromised state, invasive procedures, intubation, prolonged stay on ventilator and antibiotic usage in neonatal intensive care unit (NICU). Not many cases have been published of new-born fungemia with K. ohmeri worldwide, including in India [4]. We present an unusual case of K. ohmeri fungemia in a full-term neonate.

Case Presentation

A term male baby born to a 25-year-old primigravida mother at 39 weeks of gestation age with birth weight of 2.5kgs via normal vaginal delivery, with episodes of hypoglycaemia and multiple seizures was referred to our institution for further medical management. At the time of presentation, head to toe examination was normal and systemic examination was within normal limits. The child had hypoglycaemia and first episode of seizure at 30 hours of life following which IV fluids with glucose infusion rate (GIR) of 6mg/kg/min were initiated. However, at 40 hours of life, child was lethargic with general random blood sugar (GRBS) of 40mg/dl. Therefore, GIR of IV fluids had been increased to 8mg/kg/min. Repeat GRBS was still found to be low, as a consequence of which, IV fluids were further continued at GIR of 10mg/kg/min. At 54 hours of life, the child had 2 episodes of seizures for which IV Levetiracetam was initiated and maintenance dose Levetiracetam was made oral by day 6. Lumbar puncture was done to rule out meningitis. CSF (Cerebrospinal fluid) analysis was within normal limits. Neurosonogram done was within normal limits. GRBS was monitored every four hours. No further episodes of hypoglycaemia were noted. The child was euglycemic for next 48 hours. IV fluids were tapered and stopped by Day 7 of life. The child was initiated on feeds by day 3 of life.

Sepsis screening showed elevated CRP (C Reactive protein) levels for which the child was initiated on Cefotaxime (Meningitis Dose) along with IV Amikacin. Blood samples were sent for further microbiological analysis. Culture yielded high growth of white dry colonies on 5% sheep blood agar. Gram stain of the positive blood culture sample had shown numerous gram-positive oval-budding yeast like cells. Samples were streaked onto Sabouraud Dextrose Agar (SDA). Dry and white colonies were isolated following incubation at 30°C for 48 hours. These dry and white growths were sub-cultured onto CHROMagar Candida agar (Himedia, Mumbai, India) and colonies were interpreted according to the manufacturer’s instructions. White dry colonies changing to light pink colonies were observed on 24-48 hours of incubation. On 48-72 hours of incubation, light pink colour colonies changed to blue colour colonies (Figure 1).

Figure 1a: Gram stain of K. ohmeri isolates (gram-positive oval-budding yeast like cells) as observed under oil immersion (100X). Total Magnification: 1000x	Figure 1b: Dry and white colonies were isolated from Sabouraud Dextrose Agar (SDA) following incubation at 30°C for 48 hours.
Figure 1c: K. ohmeri isolates on CHROMagar Candida agar. White dry colonies (Figure 1c1) changing to light pink colonies were observed on 24-48 hours of incubation (Figure 1c2). On 48-72 hours of incubation, light pink colour colonies changed to blue colour colonies (Figure 1c3).

The isolate was identified as K. ohmeri by VITEK 2 Compact System (BioMérieux, Marcy L’Etoile, France) automatic identification system, as well as, matrix-assisted laser desorption/ionization - time of flight (MALDI -ToF) based automated bacterial identification system (bioMerieux, France). The anti-fungal susceptibility patterns were evaluated (Table 1) and the child was started on IV antifungal - Fluconazole. After having received three days of IV Fluconazole, the anti-fungal was made oral on day 9 of life. Repeat blood cultures were sent to rule out contamination and the cultures had repeatedly grown K. ohmeri. At day 9 of life, the child had no episodes of vomiting, seizures, icterus and was on direct breast feeding. A repeat culture of blood sample showed no growth of K. ohmeri. Clinical parameters were all within normal limits and the neonate was being discharged in a healthy clinical status. On subsequent follow-up to the hospital for evaluation, the neonate had no further episodes of seizures or hypoglycaemia.

Discussion and Conclusions

K. ohmeri was first reported as a clinical isolate in 1984 from a pleural fluid sample; however, the isolate was considered a contaminant at that time. In the same year, K. ohmeri was isolated from a blood sample of a 48-year-old diabetic patient with immunosuppression in view of renal transplantation, who subsequently died from the infection. Since then, more invasive infections with this yeast have been reported globally and considering it a true clinical pathogen, K. ohmeri have caused several life-threatening infections mainly in immunocompromised individuals. Comorbidities (like malignancy, diabetes, and rheumatism) and central venous catheter implantation are the commonest predisposing factors. Other factors that can also be a potential risk factor for K. ohmeri infections include invasive procedures which can breech the skin mucosal barrier, including surgery, catheterization, and dialysis [2, 3, 4].

In our case report, we describe an uncommon case of fungaemia in a child caused by K. ohmeri, with no known co morbidities and no risk factors. It can be concluded that infections by K. ohmeri occur in a broad range of patient categories, including neonates and children [5]. Albeit common amongst immune-compromised patients, there are risk factors also reported in children, which include: prematurity, low birth weight, prolonged ICU stay, use of medical devices, prosthetic valves, usage of broad-spectrum antibiotics, total parenteral nutrition, immunosuppression (leukemias, lymphomas) and neutropenia. To date, there is only one case reported of infection in a previously healthy child with no predisposing conditions except for encephalitis [3,6].

As a rare fungal pathogen isolated in the clinical setting, the identification of K. ohmeri was most commonly mistaken for Candida albicans, Candida glabrata, and Candida tropicalis, based on the colony morphology. In most clinical microbiology laboratory, the CHROMagar Candida chromogenic growth medium is a helpful culture medium for identification of Candida species based on the varying coloured colonies. K. ohmeri can grow yeast-like colonies on CHROMagar, the colour of which change from pink/lilac to blue in 2–3 days. Since the colour change takes time and often requires the need for continuous observation, the misidentification rate of CHROMagar in identifying K. ohmeri can be quite high (up to 100%) if only one single observation is performed in routine laboratory work. [1].

VITEK 2 ID-YST system allows for more accurate identification, even though some cases of misidentification with C. haemulonii have been illustrated [7]. Rapid identification of K. ohmeri in clinical laboratories have been successfully done in several cases since the development and use of MALDI-TOF MS has enabled rapid identification of Candida species in clinical laboratories [1].The accuracy of MALDI-TOF for K. ohmeri identification was comparable to that of PCR, hence, DNA sequencing of ITS 1 and 2 or MALDI-TOF apparently seem to be the gold standard techniques for the identification of K.ohmeri, even though their use is limited due to cost and availability in everyday practice [7].

Treatment of K. ohmeri infection includes removal of the risk factors (such as central venous catheter implantation and mechanical ventilation) and administration of appropriate antifungal agents. Various antifungal regimens were used in the treatment of K. ohmeri infection [1]. No intrinsic resistance of K. ohmeri to antifungals has been reported to date. There have been several reports of fluconazole resistance, some reports of echinocandin resistance and only one report of an isolate with high MIC's to amphotericin B [3]. Therefore, the clinical antifungal treatment strategy should be adjusted promptly according to the susceptibility reports of the clinical isolates rather than empirical drug use [1].

Abbreviations

NICU: Neonatal intensive care unit; GIC: Glucose infusion rate; GRBS: General random blood sugar; CRP: C Reactive protein; CSF: Cerebrospinal fluid analysis; MALDI -ToF: Matrix-assisted laser desorption/ionization - time of flight; SDA: Sabouraud Dextrose Agar; MIC: Minimal Inhibitory concentration

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