Candida auris, a highly infectious and drug-resistant fungal pathogen, has emerged as a significant threat to global health, since its first identification in 2009 in Japan [1]. C. auris has caused outbreaks in healthcare facilities worldwide, with high mortality rates and transmission rates [2]. Candida auris infection affects approximately 2-5% of hospitalized patients worldwide [3]. In intensive care units (ICUs), the incidence of C. auris infection can be as high as 10-20% [4]. Neonates classified as Extremely Low Birth Weight (ELBW) were those weighing less than 1000g at birth, are particularly vulnerable to C. auris infections due to their immature immune systems, prolonged hospitalization in Neonatal Intensive Care Units (NICUs), and exposure to invasive medical devices and broad-spectrum antibiotics [5,6]. The increasing incidence of C. auris infections in ELBW neonates poses significant challenges for healthcare providers, as these infections are associated with high mortality rates, prolonged hospital stays, and long-term sequelae [7].

There is scant information on the clinical course and outcome of C. auris infection in high risk neonates. We present a retrospective cohort study of C. auris infection in ELBW neonates a tertiary care neonatal intensive care unit.

Here is a case series of 5 ELBW neonates who developed C. auris infection in a tertiary neonatal intensive care unit over 1 year from September 2023 to August 2024.Figure 1: Growth of candida auris on agar.

C. auris can easily be misidentified in conventional diagnostic laboratories using biochemical typing. In our study, isolates were confirmed as C.auris with application identification methods MALDITOF (VITEK MS). It forms oval or elongated yeast cells, which are single, in pairs, or in groups. Importantly, hyphal or pseudohyphal forms seldom occur [8]. We studied the clinical, demographic profile, susceptibility of the organisms, response to treatment, end organ involvement, survival outcome of C, auris sepsis in ELBWs.

Total number of babies admitted in our NICU during the study period were 952. Amongst these 48 babies were ELBW. Nine babies had Candida sepsis, 2 babies

C.albicans, 1 candida glabrata, 1 candida parasilosis and 5 grew C. auris from blood or urine culture. Characteristics of all 5 cases are shown in Table 1. Mean gestation age and birth weight of these babies were 27 ± 2 weeks and 645 ± 85 gms respectively.

Candida sepsis was diagnosed at a mean postnatal age of 21 ±11 days of life. All babies have central line prior to infection. Two infants (40%) had associated blood culture proven Gram-negative sepsis and were under broad spectrum antibiotic therapy when they developed C. auris infection. The most common sites of Candida auris infection in ELBW neonates were blood (60%) and urine (40%), with some cases involving multiple sites (20%). Notably, 20% of cases involved infection of the central nervous system (CSF), highlighting the potential for severe and disseminated. One infant showed organ involvement in form of fungal ball in both kidneys. Literature on Candida auris sepsis in ELBWs has been shown in Table 1.

Sensitivity Pattern

The in vitro sensitivity testing revealed that Candida auris isolates from ELBW neonates exhibited a high degree of susceptibility to echinocandins, with all isolates sensitive to micafungin, caspofungin, and anidulafungin. This suggests that echinocandins may be an effective treatment option for C. auris infections. 20% cases which were initially sensitive later on next reports showed resistance to amphotericin. As the identification of C. auris and the sensitivity patterns were not available in the beginning of this outbreak, we assumed that all candida infections were similar to C. albicans and hence were treated with fluconazole. After identification of organism as C. auris and knowing the sensitivity to antifungal medications, treatment regimen was changed to amphotericin.

Laboratory Parameters

The mean CRP was 53±84. At the start of treatment, the platelet count ranged from 16,000 to 86,000, with a median of 43,000. 2 babies required RDP transfusion. During recovery, the platelet count increased substantially, ranging from 55,000 to 2,00,000, with a median of 94,000. This data shows that the treatment was effective in improving platelet count, which is a critical indicator of hematological recovery.

Outcome

The outcomes revealed a concerning trend, with four out of five cases resulting in mortality, and only one case achieving discharge. Fungal Sepsis accounting for 50% of deaths. Liver failure and Bronchopulmonary dysplasia each attributing for 1 death. The presence of sepsis as a cause of death in half of the cases highlights the need for vigilant monitoring and aggressive management of infections.

Table 1: Characteristics of ELBW neonates with Candida auris infection.

1. auris isolates have been misidentified as other candida species [9-12]. These isolates have been frequently misidentified as Candida haemulonii (a rare cause of infection in humans), Candida famata, Candida sake, and Saccharomyces species.

Phylogenetic analysis reveals C. auris’s close relationship with the C. haemulonii species complex, which has rarely been associated with invasive infections [13]. Some of the reported isolates of C. haemulonii might be C. auris. Various methods have been advocated to reduce these errors in identification [14]. The sensitivity of the organism to micafungin, caspofungin, and resistance to fluconazole was similar to other series. The mutations in the ERG and FKS, efflux pumps, and biofilm formation are potential C. auris mechanisms for resistance [15].

The reports of neonatal C. auris infections are sparse. Up till now only 3 cases of microprimies with C.auris sepsis have been reported [16]. In 2007, there was a report of four cases of multi-drug resistant candida haemulonii in neonates with 50% mortality [17]. This organism might have been C. auris. Subsequently, few reports of C. auris infections have been reported, but the majority are in the adult population. The fact that Candida auris infection is easily acquired from the environment and health-care settings is a great concern for the vulnerable population, who is at high risk in the intensive care units. Fungal infections are mostly caused by endogenous flora but C. auris infections are exogenously acquired. Contamination of the hands and clothes of physicians and nurses leads to the spread of the infection to other ICU patients. C. auris can survive up to 14 days on devices due to biofilm formation and on surfaces for up to a week. Reusable probes (temperature probes) and catheters are identified as potential sources of contamination with C. auris in ICU settings [15,18-20].

The clinical features of C. auris infection in neonates are very similar to infections caused by either bacteria or fungi. In our study, all of these neonates developed late- onset sepsis (onset after the first 72 h of age), indicating that this is a hospital-acquired infection likely due to horizontal transmission. Associated risk factors included prematurity, presence of central lines, assisted respiratory support, and treatment with broad-spectrum antibiotics for bacterial sepsis.

The overall mortality was 50% in this cohort. When C. auris sensitivity was identified, therapy was changed to amphotericin and CDC-recommended infection control guidelines were followed. As a preventive measure, Chandramati planned to use micafungin as a prophylaxis for all neonates <32 weeks for the first 2 weeks after birth or longer. Incidence of C. auris infection showed significant rate drop on 6 months of follow-up data [16]. However, usage of this strategy could lead to an increased risk of resistance to echinocandins [21]. In our center, infection control measures to prevent C. auris transmission included [22] single patient room, contact isolation, proper hand hygiene, appropriate environmental disinfection, meticulous use of antibiotics, early removal of central lines, incubator humidity reduction policy, and developed a treatment protocol to use amphotericin as a drug for candidemia based on our sensitivity pattern.

In conclusion, our study highlights the growing concern of Candida auris infections, which pose a significant threat to ELBW neonates due to their high mortality rate, rapid transmission, and antifungal resistance. This study indicates that C. auris infection is prevalent and replacing other forms of invasive fungal infection in the NICU. The clinical features, sensitivity pattern, management and outcome (morbidity and mortality) of invasive C. auris infection are presented. We feel that treatment with amphotericin and CDC recommended infection control policy together improves the outcome.

Declaration of Competing Interest

Nil.

Conflict of Interest

None.

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