The First Report of Candida Auris Infection in Vietnam

Abstract

Infection caused by Candida auris ha C. auris s rapidly become a global health threat. C. auris created a significant healthcare burden due to various complicating factors, including misidentification by commercial identification methods, potent antifungal resistance, high mortality rates and the possibility of nosocomial outbreaks through direct contact. In Vietnam, there are currently no clinical reports on C. auris infections. Here, we present four clinical cases of C. auris infections in the Department of Pulmonary Medicine of Cho Ray Hospital in southern Vietnam. Through this report, we aim to highlight the attention to the emergence of C. auris in Vietnam. Further research on C. auris infections is warranted, focusing on newly observed clinical characteristics present in all cases in this report, including hypoalbuminaemia and corticosteroid usage. Moreover, one case of resistance to amphotericin B has been identified, possibly due to prior exposure to this antifungal agent.

LEARNING POINTS

• Further research on Candida auris infections is warranted, focusing on newly observed clinical features present in all cases in this report, including hypoalbuminaemia and corticosteroid use during hospitalisation.

• While Candida auris remains susceptible to commonly used antifungal drugs, one case of resistance to amphotericin B has been documented, possibly due to prior exposure to this antifungal agent.

INTRODUCTION

Although Candida auris has only emerged in the last 15 years, this hazardous invasive fungal pathogen has rapidly spread to over 40 countries across various continents^[1]. Well-known fungal pathogens are recognised for high mortality rates, reaching up to 50% in cases of invasive infections, with 90% of deaths related to common fungi such as Cryptococcus, Candida, Aspergillus and Pneumocystis^[2]. Numerous reports on C. auris infections have indicated an increasing trend in candidaemia caused by C. auris, with an incidence ranging from 5%–30%^[3] and a mortality rate ranging from 30%–60%^[1]. The World Health Organization listed C. auris as one of the four fungal pathogens in the critical priority group for research, development, and improvement of public health in 2022^[4]. C. auris has posed a considerable strain on healthcare systems due to multiple complicating factors, such as misidentification through commercial identification methods^[5], robust resistance to antifungal drugs, high mortality rates and the potential for nosocomial outbreaks via direct contact^[1,5]. To our knowledge, there have been no previous reports of C. auris infections in Vietnam. We present four clinical cases of C. auris infection identified in the Department of Pulmonary Medicine at Cho Ray Hospital in southern Vietnam.

CASE DESCRIPTION

Although the first case of C. auris infection at the Department of Pulmonary Medicine of Cho Ray Hospital was confirmed in 2020, we did not document any additional cases from 2020 to November 2022. However, since the second isolation of C. auris in November 2022, from November 2022 to May 2023, the Department of Pulmonary Medicine has documented four cases of C. auris infection. The clinical details of the four cases are outlined in Table 1.

Table 1.

The clinical details of four patients infected with Candida auris.

	Case 1	Case 2	Case 3	Case 4
Age/Sex	59/Male	67/Male	73/Male	64/Male
Duration of hospitalisation (days)	37	27	23	73
Previous admission to a lower-level hospital	Yes	Yes	Yes	Yes
Surgery within 30 days or during hospitalisation	Tracheostomy	Tracheostomy	No	Tracheostomy
ICU admission	No	Yes	Yes	Yes
Parenteral nutrition	Yes	Yes	Yes	Yes
Corticosteroid during hospitalisation	Yes	Yes	Yes	Yes
Underlying lung disease	Respiratory failure Pneumonia Post COVID-19	Respiratory failure Pneumonia COPD History of TB Bronchiectasis	Respiratory failure Pneumonia COPD	Respiratory failure Pneumonia COPD
Underlying cardiac disease	Hypertension	Hypertension	Ischaemic heart disease Pulmonary embolism	No
Underlying liver disease	No	No	No	Acute hepatitis B
Other underlying condition	Myelodysplastic syndromes Neutropenia Malnutrition Hypoalbuminaemia	Functional bowel obstruction Septic shock Cushing syndrome Hypoalbuminaemia	Acute kidney failure Cushing syndrome Hypoalbuminaemia	Acute kidney failure Malnutrition Cushing syndrome Hypoalbuminaemia
Central venous catheter	No	Yes	Yes	No
Endotracheal tube	No	Yes	Yes	Yes
Gastric tube	Yes	Yes	No	Yes
Urinary catheter	Yes	Yes	No	No
Time from admission to positive culture results for C. auris (days)	22	31	25	10
Specimen positive for C. auris	Blood	Blood	Urine	Sputum, stool
C. auris antifungal susceptibility testing (MIC, μg/ml)
Fluconazole Caspofungin Amphotericin B	4 (S) 0.5 (S) 0.25 (S)	1 (S) 0.06 (S) 32 (R)	1 (S) 0.25 (S) 0.06 (S)	2 (S) 0.25 (S) 0.5 (S)
Antifungal use before the isolation of C. auris	No	Fluconazole Amphotericin B	No	No
Antifungal treatment after C. auris isolation	Caspofungin	Discharge before obtaining the result	Discharge before obtaining the result	Caspofungin
Other pathogen/specimen	P. aeruginosa (sputum) C. albicans (sputum)	C. tropicalis (urine) P. aeruginosa (sputum) C. tropicalis (sputum) Strongyloides stercoralis (stool)	No	K. pneumonia (sputum) A. baumannii (sputum) C. glabrata (stool)
Outcome	Survived	Died	Died	Survived

Abbreviations: ICU, intensive care unit; COPD, chronic obstructive pulmonary disease; TB, tuberculosis; MIC, minimum inhibitory concentration; S, susceptible; R, resistant.

All patients were males aged between 59 and 73, with hospital stays ranging from 23 to 73 days. All four cases shared common features, including prior admission to a lower-level hospital (100%), tracheostomy (75%), intensive care unit (ICU) admission (75%) and parenteral nutrition (100%). All four cases were diagnosed with pneumonia, respiratory failure and hypoalbuminaemia. Other known risk factors for invasive Candida infection include myelodysplastic syndromes with neutropenia (25%), malnutrition (50%) and having invasive medical devices (100%) (including central venous catheter, endotracheal tube, gastric tube, or urinary catheter).

Fifty per cent of C. auris infections were candidaemia. C. auris was identified using VITEK^® 2 Compact (bioMérieux, France) and confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (bioMérieux, France). This demonstrated sensitivity to fluconazole (minimum inhibitory concentration (MIC) by ETEST ranging from 1.0 to 4.0 μg/ml) and caspofungin (MIC ranging from 0.06 to 0.5 μg/ml). Resistance to amphotericin B was noted in one case, with an MIC of 32 μg/ml, possibly due to prior exposure to this antifungal agent. We utilised the following MIC breakpoints to establish resistance to antifungal drugs, including ≥32 μg/ml for fluconazole, ≥2 μg/ml for caspofungin and ≥2 μg/ml for amphotericin B^[6]. Caspofungin was the first choice for treatment; however, the mortality rate was 50%.

DISCUSSION

This case report is believed to be the first on C. auris infections in Vietnam, indicating that this pathogen is likely to pose a significant medical challenge due to prolonged hospital stays (23–73 days), a high mortality rate (50%), delayed diagnosis (10–31 days after admission) and a low rate of antifungal prophylaxis use (75%). This highlights the need for epidemiological studies on C. auris in Vietnam in the future.

Although limited by the number of patients in this report, we observed that over 75% of the patients had tracheostomy, previous admission to a lower-level hospital, parenteral nutrition, chronic obstructive pulmonary disease, corticosteroid during hospitalisation, Cushing syndrome, hypoalbuminaemia and invasive medical devices. Many studies have shown that risk factors for C. auris infection include kidney failure, prolonged hospital stay, invasive mechanical ventilation use^[4], urinary catheterisation (61–75.7%)^[7,8], central venous catheterisation (25–100%)^[5,9], total parenteral nutrition (47–100%)^[8], surgery (25–77%)^[5], diabetes (41%)^[7], antifungal use within 30–90 days (41%)^[7,8] and corticosteroid use during hospitalisation (24%)^[7]. A study of 27 ICUs in India concluded that the time spent in the ICU before being diagnosed with candidaemia is significantly longer for C. auris (median 25 days) compared to other non-C. auris (median 15 days)^[8]. Our study also indicates similar findings regarding risk factors for C. auris infection as observed previously, except for the high rate of patients with tracheostomy and hypoalbuminaemia. We hypothesise that C. auris may be capable of biofilm formation at the tracheostomy tube^[5], leading to prolonged infection. In the fourth clinical case, a second surgery to replace the tracheostomy tube was performed, resulting in favourable outcomes. Moreover, albumin might contribute to preventing the invasion of C. auris into the bloodstream^[10]. More studies are needed to clarify the roles of tracheostomy and hypoalbuminaemia in C. auris infection.

The MALDI-TOF MS method is recommended for identifying C. auris^[5]. Although much remains unclear about the mechanisms of antifungal resistance, C. auris is strongly resistant to common antifungal drugs including azoles, echinocandins and amphotericin B. Data from three major studies by Chow et al.^[11], Lockhart et al.^[7] and Rudramurthy et al.^[8] showed resistance rates of C. auris to fluconazole ranging from 58.1% to 93% and to amphotericin B from 13.5% to 35%. Resistance rates to voriconazole were from 2.7% to 54%, micafungin 7%, caspofungin 9.5%, with 23% to 41% resistance to at least two major antifungal classes, and 1% to 4% resistance to all three major antifungal classes. In this report, despite C. auris remaining susceptible to antifungal drugs (with only one case showing resistance to amphotericin B), the mortality rate remains high (50%). All reported deaths yielded positive results for C. auris after the patients died. In case 2, the emergence of amphotericin B resistance following prior exposure raised concerns about the rapid occurrence of drug resistance in C. auris^[1,5]. Cases of echinocandin resistance without prior exposure to echinocandin were reported, suggesting potential inter-patient transmission^[7]. Therefore, although the mechanisms of antifungal resistance in C. auris are complex, echinocandins are considered the first-line choice in treatment.

CONCLUSION

This case report represents the first regarding Candida auris infections in Vietnam. Further research is essential, particularly on the role of hypoalbuminaemia and corticosteroid use during hospitalisation in Candida auris infection. Moreover, the identification of resistance to amphotericin B in one case raises concerns, suggesting a potential link to prior exposure to this antifungal agent.