A case series of Candidozyma auris in Viet Nam

TL;DR

This report documents the first cases of Candidozyma auris in northern Vietnam, highlighting its emergence as a health threat.

Contribution

The first documented cases of C. auris in northern Vietnam, emphasizing the need for further prevalence studies.

Findings

Six cases of C. auris were identified at a hospital in northern Vietnam between 2023 and 2024.

This is the first report of C. auris in the northern region of Vietnam.

The findings underscore the importance of conducting prevalence surveys to understand the burden of C. auris.

Abstract

Candidozyma auris is an emerging health threat, especially in healthcare settings due to its resistance to several classes of antifungals leading to high mortality. In Viet Nam, the burden of this fungal pathogen is unknown because of little available data. In this report, six cases with C. auris isolation between 2023 and 2024 at the National Hospital for Tropical Diseases, a tertiary referral hospital in northern Viet Nam, are described. Our findings highlight the first report of C. auris in the north of Viet Nam and underscore the importance of prevalence surveys in the future.

Full text

Introduction

*Candidozyma auris (*formerly Candida auris) is an emerging fungal pathogen linked with healthcare-associated infections. Since the first report in 2009 in Japan, cases of nosocomial C. auris infections have been reported in over forty countries in six continents by 2020 [1, 2]. C. auris is notorious for outbreaks in healthcare facilities and high mortality due to resistance to multiple classes of antifungal agents [3, 4]. Although C. auris does not present as a frequent clinical problem yet in Viet Nam, the actual burden of C. auris is unknown due to little available data. Three case studies describing ten cases of C. auris infection in Viet Nam have been published d from the south of the country [5–7]. Here, we report six patients of isolation of C. auris from infected and colonized patients at the National Hospital for Tropical Diseases (NHTD), a 500-bed tertiary referral hospital for infectious diseases in northern Viet Nam. To our knowledge, these are the first cases described from the north of Viet Nam.

Case presentation

In this case series, six adult patients with C. auris at the Intensive Care Unit (ICU) between November 2023 and June 2024 are described, in which three were diagnosed as infection and three were colonization. Infections were defined as clinical deterioration at the time of C. auris isolation, despite antibiotic treatment, responding well to antifungal therapy. Cases where C. auris was isolated without clinical manifestations and that improved without antifungal treatment were defined as colonization. In total, C. auris was isolated 10 times, including from six endotracheal aspirate (ETA), from three central venous catheter (CVC), and once from skin. No isolate was from blood. Species identification was done using the MALDI-TOF MS (bioMérieux, Marcy l’Étoile, France). Antifungal susceptibility testing was done using the broth microdilution method [8], and the interpretation was according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2025 and Clinical and Laboratory Standards Institute (CLSI) 2022 guidelines [8, 9]. The susceptibility of four isolates is shown in Tables 1 and 2.

Table 1. Main clinical characteristics of six patients with Candidozyma auris in Northern Viet NamCharacteristicsCase 1Case 2Case 3Case 4Case 5Case 6Age653873466453SexMaleMaleMaleMaleFemaleMaleMedical historyChronic renal failureHypertensionLong-term use of steroidsUntreated hepatitis BRheumatoid arthritisHypertensionNoneHypertensionAlcoholic cirrhosisDiagnosis on admissionSurgical site infection at left tibiaAcute hepatic failureCAPMeningitisCAPCAPLength of admission before transfer63 days3 days123 days4 days1 day22 daysDiagnosis after transfer to NHTDSurgical site infectionVAPSeptic shockHepatic encephalopathyVAPSeptic shockVAPSeptic shockMeningitisViral encephalitisVAPUTIVAPSeptic shockVAPSeptic shockSpecimens for C. auris (No. of isolates)CVC (1) ^a^, ETA (1)ETA (1)CVC (1) ^a^, skin (1)ETA (2)ETA (2)CVC (1)Time from admission to first isolation6 days14 days50 days50 days13 days52 daysTime from taking sample to isolation3 days for both2 days2 day for catheter, 7 days for skin3 days for first isolate,4 days for second one3 days for first isolate,4 days for second one2 daysTime to culture negative ^b^16 days6 daysNot done16 days22 daysNot doneDeterioration at time of isolationYesNoYesNoNoYesAntifungal therapyYesNoYesYesNoYesPrior to isolation (days)NoNoFluconazole (10)Caspofungin (47)Caspofungin (14)NoNoAfter isolation (days)Caspofungin (7)Anidulafungin (14)NoCaspofungin (18)NoNoCaspofungin (6)Other potentially pathogenic organisms isolated A. baumannii

K. pneumoniae

S. maltophilia

K. pneumoniae

P. aeruginosa

A. baumannii

P. aeruginosa

C. albicans

S. maltophilia

A. baumannii

P. aeruginosa Length of admission106 days21 days91 days90 days50 days58 daysOutcome at dischargeRecoveredPoor prognosisPoor prognosisDiedRecoveredPoor prognosisInvasive procedures at time of first isolation of C. aurisMechanical ventilationYesYesYesYesYesYesCentral venous catheterYesYesYesYesYesYesArterial lineYesYesYesYesYesYesCRRTYesYesYesYesNoYesHemodialysisYesNoNoNoNoNoParenteral nutritionYesYesYesYesYesNoPlasma exchangeNoYesNoYesNoNoNote: CAP, Community-acquired pneumonia; CRRT, Continuous renal replacement therapy; ETA, Endotracheal aspiration; NHTD, National Hospital for Tropical Diseases; UTI, Urinary tract infections; VAP, Ventilator-acquired pneumonia^a^ indicates the first isolation of C. auris^b^ duration from the first isolation of C. auris to fungal culture negative

Table 2. Antifungal susceptibility testing of Candidozyma aurisCaseAzolesEchinocandinsPolyenesFluconazoleVoriconazoleAnidulafunginCaspofunginMicafunginAmphotericin B deoxycholateCase 1> 256.00 (R)> 8.000.25 (S)> 8.000.25 (S)2.00 (R)Case 2------Case 364.00 (R)0.120.12 (S)0.250.12 (S)1.00 (S)Case 4> 128.00 (R)-0.25 (S)> 8.000.50 (R)0.50 (S)Case 5------Case 6128.00 (R)-0.12 (S)> 8.000.12 (S)2.00 (R)Note: Data were presented with minimum inhibitory concentration (MIC) value and susceptibility whose interpretation according to the US (CLSI) and EUCAST guidelines. The susceptibility testing was performed on the first isolate of C. auris [8, 9]R, Resistant; S, Susceptible; -, Not done

Case 1 65M November 2023 – C. auris from CVC and ETA

The patient was admitted to a hospital in Ha Noi after a road traffic accident and had external fixation for a left tibia fracture. His medical history included stroke, hypertension, and chronic renal failure with hemodialysis since 2021. After surgery, the patient was transferred to Phu Tho provincial for 1 month, but his condition became worsened with fever and pus from the wound. He was transferred to another hospital in Ha Noi and diagnosed with surgical site infection caused by Klebsiella pneumoniae and treated with antibiotics (meropenem and colistin), drainage, and steroids. After an additional he was transferred to NHTD. He presented with fever, elevated inflammatory biomarkers (white blood cell counts [WBC] 10.4 10^9^/L, C-reactive protein [CRP] 84.3 mg/L, and procalcitonin [PCT] 29.1 ng/mL), chest X-ray showing opacities in the left lung, a fractured rib and drains in situ (tibia). A diagnosis of hospital-acquired pneumonia (HAP) and suspicion of sepsis were established. Antibiotics including doripenem and daptomycin were given, but no supplemental oxygen therapy was needed. On day 5, Acinetobacter baumannii was isolated from blood, and antibiotics were switched to ampicillin- sulbactam, colistin, and daptomycin. On day 6, C. auris was first isolated from the tip of a removed CVC originating from the referring healthcare facility, and caspofungin was initiated due to persistent fever and elevated biomarkers. Because the antifungal susceptibility testing showed MIC > 8 mg/L (upper limit of the assay) to caspofungin, antifungals were switched to anidulafungin for 14 days, which had more favourable MIC values. On day 15, the patient developed severe dyspnea, hypotension, and required mechanical ventilation with vasopressors. He was diagnosed with VAP and K. pneumoniae was isolated from ETA, for which he received treatment with meropenem and colistin. Repeat cultures of CVC for C. auris remained positive on day 11, then turned to negative on day 21. Following this, he experienced multiple episodes of VAP and was under continuous antibiotic treatment. At day 51, culture yielded a second isolate of C. auris from ETA in the presence of fever and elevated inflammatory biomarkers (WBC 16.9 10^9^/L, CRP 124.6 mg/L, and PCT 1.0 ng/mL) and under treatment with antibiotics (ampicillin-sulbactam, ceftazidime, daptomycin, and colistin). Anidulafungin was re-started for 7 days. Subsequent fungal cultures taken 9 days later remained negative. On day 64, the patient suffered from VAP caused by Stenotrophomonas maltophilia. On day 83, the patient’s condition had improved and antibiotic therapy was discontinued. At day 106, his leg was stable without drainage or swelling, and he was transferred to a lower-level hospital while still requiring mechanical ventilation.

Case 2 38M March 2024 – C. auris colonization of airways

The patient was admitted to Vinh Phuc provincial hospital for three days due to fatigue, jaundice, and then transferred to NHTD. An initial diagnosis of acute hepatic failure due to hepatitis B virus infection was made, and treatment was started with entecavir. After four days, the patient had decreased level of consciousness, upper abdominal pain, oliguria, and an increased PCT value (0.73 ng/ml). He was diagnosed with hepatic encephalopathy (ALT 1124 U/L, AST 413 U/L, total bilirubin 534.9 umol/L, direct bilirubin 370 umol/L, prothrombin time 41.2 s, INR 3.64, and serum ammonia 87.4 umol/L) and suspicion of bacterial bloodstream infection. The patient was intubated and plasma exchange and antibiotic treatment (ertapenem) were started. On day 14 antibiotic therapy was discontinued and C. auris and K. pneumoniae were isolated from ETA. Antifungal therapy and antibiotics were not given due to the patients improving clinical condition. After 6 days, a follow-up ETA culture remained negative for yeast but still grew K. pneumoniae while the patient had again deteriorated. Antibiotics (meropenem and colistin) were re-initiated for a diagnosis of VAP. On day 21, his legal representative requested for the patient to be discharged to die at home. His hepatic encephalopathy had not improved and he was not breathing by himself.

Case 3 73M February 2024 – C. auris from CVC and skin

The patient with a medical history of rheumatoid arthritis with long-term use of corticosteroids and hypertension presented at NHTD. He had been discharged 4 days ago where he had been admitted since October 2023 with severe community-acquired pneumonia (CAP), complicated by multiple episodes of VAP due to multidrug-resistant bacteria (A. baumannii,* K. pneumoniae*, and Pseudomonas aeruginosa isolated from ETA) and invasive fungal infections (C. albicans and C. parapsilosis isolated from ETA), and septic shock. The management included intubation, vasopressors, antibiotics, and antifungal therapy (oral fluconazole and caspofungin). After 123 days, he was discharged for home care at the request of his legal representatives despite being on treatment for septic shock, requiring mechanical ventilation, and persistent high levels of inflammatory biomarkers (WBC 23.1 10^9^/L, CRP 51.9 mg/L, and PCT 0.17 ng/mL). The patient was thus re-admitted after four days and was put back on ventilator, vasopressors, and antibiotics (meropenem, colistin, and vancomycin). Chest X-ray showed bilateral heterogeneous opacities. On day 20 of the second admission, P. aeruginosa was cultured from ETA and the patient again developed multiple episodes of VAP. On day 51, while treated with meropenem and fosfomycin, C. auris was first isolated from the tip of a removed CVC. Catheters were changed and an 18-day course of caspofungin was started because of clinical deterioration including a new episode of fever, hypotension, and elevated inflammatory biomarkers (WBC 17.9 10^9^/L, CRP 27.0 mg/L, and PCT 0.17 ng/mL). On day 70, C. auris was isolated from skin lesions but antifungal treatment was not re-introduced. Follow-up fungal cultures from CVC were not done, but C. auris was still isolated from skin on day 80. On day 91, the patient’s relative again requested discharge because of his poor response. At discharge, he was still requiring ventilation and had elevated biomarkers (WBC 12.4 10^9^/L, CRP 155 mg/L, and PCR 1.87 ng/mL).

Case 4 46M May 2024 – C. auris colonization in ETA

The patient without underlying disease was hospitalized in Bac Giang provincial hospital after one day of fever, severe headache, and nausea. He was diagnosed with meningitis and managed with ceftriaxone and dexamethasone. After four days, he developed a seizure and deteriorating consciousness, and required intubation and was transferred to NHTD. A diagnosis of bacterial meningitis and suspicion of encephalitis were made, and ceftriaxone was continued with addition of 30-day acyclovir. The cerebral magnetic resonance imaging (MRI) showed lesions compatible with Herpes simplex virus (HSV) infection at the putamen, insula, and temporal lobes. Cerebrospinal fluid (CSF) analysis on day 1 was suspicious for viral etiology (white cell counts 27 cells/mm^3^, glucose 5.74 mmol/L, and protein 0.47 g/L), but no pathogen in CSF was detected by culture, Xpert MTB/ RIF, HSV PCR, or JEV PCR. On day 7 after admission to NHTD, C. albicans was isolated from ETA and the patient was treated with 14 days of caspofungin. On day 17, autoimmune encephalitis was suspected due to poor recovery after treatment of meningitis and encephalitis, and an anti-N-methyl-D-aspartate receptor (anti-NMDAR) test in CSF was requested. Despite a negative result, the patient received plasma exchange and 14-day rituximab for autoimmune encephalitis. On days 50 and 79, C. auris was isolated from ETA but left untreated in the absence of clinical VAP/deterioration and inflammatory biomarkers elevation. Follow-up cultures on days 65 and 88 remained negative. During hospitalization, the patient suffered from multiple episodes of nosocomial infections, including VAP due to A. baumannii and catheter-associated urinary tract infection (CAUTI) with P. aeruginosa. After many courses of antibiotics including meropenem, linezolid, colistin, long-term corticoids, anticonvulsants, CRRT, and plasma exchange, his symptoms were getting better except for persistent convulsions. Although an improvement in the latest cerebral MRI was observed, the patient remained comatose and ventilator dependent. On day 90, he died of sudden cardiac arrest.

Case 5 64F June 2024 – C. auris colonization in ETA

The patient with a history of hypertension presented at Thai Binh provincial hospital with one day of fever and dyspnea, and was diagnosed with CAP. A chest CT scan showed consolidation across both lungs. After one day, symptoms deteriorated, and the patient was intubated and transferred to NHTD. A diagnosis of pneumonia with septic shock was made, with hypotension and high levels of inflammatory biomarkers (WBC 12.4 10^9^/L, CRP 241.9 mg/L, and PCT 2.17 ng/mL). The management consisted of vasopressors and broad-spectrum antibiotics (imipenem and vancomycin). On day 29, S. maltophilia was isolated from ETA and a diagnosis of VAP was established. On day 13, C. auris was first isolated from ETA, and again on day 29. In both instances, the follow-up cultures 5 days later remained negative. In the absence of exacerbation and good response with antibiotic therapy, no antifungal medication was initiated. On day 50, the patient, while still ventilator dependent, was transferred back to the provincial hospital.

Case 6 53F June 2024 – C. auris on CVC

The patient with a history of alcoholic liver cirrhosis was admitted at Bac Giang provincial hospital after two days of fever, severe cough, and dyspnea. He was diagnosed as having CAP. On admission, he was intubated and developed VAP on day 5 with isolation of A. baumannii from ETA. The management included antibiotics (meropenem, colistin) and CRRT. After two weeks, his condition worsened with persistent fever and low blood pressure. The patient was diagnosed with septic shock and transferred to NHTD. On day 1, ETA culture was positive for A. baumannii in addition to infiltration and opacities in the chest X-ray compatible with VAP. Broad-spectrum antibiotics comprising meropenem, colistin, ampicillin-sulbactam, and linezolid was initiated. P. aeruginosa was also isolated from ETA five days later. The patient developed multiple episodes of VAP with this pathogen and suffered from multiorgan dysfunction. On day 52, while he was on ventilator and antibiotic therapy (meropenem, colistin, and fosfomycin), C. auris was isolated from the tip of a removed CVC specimen accompanied by a new episode of fever, impairment of respiratory function, and elevated inflammatory biomarkers (WBC 8.0 10^9^/L, CRP 40.3 mg/L, and PCT 0.54 ng/mL). Caspofungin was prescribed, and the catheter was changed. However, he did not response well with regimens (WBC 13.8 10^9^/L, CRP 285.5 mg/L, and PCT 6.59 ng/L). Six days later, his legal representative asked to discharge him to die at home.

Discussion

In Viet Nam, the first report of C. auris was published in 2020 with two subsequent reports in 2024, describing a total of ten cases from the south. Our study represents the first record of colonization and infection with C. auris from the north of Viet Nam, confirming its presence throughout the country. Nevertheless, those cases were found through routine diagnostics based on clinical symptoms. IPC screening for carriage was not performed. In general, demographic and clinical characteristics of patients infected by C. auris in our study are similar to the other reports from Viet Nam [5–7]. All cases were critically ill at the time of isolation and had previously been exposed to ICU admission, mechanical ventilation, broad-spectrum antibiotics, and multiple invasive medical procedures. Those risk factors for C. auris in six cases were consistent with those in recent reviews [3, 4]. Although culture from blood and ETA/CVC was conducted as routine diagnostics on admission to ICU, in the absence of full admission screening for carriage, pre-existing carriage or local acquisition during stay in our unit could not be assessed, except case 1 whose first isolate was from the referring healthcare facility.

Three of six cases were diagnosed with invasive infection, of whom one recovered. Clinical management consisted of catheter replacement and prompt echinocandin therapy (case 1, 3, and 6). Colonization with C. auris was identified in the other three individuals without the introduction of antifungal agents. The high mortality and poor prognosis at discharge among cases in the present study are likely secondary to the critical clinical status. Moreover, as a marker of treatment response or discontinuation of contact isolation, negative results (time to culture negative) in our study did not indicate microbiologic clearance. Antifungal susceptibility testing was conducted for 4/6 isolates (due to supply issues with Sensititre plates). Compared to previous studies in Viet Nam, our isolates were highly resistant to fluconazole (four isolates) (Table 2) [5–7]. However, we currently do not have access to molecular typing or the whole genome sequencing, and no molecular epidemiology analysis was undertaken.

Because of the association with outbreaks in healthcare settings, after C. auris was isolated, patients were placed in contact isolation within a single room and nursed separately using gowns, gloves, and masks as PPE, as per hospital protocols. Transferring hospitals were informed. CVC or endotracheal tube were replaced if present. Environmental cleaning and disinfection were conducted using hydrogen peroxide. A refresher training on precautions for C. auris was mandatory for all healthcare personnel in ICU. Patient and environmental screening are not part of current C. auris protocols at our hospital. Table 3 depicts the chronological order of reports in Viet Nam [5–7]. All patients required prolonged ICU admission except for one case. In 2020, the first case report of C. auris colonization whose specimens originated from Viet Nam was isolated in Australia [5]. Two case series were totally reported in Viet Nam, in which one identified C. auris only by RT-PCR in blood [7] and one simultaneously tested both VITEK2 Compact and MALDI-TOF MS techniques [6]. AST presented the resistance varied; of note, resistance to amphotericin B was observed in six isolates. Furthermore, only one study used molecular typing and reported clade I (Table 3) [7]. Only five cases recovered, which emphasized high mortality among patients having isolation of C. auris in the resource-limited setting. To date, an official guideline for managing C. auris colonization or infection has not yet been issued in Viet Nam, posing a challenge in diagnosis and treatment for physicians. Further studies are needed to determine the prevalence, resistance, and burden of C. auris to facilitate the management.

Table 3. Chronological order of reports of Candidozyma auris in Viet NamPublicationRegion(Sample collection period)Hospital(Department of isolates)No. of patients (No. of isolates)Specimen(No. of isolates)CladeMethod of identificationAntifungal resistance(No. of isolates)Outcome at discharge(No. of patients)Ouli/2020/Australia [5]South (2019)N/A1 (1)IPC screening samples (1)N/ACulture (MALDI-TOF MS) andgenome sequencingFluconazole (1)Amphotericin B (1)Poor prognosis (1)Thong/2024/Viet Nam [6]South (2024)Cho Ray (Department of pulmonary medicine and ICU)4 (5)Blood (2)Sputum (1)Stool (1)Urine (1)N/ACulture (VITEK^®^ 2 Compact and MALDI-TOF MS)Amphotericin B (1)Recovered (2)Died (2)Hong/2024/Viet Nam [7]South (2024)N/A (ICU)5 (5)Blood (5)IRT-PCRAmphotericin B (4)Caspofungin (1)Recovered (1)Poor prognosis (2)Died (2)This reportNorth (2024)NHTD (ICU)6 (10)CVC (3)ETA (6)Skin (1)N/ACulture (MALDI-TOF MS)Fluconazole (4)Amphotericin B deoxycholate (2)Micafungin (1)Recovered (2)Poor prognosis (3)Died (1)Note: CVC, Central venous catheter; ETA, Endotracheal aspirate; ICU, Intensive care unit; IPC, Infection prevention and control; MALDI-TOF MS, Matrix assisted laser desorption/ionization time-of-flight mass spectrometry; NHTD, National Hospital for Tropical Diseases; RT-PCR, Real-time polymerase chain reaction

Conclusions

We describe the isolation of C. auris in ICU setting and confirm presence of C. auris in the north of Viet Nam. Comparison with earlier reports from the south of Viet Nam shows considerable variation in the resistance to antifungal agents and a high mortality.