Candida auris and COVID-19: A health threatening combination

Document Type : Reviews

Authors

1 Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

2 Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran

3 Molecular Medecine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

4 Department of Medical Mycology and Parasitology, School of Medicine, Babol University of Medical Sciences, Babol, Iran

5 Toxoplasmosis Research Center, Communicable Diseases, Institute, Mazandaran University of Medical Sciences, Mazandaran, Sari, Iran

6 Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

7 Department of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

10.18502/cmm.8.3.11211

Abstract

Since its first emergence in December 2019, due to its fast distribution throughout the world, SARS-COV-2 become a global concern. With the extremely increased number of hospitalized patients, this situation provided a potential basis for the transmission of nosocomial infections. Candida auris is a multidrug-resistant pathogen with improved transmission dynamics and resistance traits. During the worldwide spread of COVID-19, cases or outbreaks of C. auris colonization or infection have been reported. Resistance to antifungal drugs has been observed in the causative agents of the majority of such cases. The focus in this review is on COVID-19-associated C. auris infections (case studies/outbreaks) and the pandemic's potential effect on antifungal drug resistance.

Keywords


Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the most significant global health event since Spanish influenza in the early 20th century, is alarmingly on the rising and threatens human health and public safety [ 1 , 2 ]. Unlike influenza outbreaks, coronavirus disease 2019 (COVID-19) has spread fast all over the world, and over 100 countries have reported cases of this disease [ 1 , 3 , 4 ]. SARS-CoV-2 ranks third among members of the Coronavirus family regarding its pathogenicity; however, due to its rapid spreading, it has posed the severest threat to global health in this century [ 1 ].

The hospital mortality of COVID-19 is estimated to range from 15% to 20% and increases to 40% among patients requiring intensive care unit (ICU) admission [ 5 ]. Meanwhile, early estimates suggested that the true burden of disease and an actual number of deaths may be as much as 10 times higher than reported cases [ 4 , 6 , 7 ]. Patients with severe COVID-19 need intensive care, including mechanical ventilation, extracorporeal membrane oxygenation, continuous renal replacement therapy, glucocorticoids, and intravenous immune-globulin therapy. These interventions could predispose patients to co-infections by different microorganisms including fungi (both filamentous fungi and yeasts) [ 8 - 10 ]. Co-infections by Candida auris, due to its persistence on hospital surfaces and high resistance to antifungal drugs, are of significant value, and COVID-19 has provided a potential bed for these infections [ 11 , 12 ]. Patients admitted to ICU have the greatest risk factors for such infections [ 11 , 13 ].

Antimicrobial resistance (AMR) as another threat to global health and the economy is likely to be overshadowed by the COVID-19 pandemic [ 2 ]. Currently, infections caused by antimicrobial-resistant pathogens are responsible for nearly 700,000 deaths every year worldwide. It can be anticipated that AMR-related deaths due to the catastrophe status of the COVID-19 pandemic can reach up to 10 million deaths per year by 2050 if the world could not tackle these current states [ 14 , 15 ].

So far, cases or outbreaks of C. auris infection/colonization among COVID-19 patients have been reported [ 16 - 18 ]. In this study, we have a particular focus on the C. auris infection/colonization in patients with COVID-19 and the potential impact of this viral pandemic on antifungal drug resistance.

Candida auris in the era of COVID-19

C. auris, first isolated in Japan in 2009, is an emerging member of the Metschnikowiaceae family within the Candida/Clavispora clade [ 19 ]. To date, C. auris has been reported from at least 40 countries; therefore, it has a global distribution [ 11 , 20 , 21 ]. C. auris has been isolated as an infecting or colonizing agent from various specimens or parts of the human body including blood, urine, wounds, bile, the nares, the skin, the axilla, and the rectum of patients [ 22 , 23 ]. Furthermore, this fungus can survive on environmental surfaces and human skin for several weeks and can even tolerate some frequently used disinfectants [ 24 - 26 ]. These traits can be associated with intrahospital transmission of C. auris, leading to outbreaks [ 27 , 28 ]. In the past decade, C. auris has led to several outbreaks in hospitals worldwide and become a global health threat [ 29 ]. Invasive infections by this pathogen are usually observed in critically ill patients in ICUs and are related to high mortality rates [ 30 ].

COVID-19 has presented a great challenge for health care settings. During this viral pandemic, patients admitted to ICUs are at the greatest risk for C. auris infection/colonization [ 31 ]. In the second half of 2020, several countries, such as India, Lebanon, Italy, Brazil, Guatemala, Mexico, Peru, Panama, Colombia, and the United States, reported cases/outbreaks of co-infection by C. auris in COVID-19 patients. [ 32 - 35 ]. Accordingly, attention should be drawn to this topic to characterize various features of these co-infections. By a literature review up to September 12, 2022, 27 studies were found, of which data of COVID-19-associated C. auris infections were extractable in 14 studies (75 cases, Table 1).

Ref. Publication Year Country Sex Age Underlying Conditions Risk Factors Clade (I,II,III,IV,V) Site of infection OR Colonization Resistance Pattern Hospital stay (day) Antifungal Treatment Outcome
[ 12 ] 2020 Mexico M 51 HT, DS, Obesity MV, PICCs, UC, Antibiotic use, Steroid therapy IV Blood AMB, FLC 20-70 CAS, ANF Died
[ 12 ] 2020 Mexico M 54 HT, DS, Obesity, Asthma MV, PICCs, UC, Antibiotic use, Steroid therapy, IV Urine AMB 20-70 ISA, CAS Survived
[ 12 ] 2020 Mexico M 55 HT, DS, CAD MV, PICCs, UC, Antibiotic use, Steroid therapy IV Blood AMB 20-70 ANF Died
[ 12 ] 2020 Mexico M 51 Obesity MV, PICCs, UC, Antibiotic use, Steroid therapy IV Urine AMB 20-70 ISA, ANF Died
[ 12 ] 2020 Mexico M 64 AKD MV, PICCs, UC, Antibiotic use, Steroid therapy IV Blood, Urine AMB, FLC 20-70 CAS, VRC, AMB Died
[ 12 ] 2020 Mexico M 64 HT, Smoking, Obesity, Hypothyroidism MV, PICCs, UC, Antibiotic use, Steroid therapy IV Blood, PIC line, Urine AMB 20-70 ANF, ISA Died
[ 12 ] 2020 Mexico F 54 HT, Obesity MV, PICCs, UC, Antibiotic use, steroid therapy IV Blood AMB, FLC 20-70 AMB, CAS, VRC Died
[ 12 ] 2020 Mexico F 60 Obesity MV, PICCs, UC, Antibiotic use, Steroid therapy, IV Urine AMB 20-70 CAS, ANF, VRC Died
[ 12 ] 2020 Mexico M 58 HT, Obesity MV, PICCs, UC, Antibiotic use, Steroid therapy IV Urine AMB, FLC 20-70 ANF Died
[ 12 ] 2020 Mexico M 36 DS, Obesity MV, PICCs, UC, Antibiotic use, Steroid therapy IV Urine AMB, FLC 20-70 CAS Survived
[ 12 ] 2020 Mexico M 66 HT, DS, CAD, VHD MV, PICCs, UC, Antibiotic use, Steroid therapy, IV Urine AMB, ANF 20-70 VRC, CAS Survived
[ 12 ] 2020 Mexico M 46 Obesity MV, PICCs, UC, Antibiotic use, Steroid therapy IV Blood AMB 20-70 VRC, CAS Survived
[ 42 ] 2020 USA F 49 Seizure disorder ND ND Blood ND 14 MFG Survived
[ 33 ] 2020 India F 25 CLD, AKD Antibiotic use, CVC, UC ND Blood FLC, VOR, 5-FC 35 AMB Survived
[ 33 ] 2020 India M 52 HT, DS Antibiotic use, Steroid therapy, CVC, and UC ND Blood FLC 20 MFG, AMB Died
[ 33 ] 2020 India F 82 HT, DS, Hypothyroidism, CKD Antibiotic use, Steroid therapy, CVC, UC ND Blood FLC 60 MFG Died
[ 33 ] 2020 India F 86 CLD, IHD, DS Antibiotic use, Steroid therapy, CVC, UC ND Blood FLC 21 MFG Died
[ 33 ] 2020 India M 66 HT, DS, asthma Antibiotic use, CVC, UC ND Blood FLC, AMB 20 MFG, AMB Survived
[ 33 ] 2020 India M 71 Hypothyroidism, CKD Antibiotic use, Steroid therapy, CVC, UC ND Blood FLC, 5-FC 32 MFG Died
[ 33 ] 2020 India M 67 HT, DS, COPD Antibiotic use, steroid therapy, CVC, and UC ND Blood FLC, AMB, 5- FC 21 MFG, AMB Survived
[ 33 ] 2020 India M 72 HT, CLD Antibiotic use, Steroid therapy, CVC, UC ND Blood FLC, VOR, AMB, 5-FC 27 MFG Died
[ 33 ] 2020 India M 81 HT, DS, IHD Antibiotic use, Steroid therapy, CVC, UC ND Blood FLC, VOR, 5- FC 20 MFG Died
[ 33 ] 2020 India M 69 HT, Asthma Antibiotic use, Steroid therapy, CVC, UC ND Blood FLC, AMB, 5- FC 21 MFG Survived
[ 34 ] 2021 Italy M 70 DS, Obesity ND ND BAL (BSI) AMB, azoles ND ND Died
[ 34 ] 2021 Italy M 62 None Antibiotic use ND Surveillance swab (BSI) AMB, azoles 48 CAS Survived
[ 34 ] 2021 Italy M 69 CAD Antibiotic use ND Surveillance swab (BSI) AMB, azoles 26 AMB, CAS Died
[ 34 ] 2021 Italy M 50 None Antibiotic use ND Surveillance swab AMB, azoles ND ND Survived
[ 34 ] 2021 Italy M 62 HT Antibiotic use ND BAL (BSI) AMB, azoles 24 CAS Survived
[ 34 ] 2021 Italy M 64 Asthma, HT Antibiotic use ND Blood (BSI) AMB, azoles 29 CAS Died
[ 41 ] 2021 Italy ND ND ND ND I BAL AMB, VRC, FLC ND ND Died
[ 41 ] 2021 Italy ND ND ND ND I BAL AMB, VRC, FLC ND ND Survived
[ 41 ] 2021 Italy ND ND ND ND I Blood AMB, VRC, FLC ND ND Died
[ 41 ] 2021 Italy ND ND ND ND I BAL AMB, VRC, FLC ND ND Died
[ 41 ] 2021 Italy ND ND ND ND I Urine AMB, VRC, FLC ND ND Survived
[ 36 ] 2021 Brazil M 59 DVT MV, HD, Steroid therapy I CVC-tip MDS 49 ANF Survived
[ 36 ] 2021 Brazil F 74 CKD, DS, HT DVT , Noninvasive ventilation, HD, Steroid therapy, Antibiotic use, HD I Blood MDS 70 ANF Died
[ 40 ] 2021 USA M 72 DLP MV, Use of vasopressor agents, Antecedent Steroid therapy, Antibiotic use III Blood Echino, FLC 14 MFG Survived
[ 40 ] 2021 USA M 77 DS, HT, DLP MV, Use of vasopressor agents, Antecedent Steroid therapy, Antibiotic use III Urine FLC 28 ND Died
[ 40 ] 2021 USA F 71 MM, SCT MV, Use of vasopressor agents, Antecedent Steroid therapy, Antibiotic use III Blood FLC 24 MFG, AMB Died
[ 40 ] 2021 USA M 71 DS, HT MV, Use of vasopressor agents, Antecedent Steroid therapy, Antibiotic use III Blood FLC 24 ND Died
[ 40 ] 2021 USA F 38 SLE, HT, DS, Obesity MV, Use of vasopressor agents, Antecedent Steroid therapy, Antibiotic use III Wound FLC 32 ND Survived
[ 40 ] 2021 USA M 71 DS, HT, DLP MV, use of vasopressor agents, Antecedent Steroid therapy, Antibiotic use III Blood FLC 30 ND Died
[ 40 ] 2021 USA F 75 DS, HT, DLP MV, use of vasopressor agents, Antecedent Steroid therapy, Antibiotic use III Blood FLC 12 MFG Survived
[ 40 ] 2021 USA F 68 DS, bladder cancer MV, use of vasopressor agents, Antecedent Steroid therapy, Antibiotic use III Urine FLC 32 ND Survived
[ 40 ] 2021 USA M 65 HT MV, use of vasopressor agents, Antecedent Steroid therapy, Antibiotic use III BAL FLC 12 ND Died
[ 40 ] 2021 USA M 69 HT MV, use of vasopressor agents, Antecedent Steroid therapy, Antibiotic use III Blood FLC 28 MFG Died
[ 40 ] 2021 USA M 41 HT, CKD MV, use of vasopressor agents, Antibiotic use III Blood FLC 20 MFG Survived
[ 40 ] 2021 USA M 68 ND MV, use of vasopressor agents, Antibiotic use III Wound FLC 33 MFG Survived
[ 38 ] 2021 Brazil M 59 DVT CVC, HD, MV, UC, Antifungal therapy, Antibiotic use I CVC‐tip MDS 42 Yes Survived
[ 38 ] 2021 Brazil M 79 Biliary lithiasis CVC, MV, UC, Antifungal therapy, Antibiotic use I CVC‐tip, Axillae, Groin, Nostrils and Ear swab MDS 46 Yes Survived
[ 38 ] 2021 Brazil M 72 Stroke, dementia CVC, MV, UC, Antifungal therapy, Antibiotic use I Urine MDS 36 Yes Died
[ 38 ] 2021 Brazil M 58 HT, DS, obesity CVC, Antibiotic use I Axillae, Groins swabs MDS 27 No Survived
[ 38 ] 2021 Brazil M 63 HT, DS, Obesity CVC, Antibiotic use I Axillae, Groin and nostril Swabs MDS 18 No Survived
[ 38 ] 2021 Brazil F 75 HT, DS, Hypothyroidism CVC, HD, MV, UC, Antifungal therapy, Antibiotic use I Axillae, Groins swabs MDS 32 Yes Survived
[ 38 ] 2021 Brazil M 63 HT, DS, CKD CVC, HD, MV, UC, Antifungal therapy, Antibiotic use I Axillae, groin, nostrils and ear swabs MDS 22 Yes Survived
[ 38 ] 2021 Brazil M 77 COPD, Stroke, CKD UC, Antibiotic use I Axillae, groin, Nostrils and Ear swabs MDS 22 No Survived
[ 38 ] 2021 Brazil F 74 DS, HT, CKD, Coronary artery disease CVC, MV, HD I Blood MDS 34 Yes Died
[ 39 ] 2021 Qatar M 64 None MV, Antibiotic use, HD ND Blood AMB, FLC 47 ANF Died
[ 32 ] 2021 Lebanon M 75 ARDS ,Metastatic prostate cancer Intubated, MV, CVC, UC, Antibiotic use, Steroid therapy, Antifungal therapy ND DTA, Urine, Blood ND 40 Yes Survived
[ 32 ] 2021 Lebanon F 82 COPD, Respiratory failure MV, CVC, UC, Antibiotic use, Steroid therapy, Antifungal therapy ND DTA FLC, AMB 26 No Survived
[ 32 ] 2021 Lebanon M 68 ARDS Intubated MV, CVC, UC, Antibiotic use, Steroid therapy, Antifungal therapy ND DTA ND 50 No Survived
[ 32 ] 2021 Lebanon F 68 ARDS Intubated, MV, CVC,UC, Antibiotic use, Steroid therapy, Antifungal therapy ND DTA FLC, AMB 40 Yes Survived
[ 32 ] 2021 Lebanon M 71 Cutaneous T cell lymphoma Intubated, MV, CVC,UC, Antibiotic use, Steroid therapy, Antifungal therapy ND DTA FLC, AMB 15 Yes Survived
[ 32 ] 2021 Lebanon M 85 ARDS Intubated, MV, CVC,UC Antibiotic use, Steroid therapy, Antifungal therapy ND DTA ND 10 Yes Survived
[ 32 ] 2021 Lebanon M 79 ARDS, CLL Intubated, MV, CVC,UC, Antibiotic use, Steroid therapy, Antifungal therapy ND DTA ND 48 No Survived
[ 37 ] 2021 Turkey M 71 Stroke, DS, Donation of a single kidney, lobectomy surgery due to lung cancer Favipiravir and intravenous Dexamethasone therapy, Antibiotic use ND Blood AMB, FLC ND CAS Died
[ 44 ] 2022 India M 36 Hepatomegaly, Aplastic anemia, Malignancy, sHLH, HRF, ARDS, MOF, AKD Steroid therapy, MV ND Blood FLC 29 FLC, CAS Died
[ 45 ] 2022 Germany F 65 ARDS Steroid therapy, MV I Urine, BAL FLC, CAS 90 VRC Survived
[ 45 ] 2022 Germany M 60 Lung transplant, EAA, AKD MV I Blood, TBS FLC, CAS 73 AMB, CAS, MFG, POS Survived
[ 43 ] 2022 Italy M 64 ARDS MV, Steroid therapy, Antibiotic use ND Skin FLC 100 ANF Survived
[ 43 ] 2022 Italy M 64 Respiratory disease, Smoker, HTA, DS, ARDS MV, Steroid therapy, Antibiotic use, Antifungal therapy ND Skin FLC 16 No Died
[ 43 ] 2022 Italy F 49 Respiratory disease, HTA, DS, Autoimmune disease, ARDS MV , Steroid therapy, Antibiotic use ND Skin FLC 25 No Died
[ 43 ] 2022 Italy M 57 Autoimmune disease, ARDS MV, Steroid therapy, Immunomodulatory Agents, Antibiotic use, Antifungal therapy ND Urine FLC 28 No Died
[ 43 ] 2022 Italy F 55 HTA, Hematological disease, Malignancy, ARDS MV, Steroid therapy, Immunomodulatory Agents, Antibiotic use, Antifungal therapy ND Respiratory tract, Blood FLC 100 ANF, AMB Survived
[ 43 ] 2022 Italy F 58 Respiratory disease, HTA, DS, Autoimmune disease, ARDS MV, Steroid therapy, Antibiotic use, Antifungal therapy ND Skin FLC 66 No Survived
Abbreviations: MV: mechanical ventilation, PICCs: peripherally inserted central lines, UC: urinary catheters, CLD: chronic liver disease, AKD: acute kidney disease, HT: hypertension, DS: diabetes, IHD: Ischemic heart disease, DLP: dyslipidemia, MM: multiple myeloma, SCT: stem cell transplantation, CVC: central venous catheter, COPD: chronic obstructive pulmonary disease, DVT: Deep-seated venous thrombosis, ARDS: Acute respiratory distress syndrome, HD: HD, SLE: Systemic lupus erythematosus, CAD: Coronary artery Disease, CKD: Chronic kidney disease, BSI: blood stream infection, CLL: Chronic lymphocytic leukemia, ANF: Anidulafungin, CAS: Caspofungin, MFG: Micafungin, ISA: Isavuconazole, VRC: Voriconazole, POS: posaconazole, MAR: Multiazole-resistant, Echino: Echinocandins, MDS: Multidrug-susceptible, AMB: Amphotericin B, FLC: Fluconazole, MDS: Multidrug-susceptible, sHLH: Secondary Hemophagocytic Lymphohistiocytosis, HRF: hypoxemic respiratory failure, MOF: multi-organ failure, EAA: Exogenous allergic alveolitis, TBS: Tracheo-bronchial secretion, HTA: Arterial Hypertension, DTA: Deep Tracheal Aspirates, ND: Not define
Table 1.Characteristics of patients with COVID-19-associated Candida auris infections reported up to September 12, 2022

COVID-19-associated C. auris infection was more common in males (51/70, 72.86%) than females (19/70, 27.14%; data were not available for 5 patients). The mean±SD age of patients was 63.8±12.09 years [ 12 , 32 - 34 , 36 - 45 ]. Antibiotic use (63/68, 92.65%; data were not available for 7 patients) was the most common risk factor, followed by steroid therapy (48/68, 70.59%; data were not available for 7 patients), mechanical ventilation (48/68, 70.59%; data were not available for 7 patients), the use of urinary catheters (35/68, 51.47%; data were not available for 7 patients), central venous catheter (25/68, 36.76%; data were not available for 7 patients), peripherally inserted central lines (12/68, 17.65%; data were not available for 7 patients), and vasopressor drugs (12/68, 17.65%; data were not available for 7 patients). Regarding the comorbidities, hypertension (33/69, 47.82%; data were not available for 6 patients), diabetes mellitus (25/69, 36.23%; data were not available for 6 patients), acute respiratory distress syndrome (13/69, 18.84%; data were not available for 6 patients), and obesity (13/69, 18.84%; data were not available for 6 patients) were recorded for the patients in descending order of prevalence.

COVID-19-associated C. auris infections (cases/outbreaks) are not limited to a specific geographical region. As shown in Figure 1, they have been reported from American, European, and Asian countries. Lack of reports from other parts of the world does not necessarily mean a lack of such infections, but a lack of sufficient data, which indicates the need for further studies.

Figure 1. Global distribution of COVID-19-associated C. auris infections (cases/outbreaks) (data for Panama is extracted from the WHO epidemiological alert [ 35 ]). ADDIN

According to genetic traits, C. auris is classified in five clades [ 46 ] with different geographic distribution patterns. According to the results of the included studies, from 42 isolates with available data, 18 (42.86%), 12 (28.57%), and 12 (28.57%) were classified as clade I, III, and IV, respectively [ 12 , 36 , 38 , 40 , 41 , 45 ]. Clade I was found in Italy, Brazil, Germany, and Lebanon, while Clade III and Clade IV were mainly reported from the United States and Mexico, respectively [ 12 , 36 , 38 , 40 , 41 , 45 , 47 ].

Inter-clade difference in susceptibility pattern of C. auris is reported in some studies [ 48 ]. Results of the present review confirm the inter-clade difference. While all isolates of clades III and IV were resistant to at least one antifungal drug, 11 out of 18 isolates of clade I were susceptible to antifungal agents. As the available data might be still scarce to make a firm conclusion, special attention to genetic characterization of C. auris isolates in different studies would be beneficial in this regard and is recommended.

Due to some features, C. auris is more likely to cause a hospital outbreak than other Candida species [ 27 , 49 , 50 ]. Biofilm formation is one of these pathogenesis traits that lead to withstanding desiccation and persistence in environments and health care settings [ 51 ]. Elongated survival on environmental surfaces and healthcare-mediated exogenous transmission between patients are other facilitating factor for this fungus. As a result, outbreaks, which continue for several months and sometimes lead to the closing of intensive care units, continuously have been described [ 33 , 52 ]. During the current pandemic, the overload of ICUs has been a breeding ground for the emergence and expansion of C. auris [ 12 , 17 , 34 , 38 ]. Based on our literature review, 9 COVID-19-associated C. auris outbreaks have been reported [ 12 , 17 , 32 - 34 , 38 , 40 , 47 , 53 ]. It is noteworthy that in some of these countries including Lebanon, Brazil, Mexico, and Peru, no isolates of this pathogen had been noted prior to this period [ 12 , 32 , 35 , 38 ]. Details of the outbreaks are presented in Table 2.

Publication Year Continent Country City/State Patients (NO.) Clade (I,II,III,IV,V) Resistance Pattern Outcome Ref.
2020 North America Mexico Monterrey, Nuevo Leon 12 IV (South American) AMB:6 , AMB+FLU: 5, AMB+ANF : 1 Survived: 4 , Died: 8 [ 12 ]
2020 Asia India New Delhi 10 ND FLC: 3, FLC+AMB: 1, FLC+5-FC: 1,FLC+VOR+AMB+5-FC: 1, FLC+ AMB+5-FC: 2, FLC+VOR+5-FC: 2 Died:6, Survived:4 [ 33 ]
2021 North America USA Florida 35 ND ND Died:8 [ 17 ]
2021 Asia Lebanon Beirut 7 ND FLU+AMB: 3 Survived (Still in ICU): 7 [ 32 ]
2021 Europe Italy Genoa 6 ND AMB+azoles: 6 Died: 3, Survived: 3 [ 34 ]
2021 South America Brazil São Paulo 9 I (South Asian) MDR Died:2 , Survived:7 [ 38 ]
2021 North America USA Miami 12 III (South African) Echino: 1, FLC: 12 Died:6, Survived:6 [ 40 ]
2021 Europe Spain Valencia 56 ND Echino: 2, FLC: 56 ND [ 53 ]
2022 Asia Lebanon Beirut 32 I AMB, FLC, VOR Died:19, Survived:13 [ 47 ]
Abbreviations: MAR: Multiazole-resistant، Echino: Echinocandins, FLC: Fluconazole: MDS: multidrug-susceptible, ANF: Anidulafungin, VOR: Voriconazole, AMB: Amphotericin B, 5-FC: 5-flucytosine, ND: Not defined
Table 2.Features of COVID-19-associated C. auris outbreaks reported up to September 12, 2022

The impact of COVID-19 on AMR

One of the unforeseen and unavoidable consequences of the COVID-19 pandemic is the appearance of antimicrobial resistance [ 54 ]. It is anticipated that too much and inappropriate use of antibiotics, disinfectants, and biocides during this pandemic may raise devastating effects on antifungal resistance control and antibiotic stewardship programs [ 15 ].

In the current pandemic, hospitalized patients with COVID-19 are more predisposed to superinfections with bacterial and/or fungal pathogens which is likely to impact the mortality rates [ 55 ]. This phenomenon is especially important in the case of emerging resistant species, such as C. auris [ 55 ]. An association between antibiotic use and the emergence of candidemia by Candida species with high minimum inhibitory concentration and/or intrinsic resistance to fluconazole has been reported [ 56 , 57 ]. Along the same line, up to 94% of COVID-19 hospitalized patients receive antimicrobial agents [ 58 , 59 ], which may increase the colonization rate of Candida species, such as C. auris [ 60 ]. In our literature review, results of antifungal susceptibility testing showed that 59 out of 70 (84.29%) isolates with available data were resistant to at least one antifungal drug. Among them, 31 (44.29%) isolates were multidrug resistant, which is 14.29% higher than the CDC report (30%) [ 61 ]. As shown in Table 2, in all reported COVID-19-associated C. auris outbreaks, drug-resistant isolates play a key role, and it makes the management more complicated.

Conclusion

With the increased hospital stay and the higher need for intensive care, COVID-19 patients are at risk for C. auris infections. Regarding the specific features of this fungus, it can circulate within clinical settings and cause outbreaks. Moreover, due to the different conditions in COVID-19 patients which are in favor of the selection of drug-resistant organisms, these patients are at risk for coinfections by single or multi-drug resistant C. auris. Accordingly, attempts for timely diagnosis and targeted treatment of such infections in COVID-19 patients should be made.

Acknowledgments

None.

Authors’ contribution

Conceptualization: S.K., M.A., and S.M. Literature search: J.J., S.A.H, and I.H. Draft preparation: S.K., S.A.G, and S.M. Critical review: H.T., S.A.G, M.A, and S.M. All authors read and approved the final manuscript.

Conflicts of interest

The authors declare no competing interests.

Financial disclosure

This research received no specific grant from any funding agency, commercial or not-for-profit sectors.

References

  1. Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021; 19(3):141-54.
  2. Murray AK. The novel coronavirus COVID-19 outbreak: global implications for antimicrobial resistance. Front Microbiol. 2020; 11:1-4.
  3. Hashan MR, Smoll N, King C, Ockenden-Muldoon H, Walker J, Wattiaux A, et al. Epidemiology and clinical features of COVID-19 outbreaks in aged care facilities: A systematic review and meta-analysis. EClinicalMedicine. 2021; 33:1-16.
  4. Weston S, Frieman MB. COVID-19: knowns, unknowns, and questions. Msphere. 2020; 5(2):203-20.
  5. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020; 324(8):782-93.
  6. Triggle CR, Bansal D, Farag EABA, Ding H, Sultan AA. COVID-19: learning from lessons to guide treatment and prevention interventions. MSphere. 2020; 5(3):317-20.
  7. Salehi M, Ahmadikia K, Badali H, Khodavaisy S. Opportunistic fungal infections in the epidemic area of COVID-19: a clinical and diagnostic perspective from Iran. Mycopathologia. 2020; 185(4):607-11.
  8. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020; 395(10223):507-13.
  9. Lai CC, Wang CY, Hsueh PR. Co-infections among patients with COVID-19: The need for combination therapy with non-anti-SARS-CoV-2 agents?. J Microbiol Immunol Infect. 2020; 53(4):505-12.
  10. Nazari T, Sadeghi F, Izadi A, Sameni S, Mahmoudi S. COVID-19-associated fungal infections in Iran: A systematic review. PloS One. 2022; 17(7):1-19.
  11. Du H, Bing J, Hu T, Ennis CL, Nobile CJ, Huang G. Candida auris: Epidemiology, biology, antifungal resistance, and virulence. PLoS Pathog. 2020; 16(10):e1008921.
  12. Villanueva-Lozano H, Treviño-Rangel RJ, González GM, Ramírez-Elizondo MT, Lara-Medrano R, Aleman-Bocanegra MC, et al. Outbreak of Candida auris infection in a COVID-19 hospital in Mexico. Clin Microbiol Infect. 2021; 27(5):813-6.
  13. Vaseghi N, Sharifisooraki J, Khodadadi H, Nami S, Safari F, Ahangarkani F, et al. Global prevalence and subgroup analyses of coronavirus disease (covid‐19) associated candida auris infections (caca): a systematic review and meta‐analysis. Mycoses. 2022; 65(7):683-703.
  14. Khor WP, Olaoye O, D’arcy N, Krockow EM, Elshenawy RA, Rutter V, et al. The need for ongoing antimicrobial stewardship during the COVID-19 pandemic and actionable recommendations. Antibiotics. 2020; 9(12):1-12.
  15. Rezasoltani S, Yadegar A, Hatami B, Aghdaei HA, Zali MR. Antimicrobial resistance as a hidden menace lurking behind the COVID-19 outbreak: the global impacts of too much hygiene on AMR. Front Microbiol. 2020; 11:1-7.
  16. Moin S, Farooqi J, Rattani S, Nasir N, Zaka S, Jabeen K. C. auris and non-C. auris candidemia in hospitalized adult and pediatric COVID-19 patients; single center data from Pakistan. Med Mycol. 2021; 59(12):1238-42.
  17. Prestel C, Anderson E, Forsberg K, Lyman M, de Perio MA, Kuhar D, et al. Candida auris outbreak in a COVID-19 specialty care unit—Florida, July–August 2020. MMWR. 2021; 70(2):56.
  18. Rajni E, Singh A, Tarai B, Jain K, Shankar R, Pawar K, et al. A high frequency of Candida auris blood stream infections in COVID-19 patients admitted to intensive care units, North-western India: A case control study. Open Forum Infect Dis. 2021; 8(12):1-12.
  19. Satoh K, Makimura K, Hasumi Y, Nishiyama Y, Uchida K, Yamaguchi H. Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol Immunol. 2009; 53(1):41-4.
  20. Ruiz-Gaitán A, Martínez H, Moret AM, Calabuig E, Tasias M, Alastruey-Izquierdo A, et al. Detection and treatment of Candida auris in an outbreak situation: risk factors for developing colonization and candidemia by this new species in critically ill patients. Expert Rev Anti Infect Ther. 2019; 17(4):295-305.
  21. Schelenz S, Hagen F, Rhodes JL, Abdolrasouli A, Chowdhary A, Hall A, et al. First hospital outbreak of the globally emerging Candida auris in a European hospital. Antimicrob Resist Infect Control. 2016; 5(1):1-7.
  22. Hata DJ, Humphries R, Lockhart SR, Committee CoAPM. Candida auris: an emerging yeast pathogen posing distinct challenges for laboratory diagnostics, treatment, and infection prevention. Arch Pathol Lab Med. 2020; 144(1):107-14.
  23. Jeffery-Smith A, Taori SK, Schelenz S, Jeffery K, Johnson EM, Borman A, et al. Candida auris: a review of the literature. Clin Microbiol Rev. 2018; 31(1):29-17.
  24. Cadnum JL, Shaikh AA, Piedrahita CT, Sankar T, Jencson AL, Larkin EL, et al. Effectiveness of disinfectants against Candida auris and other Candida species. Infect Control Hosp Epidemiol. 2017; 38(10):1240-3.
  25. Piedrahita CT, Cadnum JL, Jencson AL, Shaikh AA, Ghannoum MA, Donskey CJ. Environmental surfaces in healthcare facilities are a potential source for transmission of Candida auris and other Candida species. Infect Control Hosp Epidemiol. 2017; 38(9):1107-9.
  26. Uppuluri P. Candida auris biofilm colonization on skin niche conditions. Msphere. 2020; 5(1):1-3.
  27. Eyre DW, Sheppard AE, Madder H, Moir I, Moroney R, Quan TP, et al. A Candida auris outbreak and its control in an intensive care setting. N Engl J Med. 2018; 379(14):1322-31.
  28. Taghizadeh Armaki M, Mahdavi Omran S, Kiakojuri K, Khojasteh S, Jafarzadeh J, Tavakoli M, et al. First fluconazole-resistant Candida auris isolated from fungal otitis in Iran. Curr Med Mycol. 2021; 7(1):51-4.
  29. Sabino R, Veríssimo C, Pereira ÁA, Antunes F. Candida auris, an agent of hospital-associated outbreaks: which challenging issues do we need to have in mind?. Microorganisms. 2020; 8(2):1-19.
  30. Cortegiani A, Misseri G, Giarratano A, Bassetti M, Eyre D. The global challenge of Candida auris in the intensive care unit. Crit Care. 2019; 23(1):1-3.
  31. Alfonso-Sanchez JL, Agurto-Ramirez A, Chong-Valbuena MA, De-Jesús-María I, Julián-Paches P, López-Cerrillo L, et al. The Influence of infection and colonization on outcomes in inpatients With COVID-19: are we forgetting something?. Front Public Health. 2021; 9:1-8.
  32. Allaw F, Kara Zahreddine N, Ibrahim A, Tannous J, Taleb H, Bizri AR, et al. First Candida auris outbreak during a COVID-19 pandemic in a Tertiary-Care Center in Lebanon. Pathogens. 2021; 10(2):1-10.
  33. Chowdhary A, Tarai B, Singh A, Sharma A. Multidrug-resistant Candida auris infections in critically ill coronavirus disease patients, India, April–July 2020. Emerg Infect Dis. 2020; 26(11):1-3.
  34. Magnasco L, Mikulska M, Giacobbe DR, Taramasso L, Vena A, Dentone C, et al. Spread of carbapenem-resistant Gram-negatives and Candida auris during the COVID-19 pandemic in critically ill patients: one step back in antimicrobial stewardship?. Microorganisms. 2021; 9(1):1-10.
  35. WHO. Epidemiological alert: Candida auris outbreaks in health care services. Regional Office for the Americas of the World Health Organization. 2016. https://www.paho.org/en/documents/epidemiological-alert-candida-auris-outbreaks-health-care-services-context-covid-19.
  36. de Almeida JN, Francisco EC, Hagen F, Brandão IB, Pereira FM, Presta Dias PH, et al. Emergence of Candida auris in Brazil in a COVID-19 intensive care unit. J Fungi (Basel). 2021; 7(3):1-6.
  37. Bölükbaşı Y, Erköse Genç G, Orhun G, Kuşkucu MA, Çağatay A, Önel M, et al. First Case of COVID-19 Positive Candida auris Fungemia in Turkey. Mikrobiyol Bul. 2021; 55(4):648-55.
  38. de Almeida Jr JN, Brandão IB, Francisco EC, de Almeida SLR, de Oliveira Dias P, Pereira FM, et al. Axillary Digital Thermometers uplifted a multidrug‐susceptible Candida auris outbreak among COVID‐19 patients in Brazil. Mycoses. 2021; 64(9):1062-72.
  39. Goravey W, Ali GA, Ali M, Ibrahim EB, Al Maslamani M, Hadi HA. Ominous combination: COVID‐19 disease and Candida auris fungemia—Case report and review of the literature. Clin Case Rep. 2021; 9(9):1-9.
  40. Hanson BM, Dinh AQ, Tran TT, Arenas S, Pronty D, Gershengorn HB, et al. Candida auris invasive infections during a COVID-19 case surge. Antimicrob Agents Chemother. 2021; 65(10):1-6.
  41. Pilato VD, Codda G, Ball L, Giacobbe DR, Willison E, Mikulska M, et al. Molecular epidemiological investigation of a nosocomial cluster of c. auris: evidence of recent emergence in Italy and ease of transmission during the COVID-19 Pandemic. J Fungi (Basel). 2021; 7(2):1-11.
  42. Schwartz RA, Kapila R. Cutaneous manifestations of a 21st century worldwide fungal epidemic possibly complicating the COVID‐19 pandemic to jointly menace mankind. Dermatol Ther. 2020; 33(4):1-4.
  43. Corcione S, Montrucchio G, Shbaklo N, De Benedetto I, Sales G, Cedrone M, et al. First cases of candida auris in a referral intensive care unit in piedmont region, Italy. Microorganisms. 2022; 10(8):1521.
  44. Gautam S, Sharma G, Singla S, Garg S. Case Report: secondary hemophagocytic lymphohistiocytosis (shlh) and Candida auris Fungemia in Post-acute COVID-19 Syndrome: a clinical challenge. Front Med (Lausanne). 2022; 9:1-11.
  45. Hinrichs C, Wiese‐Posselt M, Graf B, Geffers C, Weikert B, Enghard P, et al. Successful control of Candida auris transmission in a German COVID‐19 intensive care unit. Mycoses. 2022; 65(6):643-9.
  46. Spruijtenburg B, Badali H, Abastabar M, Mirhendi H, Khodavaisy S, Sharifisooraki J, et al. Confirmation of fifth Candida auris clade by whole genome sequencing. Emerg Microbes Infect. 2022; 11(1):2405-11.
  47. Allaw F, Haddad SF, Habib N, Moukarzel P, Naji NS, Kanafani ZA, et al. COVID-19 and C. auris: A case-control study from a Tertiary Care Center in Lebanon. Microorganisms. 2022; 10(5):1-17.
  48. Chow NA, Muñoz JF, Gade L, Berkow EL, Li X, Welsh RM, et al. Tracing the evolutionary history and global expansion of Candida auris using population genomic analyses. MBio. 2020; 11(2):1-15.
  49. Heaney H, Laing J, Paterson L, Walker AW, Gow NA, Johnson EM, et al. The environmental stress sensitivities of pathogenic Candida species, including Candida auris, and implications for their spread in the hospital setting. Med Mycol. 2020; 58(6):744-55.
  50. Wickes BL. Analysis of a Candida auris outbreak provides new insights into an emerging pathogen. J Clin Microbiol. 2020; 58(4):1-4.
  51. Horton MV, Nett JE. Candida auris infection and biofilm formation: going beyond the surface. Curr Clin Microbiol Rep. 2020; 7(3):51-56.
  52. Kean R, Brown J, Gulmez D, Ware A, Ramage G. Candida auris: a decade of understanding of an enigmatic pathogenic yeast. J Fungi (Basel). 2020; 6(1):1-13.
  53. Mulet Bayona JV, Tormo Palop N, Salvador García C, Fuster Escrivá B, Chanzá Aviñó M, Ortega García P, et al. Impact of the SARS-CoV-2 Pandemic in Candidaemia, Invasive Aspergillosis and Antifungal Consumption in a Tertiary Hospital. J Fungi (Basel). 2021; 7(6):1-9.
  54. Lai CC, Chen SY, Ko WC, Hsueh PR. Increased antimicrobial resistance during the COVID-19 pandemic. Int J Antimicrob Agents. 2021; 57(45):1-7.
  55. Roudbary M, Kumar S, Kumar A, Černáková L, Nikoomanesh F, Rodrigues CF. Overview on the prevalence of fungal infections, immune response, and microbiome role in COVID-19 patients. J Fungi (Basel). 2021; 7(9):1-28.
  56. Ben-Ami R, Olshtain-Pops K, Krieger M, Oren I, Bishara J, Dan M, et al. Antibiotic exposure as a risk factor for fluconazole-resistant Candida bloodstream infection. Antimicrob Agents Chemother. 2012; 56(5):2518-23.
  57. Lin MY, Carmeli Y, Zumsteg J, Flores EL, Tolentino J, Sreeramoju P, et al. Prior antimicrobial therapy and risk for hospital-acquired Candida glabrata and Candida krusei fungemia: a case-case-control study. Antimicrob Agents Chemother. 2005; 49(11):4555-60.
  58. Mason KL, Erb Downward JR, Mason KD, Falkowski NR, Eaton KA, Kao JY, et al. Candida albicans and bacterial microbiota interactions in the cecum during recolonization following broad-spectrum antibiotic therapy. Infect Immun. 2012; 80(10):3371-80.
  59. Romo JA, Kumamoto CA. On commensalism of Candida. J Fungi (Basel). 2020; 6(1):1-14.
  60. Arastehfar A, Carvalho A, Nguyen MH, Hedayati MT, Netea MG, Perlin DS, et al. Covid-19-associated candidiasis (CAC): an underestimated complication in the absence of immunological predispositions?. J Fungi (Basel). 2020; 6(4):1-13.
  61. Health UDo, Services H. CDC. Antibiotic resistance threats in the United States, 2019. US Department of Health and Human Services, Centres for Disease Control and Prevention; 2019.
Volume 8, Issue 3
September 2022
Pages 44-50
  • Receive Date: 26 May 2022
  • Revise Date: 12 October 2022
  • Accept Date: 15 October 2022
  • First Publish Date: 15 October 2022