To the Editor,
Since its emergence in December 2019, the rapid spread of coronavirus disease 2019
(COVID-19) has necessitated the expansion and transformation of healthcare facilities
worldwide to accommodate the constantly increasing numbers of patients. This situation
has provided a potential ground for the transmission of nosocomial infections [1].
Candida auris is a multidrug-resistant fungal pathogen with the capability for nosocomial
transmission. Some studies have suggested an increased risk for Candida sp. in COVID-19
patients, resulting in poor outcomes [2,3].
Here we describe an outbreak of C. auris which started in a non-COVID-19 patient at
the end of May 2020 (reported previously [4]). This occurred during the transition
of the hospital to an exclusive COVID-19 facility; the infection later spread to 12
patients in the intensive care unit (ICU).
We collected the clinical data of all the patients admitted to the hospital from April
2020 to the present date. Characteristics of the patients with a diagnosis of C. auris
infection were analysed. This study was approved by the Research Ethics Committee
of the Hospital San José Tec-Salud (registration number: P000353-COVID-19-TecSalud-CS001).
C. auris strains from 12 patients and three environmental isolates from their bedrooms
were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)
mass spectrometry (Bruker Daltonics, MALDI Biotyper) and confirmed by multilocus sequence
typing of the ITS1-5.8S-ITS2, D1/D2, RPB1 and RPB2 regions. Sequences were aligned
and analysed by MEGA v.7.0.26 and a dendrogram was delineated. Antifungal susceptibility
testing for amphotericin B (AMB), fluconazole (FLU), voriconazole (VRC), posaconazole
(POS), itraconazole (ITC), isavuconazole (ISA), anidulafungin (ANF) and caspofungin
(CAS) was performed using the Clinical and Laboratory Standards Institute (CLSI) broth
microdilution method M27-A3/S4.
Our team reported the first case of C. auris infection in May 2020. At that time the
hospital was transitioning from a general hospital to an exclusive COVID-19 facility
which included expansion of the ICU to four areas with 60 beds; this was completed
as the last non-COVID-19 patient was discharged.
Three months later an outbreak of COVID-19-associated Candida auris infections started
in three of the ICUs, affecting 12 patients. All the affected patients were under
mechanical ventilation, had peripherally inserted central lines (PICCs), urinary catheters
and prolonged hospital stay (20–70 days). C. auris was isolated from blood in six
patients (6/12; 50%), from urine in eight (8/12; 66.6%), and from both sites in two
(2/12; 16.6%). Mortality was 83.3% (5/6) among the patients with candidaemia (Table 1
A).
Table 1
(A) Clinical characteristics of 12 patients with C. auris infection and COVID-19 pneumonia.
(B) MLST and antifungal susceptibility results of the C. auris isolates from the patients
and surface sampling from an infusion pump (13) and bed rails (14 and 15)
Table 1
A. Clinical characteristics of 12 patients with C. auris infection and COVID-19 pneumonia.
No. Patient
1
2
3
4
5
6
7
8
9
10
11
12
Age
51
54
55
51
64
64
54
60
58
36
66
46
Sex
M
M
M
M
M
M
F
F
M
M
M
M
Co-infections
Pseudomonas aeruginosa
Pseudomonas aeruginosa,
Klebsiella pneumoniae
Pseudomonas aeruginosa, Candida glabrata
Pseudomonas aeruginosa, Candida glabrata, Enterococcus faecalis
Pseudomonas aeruginosa
Candida glabrata
None
Pseudomonas aeruginosa
Pseudomonas aeruginosa
Cytomegalovirus
Pseudomonas aeruginosa,
Stenotropho-monas maltofilia
None
Risk factors
HBP, DM2, Obesity
HBP, DM2, Obesity, Asthma
HBP, DM2,CAD
Obesity
AKI
HBP, Smoking, Obesity, Hipothyroidism
HBP, Obesity.
Obesity
HBP, Obesity
DM2, Obesity
HBP, DM2, CAD, VHD
Obesity
Antibiotics
CTR, CAZ/ABI, MEM, LZD
MEM, LZD, VAN, TZP, VAN,CTZ/TAZO
CRO, MEM, LZD, CAZ/ABI
CRO, MEM, LZD, CTZ/TZP, CST
CRO, LZD, CAZ, MEM, CAZ/ABI
CRO, CAZ,TZP
AZM, LZD, CRO, VAN, CTZ/TZP
CRO, LZD, CAZ, CAZ/ABI, VAN
CTZ/TZP, VAN, CRO, CST
CRO, LZD, CAZ, MEM, VGV
TZP, MEM, CTZ/TZP, METRO
CRO, MEM, CAZ/ABI, LZD
SARS-CoV-2 treatment
LPV/RTV, RBV, BARI, PLASMA
LPV/RTV, RBV, BARI
LPV/RTV, RBV, BARI
LPV/RTV, RBV, BARI, PLASMA
LPV/RTV, RBV, BARI
LPV/RTV, RBV, BARI, TOCI, PLASMA
LPV/RTV, RBV, BARI,
LPV/RTV, RBV, BARI, PLASMA
LPV/RTV, RBV, BARI
LPV/RTV, RBV, BARI, TOCI, PLASMA
LPV/RTV, RBV, BARI
LPV/RTV, RBV, BARI
Steroids
Dex 6mg QDHidro 100mg BID
Dex 6mg QDMetil 60mg BID
Dex 6mg QDHidro 100 BID
Dex 6mg QD
Metil 40mg BID
Metil40mg BID
Dex 6mgQD
Metil 125mg BID
Hidro100mgTID
Metil 60mg BIDHidro 100mg TID
Dex 6mg QDMetil 60mg BID
Dex 6mg QDMetil 60mg BID
Cumulative dose of steroids (mg prednisone)
1480mg
1580
1360
1440
1300
1000
1240
5000
2025
2550
1320
3280
Antifungals
CAS, ANF
ISA, CAS
ANF
ISA, ANF
CAS, VRC, AMB (intravesical)
ANF, ISA
AMB, CAS, VRC
CAS, ANF, VRC
ANF
CAS
VRC, CAS
VRC, CAS
Interleukin 6 (pg/mL)
270.5
NA
89.56
192.2
9.29
44.13
798.3
NA
235.9
203.6
NA
NA
D dimer (ng/mL)
831
383
254
2000
5516
150
2117
143
16,111
448
280
84
Ferritin (ng/mL)
1563
3187
1701
11,007
4163
3694
1199
658
2235
3292
2030
1307
Culture
Blood
Urine
Blood
Urine
Blood and Urine
Blood, PIC line and Urine
Blood
Urine
Urine
Urine
Urine
Blood
∗Days to 1st. positive culture
37
17
29
36
13
10
31
16
27
22
11
27
Outcome
Died
Survived
Died
Died
Died
Died
Died
Died
Died
Survived (Hospital transfer)
Survived
Survived
B. MLST and antifungal susceptibility results of the C. auris isolates from the patients
and surface sampling from an infusion pump (13) and bed rails (14 and 15).
No. Isolate
GenBank accession numbers (ITS-D1/D2-RPB1-RPB2)
ST cluster
MIC (μg/mL)
AMB
FLC
VRC
POS
ITC
ISA
ANF
CAS
1
MW087107-MW089312-MW091400- MW113720
IV
4
64
1
0.5
2
0.5
1
1
2
MW087108-MW089313-MW091401- MW113721
IV
4
16
0.25
<0.03
0.25
0.06
1
1
3
MW087109-MW089314-MW091402- MW113722
IV
2
16
<0.03
<0.03
0.5
0.25
0.5
0.5
4
MW087110-MW089315-MW091403- MW113723
IV
2
16
0.5
0.06
2
0.5
1
1
5
MW087111-MW089316-MW091404- MW113724
IV
2
64
0.25
0.06
0.125
0.125
0.5
1
6
MW087112-MW089317-MW091405- MW113725
IV
2
16
0.125
0.03
0.25
1
1
0.5
7
MW087113-MW089318-MW091406- MW113726
IV
4
64
0.5
0.5
1
0.5
0.5
1
8
MW087114-MW089319-MW091407- MW113727
IV
2
32
0.25
0.03
0.5
0.125
0.5
1
9
MW087115-MW089320-MW091408- MW113728
IV
4
64
1
0.125
0.50
0.125
0.5
1
10
MW087116-MW089321-MW091409- MW113729
IV
4
32
0.125
0.125
0.125
0.06
0.5
1
11
MW087117-MW089322-MW091410- MW113730
IV
4
8
0.06
<0.03
0.06
0.125
4
0.5
12
MW087118-MW089323-MW091411- MW113731
IV
2
8
0.125
<0.03
0.06
0.125
0.5
1
13
MW087119-MW089324-MW091412- MW113732
IV
4
32
0.06
0.06
0.125
0.25
1
2
14
MW087120-MW089325-MW091413- MW113733
IV
4
16
0.125
0.06
0.125
0.25
2
0.5
15
MW087121-MW089326-MW091414- MW113734
IV
4
32
0.125
0.25
0.5
0.5
1
1
CTR: ceftaroline; CAZ: ceftazidime; CAZ/ABI: ceftazidime/abivactam; CRO: ceftriaxone;
CTZ/TZP: ceftolozane/tazobactam; CST: colistin; AZM: azithromycin; VAN: vancomycin;
MEM: meropenem; MTZ: metronidazole; TZP: piperacillin/tazobactam; ISA: isavuconazol;
ANF: anidulafungin; CAS: caspofungin; AMB: amphotericin B; VRC: voriconazole; LPV/RTV:
lopinavir/ritonavir; VGV: valgancyclovir; Metil: methylprednisolone; Hidro: hydrocortisone,
DEX: dexametasone; BARI: baricitinib; TOCI: tocilizumab; CAD: coronary artery disease;
VHD: valvular heart disease; HBP: high blood pressure; DM2: diabetes mellitus type
2; AKI: acute kidney injury; NA: not available; PIC: peripherally inserted central
catheter.
AMB: amphotericin B; FLC: fluconazole; VRC: voriconazole; POS: posaconazole; ITC:
itraconazole; ISA: isavuconazole; ANF: anidulafungin; CAS: caspofungin; MIC: minimal
inhibitory concentration; ST: sequence typing.
∗
Number of days elapsed from hospital admission to the first positive culture for C. auris.
Sequences of the genes used for the 15 C. auris isolates clustered together in the
dendrogram performed with the sequence previously reported from a non-COVID-19 patient,
which belonged to the Clade IV (South American) [4], suggesting a very close relationship.
Antifungal susceptibility testing showed that all the isolates (15/15) were resistant
to AMB (MIC ≥2 μg/mL), just one isolate was resistant to ANF (MIC ≥4 μg/mL), one to
CAS (MIC ≥2 μg/mL) and eight isolates (8/15; 53.3%) were resistant to FLU (MIC ≥32
μg/mL). Eight isolates were multidrug-resistant (resistance to two major classes of
antifungals) (Table 1B).
Numerous reports have described COVID-19 co-infections by fungal pathogens, especially
in critically ill patients. As stated in the work of Arasthefar et al. [5], classic
risk factors commonly found in these patients include diabetes mellitus, use of multiple
antibiotics, renal failure, and use of central venous catheters, but other factors
specifically associated with COVID-19—such as excessive corticosteroid use, which
has an immunosuppressive effect on neutrophils and macrophages—might also contribute
to this problem. Nonetheless, a lot of interest still exists in elucidating a relationship
between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune response
and predisposition to Candida infection [2].
In our report 12 patients have presented COVID-19-associated C. auris infection, and
so far only three environmental samples have yielded this pathogen. The prolonged
lag between the first case 3 months ago and current cases is thought to be due to
measures taken during the transformation process from a general hospital to a COVID-19-exclusive
facility, such as reinforcement of hand washing compliance and use of personal protective
equipment (PPE). Chowdhary et al. [6] theorized that transmission of COVID-19-associated
C. auris by health personnel is unlikely because of the use of PPE. The 15 isolates
of C. auris were non-susceptible to AMB and FLU, which are the main antifungal drugs
used in most of the hospitals in Mexico.
This study has some limitations as it was conceived as a description of an outbreak;
as such, there is no control group, and findings may not be generalizable to other
populations. Nonetheless mortality in patients with COVID-19-associated C. auris bloodstream
infection was exceedingly high, five of six patients died even with antifungal treatment;
strict control of risk factors, such as central line care bundles, corticosteroids
and antibiotic stewardship, must therefore be implemented to avoid the lethal combination
of these two emergent infectious threats.
Author contributions
HV-L, RJT-R and GMG contributed to drafting and revising the article, as well as in
the conception and design of the study. RL-M, MTR-E and NG-Ch contributed to the acquisition
and interpretation of data. FC-L, MCA-B, CEG-L and GT-A contributed to revision and
final approval of the report. MFM-R participated in the analysis and interpretation
of data, drafting and final approval of the version to be submitted.
Transparency declaration
All authors declare no conflicts of interest. This work was supported by internal
resources of the department.