Journal of Medical Mycology 31 (2021) 101168

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Journal of Medical Mycology

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Case report

COVID-19 and Candida duobushaemulonii superinfection: A case report

Bassem Awadaa,1, Walid Alamb,1,*, Maria Chalfounc, George Arajd, Abdul Rahman Bizria
a
Department of Internal Medicine, Division of Infectious Diseases, American University of Beirut Medical Center, Beirut, Lebanon
b
Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
c
Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon
d
Department of Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon

A R T I C L E I N F O A B S T R A C T

Article History: Introduction: Critically ill COVID-19 patients are at high risk for nosocomial bacterial and fungal infections
Received 1 March 2021 due to several predisposing factors such as intensive care unit stay, mechanical ventilation, and broad-spec-
Revised 11 June 2021 trum antibiotics. Data regarding multidrug resistant (MDR) Candida species in COVID-19 patients is scarce,
Accepted 11 June 2021
and nonexistent regarding Candida duobushaemulonii superinfections.
Available online 16 June 2021
Case description: A 34-year-old male presented to our institution with acute respiratory distress syndrome
(ARDS) due to COVID-19 infection and developed Candida duobushaemulonii fungemia after multiple courses
Keywords:
of antibiotics and prolonged mechanical ventilation. He died after recurrent pneumothorax led to respiratory
COVID-19
Candida duobushaemulonii
failure and cardiac arrest.
ICU Discussion: Bacterial and fungal infections are common complications of viral pneumonia in critically ill
Multidrug resistance patients. Data regarding these infections in COVID-19 patients has been poorly studied with only a few cases
Mechanical ventilation reporting secondary infection, mostly without identifying specific pathogens. Prolonged hospital stays, inva-
Broad-spectrum antibiotics sive interventions (central venous catheter, mechanical ventilation), and the use of broad-spectrum antibiot-
ics in COVID-19 infections could carry a high risk of bacterial and/or fungal superinfections.
Conclusion: Strategies to improve outcome in COVID-19 ICU patients should include early recognition of can-
didemia and appropriate antifungal therapy.
© 2021 SFMM. Published by Elsevier Masson SAS. All rights reserved.

Introduction and is emerging as a rare cause of invasive fungal infections with a

multidrug resistant profile [5].
1.9 million deaths globally have been linked to the COVID-19 pan- We report a case of Candida duobushaemulonii candidemia in a
demic with 88 million cumulative cases reported as of January 12, patient with prolonged ICU stay due to a complicated case of severe
2021 [1]. Critically ill patients with COVID-19 are at high risk of COVID-19 infection. To our knowledge, no data exists in the literature
developing acute respiratory distress syndrome (ARDS), requiring in this setting.
intensive care and mechanical ventilation, predisposing them to nos-
ocomial bacterial and fungal infections [2,3]. In India, candidemia Case description
affected 15 critically ill coronavirus disease patients admitted to an
intensive care unit (ICU), with two third of cases attributed to multi- A 34-year-old male without a history of comorbidities presented
drug resistant Candida auris [4]. Data regarding multidrug resistant to our tertiary care center in Beirut, Lebanon from Gabon, Central
(MDR) Candida species in COVID-19 patients is scarce, and nonexis- Africa with severe COVID-19 infection and ARDS. He was hospitalized
tent regarding Candida duobushaemulonii superinfections. Candida in Gabon and his medical course was complicated by acute pulmo-
duobushaemulonii is a yeast that is closely related to Candida auris nary embolism treated with recombinant tissue plasminogen activa-
tor (rtPA), with subarachnoid hemorrhage (SAH) developing as
sequela, and a superimposed bacterial pneumonia for which he
Abbreviations: rtPa, recombinant tissue plasminogen activator; DTA, deep tracheal
aspirate; COVID-19, coronavirus disease 2019; ARDS, acute respiratory distress syn- received levofloxacin and imipenem.
drome; S. maltophilia, Stenotrophomonas maltophilia; TMP-SMX, trimethoprim/sulfa- Patient presented 16 days post his COVID-19 infection to our insti-
methoxazole; MIC, minimum inhibitory concentration; CAUTI, catheter associated tution. He was intubated, sedated and off vasopressors. His labs are
urinary tract infection; VAP, ventilator associated pneumonia reported and summarized in (Table 1) and were significant for ele-
* Corresponding author at: Department of Internal Medicine, American University of
Beirut Medical Center, Hamra, Beirut, Lebanon.
vated pro-inflammatory markers (d-dimer, ferritin, CRP, progressive
E-mail address: [email protected] (W. Alam). thrombocytosis) and neutrophilia (80-90%). SARS-CoV-2 PCR was
1
Joint first authors. positive on admission. CT chest showed severe ARDS with typical

https://doi.org/10.1016/j.mycmed.2021.101168
1156-5233/© 2021 SFMM. Published by Elsevier Masson SAS. All rights reserved.
B. Awada, W. Alam, M. Chalfoun et al. Journal of Medical Mycology 31 (2021) 101168

Table 1
Brief summary of the lab results during the patient’s stay.

16/6/2020 20/6/2020 26/6/2020 4/7/2020 16/7/2020 26/7/2020 2/8/2020 10/8/2020

WBC (/cu.mm) 8,600 12,100 11,900 10,300 7,600 9,200 9,200 13,000
Neutrophils 93% 91% 85% 79% 82% 90% 90% 88%
Lymphocytes 4% 3% 6% 9% 10% 7% 6% 5%
Hb (g/dl) 10.6 10.8 10.3 9.5 8.5 8.5 8.4 9.4
Platelets (/cu.mm) 164,000 194,000 366,000 360,000 355,000 352,000 401,000 562,000
Cr (mg/) 1 0.6 0.6 0.4 0.3 0.2 0.2 0.2
Na (mmol/L) 144 141 146 141 138 136 135 137
K (mmol/L) 4.8 5 5.3 4.4 4.1 4.8 4 4.5
Chloride (mmol/L) 100 102 106 92 90 92 90 93
SGPT (IU/L) 61
SGOT (IU/L) 86
Alkaline phosphate (IU/L) 96
Bilirubin total (mg/dl) 0.7
Bilirubin direct (mg/dl) 0.5
Ferritin (ng/ml) 2,207 1109 820 667
D dimer (ng/ml) 3,862 2,160 1,825
INR 1.9 1.2
PTT (seconds) 29.6 27.1
Procalcitonin (ng/ml) 6.9 0.7 0.06 0.16 0.32 0.07
CRP (mg/L) 217.3 21.1 13.2 31 27.7 24.8 43.9 85.6
Troponin T (ng/ml) 0.06
Blood parasite smear Negative
COVID-19 PCR Positive

picture of COVID-19 infection (Fig. 1). Due to the lack of data regard- Antibiotics were discontinued following completion of fourteen
ing local resistance in Gabon and the patient’s recent history of multi- days of therapy and clinical improvement. Antifungal therapy with
ple antibiotic use and long ICU stay, the decision was made to start fluconazole was kept. Patient initially improved clinically but he
meropenem for superimposed pneumonia. Blood, urine, and deep developed hypotension a week later with elevation of his inflamma-
tracheal aspirate (DTA) cultures were taken beforehand. DTA cultures tory markers (Table 1). Blood cultures were taken from his central
grew Stenotrophomonas maltophilia sensitive to levofloxacin and tri- line and peripheral lines. He was started on inhaled colistin and tige-
methoprim/sulfamethoxazole (TMP-SMX), and patient was subse- cycline. Central line blood cultures grew Candida non-albicans, and
quently started on levofloxacin. He was shifted to TMP-SMX after a caspofungin was started. Speciation and susceptibility testing
new isolate of S. maltophilia from DTA was found to be resistant to revealed Candida duobushaemulonii, susceptible to flucytosine
levofloxacin. He developed catheter acquired urinary tract infection (Table 2). Susceptibility data for other anti-fungals is not available.
(CAUTI) and ventilator associated pneumonia (VAP) and progressed His stay was again complicated by recurrent pneumothoraces leading
into septic shock. He was started on amikacin and tigecycline as his to respiratory failure followed by cardiac arrest and death.
cultures grew carbapenem-resistant Enterobacteriaceae (CRE) Entero-
bacter cloacae with high minimal inhibitory concentrations (MICs) of
Discussion
ceftazidime/avibactam and carbapenems. Five days later, new DTA
and urine cultures were taken and were positive for Candida non-
Bacterial and fungal infections are common complications of viral
albicans, mainly multi-sensitive Candida parapsilosis in the urine and
pneumonia, especially in critically ill patients, leading to increased
Candida lusitaniae in the DTA. He was subsequently started on intra-
mortality rate [6]. Nosocomial fungal infections, particularly Candidi-
venous fluconazole.
asis and Aspergillosis, are frequently seen in immunocompromised
patients that exhibit predisposing risk factors such as neutropenia,
compromised neutrophil function, cell-mediated immune dysfunc-
tion, and disruption of mucosal integrity [7,8]. In 2017, a team in
France analyzed the proportion of fungemia associated with uncom-
mon yeast species and the predisposing factors in 338 cases.
The study demonstrated the existence of 35 species with different
susceptibility profiles to antifungal drugs and a predisposition to
patients who are immunocompromised or have received prior anti-
fungal therapy [9]. COVID-19 has been found to cause immune dysre-
gulation and hyperinflammation in severe cases potentially
contributing to the development of nosocomial infections in severely
ill patients [10−12]. Nevertheless, limited data regarding bacterial
and fungal infections in COVID-19 patients has been published [6].

Table 2
Fungal susceptibility of Candida duobushaemulonii based on Vitek
testing and interpretation.

Candida duobushaemulonii Interpretation

Amphotericin B 8 ug/mL Resistant

Fig. 1. CT chest showing diffuse ground gland abnormalities with peripheral consoli- Flucytosine ≤ 1 ug/mL Susceptible
dations. Findings suggestive of severe COVID-19 infection. Voriconazole 4 ug/mL Resistant

2
B. Awada, W. Alam, M. Chalfoun et al. Journal of Medical Mycology 31 (2021) 101168

Although the mechanism is still unclear, patients with severe COVID- Authors’ contribution
19 are at similar risk of invasive fungal infections as patients with
severe influenza [13]. However, a review of the literature showed Dr. Bassem Awada contributed to the investigation and writing
that even when secondary infection data was available, the antibiot- the original draft.
ics use rate (94%−100%) was much higher than the reported inci- Dr. Walid Alam contributed to the investigation, writing the origi-
dence of secondary infection (10%−15%), potentially increasing the nal draft, and review and editing.
risk of fungal infections due to endogenous fungi such as Candida Maria Chalfoun contributed to writing the original draft.
species [6,7]. A meta-analysis found three studies that reported four Dr. George Araj contributed to the investigation and formal
fungal pathogens in COVID-19 patients: Candida albicans, Candida analysis.
glabrata, Aspergillus flavus and Aspergillus fumigatus [14]. Dr. Abdul Rahman Bizri was responsible for conceptualization and
No data in the literature currently exists regarding Candida duo- contributed to the review and editing.
bushaemulonii superinfection in COVID-19 patients. A member of the
Candida haemulonii species complex, Candida duobushaemulonii has Funding
been found to be invasive and resistant to drugs [15]. In 2018, a geno-
mic study found that Candida auris and Candida duobushaemulonii No funding was received for this work.
were closely related phylogenetically [16]. Recently, a study found
that six patients admitted to the ICU for severe COVID-19 were colo-
nized by Candida auris and four of them developed candidemia. Test- Ethics and patient consent
ing showed resistance of all strains to amphotericin-B and azoles but
susceptibility to echinocandins [17]. The increased reports of Candida We acknowledge that approval from the American University of
auris co-infection in severely ill COVID-19 patients and the close phy- Beirut ethical committee was sought where necessary, and guidelines
logenetic relation between Candida auris and Candida duobushaemu- on consent were followed. Informed consent was obtained from the
lonii could signify that Candida duobushaemulonii superinfection is patient’s family.
underdiagnosed. In fact, in a study done by Jurado-Martin et al, 150
isolates were reanalyzed using novel PCR approaches to identify mul- Conflict of Interest
tidrug-resistant complex of uncommon Candida species that were
missed by regular phenotypic testing [18]. The study found that the The authors have no conflict of interest.
prevalence of C. duobushaemulonii was likely underestimated and
that the species was initially associated with superficial infections Acknowledgment
before emerging as a cause of invasive candidiasis. The identified iso-
lates also showed reduced susceptibility to fluconazole, itraconazole, None
and amphotericin B [18]. In our case, the pathogen was found to be
susceptible to flucytosine with casponfungin already having been
started empirically, but speciation and susceptibility results had References
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