Increased incidence of candidemia in critically ill patients during the Coronavirus Disease 2019 (COVID-19) pandemic

Papadimitriou-Olivgeris, Matthaios; Kolonitsiou, Fevronia; Kefala, Sotiria; Spiliopoulou, Anastasia; Aretha, Diamanto; Bartzavali, Christina; Siapika, Argyro; Marangos, Markos; Fligou, Fotini

doi:10.1016/j.bjid.2022.102353

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Original Article • Braz J Infect Dis 26 (02) • 2022 • https://doi.org/10.1016/j.bjid.2022.102353 copy

Increased incidence of candidemia in critically ill patients during the Coronavirus Disease 2019 (COVID-19) pandemic

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background

Patients with severe Coronavirus Disease 2019 (COVID-19) are treated with corticosteroids.

Aim

We aimed to evaluate the role of corticosteroid treatment in candidemia development during the COVID-19 pandemic.

Methods

This retrospective study was conducted in a Greek ICU, from 2010 to August 2021, encompassing a pre-pandemic and a pandemic period (pandemic period: April 2020 to August 2021). All adult patients with candidemia were included.

Results

During the study period, 3,572 patients were admitted to the ICU, 339 patients during the pandemic period, of whom 196 were SARS-CoV-2-positive. In total, 281 candidemia episodes were observed in 239 patients, 114 in the pandemic period. The majority of candidemias in both periods were catheter-related (161; 50.4%). The incidence of candidemia in the pre-pandemic period was 5.2 episodes per 100 admissions, while in the pandemic period was 33.6 (p < 0.001). In the pandemic period, the incidence among COVID-19 patients was 38.8 episodes per 100 admissions, while in patients without COVID-19 incidence was 26.6 (p= 0.019). Corticosteroid administration in both periods was not associated with increased candidemia incidence.

Conclusions

A significant increase of candidemia incidence was observed during the pandemic period in patients with and without COVID-19. This increase cannot be solely attributed to immunosuppression (corticosteroids, tocilizumab) of severe COVID-19 patients, but also to increased workload of medical and nursing staff.

Keywords
Candidemia; COVID-19; SARS-CoV-2; Critically-ill patients; ICU; Corticosteroids

	Pre-pandemic period (January 2010‒March 2020)			Pandemic period (April 2020‒August 2021)							p^a a Comparison between pandemic and pre-pandemic period.
	Without corticosteroids	With corticosteroids	All patients	Without COVID-19			COVID-19			All patients
	Without corticosteroids	With corticosteroids	All patients	Without corticosteroids	With corticosteroids	All patients	Without corticosteroids	With corticosteroids	All patients	All patients
ICU admissions	1337	1896	3233	85	58	143	14	182	196	339
Candidemia episodes	50	117	167	21	17	38	3	73	76	114
Candidemia episodes per 100 admissions	3.7	6.2	5.2	24.7	29.3	26.6	21.4	40.1	38.8	33.6	<0.001
Candidemia episodes per 1000 patient-days	2.6	6.6	4.5	13.0	14.9	13.8	17.4	19.2	19.1	16.9	<0.001
ICU mortality	20.1%	43.0%	30.0%	32.9%	43.1%	37.1%	42.9%	59.3%	58.2%	49.2%	<0.001

Characteristics	Pandemic period			Pre-pandemic period
Characteristics	Without COVID-19 (n= 38)	With COVID-19 (n= 77)	p^a a Comparison of pandemic patients with and without SARS-CoV-2 infection.	All patients (n= 167)	p^b b Comparison of pandemic patients without SARS-CoV-2 infection and pre-pandemic patients.	p^c c Comparison of pandemic patients with SARS-CoV-2 infection and pre-pandemic patients.
Demographics
Age (years)	63.5 (55.0‒72.0)	68.0 (59.0‒77.0)	0.063	58.0 (45.5‒71.0)	0.081	<0.001
Male sex	24 (63.2%)	48 (62.3%)	1.000	103 (61.7%)	1.000	1.000
Comorbidities
Diabetes mellitus	8 (21.1%)	22 (28.6%)	0.500	26 (15.6%)	0.468	0.024
Chronic obstructive pulmonary disease	3 (7.9%)	12 (15.6%)	0.379	17 (10.2%)	1.000	0.287
Chronic heart failure	1 (2.6%)	1 (1.3%)	1.000	7 (4.2%)	1.000	0.441
Chronic kidney disease	0 (0%)	5 (6.5%)	0.169	9 (5.6%)	0.215	0.770
Malignancy	4 (10.5%)	73 (9.1%)	0.217	23 (13.8%)	0.792	0.024
Immunosuppressive therapy (before admission)	1 (2.6%)	6 (7.8%)	0.422	13 (7.8%)	0.475	1.000
Obesity	9 (23.7%)	30 (39.0%)	0.143	38 (22.8%)	1.000	0.014
Overweight or obese	25 (65.8%)	67 (87.0%)	0.012	111 (66.5%)	1.000	0.001
Charlson Co-morbidity Index	3.0 (1.0‒7.0)	4.0 (2.0‒7.0)	0.107	3.0 (1.0‒5.0)	0.686	0.003
Hospitalization data
Corticosteroid administration	17 (44.7%)	73 (94.8%)	<0.001	117 (70.1%)	0.004	<0.001
Tocilizumab	0 (0%)	62 (80.5%)	<0.001	0 (0%)	‒	<0.001
Days at risk (from ICU admission to first episode of candidemia)^d d Among 239 episodes of candidemia.	21.5 (12.8‒39.0)	13.0 (6.0‒18.5)	<0.001	12.0 (6.0‒25.0)	0.003	0.426
Prior hospitalization	15 (39.5%)	54 (70.1%)	0.002	51 (30.5%)	0.337	<0.001
Days at risk (from hospital admission to first episode of candidemia) ^d d Among 239 episodes of candidemia.	30.0 (16.0‒49.0)	18.0 (12.0‒26.0)	<0.001	20.0 (10.0‒33.0)	0.005	0.756
Prior surgery (within a month form candidemia)	17 (44.7%)	6 (7.8%)	<0.001	71 (42.5%)	0.857	<0.001
Prior antimicrobial administration (within a month form candidemia)	38 (100%)	77 (100%)	‒	167 (100%)	‒	‒
Prior antifungal administration (within a month form candidemia)	26 (68.4%)	31 (40.3%)	0.006	101 (60.5%)	0.460	0.004
Azoles	4 (10.5%)	1 (1.3%)		26 (15.6%)
Fluconazole	4 (10.5%)	0 (0%)		25 (15.0%)
Voriconazole	0 (0%)	1 (1.3%)		2 (1.2%)
Echinocandins	24 (63.2%)	23 (29.9%)		92 (55.1%)
Anidulafungin	19 (50.0%)	20 (26.0%)		43 (25.7%)
Caspofungin	2 (5.3%)	2 (2.6%)		31 (18.6%)
Micafungin	5 (13.2%)	2 (2.6%)		25 (15.0%)
Liposomal-Amphotericin B	2 (5.3%)	11 (14.3%)		10 (6.0%)
Infection data
Type of candidemia
Unknown origin	14 (36.8%)	35 (45.5%)	0.427^e e Unknown origin compared to known origin candidemia.	62 (37.1%)	1.000^e e Unknown origin compared to known origin candidemia.	0.260^e e Unknown origin compared to known origin candidemia.
Catheter-related	21 (55.3%)	37 (48.1%)		84 (50.3%)
Secondary^f f 18 urinary tract infection, 9 intra-abdominal infection, 2 nosocomial meningitis.	3 (7.9%)	5 (6.5%)		21 (12.6%)
Candida spp
C. albicans	3 (7.9%)	25 (32.5%)	0.005^g g C. albicans compared to non-albicans Candida.	48 (28.7%)	0.004^g g C. albicans compared to non-albicans Candida.	0.552^g g C. albicans compared to non-albicans Candida.
C. parapsilosis	28 (73.7%)	39 (50.5%)		85 (50.9%)
C. glabrata (N. glabrataa)	5 (13.2%)	5 (6.5%)		14 (8.4%)
C. tropicalis	2 (5.3%)	5 (6.5%)		16 (9.6%)
Other species^h h Three C. lusitaniae (Clavispora lusitaniae), three C. krusei (Pichia kudriavzevii), one C. guilliermondii (Meyerozyma guilliermondii).	0 (0%)	3 (3.9%)		4 (2.4%)
Outcome
14-day mortality	11 (28.9%)	24 (31.2%)	1.000	38 (22.8%)	0.407	0.205
ICU mortality	19 (50.0%)	51 (66.2%)	0.107	93 (55.7%)	0.590	0.126

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[1] ⁎Corresponding author. E-mail address: Matthaios.Papadimitriou-Olivgeris@chuv.ch (M. Papadimitriou-Olivgeris).