Opportunistic Candida Infections in Critical COVID-19 Patients.

The frequency of opportunistic fungal infections in critically ill patients whose intensive care unit stays are prolonged due to coronavirus disease 2019 (COVID-19) is higher than in the period before COVID-19. We planned this study to improve the management of Candida infections by defining the Candida species, the etiology of infections caused by Candida species, and the antifungal susceptibility of the species. This retrospective study included patients older than 18 hospitalized in the intensive care unit (ICU) with a definitive diagnosis of COVID-19 for seven months (from March 2021 to September 2021). All study data that we recorded in a standard study form were analyzed with TURCOSA (Turcosa Analytics Ltd. Co., Turkey, www.turcosa.com.tr) statistical software. The patients were evaluated in four groups as group 1 (candidemia patients, n = 78), group 2 (candiduria patients, n = 189), group 3 (control patients, n = 57), and group 4 (patients with candidemia in urine cultures taken before Candida was detected in blood culture, n = 42). Candida species were identified using both conventional and VITEK® 2 (BioMérieux, France) methods. The antifungal susceptibility of fungi was determined using the E test method. Of the 5,583 COVID-19 patients followed during the study period, 78 developed candidemia, and 189 developed candiduria. The incidence of candidemia (per 1,000 admissions) was determined to be 1.6. As a result of statistical analysis, we found that Candida albicans was the dominant strain in candidemia and candiduria, and there was no antifungal resistance except for naturally resistant strains. Candida strains grown in blood and urine were the same in 40 of 42 patients. Mortality was 69.2% for group 1, 60.4% for group 2, and 57.8% for group 3. Antifungals were used in 34 (43.5%) patients from group 1, and 95 (50.2%) from group 2. In the candidemia group without antifungal use, mortality was quite high (77.2%). Antifungal use reduced mortality in the group 2 (p < 0.05). Length of ICU stays, comorbidity, broad-spectrum antibiotics, and corticosteroids are independent risk factors for candidemia in critically ill COVID-19 patients. Our study contributes to the knowledge of risk factors for developing COVID-19-related candida infections. The effect of candiduria on the development of candidemia in critically ill COVID-19 patients should be supported by new studies.

Risk Factors for Candidemia in Intensive Care Unit: A Matched Case Control Study from North-Western India.

Candidemia is one of the significant causes of mortality amongst critically ill patients in Intensive Care Units (ICUs). This study aimed to assess the incidence, risk factors and antifungal susceptibility pattern in candidemia cases admitted in ICU in a tertiary care hospital in Jaipur, Rajasthan from June 2021 to November 2021. Candida species isolated from blood culture of clinically suspected patients of sepsis were defined as candidemia cases. Blood culture and antifungal susceptibility testing were performed as per standard laboratory protocol. Analyses of risk factors was done between candidemia cases and matched controls in a ratio of 1 : 3. Forty-six candidemic cases and 150 matched controls were included in the study. C. tropicalis was the most prevalent species (22/46; 48%) followed by C. auris (8/46; 17%) and C. albicans (7/46; 15%). Candida species showed good sensitivity to echinocandins (97%) followed by amphotericin B (87%) and voriconazole (80%). In multivariate analysis, longer stay in ICU, presence of an indwelling device, use of immunosuppressive drugs and positive SARS-CoV-2 infection were associated with increased risk of candidemia. The constant evaluation of risk factors is required as prediction of risks associated with candidemia may help to guide targeted preventive measures with reduced morbidity and mortality.

Morbidity and mortality of hospitalised patients with candidemia during the various severe acute respiratory syndrome coronavirus 2 pandemic waves: A multicentre evaluation of 248 US hospitals.

BACKGROUND: Studies evaluating outcomes of COVID-19 patients with candidemia are limited and have only evaluated a single timepoint during the pandemic. OBJECTIVES: To compare the prevalence and outcomes associated with candidemia in patients based on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) status and through the various pandemic waves (1 March 2020-5 March 2022). PATIENTS/METHODS: Multicentre, retrospective cohort analysis of data from 248 US medical facilities using the BD Insights Research Database (Becton, Dickinson and Company, Franklin Lakes, New Jersey, USA). Eligible patients were adults aged ≥18 years who were hospitalised for >1 day, had a SARS-CoV-2 test and a positive blood culture for Candida spp. RESULTS: During the study time frame, there were 2,402,879 hospital admissions; 234,903 (9.7%) and 2,167,976 (90.3%) patients were SARS-CoV-2 positive and negative, respectively. A significantly higher rate of candidemia/1000 admissions was observed in SARS-CoV-2-positive patients compared to SARS-CoV-2-negative patients (3.18 vs. 0.99; p < .001). The highest candidemia rate for SARS-CoV-2-positive patients was observed during the Alpha SARS-CoV-2 wave (June 2020-August 2020) with the lowest candidemia rate during the Omicron wave. Hospital mortality was significantly higher in SARS-CoV-2-positive patients compared to SARS-CoV-2-negative patients with candidemia (59.6% vs. 30.8%; p < .001). When evaluating the mortality rate through the various pandemic waves, the rate for the overall population did not change. CONCLUSIONS: Our study indicates high morbidity and mortality for hospitalised patients with COVID-19 and candidemia which was consistent throughout the pandemic. Patients with COVID-19 are at an increased risk for candidemia; importantly, the magnitude of which may differ based on the circulating variant.

Determinants of fluconazole resistance and echinocandin tolerance in C. parapsilosis isolates causing a large clonal candidemia outbreak among COVID-19 patients in a Brazilian ICU.

Patients presenting with severe COVID-19 are predisposed to acquire secondary fungal infections such as COVID-19-associated candidemia (CAC), which are associated with poor clinical outcomes despite antifungal treatment. The extreme burden imposed on clinical facilities during the COVID-19 pandemic has provided a permissive environment for the emergence of clonal outbreaks of multiple Candida species, including C. auris and C. parapsilosis. Here we report the largest clonal CAC outbreak to date caused by fluconazole resistant (FLZR) and echinocandin tolerant (ECT) C. parapsilosis. Sixty C. parapsilosis strains were obtained from 57 patients at a tertiary care hospital in Brazil, 90% of them were FLZR and ECT. Although only 35.8% of FLZR isolates contained an ERG11 mutation, all of them contained the TAC1L518F mutation and significantly overexpressed CDR1. Introduction of TAC1L518F into a susceptible background increased the MIC of fluconazole and voriconazole 8-fold and resulted in significant basal overexpression of CDR1. Additionally, FLZR isolates exclusively harboured E1939G outside of Fks1 hotspot-2, which did not confer echinocandin resistance, but significantly increased ECT. Multilocus microsatellite typing showed that 51/60 (85%) of the FLZR isolates belonged to the same cluster, while the susceptible isolates each represented a distinct lineage. Finally, biofilm production in FLZR isolates was significantly lower than in susceptible counterparts Suggesting that it may not be an outbreak determinant. In summary, we show that TAC1L518F and FKS1E1393G confer FLZR and ECT, respectively, in CAC-associated C. parapsilosis. Our study underscores the importance of antifungal stewardship and effective infection control strategies to mitigate clonal C. parapsilosis outbreaks.

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

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.

Prevalence, risk factors, treatment and outcome of multidrug resistance Candida auris infections in Coronavirus disease (COVID-19) patients: A systematic review.

BACKGROUND: Candida auris is an emerging multidrug-resistant pathogen in intensive care settings (ICU). During the coronavirus disease 19 (COVID-19) pandemic, ICU admissions were overwhelmed, possibly contributing to the C. auris outbreak in COVID-19 patients. OBJECTIVES: The present systematic review addresses the prevalence, underlying diseases, iatrogenic risk factors, treatment and outcome of C. auris infections in COVID-19 patients. METHODS: MEDLINE, Scopus, Embase, Web of Science and LitCovid databases were systematically searched with appropriate keywords from 1 January 2020 to 31 December 2021. RESULTS: A total of 97 cases of C. auris were identified in COVID-19 patients. The pooled prevalence of C. auris infections (encompassing candidemia and non-candidemia cases) in COVID-19 patients was 14%. The major underlying diseases were diabetes mellitus (42.7%), hypertension (32.9%) and obesity (14.6%), followed by the iatrogenic risk factors such as a central venous catheter (76.8%%), intensive care unit (ICU) stay (75.6%) and broad-spectrum antibiotic usage (74.3%). There were no significant differences in underlying disease and iatrogenic risk factors among C. auris non-candidemia/colonisation and C. auris candidemia cases. The mortality rate of the total cohort is 44.4%, whereas, in C. auris candidemia patients, the mortality was 64.7%. CONCLUSION: This study shows that the prevalence of C. auris infections remains unchanged in the COVID-19 pandemic. Hospital-acquired risk factors may contribute to the clinical illness. Proper infection control practices and hospital surveillance may stop future hospital outbreaks during the pandemic.

Incidence and risk factors for COVID-19 associated candidemia (CAC) in ICU patients.

BACKGROUND: Critically ill COVID-19 patients have a high risk for the development of candidemia due to being exposed to both well-defined classical risk factors and COVID-19-specific risk factors in ICU. OBJECTIVES: In this study, we investigated the incidence of candidemia in critically COVID-19 patients, and the independent risk factors for candidemia. PATIENTS/METHODS: COVID-19 patients hospitalised in ICU during 1-year period (August 2020 to August 2021) were included. Clinical and laboratory characteristics of all COVID-19 patients, applied treatments, and invasive procedures that may predispose to candidemia were recorded. RESULTS: Of 1229 COVID-19 patients, 63 developed candidemia. Candidemia incidence rate was 4.4 episodes per 1000 ICU days. The most common species was Candida albicans (52.3%). Only 37 patients (58.7%) received antifungal therapy. The presence of central venous catheter (OR 4.7, 95% CI 1.8-12.2, p < .005), multifocal candida colonisation (OR 2.7, 95% CI 1.4-5.2, p < .005), a prolonged ICU stay (≥14 days) (OR 1.9, 95% CI 1.08-3-37, p < .05), the absence of chronic lung disease (OR 0.4, 95% CI 0.1-0.9, p < .05) and the absence of corticosteroid use (OR 0.3, 95% CI 0.14-0.52, p < .0001) were significantly associated with candidemia. CONCLUSIONS: Our study filled the knowledge gap in the literature about the impact of COVID-19-associated risk factors for the development of candidemia. The classical risk factors for candidemia had a significant effect on candidemia, and contrary to expectations, corticosteroids had a protective effect against the development of candidemia. The results of these studies showing interesting effects of corticosteroids in critically ill COVID-19 patients should be confirmed by further studies.

[First Case of COVID-19 Positive Candida auris Fungemia in Turkey]. / Türkiye'de Ilk COVID-19 Pozitif Candida auris Fungemi Olgusu.

Candida auris is a species of fungus that has gained importance in recent years owing to its ability to cause hospital infections and epidemics, resistant to antifungal agents and disinfection processes and frequently misidentified by commercial systems. Hospital outbreaks caused by C.auris have been reported from some countries. It has been determined that C.auris has lower virulence than Candida albicans; however, it is associated with high mortality rates in immunocompromised individuals. An increase in the incidence of invasive fungal infections which can lead to serious complications and death, has been identified in severe coronavirus-2019 (COVID-19) patients or immunocompromised individuals with underlying disease. Studies demonstrated an increase in the frequency of C.auris isolation in COVID-19 patients with candidemia. In this report, the first case of COVID-19 positive C.auris fungemia detected in Turkey was presented. A 71-year-old male patient with a history of myocardial infarction, diabetes mellitus, donation of a single kidney and lobectomy surgery due to lung cancer was hospitalized in the pandemic thoracic surgery service due to the findings consistent with viral pneumonia on thoracic computed tomography. Favipiravir 2 x 600 mg and intravenous dexamethasone 1 x 6 mg therapy was administered. The patient tested positive for SARS-CoV-2 polymerase chain reaction, and severe involvement of the left lung was detected in the following days. Antibiotics were administered, followed by insertion of a right jugular vein catheter and initation of tocilizumab. The patient was transferred to the intensive care unit due to increased respiratory distress. Yeast growth was detected in the patient's hemoculture. The yeast strain could not be identified using API ID 32C (bioMerieux, France) (Sacchromyces kluyveri, Candida sake, unacceptable profile), but was identified as C.auris using the VITEK MALDI TOF MS (bioMerieux, France) (99.9%) system and confirmed by sequencing. The minimum inhibitor concentration values were detected as 3 µg/ml for amphotericin B; > 256 µg/ml for fluconazole; 0.19 µg/ml for voriconazole; 0.19 µg/ml for itraconazole; 0.016 µg/ml for posaconazole; 1 µg/ml for caspofungin and 0.094 µg/ml for anidulafungin by using the antibiotic gradient method. The patient's initial treatment comprised meropenem 3 x 1 g, vancomycin 2 x 1 g, caspofungin 1 x 70 mg, and continued as caspofungine 1 x 50 mg after the loading dose, and vancomycin 1 x 1 g/48 hours from the third day of treatment. The patient died on the ninth day after developing candidemia. The present case is the first case of fungemia caused by C.auris in a COVID-19 positive patient in Turkey, and it emphasizes the need of caution for fungemia due to C.auris in intensive care units in our country which has a high COVID-19 incidence.

C. auris and non-C. auris candidemia in hospitalized adult and pediatric COVID-19 patients; single center data from Pakistan.

We compared candidemia due to Candida auris and other non-C.auris cases in hospitalized COVID-19 patients over a period of 9 months at our institution. Candidemia cases in all admitted patients (with or without COVID-19) from April to December 2020 were identified. Electronic records were accessed to record clinical data of COVID-19 patients with candidemia. For statistical analysis, independent samples Mann-Whitney U test was used for continuous and Fisher's exact test was used for categorical variables.A total of 26 candidemia cases (four C.auris, 22 non-C.auris) in 2438 admitted COVID-19 (10.7 per 1000 admissions) and 59 candidemia cases (six C.auris, 53 non-C.auris) in admitted non-COVID patients (8.2 per 1000 admission) were identified. The proportion of C.auris candidemia in COVID-19 and non-COVID-19 patients was 15.4 and 10%, respectively. 4/26 of COVID-19 candidemia patients were aged ≤ 15 years (10 months--15 years). Comparison of C.auris and non-C. auris candidemia cases reveal significant difference in prior antifungal exposure, present in 100% C. auris candidemia versus 27% non-C. auris candidemia patients (P-value 0.014). Although not statistically significant, C. auris candidemia patients had a longer stay in hospital before candidemia (20 vs. 9 days), higher isolation rate of multidrug resistant bacteria (100 vs. 50%), increased rate of prior colonization of Candida species (50 vs. 14%) and lower mean beta-d-glucan levels (48.73 pg/ml vs. 138.146 pg/ml). Both C. auris and non-C. auris COVID-19 patients had similar mortality rate (67 vs. 65%). A significant number of critically ill COVID-19 patients developed candidemia in our study highlighting the need for prompt diagnosis and management. LAY SUMMARY: 26 candidemia cases (4 Candida auris;22 non-C. auris) in COVID-19 patients (April-December 2020) are reported from Pakistan. Compared to non-C. auris, C. auris candidemia patients had higher prior antifungal exposure, longer hospital stay, higher rates of MDR bacteria and Candida colonization.

Clinical characteristics and risk factors for COVID-19-associated Candidemia.

Patients with COVID-19-associated candidemia (CAC) in an intensive care unit (ICU) were matched 1:2 with those without candidemia, based on ICU admission date and length of stay in ICU being at least equal to that before candidemia in the corresponding case. The incidence rate of CAC was 2.34 per 1000 ICU days. Eighty cases could be matched to appropriate controls. In the multivariate conditional logistic regression analysis, age (P 0.001), and sequential organ failure assessment score (P 0.046) were the only risk factors independently associated with CAC. Tocilizumab and corticosteroids therapy were not independently associated with candidemia. LAY SUMMARY: In COVID-19 patients who need medical care in an intensive care unit, the risk of developing bloodstream Candida infection is higher in older patients and in those who have a more severe critical illness. Treatment with steroids or tocilizumab does not seem to affect the risk of candida bloodstream infection in these patients.

Incidence of candidaemia in prolonged venovenous extracorporeal membrane oxygenation.

This single-centre retrospective study reports the dynamics of the incidence of candida bloodstream infection (CBSI) in 145 patients receiving venovenous extracorporeal membrane oxygenation (ECMO) for respiratory support between January 2014 and December 2018. The incidence rate and odds ratio (OR) of CBSI were calculated, stratified by week of ECMO exposure. Weekly incidence increased throughout the ECMO run, with an increasing trend in OR (P=0.005), and a window of continued risk after decannulation was observed. Of the 13 patients who developed CBSI, five (38%) received empirical micafungin treatment before positive culture due to clinical suspicion. There is a need for prospective studies aiming to improve ECMO diagnostic stewardship practices and discourage unnecessary antifungal prophylaxis or empiric management.

COVID-19 and invasive fungal coinfections: A case series at a Brazilian referral hospital.

BACKGROUND: COVID-19 co-infections have been described with different pathogens, including filamentous and yeast fungi. METHODOLOGY: A retrospective case series study conducted from February to December 2020, at a Brazilian university hospital. Data were collected from two hospital surveillance systems: Invasive fungal infection (IFI) surveillance (Mycosis Resistance Program - MIRE) and COVID-19 surveillance. Data from both surveillance systems were cross-checked to identify individuals diagnosed with SARS-CoV-2 (by positive polymerase chain reaction (PCR)) and IFI during hospital stays within the study period. RESULTS: During the study period, 716 inpatients with COVID-19 and 55 cases of IFI were identified. Fungal co-infection with SARS-CoV-2 was observed in eight (1%) patients: three cases of aspergillosis; four candidemia and one cryptococcosis. The median age of patients was 66 years (IQR 58-71 years; range of 28-77 years) and 62.5% were men. Diagnosis of IFI occurred a median of 11.5 days (IQR 4.5-23 days) after admission and 11 days (IQR 6.5-16 days) after a positive PCR result for SARS-CoV-2. In 75% of cases, IFI was diagnosed in the intensive care unit (ICU). Cases of aspergillosis emerged earlier than those of candidemia: an average of 8.6 and 28.6 days after a positive PCR for SARS-CoV-2, respectively. All the patients with both infections ultimately died. CONCLUSION: A low rate of COVID-19 co-infection with IFI was observed, with high mortality. Most cases were diagnosed in ICU patients. Aspergillosis diagnosis is highly complex in this context and requires different criteria.

Epidemiology and Mycology of Candidaemia in non-oncological medical intensive care unit patients in a tertiary center in the United States: Overall analysis and comparison between non-COVID-19 and COVID-19 cases.

The epidemiology and mycology of invasive candidiasis in the ICU is well-described in certain types of critically ill patients but not in others. One population that has been scarcely studied is non-neutropenic patients admitted specifically to medical ICUs. Even less is known about the broader category of medical ICU patients without active oncological disease. This group constitutes a very large share of the patients requiring critical care across the globe, especially in the era of the SARS-CoV-2 pandemic. We analysed medical ICU candidaemia episodes that occurred in non-oncological patients in our tertiary academic centre in the United States from May 2014 to October 2020 to determine the incidence and species distribution of the associated isolates. We then separately considered non-COVID-19 and COVID-19 cases and compared their characteristics. In the non-COVID-19 group, there were 38 cases for an incidence of 1.1% and rate of 11/1000 admissions. In the COVID-19 group, there were 12 cases for an incidence of 5.1% and rate of 51/1000 admissions. In the entire sample, as well as separately in the non-COVID-19 and COVID-19 groups,Candida albicans accounted for a minority of isolates. Compared to non-COVID-19 patients with candidaemia, COVID-19 patients had lower ICU admission SOFA score but longer ICU length of stay and central venous catheter dwell time at candidaemia detection. This study provides valuable insight into the incidence and species distribution of candidaemia cases occurring in non-oncological critically ill patients and identifies informative differences between non-COVID-19 and COVID-19 patients.

Increased incidence of candidemia in a tertiary care hospital with the COVID-19 pandemic.

BACKGROUND: The incidence of candidemia in our hospital has been stable over an 18-year period (1.3 episodes per 1000 admissions). Since March 2020, we have observed an increase in cases of candidemia. METHODS: In March 2020, the hospital was prepared to receive patients with COVID-19, with cancellation of elective procedures, discharge of less sick patients and the activation of beds for COVID-19. We compared the incidence of candidemia in 2 periods: from January 2019 to February 2020 (period 1) and from March to September 2020 (period 2). RESULTS: We diagnosed 41 episodes of candidemia, 16 in period 1 and 25 in period 2 (9 COVID-19 patients). Compared with non-COVID-19 patients, COVID-19 patients with candidemia were more likely to be under mechanical ventilation (100% vs. 34.4%, P < .001). The median number of monthly admissions in period 1 and 2 was 723 (interquartile range 655-836) and 523 (interquartile range 389-574), respectively. The incidence of candidemia (per 1000 admissions) was 1.54 in period 1 and 7.44 in period 2 (P < .001). In period 2, the incidence of candidemia (per 1000 admissions) was 4.76 if we consider only cases of candidemia in non-COVID-19 patients, 2.68 if we consider only cases of candidemia in COVID-19 patients and 14.80 considering only admissions of patients with COVID-19. CONCLUSIONS: The increase in the incidence of candidemia in our hospital may be attributed to 2 factors: a reduction in the number of admissions (denominator) and the occurrence of candidemia in COVID-19 patients.

Cutaneous manifestations of a 21st century worldwide fungal epidemic possibly complicating the COVID-19 pandemic to jointly menace mankind.

In view of the new viral COVID-19 pandemic, the fungal Candida auris epidemic still in progress worldwide highlights non-Candida albicans candidal infections. We describe an immunocompetent woman with a cutaneous manifestation of Candida parasilopsis fungemia, a prominent eschar, which proved to be the nidus for the candidemia. We stress the value of selectively removing eschars. C. parasilopsis and C. auris are increasingly important causes of sepsis and wound infections. We emphasize that commercially available biochemical-based tests may misidentify C. auris as C. parapsilosis, and stress the added danger of C. auris to critically ill-hospitalized COVID-19 patients. Any health care facility with evidence of infection or colonization with C. auris requires very close monitoring, since this fungus is a nosocomial threat comparable to SARS-CoV-2 in its mortality and fomite adhesiveness! Both organisms have the potential to be transmitted as nosocomial pathogens; health care workers need to follow strict CDC guidelines. During this COVID-19 pandemic, every health care facility should closely monitor for the possible deadly combination of the SARS-CoV-2 and C. auris. The identification of C. auris necessitates use of sophisticated technology not readily available to make this essential diagnosis since C. auris is multi-drug resistant and isolation precautions would become paramount.

Bloodstream infections in critically ill patients with COVID-19.

BACKGROUND: Little is known about the incidence and risk of intensive care unit (ICU)-acquired bloodstream infections (BSI) in critically ill patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: This retrospective, single-centre study was conducted in Northern Italy. The primary study objectives were as follows: (a) to assess the incidence rate of ICU-acquired BSI and (b) to assess the cumulative risk of developing ICU-acquired BSI. RESULTS: Overall, 78 critically ill patients with COVID-19 were included in the study. Forty-five episodes of ICU-acquired BSI were registered in 31 patients, with an incidence rate of 47 episodes (95% confidence interval [CI] 35-63) per 1000 patient-days at risk. The estimated cumulative risk of developing at least one BSI episode was of almost 25% after 15 days at risk and possibly surpassing 50% after 30 days at risk. In multivariable analysis, anti-inflammatory treatment was independently associated with the development of BSI (cause-specific hazard ratio [csHR] 1.07 with 95% CI 0.38-3.04 for tocilizumab, csHR 3.95 with 95% CI 1.20-13.03 for methylprednisolone and csHR 10.69 with 95% CI 2.71-42.17 for methylprednisolone plus tocilizumab, with no anti-inflammatory treatment as the reference group; overall P for the dummy variable = 0.003). CONCLUSIONS: The incidence rate of BSI was high, and the cumulative risk of developing BSI increased with ICU stay. Further study will clarify if the increased risk of BSI we detected in COVID-19 patients treated with anti-inflammatory drugs is outweighed by the benefits of reducing any possible pro-inflammatory dysregulation induced by SARS-CoV-2.