Increased Deaths From Fungal Infections During the Coronavirus Disease 2019 Pandemic—National Vital Statistics System, United States, January 2020–December 2021

Background: The COVID-19 pandemic had a relevant impact on the organization of intensive care units (ICU) and may have reduced the overall compliance with healthcare-associated infections (HAIs) prevention programs. Invasively ventilated patients are at high risk of ICU-associated infection, but there is little evidence regarding the impact of the pandemic on their occurrence in non-COVID-19 patients. Moreover, little is known of antibiotic prescription trends in the ICU during the first wave of the pandemic. The purpose of this investigation is to assess the incidence, characteristics, and risk factors for ICU-associated HAIs in a population of invasively ventilated patients affected by non-COVID-19 acute respiratory failure (ARF) admitted to the ICU in the first wave of the COVID-19 pandemic, and to evaluate the ICU antimicrobial prescription strategies. Moreover, we compared HAIs and antibiotic use to a cohort of ARF patients admitted to the ICU the year before the pandemic during the same period. Methods: this is a retrospective, single-centered cohort study conducted at S. Anna University Hospital (Ferrara, Italy). We enrolled patients admitted to the ICU for acute respiratory failure requiring invasive mechanical ventilation (MV) between February and April 2020 (intra-pandemic group, IP) and February and April 2019 (before the pandemic group, PP). We excluded patients admitted to the ICU for COVID-19 pneumonia. We recorded patients’ baseline characteristics, ICU-associated procedures and devices. Moreover, we evaluated antimicrobial therapy and classified it as prophylactic, empirical or target therapy, according to the evidence of infection at the time of prescription and to the presence of a positive culture sample. We compared the results of the two groups (PP and IP) to assess differences between the two years. Results: One hundred and twenty-eight patients were screened for inclusion and 83 patients were analyzed, 45 and 38 in the PP and I group, respectively. We found a comparable incidence of HAIs (62.2% vs. 65.8%, p = 0.74) and multidrug-resistant (MDR) isolations (44.4% vs. 36.8% p= 0.48) in the two groups. The year of ICU admission was not independently associated with an increased risk of developing HAIs (OR = 0.35, 95% CI 0.16–1.92, p = 0.55). The approach to antimicrobial therapy was characterized by a significant reduction in total antimicrobial use (21.4 ± 18.7 vs. 11.6 ± 9.4 days, p = 0.003), especially of target therapy, in the IP group. Conclusions: ICU admission for non-COVID-19 ARF during the first wave of the SARS-CoV-2 pandemic was not associated with an increased risk of ICU-associated HAIs. Nevertheless, ICU prescription of antimicrobial therapy changed and significantly decreased during the pandemic.

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“…and Candida spp. [ 34 ]. Poor data are available on non-COVID-19 patients admitted during the pandemic.…”

Section: Discussionmentioning

confidence: 99%

Effect of the Pandemic Outbreak on ICU-Associated Infections and Antibiotic Prescription Trends in Non-COVID19 Acute Respiratory Failure Patients

Bussolati

Cultrera

Quaranta

et al. 2022

JCM

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“…and Candida spp.—was observed. [ 20 ]. In this context, the development of new strategies to manage fungal infections is crucial—especially for infections caused by fungi resistant to classic antifungal drugs.…”

Section: Discussionmentioning

confidence: 99%

Digoxin Derivatives Sensitize a Saccharomyces cerevisiae Mutant Strain to Fluconazole by Inhibiting Pdr5p

Moraes

Tessis

Rollin-Pinheiro

et al. 2022

JoF

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The poor outcome of treatments for fungal infections is a consequence of the increasing incidence of resistance to antifungal agents, mainly due to the overexpression of efflux pumps. To surpass this mechanism of resistance, a substance able to inhibit these pumps could be administered in association with antifungals. Saccharomyces cerevisiae possesses an efflux pump (Pdr5p) homologue to those found in pathogenic yeast. Digoxin is a natural product that inhibits Na+, K+-ATPase. The aim of this study was to evaluate whether digoxin and its derivatives (i.e., DGB, digoxin benzylidene) can inhibit Pdr5p, reversing the resistance to fluconazole in yeasts. An S. cerevisiae mutant strain that overexpresses Pdr5p was used in the assays. The effects of the compounds on yeast growth, efflux activity, and Pdr5p ATPase activity were measured. All derivatives enhanced the antifungal activity of fluconazole against S. cerevisiae, in comparison to fluconazole alone, with FICI values ranging from 0.031 to 0.500. DGB 1 and DGB 3 presented combined effects with fluconazole against a Candida albicans strain, with fractional inhibitory concentration index (FICI) values of 0.625 and 0.281, respectively The compounds also inhibited the efflux of rhodamine 6G and Pdr5p ATPase activity, with IC50 values ranging from 0.41 μM to 3.72 μM. The results suggest that digoxin derivatives impair Pdr5p activity. Considering the homology between Pdr5p and efflux pumps from pathogenic fungi, these compounds are potential candidates to be used in association with fluconazole to treat resistant fungal infections.

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“…Based on reports of fungal secondary infections in COVID-19 patients, we examined patients prior to the RECOVERY publication to assess the potential impact of glucocorticoid use. [8][9][10][11] Two recent meta-analyses of randomized trials found consistent benefits of steroids in COVID-19 without any major adverse effects. 5,12 However, the reports acknowledged uncertainty about adverse event rates due to variable definitions and inconsistent reporting of serious adverse effects across studies.…”

Section: Introductionmentioning

confidence: 99%

Secondary infections in critically ill patients with COVID-19 receiving steroid therapy

Pearce,

Zawaydeh,

McGuire

et al. 2023

Science Progress

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Secondary infections can occur during or after the treatment of an initial infection. Glucocorticoids may decrease mortality in patients with severe COVID-19; however, risk of secondary infection is not well described. Our primary objective was to investigate the risk of secondary infection among critically ill patients with COVID-19 treated with glucocorticoids. We examined patients with COVID-19 being treated in the intensive care unit at two academic medical centers from 1 to 7/2020. One hundred-seven patients were included. Of these, 31 received steroids and 76 patients did not. Analysis of the larger cohort was performed followed by a matched pairs analysis of 22 steroid and 22 non-steroid patients. Secondary infection was seen in 14 patients (45.2%) receiving steroids compared to 35(46.1%) not receiving steroids (p = 0.968). Secondary infections were most frequently encountered in the respiratory tract. Escherichia coli and Staphylococcus aureus were the most frequently identified organisms. Mortality was 16.1% in the steroid-treated group compared to 23.7% in the control group (p = 0.388). After performing matched pairs analysis and multivariable logistic regression there was no significant difference between secondary infection or mortality and steroid receipt. Secondary infections were common among critically ill patients with COVID-19, but the incidence of secondary infection was not significantly impacted by steroid treatment.

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Increased Deaths From Fungal Infections During the Coronavirus Disease 2019 Pandemic—National Vital Statistics System, United States, January 2020–December 2021

Cited by 43 publications

References 35 publications

Effect of the Pandemic Outbreak on ICU-Associated Infections and Antibiotic Prescription Trends in Non-COVID19 Acute Respiratory Failure Patients

Effect of the Pandemic Outbreak on ICU-Associated Infections and Antibiotic Prescription Trends in Non-COVID19 Acute Respiratory Failure Patients

Digoxin Derivatives Sensitize a Saccharomyces cerevisiae Mutant Strain to Fluconazole by Inhibiting Pdr5p

Secondary infections in critically ill patients with COVID-19 receiving steroid therapy

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