No abstract

The funder had no role in the design and conduct of the study, collection, management, analysis,

Rational To evaluate the respective impact of standard oxygen, high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) on oxygenation failure rate and mortality in COVID-19 patients admitted to intensive care units (ICUs). Methods Multicenter, prospective cohort study (COVID-ICU) in 137 hospitals in France, Belgium, and Switzerland. Demographic, clinical, respiratory support, oxygenation failure, and survival data were collected. Oxygenation failure was defined as either intubation or death in the ICU without intubation. Variables independently associated with oxygenation failure and Day-90 mortality were assessed using multivariate logistic regression. Results From February 25 to May 4, 2020, 4754 patients were admitted in ICU. Of these, 1491 patients were not intubated on the day of ICU admission and received standard oxygen therapy (51%), HFNC (38%), or NIV (11%) (P < 0.001). Oxygenation failure occurred in 739 (50%) patients (678 intubation and 61 death). For standard oxygen, HFNC, and NIV, oxygenation failure rate was 49%, 48%, and 60% (P < 0.001). By multivariate analysis, HFNC (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.36–0.99, P = 0.013) but not NIV (OR 1.57, 95% CI 0.78–3.21) was associated with a reduction in oxygenation failure). Overall 90-day mortality was 21%. By multivariable analysis, HFNC was not associated with a change in mortality (OR 0.90, 95% CI 0.61–1.33), while NIV was associated with increased mortality (OR 2.75, 95% CI 1.79–4.21, P < 0.001). Conclusion In patients with COVID-19, HFNC was associated with a reduction in oxygenation failure without improvement in 90-day mortality, whereas NIV was associated with a higher mortality in these patients. Randomized controlled trials are needed.

Background Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring intensive care unit (ICU) have a high incidence of hospital-acquired infections; however, data regarding hospital acquired bloodstream infections (BSI) are scarce. We aimed to investigate risk factors and outcome of BSI in critically ill coronavirus infectious disease-19 (COVID-19) patients. Patients and methods We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU study) that included 4010 COVID-19 ICU patients. For the present analysis, only those with data regarding primary outcome (death within 90 days from admission) or BSI status were included. Risk factors for BSI were analyzed using Fine and Gray competing risk model. Then, for outcome comparison, 537 BSI-patients were matched with 537 controls using propensity score matching. Results Among 4010 included patients, 780 (19.5%) acquired a total of 1066 BSI (10.3 BSI per 1000 patients days at risk) of whom 92% were acquired in the ICU. Higher SAPS II, male gender, longer time from hospital to ICU admission and antiviral drug before admission were independently associated with an increased risk of BSI, and interestingly, this risk decreased over time. BSI was independently associated with a shorter time to death in the overall population (adjusted hazard ratio (aHR) 1.28, 95% CI 1.05–1.56) and, in the propensity score matched data set, patients with BSI had a higher mortality rate (39% vs 33% p = 0.036). BSI accounted for 3.6% of the death of the overall population. Conclusion COVID-19 ICU patients have a high risk of BSI, especially early after ICU admission, risk that increases with severity but not with corticosteroids use. BSI is associated with an increased mortality rate.

Oxidizing agents like hypochlorous acid (HOCl) have antimicrobial activity. We developed an integrated electrochemical scaffold or ‘e-scaffold’ that delivers a continuous low dose of HOCl aimed at targeting microbial biofilms without exceeding concentrations toxic to humans, as a prototype of a device being developed to treat wound infections in humans. In this work, we tested the device against 33 isolates of bacteria (including isolates with acquired antibiotic resistance) grown as in vitro biofilms, alongside 12 combinations of dual-species in vitro biofilms. Biofilms were grown on the bottoms of 12-well plates for 24 hours. An integrated e-scaffold was placed atop each biofilm and polarized at 1.5V for 1, 2 or 4 hours. HOCl was produced electrochemically by oxidizing chloride ions (Cl-) in solution to chlorine (Cl2); dissolved Cl2 spontaneously dissociates in water to produce HOCl. The cumulative concentration of HOCl produced at the working electrode in each well was estimated to be 7.89, 13.46, and 29.50 mM after 1, 2 and 4 hours of polarization, respectively. Four hours of polarization caused an average reduction of 6.13 log10 CFU/cm2 (±1.99 log10 CFU/cm2) of viable cell counts of mono-species biofilms and 5.53 log10 CFU/cm2 (±2.31 log10 CFU/cm2) for the 12 dual-species biofilms studied. The described integrated e-scaffold reduces viable bacterial cell counts in biofilms formed by an array of antibiotic-susceptible and -resistant bacteria alone and in combination.

Hydrogen peroxide (H2O2) and hypochlorous acid (HOCl) are biocides used for cleaning and debriding chronic wound infections, which often harbor drug resistant bacteria. Here, we evaluated the in vitro activity of H2O2 and HOCl against 27 isolates of eight bacterial species involved in wound infections. Minimum inhibitory concentrations (MICs) and minimum biofilm bactericidal concentrations (MBBCs) were measured. When compared to their respective MICs, MBBCs of isolates exposed to H2O2 were 16- to 1,024-fold higher and those exposed to HOCl were 2- to 4-fold higher. We evaluated selection of resistance after exposure of Staphylococcus aureus and Pseudomonas aeruginosa biofilms to 10 iterations of electrochemically generated HOCl or H2O2 delivered using electrochemical scaffolds (e-scaffolds), observing no decrease in anti-biofilm effects with serial exposure to e-scaffold-generated H2O2 or HOCl. 24-hour exposure to H2O2-generating e-scaffolds consistently decreased colony forming units (CFUs) of S. aureus and P. aeruginosa biofilms by ∼5.0-log10 and ∼4.78-log10 through 10 iterations of exposure, respectively. 4-hour exposure to HOCl-generating e-scaffolds consistently decreased CFUs of S. aureus biofilms by ∼4.9-log10, and 1-hour exposure to HOCl-generating e-scaffolds consistently decreased CFUs of P. aeruginosa biofilms by ∼1.57-log10. These results suggest that HOCl has similar activity against planktonic and biofilm bacteria, whereas the activity of H2O2 is less against biofilm than planktonic bacteria, and that repeat exposure to either biocide, generated electrochemically under the experimental conditions studied, does not lessen antibiofilm effects.

Chronic wound infections caused by biofilm-forming microorganisms represent a major burden to healthcare systems. Treatment of chronic wound infections using conventional antibiotics is often ineffective due to the presence of bacteria with acquired antibiotic resistance and biofilm-associated antibiotic tolerance. We previously developed an electrochemical scaffold that generates hydrogen peroxide (H 2 O 2 ) at low concentrations in the vicinity of biofilms. The goal of this study was to transition our electrochemical scaffold into an H 2 O 2 -generating electrochemical bandage (e-bandage) that can be used in vivo. The developed e-bandage uses a xanthan gum-based hydrogel to maintain electrolytic conductivity between e-bandage electrodes and biofilms. The e-bandage is controlled using a lightweight, battery-powered wearable potentiostat suitable for use in animal experiments. Weshow that e-bandage treatment reduced colony-forming units of Acinetobacter buamannii biofilms (treatment vs. control) in 12 h (7.32 ± 1.70 vs. 9.73 ± 0.09 log 10 [CFU/cm 2 ]) and 24 h (4.10 ± 12.64 vs. 9.78 ± 0.08 log 10 [CFU/cm 2 ]) treatments, with 48 h treatment reducing viable cells below the limit of detection of quantitative and broth cultures. The developed H 2 O 2 -generating e-bandage was effective against in vitro A. baumannii biofilms and should be further evaluated and developed as a potential alternative to topical antibiotic treatment of wound infections.

Biofilms formed by antibiotic-resistant bacteria in wound beds present unique challenges in terms of treating chronic wound infections; biofilms formed by one or more than one bacterial species are often involved. In this work, the in vitro anti-biofilm activity of a novel electrochemical bandage (e-bandage) composed of carbon fabric and controlled by a wearable potentiostat, designed to continuously deliver low amounts of hydrogen peroxide (H 2 O 2 ) was evaluated against 34 mono-species and 12 dual-species membrane bacterial biofilms formed by Staphylococcus aureus , S. epidermidis , Enterococcus faecium , E. faecalis , Streptococcus mutans , Escherichia coli , Pseudomonas aeruginosa , Acinetobacter baumannii , Klebsiella pneumoniae , Cutibacterium acnes , and Bacteroides fragilis . Biofilms were grown on polycarbonate membranes placed atop agar plates. An e-bandage, which electrochemically reduces dissolved oxygen to H 2 O 2 when polarized at −0.6 V Ag/AgCl , was then placed atop each membrane biofilm and polarized continuously for 12, 24, and 48 h using a wearable potentiostat. Time-dependent decreases in viable CFU counts of all mono- and dual-species biofilms were observed after e-bandage treatment. 48 h of e-bandage treatment resulted in an average reduction of 8.17 ± 0.40 and 7.99 ± 0.32 log 10 CFU/cm 2 for mono- and dual-species biofilms, respectively. Results suggest that the described H 2 O 2 producing e-bandage can reduce in vitro viable cell counts of biofilms grown either in mono- or dual-species forms, and should be further developed as a potential antibiotic-free treatment strategy for treating chronic wound infections.