Efficacy of cefiderocol- vs colistin-containing regimen for treatment of bacteraemic ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii in patients with COVID-19.

INTRODUCTION: Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in patients hospitalized in intensive care units (ICUs) is an important and challenging complication, including in patients with coronavirus disease 2019 (COVID-19). Considering the poor lung penetration of most antibiotics, including intravenous colistin due to the poor pharmacokinetics/pharmacodynamics at the infection site, the choice of the best antibiotic regimen is still being debated. METHODS: This single-centre, observational study was conducted from March 2020 to August 2022, and included all patients hospitalized consecutively with VAP and concomitant bloodstream infection due to CRAB in the COVID-ICU. The main goal of the study was to evaluate risk factors associated with survival or death at 30 days from VAP onset. A propensity score for receiving therapy was added to the model. RESULTS: During the study period, 73 patients who developed VAP and concomitant positive blood cultures caused by CRAB were enrolled in the COVID-ICU. Of these patients, 67 (91.7%) developed septic shock, 42 (57.5%) had died at 14 days and 59 (80.8%) had died at 30 days. Overall, 54 (74%) patients were treated with a colistin-containing regimen and 19 (26%) were treated with a cefiderocol-containing regimen. Cox regression analysis showed that chronic obstructive pulmonary disease and age were independently associated with 30-day mortality. Conversely, cefiderocol-containing regimens and cefiderocol + fosfomycin in combination were independently associated with 30-day survival, as confirmed by propensity score analysis. CONCLUSIONS: This real-life study in patients with bacteraemic VAP caused by CRAB provides useful suggestions for clinicians, showing a possible benefit of cefiderocol and its association with fosfomycin.

Surveillance of device associated infections in intensive care units at a Saudi Arabian Hospital, 2017-2020.

BACKGROUND: Device-associated infections (DAIs) are important components of healthcare associated infection and are associated with increased morbidity and mortality. This study describes DAIs across different intensive care units (ICUs) in a hospital in Saudi Arabia. METHODS: The study was conducted between 2017 and 2020 and followed the definitions of National Healthcare Safety Network (NHSN) for DAIs. The calculated the rates of ventilator-associated events (VAE), catheter-associated urinary tract infections (CAUTI) and central line-associated blood stream infections (CLABSI) followed NHSN definitions. RESULTS: During the study period, there were 82 DAIs in adult ICUs and of these 16 (19.5%) were CLABSI, 26 (31.7%) were CAUTI and 40 (48.7%) were VAE. The overall rates for adult ICUs were 1.6, 1.9, 3.8 per 1000 device-days for CAUTI, CLABSI and VAE, respectively. The device-utilization ratio was 0.5, 0.6, and 0.48 for urinary catheters, central lines, and ventilators, respectively. VAE rates for medical and surgical ICU were about 2.8 times the rate in the coronary care unit and the rates were high in 2020 corresponding with the COVID-19 pandemic. Of the adult ICUS, medical ICU had a CLABSI rate of 2.13/1000 device-days and was about double the rate in surgical and cardiac ICU. For CAUTI, the rates per 1000 device-days were 2.19, 1.73, and 1.65 for medical, surgical, and coronary ICUs, respectively. The rate of CLABSI per 1000 device-days for pediatric and neonatal ICUs were 3.38 and 2.28, respectively. CONCLUSIONS: CAUTI was the most common infections among adult ICUs and medical ICU had higher rates than other adult ICUs. VAE rate was higher in the first year of the COVID-19 pandemic, indicating increased device-use, change in patients characteristics as well as possible change in practices across the ICUs.

Impact of tooth brushing on oral bacteriota and health care-associated infections among ventilated COVID-19 patients: an intervention study.

BACKGROUND: Up to 48% of ventilated coronavirus disease 2019 (COVID-19) patients develop ventilator-associated pneumonia (VAP) during hospitalization in an ICU. Dysbiotic oral microbiota can colonize the lower respiratory tract and lead to VAP. It is recommended to introduce oral care strategies in the ICU to prevent VAP. In this study, we observed the impact of an oral hygienic protocol with tooth brushing on cultivable oral bacteriota, the incidence of HAI and patient safety among mechanically ventilated COVID-19 patients in an ICU setting. METHODS: In this prospective cohort study, we recruited 56 adult COVID-19 patients who qualified for mechanical ventilation. Patients were divided into 2 groups depending on the oral care procedure: standard and extended oral procedures with tooth brushing. Oral bacteriota samples were taken first within 36 h and after 7 days of intubation. Microorganisms were identified by MALDI/TOF mass spectrometry. bacterial health care-associated infection (HAI) cases were retrospectively analyzed by etiology. A PFGE study was performed for Klebsiella pneumoniae to check for clonal spreading of strains from oral bacteriota samples and HAI cases. RESULTS: We observed significant dysbiosis and a decrease in cultivable oral bacteriota diversity, with a high frequency of potentially pathogenic species, including Acinetobacter baumannii and K. pneumoniae. The HAI incidence rate was high (55.2/1000 patient-days), most commonly of K. pneumoniae and A. baumannii etiologies, which correlated with the presence of A. baumannii and K. pneumoniae in the oral samples. Strains isolated from VAP cases were the same as oral isolates in 8 cases. The procedure with tooth brushing led to less frequent identification of A. baumannii in oral samples (55.6% vs. 5.3%, p = 0.001); however, it did not decrease the incidence of HAIs. CONCLUSIONS: Dysbiotic oral bacteriota is an important source of respiratory pathogens. The introduction of tooth brushing in oral hygiene protocols in an ICU setting was effective in decreasing the extent of oral bacteriota dysbiosis; however, it did not reduce the risk of HAIs or mortality. TRIAL REGISTRATION: 1072.6120.333.2020.

Bacterial superinfections in critically ill COVID-19 patients – experiences from University Hospital Dubrava tertiary COVID-19 center

Goal:To determine incidence of bacterial superinfections, causative pathogens demographic data, relevant laboratory parameters and outcomes in critically ill COVID-19 patients treated in primary respiratory intensivist center (PRIC) UH Dubrava. Patients and methods: In this retrospective observational study, clinical and laboratory data of 692 critically ill patients treated in PRIC UH Dubrava between March 1st 2020. and February 1st 2021. was collected using the hospital information system software (BIS) and statistical analysis was performed using the jamovi statistical package. Results: Out of 692 patients admitted to the ICU, 383 acquired bacterial or fungal superinfections. 305 acquired pneumonia, 133 bloodstream infections and 120 urinary infections. 66.3% of patients were males, and bacterial superinfections were more common in patients admitted from hospital wards or external ICUs. Out of 305 patients with pneumonia, 295 were receiving mechanical ventilation and satisfied the criteria for ventilator associated pneumonia. Patients with bloodstream infections maintained elevated neutrophil lymphocyte ratio, lymphopenia and elevated CRP levels on day 7 compared to those without BSI. Urinary infections were more common in females, and did not have an effect on outcomes. All patients that developed superinfections had prolonged ICU and hospital stay. Conclusion: Incidence of bacterial superinfections in critically ill COVID-19 patients is 55.3%. Most common infections are ventilator associated pneumonia, bloodstream infections and urinary infections. Most common pathogens are multi-drug resistant pathogens. Patients with bacterial superinfections have longer ICU and hospital stay, and in these patients, persistent elevation of NLR ratio and worsening of lymphopenia are characteristic for patients with worse outcomes © 2022 Hrvatski Lijecnicki Zbor. All rights reserved.

Unintended impact of COVID-19 pandemic on the rate of catheter related nosocomial infections and incidence of multiple drug resistance pathogens in three intensive care units not allocated to COVID-19 patients in a large teaching hospital.

BACKGROUND: The prevalence of resistant hospital infections in the intensive care unit (ICU) increases mortality and antibiotic resistance. COVID-19 pandemic may have unintended impact on nosocomial infections (NI) and the prevalence of resistant microorganism. METHODOLOGY: The present non-interventional study was performed by a pre and a post survey each lasting 8 months before (March-October 2019) and after (March-October 2020) the onset of COVID-19 pandemic in three ICU's, not allocated to COVID-19 patients, in Nemazee Hospital, Shiraz, Iran. The rates of the following nosocomial infections were compared at pre- and post-pandemic period: ventilator associated pneumonia (VAP), central line associated blood stream infection (CLABSI), catheter-associated urinary tract infections (CAUTI) and incidence of multiple drug resistance (MDR) pathogens. RESULTS: Pre-pandemic and pandemic incidence of VAP was 23.5 and 17.2 cases per 1000 device-days, respectively; an absolute decrease of 27%. The main reason for the decrease in the rate of VAP during the pandemic was a significant decrease in the rate of VAP caused by Acinetobacter baumannii; from 39 to 17% in total VAP episodes. The rate of VAP associated with other microorganisms remained relatively unchanged from 14.2 cases in pre-pandemic period to 14.3 cases per 1000 MV-days during the pandemic (P = 0.801). Pre-pandemic incidence of CLABSI was 7.3 cases and, in pandemic period, was 6.5 cases per 1000 device-days (IRR = 0.88, 95% CI 0.43-1.73, P = 0.703). Pre-pandemic incidence of CAUTI was 2 and in pandemic period, was 1.4 cases per 1000 device-days (IRR = 0.70, 95% CI 0.22-1.98, P = 0.469). CONCLUSION: The results of the present study showed a decrease in the incidence of VAP in critically ill non-COVID-19 patients during the pandemic compared to before the pandemic, especially regarding Acinetobacter baumannii.

Prognostic evaluation of Acinetobacter baumannii ventilator-associated pneumonia in COVID-19.

Background: Since the emergence of the pandemic of SARS-CoV-2, a high reported incidence of VAP in COVID-19 sustained by carbapenem resistant Acinetobacter baumannii (CRAB) has been observed, but data are scarce to date. Materials and methods: We retrospectively collected COVID-19 patients who developed CRAB-VAP - defined according to Center for Diseases Control (CDC) 2020 criteria and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) or Infectious Diseases Society of America (IDSA) guidelines - to describe characteristics and outcome. Results: Among 21 patients with CRAB-VAP in COVID-19, median age was 66 years (IQR 41-80). Median time of VAP-onset was 7 days (IQR 0-28 days) from ICU - admission and 76.2% had septic shock. Treatment regimens were all colistin-based, in 28% (n=6) including ampicillin/sulbactam and rifampicin. In three cases, cefiderocol was started as rescue. Survival rate at 28-days was 35% (n=7). Conclusion: Non-fermenting Gram-negative bacteria are an emerging aetiology of VAP in COVID-19 patients. This underscores the urgent need for proper microbiological identification to address therapies and infection control protocols.

Incidence, Outcomes and Risk Factors of Recurrent Ventilator Associated Pneumonia in COVID-19 Patients: A Retrospective Multicenter Study.

Background: High incidence of ventilator associated pneumonia (VAP) has been reported in critically ill patients with COVID-19. Among these patients, we aimed to assess the incidence, outcomes and risk factors of VAP recurrences. Methods: We conducted an observational retrospective study in three French intensive care units (ICUs). Patients admitted for a documented COVID-19 from March 2020 to May 2021 and requiring mechanical ventilation (MV) for ≥48 h were included. The study main outcome was the incidence of VAP recurrences. Secondary outcomes were the duration of MV, ICU and hospital length of stay and mortality according to VAP and recurrences. We also assessed the factors associated with VAP recurrences. Results: During the study period, 398 patients met the inclusion criteria. A total of 236 (59%) of them had at least one VAP episode during their ICU stay and 109 (46%) of these patients developed at least one recurrence. The incidence of VAP recurrence considering death and extubation as competing events was 29.6% (IC = [0.250−0.343]). Seventy-eight percent of recurrences were due to the same bacteria (relapses). Patients with a VAP recurrence had a longer duration of MV as compared with one VAP and no VAP patients (41 (25−56) vs. 16 (8−30) and 10 (5−18) days; p < 0.001) and a longer ICU length of stay (46 (29−66) vs. 22 (12−36) and 14 (9−25) days; p < 0.001). The 90-day mortality was higher in the recurrence group as compared with the no VAP group only (31.2 vs. 21.0% (p = 0.021)). In a multivariate analysis including bacterial co-infection at admission, the use of immunosuppressive therapies and the bacteria responsible for the first VAP episode, the duration of MV was the only factor independently associated with VAP recurrence. Conclusion: In COVID-19 associated respiratory failure, recurrences affected 46% of patients with a first episode of VAP. VAP recurrences were mainly relapses and were associated with a prolonged duration of MV and ICU length of stay but not with a higher mortality. MV duration was the only factor associated with recurrences.

Rapid diagnostic tests in the management of pneumonia.

INTRODUCTION: Pneumonia is one of the main causes of mortality associated with infectious diseases worldwide. Several challenges have been identified in the management of patients with pneumonia, ranging from accurate and cost-effective microbiological investigations, prompt and adequate therapeutic management, and optimal treatment duration. AREAS COVERED: In this review, an updated summary on the current management of pneumonia patients is provided and the epidemiological issues of infectious respiratory diseases, which in the current pandemic situation are of particular concern, are addressed. The clinical and microbiological approaches to pneumonia diagnosis are reviewed, including discussion about the new molecular assays pointing out both their strengths and limitations. Finally, the current recommendations about antibiotic treatment are examined and discussed depending on the epidemiological contexts, including those with high prevalence of multidrug-resistant bacteria. EXPERT OPINION: We claim that rapid diagnostic tests, if well-positioned in the diagnostic workflow and reserved for the subset of patients who could most benefit from these technologies, may represent an interesting and feasible tool to optimize timing of targeted treatments especially in terms of early de-escalation or discontinuation of antibiotic therapy.

Ceftazidime/Avibactam in Ventilator-Associated Pneumonia Due to Difficult-to-Treat Non-Fermenter Gram-Negative Bacteria in COVID-19 Patients: A Case Series and Review of the Literature.

Ventilator-associated pneumonia (VAP) in critically ill patients with COVID-19 represents a very huge global threat due to a higher incidence rate compared to non-COVID-19 patients and almost 50% of the 30-day mortality rate. Pseudomonas aeruginosa was the first pathogen involved but uncommon non-fermenter gram-negative organisms such as Burkholderia cepacea and Stenotrophomonas maltophilia have emerged as other potential etiological causes. Against carbapenem-resistant gram-negative microorganisms, Ceftazidime/avibactam (CZA) is considered a first-line option, even more so in case of a ceftolozane/tazobactam resistance or shortage. The aim of this report was to describe our experience with CZA in a case series of COVID-19 patients hospitalized in the ICU with VAP due to difficult-to-treat (DTT) P. aeruginosa, Burkholderia cepacea, and Stenotrophomonas maltophilia and to compare it with data published in the literature. A total of 23 patients were treated from February 2020 to March 2022: 19/23 (82%) VAPs were caused by Pseudomonas spp. (16/19 DTT), 2 by Burkholderia cepacea, and 6 by Stenotrophomonas maltophilia; 12/23 (52.1%) were polymicrobial. Septic shock was diagnosed in 65.2% of the patients and VAP occurred after a median of 29 days from ICU admission. CZA was prescribed as a combination regimen in 86% of the cases, with either fosfomycin or inhaled amikacin or cotrimoxazole. Microbiological eradication was achieved in 52.3% of the cases and the 30-day overall mortality rate was 14/23 (60.8%). Despite the high mortality of critically ill COVID-19 patients, CZA, especially in combination therapy, could represent a valid treatment option for VAP due to DTT non-fermenter gram-negative bacteria, including uncommon pathogens such as Burkholderia cepacea and Stenotrophomonas maltophilia.

Complications of invasive mechanical ventilation in critically Ill Covid-19 patients - A narrative review.

Critically ill COVID-19 patients have to undergo positive pressure ventilation, a non-physiological and invasive intervention that can be lifesaving in severe ARDS. Similar to any other intervention, it has its pros and cons. Despite following Lung Protective Ventilation (LPV), some of the complications are frequently reported in these critically ill patients and significantly impact overall mortality. The complications related to invasive mechanical ventilation (IMV) in critically ill COVID-19 patients can be broadly divided into pulmonary and non-pulmonary. Among pulmonary complications, the most frequent is ventilator-associated pneumonia. Others are barotrauma, including subcutaneous emphysema, pneumomediastinum, pneumothorax, bullous lesions, cardiopulmonary effects of right ventricular dysfunction, and pulmonary complications mimicking cardiac failure, including pulmonary edema. Tracheal complications, including full-thickness tracheal lesions (FTTLs) and tracheoesophageal fistulas (TEFs) are serious but rare complications. Non-Pulmonary complications include neurological, nephrological, ocular, and oral complications.

Elevated Rates of Ventilator-Associated Pneumonia and COVID-19 Associated Pulmonary Aspergillosis in Critically Ill Patients with SARS-CoV2 Infection in the Second Wave: A Retrospective Chart Review.

Due to multiple risk factors, the rate of ventilator-associated pneumonia in critically ill COVID-19 patients has been reported in a range of 7.6% to 86%. The rate of invasive pulmonary aspergillosis in this cohort has been reported at 4% to 30%. We undertook a retrospective chart review of 276 patients who were admitted to intensive care in a large university hospital. The period studied included patients from 23 February 2014 to 12 May 2021. Four groups were collected: COVID-19 Wave 1, COVID-19 Wave 2, influenza, and community-acquired pneumonia. Clinical characteristics, outcomes, and microbiological cultures were recorded. The incidence of ventilator-associated pneumonia in COVID-19 Wave 1, COVID-19 Wave 2, influenza, and community-acquired pneumonia was 5.45%, 27.40%, 16.67%, and 3.41%, respectively (p < 0.001). The rate of invasive pulmonary aspergillosis was 0%, 9.59%, 13.33%, and 6.82%, respectively (p < 0.001). A significantly elevated rate of ventilator-associated pneumonia and invasive pulmonary aspergillosis was noted in the second wave of COVID-19 when compared to the first. This was accompanied by an increase in the mortality rate. Increased steroid use was an independent risk factor for ventilator-associated pneumonia and invasive pulmonary aspergillosis across all four groups. Despite an increased understanding of this disease, no clinical trials have shown any promising therapeutic options at present.

Bacterial Ventilator-Associated Pneumonia in COVID-19 Patients: Data from the Second and Third Waves of the Pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, many patients requiring invasive mechanical ventilation were admitted to intensive care units (ICU) for COVID-19-related severe respiratory failure. As a matter of fact, ICU admission and invasive ventilation increased the risk of ventilator-associated pneumonia (VAP), which is associated with high mortality rate and a considerable burden on length of ICU stay and healthcare costs. The objective of this review was to evaluate data about VAP in COVID-19 patients admitted to ICU that developed VAP, including their etiology (limiting to bacteria), clinical characteristics, and outcomes. The analysis was limited to the most recent waves of the epidemic. The main conclusions of this review are the following: (i) P. aeruginosa, Enterobacterales, and S. aureus are more frequently involved as etiology of VAP; (ii) obesity is an important risk factor for the development of VAP; and (iii) data are still scarce and increasing efforts should be put in place to optimize the clinical management and preventative strategies for this complex and life-threatening disease.

Minimum irradiance required to inhibit microbial growth to prevent ventilatorassociated pneumonia by an endotracheal tube equipped with blue LEDs

Artificial respiration is saving lives especially in the COVID-19 pandemic, but it also carries the risk to cause ventilator-Associated pneumonia (VAP). VAP is one of the most common and severe nosocomial infections, often leading to death and adding a major economic burden to the healthcare system. To prevent a proliferation of microbial pathogens that cause VAP, an endotracheal tube (ETT) equipped with blue LEDs (LED-ETT) was developed. This blue wavelength exhibits antimicrobial properties but may also harm human tracheal cells at higher irradiances. Therefore, the aim of this study was to find the minimal required irradiance for microbial reduction of 1 log level in 24 h by applying LED-ETTs. A LED-ETT with 48 blue LEDs (450 nm) was fixed in a glass tube, which served as a trachea model. The investigation was carried out with irradiations of 4.2, 6.6 and 13.4 mW/cm² at 37 °C for 24 h. The experiments were performed with Acinetobacter kookii as a surrogate of Acinetobacter baumannii, which is classified as critical by the WHO. Samples of A. kookii suspensions were taken every 4 h during irradiation from the trachea model. Bacteria concentrations were quantified by determining colony forming units (CFU)/ml. A homogeneous irradiance of only 4.2 mW/cm² generated by the blue LEDs, at a LED forward current of 3.125 mA, is sufficient to achieve a 1 log reduction of A. kookii within 24 h. The total irradiation dose within this period was 360 J/cm2. Human cells survive this dose without cellular damage. Previous studies revealed that the pathogen A. baumannii is even more sensitive to blue light than A. kookii. Therefore, blue LED-ETTs are expected to reduce A. baumannii without harming human tracheal cells. © 2021 by Walter de Gruyter Berlin/Boston.

Nanomedicine formulations for respiratory infections by inhalation delivery: Covid-19 and beyond.

For respiratory infections treatment and prevention, we analyze for the first time the possibility of providing a broad range medication based on metallic nanoparticles colloids (NpC) delivery by controlled aerosol inhalation. (i) Based on in-vitro data combined with aerosol deposition characteristics in the respiratory system, we calculate the required effective formulations, dosages and delivery parameters for an aerosol inhalation treatment. The goal is to achieve an effective NpC inhibitory concentration (IC) in the target airway surface liquid (ASL); (ii) We evaluate the clinical safety of such dosages, drawing on information from animal testing data and regulatory limits in the USA for such nanoparticles aerosol inhalation safety. Our analysis indicates a wide range of potentially safe and effective dosages that can be clinically explored, targeting the upper respiratory and bronchial tree system. Similar dosages can also provide antibacterial effectiveness for prophylactic treatment in hospital intensive care units to lower the risk of ventilator-associated pneumonia (VAP). Our calculations are phenomenological, independent of mechanisms. Nevertheless, we highlight a mechanism of action by which any suitably designed NpC, with nanoparticles sized 2-10 nm and having a large negative zeta-potential, preferentially bind to viruses with predominantly positively-charged spike proteins. These will be ineffective against viruses with predominantly negatively-charged spike proteins. Accordingly, the popular silver metal base for NpC serves just as a construction ingredient, and other metal or metal-oxides which can serve to construct the noted nanoparticle properties would be similarly effective. We suggest that inhalation delivery of the proposed antiviral formulations could be applied as a first-line intervention while respiratory infections are primarily localized to the upper respiratory system and bronchial tree.

Prevention of hospital-acquired infections: A construct during Covid-19 pandemic.

INTRODUCTION: Hospital-acquired infection (HAI) rates were reported to have declined in healthcare settings during the Covid-19 pandemic. Needless to mention that HAI is of paramount interest and relevance to a primary care physician who need to care from womb to tomb inside pandemic. OBJECTIVES: This study was conducted to find the impact of Covid-19 pandemic on the four parameters of HAIs, namely, catheter-associated urinary tract infections (CAUTI), central-line-associated bloodstream infections (CLABSI), ventilator-associated pneumonia (VAP) and surgical site infections (SSIs) with hand hygiene compliance rates among healthcare workers. MATERIALS AND METHODS: This retrospective data mining was undertaken in a 700 bed multispecialty teaching hospital in the Eastern India which was a Government of Bihar approved speciality Covid Care Hospital. Data from the monthly routine infection control monitoring and surveillance activities was collated from January 2019 to December 2020. Control charts with upper and lower control limit set at mean ± 1 SD were used to monitor monthly trends of HAIs. RESULTS: The CAUTI rates reduced by 28.01%; the CLABSI rates declined by 37.61%, the SSI rates reduced by 62.39%, while the highest VAP rates were reported in November 2019 (1.9 per 1000 ventilator days). The hand hygiene compliance rates from January 2019 to December 2020 among different healthcare staffs showed a sharply rising trend. CONCLUSION: Covid-19 pandemic highlighted paramount importance regarding compliance to hand hygiene and implementation of standard infection control practices as recommended by World Health Organisation and Centres for Diseases Control and Prevention (CDC), which can drastically reduce range of HAIs.

Clinical presentation of secondary infectious complications in COVID-19 patients in intensive care unit treated with tocilizumab or standard of care.

OBJECTIVES: The hypothesis of this study is that tocilizumab should affect common signs of infection due to its immunosuppressive properties. Primary aim of the study was to investigate whether the administration of tocilizumab to critically ill patients with COVID-19, led to a different clinical presentation of infectious complications compared to patients who did not receive tocilizumab. Secondary aim was investigating differences in laboratory parameters between groups. METHODS: Single-centre retrospective study, enrolling COVID-19 patients who developed a microbiologically confirmed infectious complication [ventilator associated pneumonia or bloodstream infection] after intensive care unit [ICU] admission and either treated with tocilizumab or not [controls]. RESULTS: A total of 58 patients were included, 25 treated with tocilizumab and 33 controls. Median time from tocilizumab administration to infection onset was 10 days [range 2-26]. Patients were 78% male, with median age 65 years [range 45-79]. At first clinical presentation of the infectious event, the frequency of hypotension [11/25, 44% vs. 11/33, 33%], fever [8/25, 32% vs. 10/33, 30%] or hypothermia [0/25,0%, vs. 2/33, 6%], and oxygen desaturation [6/25, 28% vs 4/33, 12%], as well as the frequency of SOFA score increase of ≥ 2 points [4/25, 16%,vs. 4/33, 12%] was similar in tocilizumab treated patients and controls [p>0.1 for all comparisons]. Among laboratory parameters, C-Reactive Protein elevation was reduced in tocilizumab treated patients compared to controls [8/25, 32% vs. 22/33, 67%, p=0.009]. CONCLUSION: The clinical features of infectious complications in critically ill patients with COVID-19 admitted to ICU were not affected by tocilizumab.

Acute necrotic hemorrhagic leukoencephalitis related to COVID-19: a report of 2 cases.

Acute necrotic hemorrhagic leukoencephalitis (ANHLE) is a subform of acute disseminating leukoencephalitis which is a post viral or vaccination uncommon disease with poor prognosis. Radiological findings include multiple or diffuse lesions involving the white matter and sparing the cortex with or without rim enhancement. In addition to areas of hemorrhages with possible involvement of basal ganglia and thalami. We describe the imaging findings for 2 cases of ANHLE; a 59-years-old male and a 47-years-old female. Both of them were tested positive of SARS-COVID2 with presentation of consciousness loss and respiratory failure. CT and MRI brain show global white matter changes associated with acute hemorrhagic necrosis, although uncommon, are compatible with postviral acute necrotic hemorrhagic leukoencephalitis with end point of death for the first patient and coma for the second patient.

Fatal VAP-related pulmonary aspergillosis by Aspergillus niger in a positive COVID-19 patient.

Invasive pulmonary aspergillosis, known as a complication in patients with severe respiratory syndromes, recently showed a correlation with COVID-19 pneumonia, and the clinical characteristics of COVID-19 associated pulmonary aspergillosis (CAPA) have been described. Unfortunately, infections by the Aspergillus genus are often diagnosed in post-mortem time, because of diagnostic delays and a rapid worsening of respiratory conditions. Literature data document, in fact, only few cases of COVID-19 Aspergillus niger coinfection. The aim of this study was to describe a case of a VAP-related probable pulmonary aspergillosis by Aspergillus niger in a COVID-19 patient. Despite the definition of fungal etiology and the rapid administration of antifungal therapy, the patient died while on ventilator support because of severe respiratory impairment.