Pan-drug resistant Providencia rettgeri contributing to a fatal case of COVID-19.

Following prolonged hospitalization that included broad-spectrum antibiotic exposure, a strain of Providencia rettgeri was cultured from the blood of a patient undergoing extracorporeal membrane oxygenation treatment for hypoxic respiratory failure due to COVID-19. The strain was resistant to all antimicrobials tested including the novel siderophore cephalosporin, cefiderocol. Whole genome sequencing detected ten antimicrobial resistance genes, including the metallo-ß-lactamase bla NDM-1, the extended-spectrum ß-lactamase bla PER-1, and the rare 16S methyltransferase rmtB2.

Timing and causes of death in severe COVID-19 patients.

BACKGROUND: Previous studies reporting the causes of death in patients with severe COVID-19 have provided conflicting results. The objective of this study was to describe the causes and timing of death in patients with severe COVID-19 admitted to the intensive care unit (ICU). METHODS: We performed a retrospective study in eight ICUs across seven French hospitals. All consecutive adult patients (aged ≥ 18 years) admitted to the ICU with PCR-confirmed SARS-CoV-2 infection and acute respiratory failure were included in the analysis. The causes and timing of ICU deaths were reported based on medical records. RESULTS: From March 1, 2020, to April 28, 287 patients were admitted to the ICU for SARS-CoV-2 related acute respiratory failure. Among them, 93 patients died in the ICU (32%). COVID-19-related multiple organ dysfunction syndrome (MODS) was the leading cause of death (37%). Secondary infection-related MODS accounted for 26% of ICU deaths, with a majority of ventilator-associated pneumonia. Refractory hypoxemia/pulmonary fibrosis was responsible for death in 19% of the cases. Fatal ischemic events (venous or arterial) occurred in 13% of the cases. The median time from ICU admission to death was 15 days (25th-75th IQR, 7-27 days). COVID-19-related MODS had a median time from ICU admission to death of 14 days (25th-75th IQR: 7-19 days), while only one death had occurred during the first 3 days since ICU admission. CONCLUSIONS: In our multicenter observational study, COVID-19-related MODS and secondary infections were the two leading causes of death, among severe COVID-19 patients admitted to the ICU.

Secondary infections in mechanically ventilated patients with COVID-19: An overlooked matter?

OBJECTIVE: The susceptibility to infection probably increases in COVID-19 patients due to a combination of virusand drug-induced immunosuppression. The reported rate of secondary infections was quite low in previous studies. The objectives of our study were to investigate the rate of secondary infections, risk factors for secondary infections and risk factors for mortality in COVID-19 critically ill patients. METHODS: We performed a single-center retrospective study in mechanically ventilated critically ill COVID-19 patients admitted to our Critical Care Unit (CCU). We recorded the patients' demographic data; clinical data; microbiology data and incidence of secondary infection during CCU stay, including ventilator-associated pneumonia (VAP) and nosocomial bacteremia (primary and secondary). RESULTS: A total of 107 patients with a mean age 62.2 ± 10.6 years were included. Incidence of secondary infection during CCU stay was 43.0% (46 patients), including nosocomial bacteremia (34 patients) and VAP (35 patients). Age was related to development of secondary infection (65.2 ± 7.3 vs. 59.9 ± 12.2 years, p=0.007). Age ≥ 65 years and secondary infection were independent predictors of mortality (OR=2.692, 95% CI 1.068-6.782, p<0.036; and OR=3.658, 95% CI 1.385- 9.660, p=0.009, respectively). The hazard ratio for death within 90 days in the ≥ 65 years group and in patients infected by antimicrobial resistant pathogens was 1.901 (95% CI 1.198- 3.018; p= 0.005 by log-rank test) and 1.787 (95% CI 1.023-3.122; p= 0.036 by log-rank test), respectively. CONCLUSIONS: Our data suggest that the incidence of secondary infection and infection by antimicrobial resistant pathogens is very high in critically ill patients with COVID-19 with a significant impact on prognosis.

Ventilator-associated bacterial pneumonia in coronavirus 2019 disease, a retrospective monocentric cohort study.

INTRODUCTION: Severe coronavirus 2019 disease (CoViD-19) may lead to respiratory failure and mechanical ventilation. Therefore, ventilator associated pneumonia (VAP) may complicate the course of the disease. The aim of the current article was to investigate possible predictive factors for bacterial VAP on a retrospective manner, in a cohort of mechanically ventilated CoViD-19 patients. Additionally, determinant factors of lethality were analyzed. METHODS: Medical records of patients hospitalized in the intensive care units (ICU) at the university hospital UZ Brussel during the epidemic were reviewed. VAP was defined following the National Healthcare Safety Network 2017 criteria. Univariate and multivariate logistic regressions analyses were performed. RESULTS: Among the 39 patients included in the study, 54% were diagnosed with bacterial VAP. Case fatality rate was 44%, but 59% of the deceased patients had a do-not-resuscitate status. Multivariate logistic regression for prediction of VAP showed significant differences in duration of ICU hospitalization and in minimal lung compliance. Additional analyses were performed on CoViD-19 patients who were affected by bacterial respiratory superinfection. The responsible pathogens correspond to the commonly found bacteria in VAP. However, 71% of the isolated germs were multi-drug resistant and bacteraemia was reported in 38%. Multivariate analyses for prediction of lethality found significant difference in SOFA score. CONCLUSIONS: Mechanically ventilated CoViD-19 patients might frequently develop VAP. Longer ICU hospitalization was associated with pulmonary superinfection in the current cohort. Moreover, decreased minimal lung compliance was correlated to VAP and higher SOFA score at VAP diagnosis was associated with lethality.

Lipoprotein concentrations over time in the intensive care unit COVID-19 patients: Results from the ApoCOVID study.

INTRODUCTION: Severe acute respiratory syndrome coronavirus2 has caused a global pandemic of coronavirus disease 2019 (COVID-19). High-density lipoproteins (HDLs), particles chiefly known for their reverse cholesterol transport function, also display pleiotropic properties, including anti-inflammatory or antioxidant functions. HDLs and low-density lipoproteins (LDLs) can neutralize lipopolysaccharides and increase bacterial clearance. HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) decrease during bacterial sepsis, and an association has been reported between low lipoprotein levels and poor patient outcomes. The goal of this study was to characterize the lipoprotein profiles of severe ICU patients hospitalized for COVID-19 pneumonia and to assess their changes during bacterial ventilator-associated pneumonia (VAP) superinfection. METHODS: A prospective study was conducted in a university hospital ICU. All consecutive patients admitted for COVID-19 pneumonia were included. Lipoprotein levels were assessed at admission and daily thereafter. The assessed outcomes were survival at 28 days and the incidence of VAP. RESULTS: A total of 48 patients were included. Upon admission, lipoprotein concentrations were low, typically under the reference values ([HDL-C] = 0.7[0.5-0.9] mmol/L; [LDL-C] = 1.8[1.3-2.3] mmol/L). A statistically significant increase in HDL-C and LDL-C over time during the ICU stay was found. There was no relationship between HDL-C and LDL-C concentrations and mortality on day 28 (log-rank p = 0.554 and p = 0.083, respectively). A comparison of alive and dead patients on day 28 did not reveal any differences in HDL-C and LDL-C concentrations over time. Bacterial VAP was frequent (64%). An association was observed between HDL-C and LDL-C concentrations on the day of the first VAP diagnosis and mortality ([HDL-C] = 0.6[0.5-0.9] mmol/L in survivors vs. [HDL-C] = 0.5[0.3-0.6] mmol/L in nonsurvivors, p = 0.036; [LDL-C] = 2.2[1.9-3.0] mmol/L in survivors vs. [LDL-C] = 1.3[0.9-2.0] mmol/L in nonsurvivors, p = 0.006). CONCLUSION: HDL-C and LDL-C concentrations upon ICU admission are low in severe COVID-19 pneumonia patients but are not associated with poor outcomes. However, low lipoprotein concentrations in the case of bacterial superinfection during ICU hospitalization are associated with mortality, which reinforces the potential role of these particles during bacterial sepsis.