Ventilator-Associated Pneumonia in COVID-19 Patients Admitted in Intensive Care Units: Relapse, Therapeutic Failure and Attributable Mortality—A Multicentric Observational Study from the OutcomeRea Network

Abstract

Introduction: Ventilator-associated pneumonia (VAP) incidence is high among critically ill COVID-19 patients. Its attributable mortality remains underestimated, especially for unresolved episodes. Indeed, the impact of therapeutic failures and the determinants that potentially affect mortality are poorly evaluated. We assessed the prognosis of VAP in severe COVID-19 cases and the impact of relapse, superinfection, and treatment failure on 60-day mortality. Methods: We evaluated the incidence of VAP in a multicenter prospective cohort that included adult patients with severe COVID-19, who required mechanical ventilation for ≥48 h between March 2020 and June 2021. We investigated the risk factors for 30-day and 60-day mortality, and the factors associated with relapse, superinfection, and treatment failure. Results: Among 1424 patients admitted to eleven centers, 540 were invasively ventilated for 48 h or more, and 231 had VAP episodes, which were caused by Enterobacterales (49.8%), P. aeruginosa (24.8%), and S. aureus (22%). The VAP incidence rate was 45.6/1000 ventilator days, and the cumulative incidence at Day 30 was 60%. VAP increased the duration of mechanical ventilation without modifying the crude 60-day death rate (47.6% vs. 44.7% without VAP) and resulted in a 36% increase in death hazard. Late-onset pneumonia represented 179 episodes (78.2%) and was responsible for a 56% increase in death hazard. The cumulative incidence rates of relapse and superinfection were 45% and 39.5%, respectively, but did not impact death hazard. Superinfection was more frequently related to ECMO and first episode of VAP caused by non-fermenting bacteria. The risk factors for treatment failure were an absence of highly susceptible microorganisms and vasopressor need at VAP onset. Conclusions: The incidence of VAP, mainly late-onset episodes, is high in COVID-19 patients and associated with an increased risk of death, similar to that observed in other mechanically ventilated patients. The high rate of VAP due to difficult-to-treat microorganisms, pharmacokinetic alterations induced by renal replacement therapy, shock, and ECMO likely explains the high cumulative risk of relapse, superinfection, and treatment failure.

After SARS-CoV-2 Pandemics: New Insights into ICU-Acquired Pneumonia

“…In fact, VAP is the most important nosocomial infection we have faced during the pandemics. In a retrospective analysis of mechanically ventilated SARS-CoV-2 ARF in France, Moreno et al reported an incidence of more than 50% [ 8 ], which is consistent with the findings of the French multicenter OUTCOME-REA group and a systematic literature review [ 9 ]. All studies reported a high risk of VAP, mainly occurring late during mechanical ventilation, due to Staphylococcus aureus, non-fermentative Gram-negative bacteria, and multidrug-resistant Enterobacterales.…”

“…All studies reported a high risk of VAP, mainly occurring late during mechanical ventilation, due to Staphylococcus aureus, non-fermentative Gram-negative bacteria, and multidrug-resistant Enterobacterales. VAP occurred in the most severe patients, who were more likely to receive corticosteroids, and is associated with low viral clearance [ 8 , 9 , 10 ].…”

Antimicrobial resistance burden pre and post-COVID-19 pandemic with mapping the multidrug resistance in Egypt: a comparative cross-sectional study

“…In the same vein, Pałka et al 29 demonstrated high prevalence of XDR organisms of 22.6% in the intensive care unit (ICU) and 14.8% in non-ICUs among all isolate especially XDR- A. baumannii . Increasing MDR post COIVD-19 might be linked to human factors including delayed care, increasing device usage, and inappropriate use of antibiotics in the trial of treat the complications of COVID-19 pandemic 3 , 30 . The disparity in the distribution of MDR and XDR in Egypt before and after the pandemic could be attributed to the different AMR response plans in each governorate, highlighting the importance of developing a national AMR response plan for Egypt.…”

Cefiderocol Treatment for Severe Infections due to Difficult-to-Treat-Resistant Non-Fermentative Gram-Negative Bacilli in ICU Patients: A Case Series and Narrative Literature Review

“…The high rate of relapse could be partially explained by the proportion of patients with SARS-CoV-2 acute respiratory failure and VAP. Relapses and superinfections were more frequently seen in those particular patients, with identified risk factors, such as being treated for non-fermentative GNB infections, requiring ECMO, and being treated with other broad-spectrum antimicrobials [ 41 ]. Despite acceptable plasma trough level, concentration obtained in the alveolar fluid may have been insufficient to eradicate the high inoculum of DTR non-fermentative GNB recovered from VAP episodes [ 26 ].…”