Bacterial Pneumonia in Brain-Dead Patients: Clinical Features and Impact on Lung Suitability for Donation.

OBJECTIVES: To appraise the epidemiological features of bacterial pneumonia and its impact on lung suitability for donation in brain-dead patients managed with protective ventilatory settings. DESIGN: Retrospective observational study. SETTING: Six ICUs from two university-affiliated hospitals. PATIENTS: Brain-dead adult patients managed in the participating ICUs over a 4-year period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 231 included patients, 145 (62.8%) were classified as ideal or extended-criteria potential lung donors at ICU admission and the remaining 86 patients having baseline contraindication for donation. Culture-proven aspiration pneumonia and early-onset ventilator-associated pneumonia occurred in 54 patients (23.4%) and 15 patients (6.5%), respectively (overall pneumonia incidence, 29.9%). Staphylococcus aureus and Enterobacterales were the most common pathogens. Using mixed-effects Cox proportional hazard models, age (adjusted hazard ratio, 0.98; 95% CI [0.96-0.99]), anoxic brain injury (3.55 [1.2-10.5]), aspiration (2.29 [1.22-4.29]), and not receiving antimicrobial agents at day 1 (3.56 [1.94-6.53]) were identified as independent predictors of pneumonia occurrence in the whole study population. Analyses restricted to potential lung donors yielded similar results. Pneumonia was associated with a postadmission decrease in the PaO2/FIO2 ratio and lower values at brain death, in the whole study population (estimated marginal mean, 294 [264-323] vs 365 [346-385] mm Hg in uninfected patients; p = 0.0005) as in potential lung donors (299 [248-350] vs 379 [350-408] mm Hg; p = 0.04; linear mixed models). Lungs were eventually retrieved in 31 patients (34.4%) among the 90 potential lung donors with at least one other organ harvested (pneumonia prevalence in lung donors (9.7%) vs nondonors (49.2%); p = 0.0002). CONCLUSIONS: Pneumonia occurs in one-third of brain-dead patients and appears as the main reason for lung nonharvesting in those presenting as potential lung donors. The initiation of antimicrobial prophylaxis upon the first day of the ICU stay in comatose patients with severe brain injury could enlarge the pool of actual lung donors.

Antibiotics with activity against intestinal anaerobes and the hazard of acquired colonization with ceftriaxone-resistant Gram-negative pathogens in ICU patients: a propensity score-based analysis.

BACKGROUND: Intestinal colonization resistance is mainly exerted by commensal anaerobes. OBJECTIVES: To assess whether exposure to non-carbapenem antibiotics with activity against intestinal anaerobes (namely, piperacillin/tazobactam, amoxicillin/clavulanate and metronidazole) may promote the acquisition of gut colonization with ceftriaxone-resistant Gram-negative bacteria (CFR-GNB) in ICU patients. PATIENTS AND METHODS: All patients with a first stay >3 days in a single surgical ICU over a 30 month period were retrospectively included. Rectal carriage of CFR-GNB (i.e. ESBL-producing Enterobacteriaceae, AmpC-hyperproducing Enterobacteriaceae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and CFR Acinetobacter baumannii) was routinely screened for at admission then weekly. The impact of anti-anaerobe antibiotics was investigated in propensity score (PS)-matched cohorts of patients exposed and not exposed to these drugs and through PS-based inverse probability of treatment weighting on the whole study cohort, treating in-ICU death or discharge as competing risks for CFR-GNB acquisition. RESULTS: Among the 352 included patients [median ICU stay 16 (9-30) days, in-ICU mortality 12.2%], 120 (34.1%) acquired one or more CFR-GNB, mostly AmpC-hyperproducing Enterobacteriaceae (17.6%) and P. aeruginosa (14.8%). Exposure to anti-anaerobe antibiotics was the main predictor of CFR-GNB acquisition in both the PS-matched cohorts [adjusted HR (aHR) 3.92, 95% CI 1.12-13.7, P = 0.03] and the whole study cohort (aHR 4.30, 95% CI 1.46-12.63, P = 0.01). Exposure to other antimicrobials-especially ceftriaxone and imipenem/meropenem-exerted no independent impact on the likelihood of CFR-GNB acquisition. CONCLUSIONS: Exposure to non-carbapenem antibiotics with activity against intestinal anaerobes may predispose to CFR-GNB acquisition in ICU patients. Restricting the use of these drugs appears to be an antibiotic stewardship opportunity.

Clinical impact of ventilator-associated pneumonia in patients with the acute respiratory distress syndrome: a retrospective cohort study.

BACKGROUND: The clinical impact and outcomes of ventilator-associated pneumonia (VAP) have been scarcely investigated in patients with the acute respiratory distress syndrome (ARDS). METHODS: Patients admitted over an 18-month period in two intensive care units (ICU) of a university-affiliated hospital and meeting the Berlin criteria for ARDS were retrospectively included. The association between VAP and the probability of death at day 90 (primary endpoint) was appraised through a Cox proportional hazards model handling VAP as a delay entry variable. Secondary endpoints included (i) potential changes in the PaO2/FiO2 ratio and SOFA score values around VAP (linear mixed modelling), and (ii) mechanical ventilation (MV) duration, numbers of ventilator- and vasopressor-free days at day 28, and length of stay (LOS) in patients with and without VAP (median or absolute risk difference calculation). Subgroup analyses were performed in patients with COVID-19-related ARDS and those with ARDS from other causes. RESULTS: Among the 336 included patients (101 with COVID-19 and 235 with other ARDS), 176 (52.4%) experienced a first VAP. VAP induced a transient and moderate decline in the PaO2/FiO2 ratio without increase in SOFA score values. VAP was associated with less ventilator-free days (median difference and 95% CI, - 19 [- 20; - 13.5] days) and vasopressor-free days (- 5 [- 9; - 2] days) at day 28, and longer ICU (+ 13 [+ 9; + 15] days) and hospital (+ 11.5 [+ 7.5; + 17.5] days) LOS. These effects were observed in both subgroups. Overall day-90 mortality rates were 35.8% and 30.0% in patients with and without VAP, respectively (P = 0.30). In the whole cohort, VAP (adjusted HR 3.16, 95% CI 2.04-4.89, P < 0.0001), the SAPS-2 value at admission, chronic renal disease and an admission for cardiac arrest predicted death at day 90, while the COVID-19 status had no independent impact. When analysed separately, VAP predicted death in non-COVID-19 patients (aHR 3.43, 95% CI 2.11-5.58, P < 0.0001) but not in those with COVID-19 (aHR 1.19, 95% CI 0.32-4.49, P = 0.80). CONCLUSIONS: VAP is an independent predictor of 90-day mortality in ARDS patients. This condition exerts a limited impact on oxygenation but correlates with extended MV duration, vasoactive support, and LOS.