Search Results (590)

Introduction: Ventilator-associated pneumonia (VAP) is associated with increased morbidity and mortality. Early-onset (EOVAP) and late-onset (LOVAP) VAP differ in risk factors, microbiology, and outcomes. Methods: A retrospective cohort study of adult ICU patients admitted to a tertiary hospital between May 2020 and May 2022 compared EOVAP and LOVAP. Results: 194 patients were included (73.7% male), with a median age of 61 years. A total of 70.6% were admitted to the ICU for infection-related respiratory failure, predominantly due to COVID-19 (59.3%). EOVAP represented 21% and LOVAP 79% of cases, with median days to diagnosis of 4 and 11, respectively. Empirical antibiotic therapy was adequate in both groups; de-escalation was possible in 26.8%, and escalation due to treatment failure was required in 13.4%. The most commonly prescribed initial antibiotic was piperacillin–tazobactam (45%). Broad-spectrum antibiotic use did not differ between groups. Amoxicillin–clavulanate resistance was high in both groups (LOVAP 62.1%; EOVAP 48.8%), and piperacillin–tazobactam resistance was more frequent in LOVAP (41.2%). Follow-up cultures showed a high persistence rate (73.2%), with no significant change in resistance patterns. Conclusions: VAP remains common in the ICU, and the COVID-19 pandemic significantly impacted the already complex epidemiology of VAP. High resistance rates to amoxicillin–clavulanate and frequent isolation of MDR pathogens challenge empirical treatment based on onset timing, supporting empiric antibiotic selection guided by local microbiological ecology. Full article

Pulmonary hypertension complicating chronic obstructive pulmonary disease (COPD-PH) has a worse prognosis than airflow limitation alone but its pathogenesis is thought to be primarily due to alveolar hypoxia affecting pulmonary circulation. Two observations are not fully explained by this model. First, the majority of exacerbations of COPD are infectious and there is a stable frequent-exacerbator phenotype that is not fully accounted for by spirometric severity. Second, the airways of COPD are not sterile. They are home to a resident microbial community that changes as the disease progresses and the gut microbial community also undergoes disease-associated changes. This review examines whether microbial factors actively contribute to pulmonary vascular remodelling or merely reflect advanced disease. Three candidate exposures are considered: chronic airway colonisation, dysbiosis of the airway and gut communities and recurrent infectious exacerbation. We then examine the virulence mechanisms and host-recognition pathways of non-typeable Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa, rhinovirus, influenza viruses, respiratory syncytial virus and SARS-CoV-2. We then trace the pathways linking microbial recognition to vascular injury: Toll-like receptor signalling and NF-κB activation; interleukin-6, tumour necrosis factor-α and interleukin-1β; endothelin-1 upregulation against nitric oxide depletion; reactive oxygen species and hypoxia-inducible factor signalling converging with hypoxic pulmonary vasoconstriction; and, along the gut–lung axis, lipopolysaccharide translocation, trimethylamine N-oxide and depletion of short-chain fatty acid-producing taxa. Therapeutically, there is evidence and a vascular rationale for interventions that decrease exacerbation frequency. Pulmonary vasodilators have a sound physiological rationale, although their clinical efficacy is frequently limited by worsening ventilation–perfusion mismatch. Current evidence supports biological plausibility rather than demonstrated causality: no direct longitudinal human study has established that microbial alterations or microbial exposure cause pulmonary vascular remodelling in COPD-PH. We identify study designs capable of directly testing this hypothesis. Full article

Objectives: The collaborative “Stop Hospital Infection 2.0”, implemented in Portugal between 2023 and 2025, aimed to reduce the incidence of catheter-associated urinary tract infection (CAUTI), ventilator-associated pneumonia (VAP) and central-line associated bloodstream infection (CLABSI) by 50.0% in 21 hospitals. Methods: The project followed the Breakthrough Series methodology. Each team was to audit the national preventive bundles, using a Kamishibai card, and drive changes using plan–do–study–act cycles. Before the project, teams reported their 6-month baseline incidence levels. The main outcome was the incidence of infection. The secondary outcome was the proportion of teams that achieved a ≥50.0% reduction in incidence. The number of infections, deaths and bed-days potentially prevented, and costs saved during the project were estimated, along with the potential gains in the future. Results: Incidence rate for teams reporting at least 36 months decreased 47.6% in CAUTI (4.8 to 2.5 infections/1000 device-days), 66.1% in CLABSI (1.5 to 0.5 infections/1000 device-days) and 50.0% in VAP (9.9 to 5.0 infections/1000 intubation-days). The proportion of teams achieving a reduction of at least 50% in infection incidence was 60.0%, 100% and 57.1%, respectively. Teams reporting ≥24 months may have prevented 465 HAI, 108 deaths, 4526 bed-days and saved 8,375,841 euros. In the future, the teams who reported for at least 36 months may avoid 150 cases, 36 deaths, 1538 bed-days and 2,693,546 euros, yearly. Conclusions: A national collaborative focused on evidence-based bundles may be effective in decreasing the incidence of CAUTI, CLABSI and VAP in adult intensive care units. Full article

Ventilator-associated pneumonia (VAP) is a life-threatening condition most frequently associated with the use of endotracheal tubes (ETs). This study describes the development of macroporous p(HEMA) hydrogels as removable antimicrobial liners for ETs to help prevent VAP. Hydrogels were prepared by free-radical polymerisation using varying sodium chloride concentrations and 40% or 60% w/w water. Increasing NaCl concentration enhanced porosity but reduced mechanical strength and improved swelling and gentamicin loading of hydrogels containing 60% w/w but not 40% w/w water. Gentamicin release was more controlled at lower NaCl concentrations, whereas hydrogels with higher porosity promoted rapid release. The formulation containing 60% w/w water and 0.1 M NaCl provided the best balance of mechanical integrity, drug uptake, sustained antimicrobial activity, and reduced bacterial adherence. Nebulisation studies showed that gentamicin-loaded hydrogels eradicated adherent bacteria and prevented recovery of viable organisms after repeated bacterial challenges. These findings indicate that macroporous p(HEMA) hydrogel liners offer a promising strategy for reducing endotracheal tube-associated infection. Full article

Background/Objectives: Healthcare-associated infections (HAIs) frequently complicate aneurysmal subarachnoid hemorrhage (aSAH) requiring neurocritical care. We assessed their incidence, timing, microbiology, associated factors, and outcomes. Methods: This retrospective, single-center cohort study included 106 consecutive adults with acute aSAH admitted to a neurocritical care unit during 2019–2024. Time to first HAI was analyzed using cause-specific Cox regression with competing risks; to limit immortal-time bias, HAI was modeled as a time-dependent exposure in outcome analyses. Results: HAIs occurred in 47 patients (44.3%; 95% CI 35.2–53.8); median onset was 10 days (IQR 8–12). Seventy-six episodes were recorded; site-specific figures denote affected patients, with no recurrent same-site episodes: ventilator-associated pneumonia, 30 (28.3%); catheter-associated urinary tract infection, 24 (22.6%); cerebrospinal fluid infections, 13 (12.3%); and central line-associated bloodstream infection, 9 (8.5%). Acinetobacter baumannii predominated, accounting for all extensively drug-resistant isolates. High World Federation of Neurosurgical Societies grade was associated with the first HAI (HR 4.168; 95% CI 2.072–8.384), as was higher modified Fisher grade in sensitivity analysis (HR 2.886; 95% CI 1.237–6.735). Time-dependent HAI was associated with a lower hazard of live discharge (HR 0.295; 95% CI 0.164–0.529) but not with in-hospital mortality (HR 1.178; 95% CI 0.478–2.902). Its association with the discharge Glasgow Outcome Scale (GOS) was threshold-dependent (GOS ≤ 1: OR 0.715, 95% CI 0.264–1.933; GOS ≤ 3: OR 7.939, 95% CI 2.580–24.436). Conclusions: HAIs affected nearly half of this cohort. Greater initial severity was associated with a higher hazard of first HAI; HAI, in turn, was associated with prolonged hospitalization and unfavorable functional outcome, but not with mortality. These associations are observational, not causal. Surveillance, timely diagnosis, and infection prevention remain integral to neurocritical care in aSAH. Full article

Background: Optimal tracheostomy timing remains controversial due to conflicting evidence across published systematic reviews. To clarify this ambiguity within specific patient populations (critically ill, traumatic brain injury, stroke, trauma, COVID-19, and spinal cord injury), an umbrella review of systematic reviews was conducted comparing early versus late tracheostomy or prolonged intubation. Additionally, potential benefits in clinical outcomes were evaluated across a mixed-etiology cohort of mechanically ventilated patients. Methods: MEDLINE, Embase, Cochrane Library, and Web of Science were searched from inception through July 2024. Systematic reviews evaluating the impact of tracheostomy timing on mechanical ventilation duration, ventilator-associated pneumonia risk, ICU/hospital length of stay, and mortality were included. Two authors independently extracted data using a standardized form. Methodological quality was assessed via AMSTAR 2 and certainty of evidence via GRADE. Random-effects meta-analyses were conducted for each outcome, stratified by study design (RCTs vs. non-RCTs), with subgroup analyses exploring patient subpopulations. Results: Evidence was synthesized from 9 systematic reviews (24 unique RCTs, 54 non-RCTs). In RCTs, moderate certainty evidence suggests that early tracheostomy reduces ventilator-associated pneumonia (OR 0.66, 95% CI 0.46 to 0.94, p = 0.02) and mechanical ventilation duration (MD −3.76 days, 95% CI −6.01 to −1.52, p < 0.001) compared to late tracheostomy or prolonged intubation. Early tracheostomy may reduce ICU length of stay (MD −6.64 days, 95% CI −9.92 to −3.35, p < 0.001, low certainty). The effect of early tracheostomy on hospital length of stay and mortality remains uncertain. Conclusions: Early tracheostomy shows potential to reduce ventilator-associated pneumonia and mechanical ventilation duration in mixed-etiology cohorts. It may also be associated with shorter ICU length of stay, while its effect on mortality and hospital stay remains uncertain. Future research should establish standardized definitions of tracheostomy timing and prioritize high-quality, etiology-specific RCTs in underrepresented cohorts (e.g., traumatic brain injury, stroke, spinal cord injury). Full article

Background: Precision diagnostics are more and more important in intensive care units (ICUs), where rapid identification of infectious agents and antimicrobial resistance determinants is crucial for timely and appropriate treatment. Conventional microbiological methods are frequently limited by long turnaround times and reduced sensitivity, which may delay appropriate treatment. Nanopore sequencing allows rapid, direct, and long-read sequencing of DNA/RNA molecules without the need for amplification, avoiding biases introduced by NGS during amplification and library preparation and generating data in real time. Objectives: This narrative review aims to summarize current knowledge of nanopore technology in the ICU, discuss nanopore principles and current clinical applications in intensive care medicine, highlight its advantages and limitations, and explore future perspectives for integrating nanopore-based diagnostics into precision critical care. Methods: A literature search was performed using PubMed and Web of Science. The literature search was conducted with no lower restriction, covering English-language publications. Results: Nanopore sequencing enables real-time, long-read, single-molecule analysis of native nucleic acid molecules, rapid pathogen identification, antimicrobial resistance profiling, metagenomic analysis, and direct sequencing without amplification. Recent studies have proved the clinical utility of nanopore sequencing in critically ill patients with sepsis, bloodstream infections, hospital-acquired pneumonia, ventilator-associated pneumonia, and fungal and viral infections. Its portability, rapid turnaround time, and potential for point-of-care implementation make it particularly attractive for ICU settings. Conclusions: Nanopore sequencing technology represents a promising molecular diagnostic tool, but wider clinical implementation warrants further larger studies with clinical outcome endpoints, standardized bioinformatic pipelines, and clearer validation pathways. Full article

Acute respiratory distress syndrome (ARDS) represents a major cause of morbidity and mortality in critically ill patients and is most frequently triggered by severe respiratory infections, including nosocomial pneumonia. Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) are highly prevalent in intensive care units and share overlapping pathophysiological mechanisms with ARDS. Despite this close interrelationship, the proportion of patients with nosocomial pneumonia who subsequently develop ARDS remains poorly defined, underscoring the need to identify potential predisposing factors and improve early recognition of patients at risk. While the development of pneumonia in patients with an established diagnosis of ARDS has been extensively investigated, limited data are available on patients who develop ARDS as a complication of HAP/VAP. This narrative review summarizes the limited direct evidence on this topic and discusses potential clinical characteristics, risk factors, and predictive tools, while considering indirect evidence from CAP and broader ARDS populations. Full article

Background/Objectives: Acinetobacter baumannii is a major cause of infections in Intensive Care Units (ICUs), driving mortality through high-level antimicrobial resistance. This study utilized whole-genome sequencing (WGS) to evaluate the phenotypic, genotypic and virulence features of carbapenem-resistant A. baumannii (CRAB), which has caused ventilator-associated pneumonia/tracheobronchitis (VAP/VAT) in the ICU of the University Hospital of Split, Croatia. Methods: Over 1 year, lower respiratory tract specimens from 79 VAP/VAT patients were analyzed. CRAB isolates were identified via MALDI-TOF MS and evaluated for antimicrobial susceptibility, and a representative subset underwent WGS and multilocus sequence typing (MLST). Results: Out of 106 specimens, 18 non-duplicate CRAB strains were isolated. Five isolates underwent genomic analysis, identifying two globally distributed, high-risk Pasteur lineages: ST2 and ST492. These lineages displayed distinct resistomes: ST2 carried bla_OXA-23 and bla_ADC-73, while ST492 harbored plasmid-borne bla_OXA-72 (Rep3-T1/AB082 cluster) and bla_ADC-30. All isolates shared aminoglycoside/macrolide-resistance genes, conserved efflux pumps, and virulence determinants (bau, bas, ent, bar) crucial for acinetobactin synthesis and respiratory colonization. Phylogenetic analysis confirmed regional circulation and genetic links to neighboring countries. Conclusions: This study highlights the evolutionary dynamics of endemic CRAB lineages in a Croatian ICU and their global dissemination, which poses a critical threat, demanding strict infection control and novel therapeutics. Full article

Background: Pandrug-resistant (PDR) Acinetobacter baumannii represents a major therapeutic challenge in regions where carbapenem-resistant A. baumannii (CRAB) is endemic. Whether the PDR phenotype independently worsens clinical outcomes beyond the effects of disease severity and therapeutic limitations remains uncertain. This study compared the characteristics, management, and outcomes of severe infections caused by PDR and carbapenem-resistant, colistin-susceptible A. baumannii. Methods: We conducted a retrospective analysis of prospectively collected data across 11 tertiary-care hospitals in Greece (February 2022–June 2024). Consecutive adults with bloodstream infection or hospital-acquired/ventilator-associated pneumonia caused by CRAB or PDR A. baumannii were enrolled. The primary outcome was 14-day clinical failure; secondary outcomes included 28-day mortality, microbiological eradication, organ dysfunction, and organ-support-free days. Multivariable logistic and Cox regression analyses, before and after propensity score matching, were performed to adjust for confounding. Results: Among 142 patients, 91 (64%) had PDR and 51 (36%) had carbapenem-resistant, colistin-susceptible infections. Clinical failure occurred in 41% of patients and did not differ significantly between PDR and CRAB infections (39% vs. 45%; p = 0.440). Twenty-eight-day mortality was 33% and 22%, respectively (p = 0.139). After adjustment, the PDR phenotype was not independently associated with clinical failure or mortality. Higher APACHE II score and pneumonia independently predicted clinical failure, whereas sulbactam-containing therapy was associated with lower odds of failure (OR 0.24, 95% CI 0.07–0.79). Older age, higher SOFA score, impaired lactate clearance, and tigecycline-containing therapy independently predicted 28-day mortality. In matched analysis, PDR showed a non-significant upward trend in 28-day mortality (HR 2.36, 95% CI 0.97–5.76; p = 0.059). Conclusions: In severe A. baumannii infections, the PDR phenotype was not an independent determinant of clinical failure or short-term mortality. Patient severity and antimicrobial strategy were major outcome correlates; treatment associations should be interpreted cautiously given the observational design. Full article

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with substantial morbidity and mortality, highlighting the need for simple and reliable biomarkers for early risk stratification. The C-reactive protein to albumin ratio (CAR) and the modified Glasgow Prognostic Score (mGPS) reflect systemic inflammation and nutritional status, but their prognostic value in hospitalized patients with AECOPD remains incompletely defined. This study aimed to evaluate the associations of CAR and mGPS with one-year mortality and indicators of disease severity in hospitalized patients with AECOPD. Methods: In this retrospective single-center cohort study, 1556 adult patients hospitalized with a primary diagnosis of AECOPD between January 2020 and January 2026 were included. Patients with concomitant pneumonia and other major inflammatory conditions were excluded. Demographic, clinical, laboratory, arterial blood gas, and pulmonary function data were retrospectively analyzed. CAR was calculated from admission C-reactive protein and serum albumin levels, whereas mGPS was determined according to established criteria. Independent predictors of one-year mortality were identified using multivariable logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminatory performance of CAR. Results: During the one-year follow up, 140 patients (9.0%) died. Compared with survivors, non-survivors had significantly higher CRP levels, higher CAR values, lower serum albumin levels, more severe hypercapnia and acidosis, and higher rates of intensive care unit admission and invasive mechanical ventilation (all p < 0.001). The distribution of mGPS differed significantly according to mortality status, with patients in the mGPS 2 category exhibiting the highest mortality rates (p < 0.001). After adjustment for clinically relevant covariates, age, acidosis, invasive mechanical ventilation, and CAR remained independently associated with one-year mortality. CAR demonstrated excellent discriminatory performance for predicting one-year mortality (AUC 0.907, 95% CI 0.893–0.922; p < 0.001), with an optimal cut-off value of >3.96, yielding 98.6% sensitivity and 84.3% specificity. Increasing mGPS scores were associated with progressively worse clinical outcomes, including higher rates of intensive care unit admission, invasive mechanical ventilation, in-hospital mortality, and one-year mortality. Conclusions: Inflammation and nutrition-based biomarkers are closely associated with disease severity and one-year mortality in hospitalized patients with AECOPD. CAR remained an independent predictor of one-year mortality and demonstrated excellent discriminatory performance, supporting its role as a simple and readily available complementary biomarker for prognostic assessment. Increasing mGPS scores were associated with progressively worse clinical outcomes, suggesting that mGPS may also contribute to risk stratification in hospitalized patients with AECOPD. Prospective multicenter studies with external validation are warranted to confirm these findings and to further define the prognostic value of these biomarkers. Full article

Background: Legionella pneumophila is a rare but severe cause of community-acquired pneumonia and can lead to acute respiratory distress syndrome (ARDS). Awake prone positioning (APP) has been recognized as an effective adjunct for non-intubated patients with hypoxemic respiratory failure, primarily studied in coronavirus disease 2019 (COVID-19) and other ARDS etiologies. Its application in Legionella-associated ARDS remains poorly documented. Therefore, in this work, we present a case of Legionella-associated ARDS successfully managed with APP, high-flow nasal cannula (HFNC), non-invasive ventilation (NIV), levofloxacin, and corticosteroids. Case presentation: A 62-year-old male with multiple comorbidities, including type 2 diabetes mellitus (T2DM) and a history of coronary artery bypass surgery, presented with a 3-day history of productive cough, exertional dyspnea, and general malaise. Oxygen saturation on admission was 90%, with fever and tachycardia. Inflammatory markers were markedly elevated. Chest computed tomography (CT) revealed extensive bilateral pulmonary infiltrates. Despite a negative urinary Legionella antigen test, sputum polymerase chain reaction (PCR) confirmed Legionella pneumophila on day 2. A Horowitz index of 147 mmHg on day 2 established moderate ARDS. The patient was treated with HFNC oxygen therapy, NIV, and APP for up to 12 h daily. Antibiotic therapy was initiated with amoxicillin/clavulanic acid and clarithromycin, subsequently streamlined to levofloxacin upon microbiological confirmation. Methylprednisolone 40 mg/day was administered for 8 days as adjunctive ARDS therapy. The patient demonstrated gradual clinical and respiratory improvement without requiring endotracheal intubation. Follow-up chest CT on day 7 showed regression of bilateral consolidations and ground-glass opacities (GGOs). The patient was transferred to pulmonary rehabilitation on day 11 and completed antibiotic therapy as an outpatient. Conclusions: This case illustrates the successful use of APP combined with HFNC and NIV alongside standard medical therapies, including appropriate antibiotics and corticosteroids, to avoid intubation in moderate ARDS secondary to Legionella pneumonia. Early initiation of APP may be a valuable strategy in Legionella-associated ARDS in carefully selected patients. Full article

Mucosal microbiota contribute broadly to host defense and immune homeostasis, while the lung and gut microbiota form a particularly important bidirectional ecological and immunological network that shapes pulmonary host defense, inflammatory injury, and tissue repair. In pneumonia, loss of colonization resistance and altered microbial metabolite production may weaken innate and adaptive immunity; respiratory infection, antibiotics, and critical-care exposures can, in turn, remodel both microbial communities. In acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), intestinal barrier failure, circulating microbial products, immune cell trafficking and, in selected settings, lymphatic or hematogenous dissemination of gut-derived organisms may aggravate alveolar–capillary injury. Alveolar macrophages integrate these signals through pattern-recognition, metabolic, and epigenetic pathways, linking microbial ecology to pathogen clearance and inflammatory resolution. The evidence, however, remains uneven. Mechanistic causality rests largely on animal studies, most human data are associative, and trials of microbiota-directed interventions are heterogeneous and strain-specific. This Review examines bacterial and viral pneumonia, sepsis-associated ALI and ventilator-associated injury; separates mechanistic, observational, and interventional evidence; and evaluates probiotics, live biotherapeutic products, microbial metabolites, and dietary approaches. Translation will depend on longitudinal sampling, source-resolved microbial tracking, metabolite-informed patient stratification, and adequately powered trials with clinically relevant endpoints. Full article

Background/Objectives: Retained airway secretions are a common complication of mechanical ventilation and a major contributor to ventilator-associated pneumonia. Airway Pressure Release Ventilation following a Time-Controlled Adaptive Ventilation protocol (APRV-TCAV) has been anecdotally observed to improve secretion clearance, but the mechanism is not well established. Because TCAV sets the release time (TLow) from each patient’s own expiratory flow decay, we hypothesized that the resulting expiratory-dominant flow profile would generate a net antegrade force on secretions. This bench study compared secretion movement between APRV-TCAV and conventional Volume-Control Continuous Mandatory Ventilation (VC-CMV), with and without an in-line oscillatory device. Methods: A critical care ventilator was connected to a 3 L test lung via a 7 mm endotracheal tube (ETT). Simulated mucus (1% guar gum) was instilled into the ETT, and secretion movement was measured under VC-CMV (positive end-expiratory pressure (PEEP) 5, 10, 15 cmH₂O) and APRV-TCAV (PHigh 20, 25, 30 cmH₂O; PLow 0 cmH₂O). Each condition was repeated with an in-line oscillatory device. Results: All VC-CMV settings produced retrograde secretion movement toward the test lung; all APRV-TCAV settings produced antegrade movement. The largest antegrade movement was observed at the widest PHigh-to-PLow differential. Adding the oscillatory device raised peak expiratory flow above peak inspiratory flow in every condition, yet abolished antegrade movement under APRV-TCAV. Conclusions: In this bench study, APRV-TCAV reversed the direction of secretion movement within the ETT, with larger antegrade movement at wider PHigh-to-PLow differentials. This suggests a potential mechanism by which the ventilator flow profile itself may influence secretion movement. The directional effect depended on the intact release-phase waveform and was abolished by in-line oscillatory therapy despite preserved peak flow asymmetry. Full article

Background/Objectives: Whether the prognostic contribution of low skeletal muscle mass varies with age in ventilated patients is untested. We assessed whether the association between low computed tomography (CT)-derived thoracic muscle area and ventilator-liberation outcomes differs by age. Methods: This single-center retrospective cohort included 607 adults with pneumonia requiring invasive ventilation in the intensive care unit (ICU) between 2016 and 2021. Thoracic muscle area was quantified by deep-learning segmentation of the whole thoracic musculature (first to twelfth thoracic vertebra) on the chest CT obtained closest to ICU admission and normalized to the length of the thoracic spine (median offset 0 days; 86% within ±7 days, before or after); low thoracic muscle area was the sex-specific lowest quartile. The primary outcome was composite weaning failure (extubation failure, tracheostomy, or ventilation >21 days). Multivariable logistic regression stratified at 75 years tested a muscle-area-by-age interaction. Results: Composite weaning failure occurred in 290 patients (47.8%). In fully adjusted complete-case models (n = 539), low thoracic muscle area was associated with composite weaning failure in younger patients (adjusted odds ratio 3.63; 95% CI 1.67–7.87) but not significantly in older patients (1.68; 0.91–3.13); the age interaction was not significant (p = 0.061) and was removed by height-normalization and by correction for multiple comparisons. A graded association across muscle-area quartiles was present in both strata (lowest vs. highest quartile: younger 4.79, older 2.53). Low thoracic muscle area was not associated with ICU mortality in either stratum, although an exploratory landmark analysis showed higher 7-day mortality in younger patients with low muscle area (20.6% vs. 10.8%). Conclusions: Low CT-derived thoracic muscle area was associated with composite weaning failure in both age strata, with a larger point estimate in patients younger than 75 years, although the age interaction was not significant in the fully adjusted model and was removed by height-normalization and by correction for multiple comparisons. The graded association in both age strata is hypothesis-generating and requires prospective validation. Full article