Search Results (47)

Background/Objectives: Severe community-acquired pneumonia (CAP) can be fatal and requires the rapid and appropriate administration of antibiotics. Rapid multiplex PCR pneumonia panels are widely used tools for antimicrobial de-escalation and stewardship; however, their role in driving antibiotic escalation in severe pneumonia requiring intensive care is less well characterized. Methods: We retrospectively analyzed 288 adults with severe CAP who were admitted to the intensive care unit (ICU) of a tertiary hospital and underwent lower-respiratory BioFire FilmArray Pneumonia Panel (BFPP) testing between April 2023 and September 2024. The primary outcome was antibiotic escalation, defined as addition of an agent or a change to broader-spectrum therapy after the BFPP result, and its associated factors. Secondary outcomes were in-hospital mortality, hospital and ICU length of stay (LOS), and ventilator duration according to the antibiotic escalation. Results: Patients were elderly (median 72 years old; 60.8% male) and critically ill (median SOFA 8; median APACHE-II 19; shock 49.0%; mechanical ventilation 56.9%). The panel was positive in 66.3% of cases, and results were obtained with a median turnaround time of 2 h versus 67 h for sputum culture. After the panel, antibiotics were escalated in 34.0% of cases, de-escalated in 2.8%, discontinued in 0.7%, and unchanged in 62.5%. Escalation was independently associated with resistance gene detection (adjusted odds ratio [aOR] 3.15, 95% CI 1.71–5.82), panel positivity (aOR 1.97, 95% CI 1.02–3.80), and SOFA score (aOR 1.10 per point, 95% CI 1.01–1.19). Thirty-day mortality, in-hospital mortality, hospital LOS, ICU LOS, and ventilator duration did not differ between escalation and non-escalation groups. Conclusions: In severe CAP requiring intensive care and managed with a comparatively narrow initial empirical regimen, panel testing was predominantly followed by antibiotic escalation rather than de-escalation, particularly when resistance genes were detected. No statistically measurable difference in clinical outcomes was observed, but the study was not powered to exclude any clinically meaningful benefit or harm of escalation. Full article

Background: Ventilator-associated pneumonia (VAP) is a common and serious nosocomial infection in mechanically ventilated preterm infants and is increasingly caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative organisms. Tigecycline, a glycylcycline with broad activity against many such pathogens, is not approved below 18 years of age and carries a boxed warning for excess mortality that is most pronounced in hospital-acquired and ventilator-associated pneumonia. Its role, if any, in preterm infants with VAP is undefined. Objectives: To systematically identify and appraise all human evidence on the efficacy (clinical cure, microbiological eradication, survival) and safety (adverse events, mortality) of tigecycline used to treat VAP or nosocomial pneumonia during mechanical ventilation in preterm infants and neonates. Methods: A PRISMA 2020 structured search of PubMed/MEDLINE, Cochrane CENTRAL, Scopus, trial registries, regulatory documents, Google Scholar and reference lists was designed without language or date restrictions. Eligible reports described tigecycline treatment of pneumonia/VAP in neonates or young infants; pediatric case series and syntheses were retained as contextual evidence. Because only case reports and small non-comparative series were anticipated, a narrative synthesis was pre-specified; JBI tools and GRADE were planned for appraisal and certainty. Results: No randomized controlled trial, controlled observational study, or study dedicated to tigecycline for VAP in preterm infants was identified. Direct evidence meeting the full eligibility criteria (preterm neonate, VAP specifically, separately extractable outcomes) was limited to two case reports of extremely preterm neonates with VAP successfully weaned after tigecycline-based salvage combination therapy. Six further neonatal/young-infant reports initially considered were, on full-text re-review, reclassified as contextual (not index) evidence because they described non-VAP infections (sepsis, or CNS infections such as ventriculitis/meningitis), non-preterm ages, or mixed-infection series without separable VAP data. Reported outcomes were generally favorable in published cases but are subject to severe selection and publication bias; thrombocytopenia, hypofibrinogenemia and hepatic enzyme elevation were the principal adverse signals, against a class-level mortality signal concentrated in VAP. Quantitative pooling was not appropriate. The overall certainty of evidence was very low. Conclusions: There is no direct, credible efficacy or safety evidence supporting tigecycline for VAP in preterm infants. Available data neither establish benefit nor exclude harm. Based on this very-low-certainty evidence and on regulatory/class-level safety data rather than on demonstrated efficacy, tigecycline warrants consideration only as a last-resort, combination salvage option for culture-confirmed pan- or extensively drug-resistant pathogens when no safer alternative exists, with intensive monitoring and, ideally, within a registry or trial. Adequately designed neonatal pharmacokinetic and comparative safety studies are urgently needed. Registration: PROSPERO CRD420261450972 (registered 14 July 2026). 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/Objective: To externally validate our previously published machine learning model for identifying hospitalized patients with community-acquired pneumonia (CAP) at low risk of respiratory deterioration or death using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Methods: This is a retrospective cohort study of adult patients (≥18 years) who were admitted with CAP and acute hypoxemic respiratory failure using the publicly available MIMIC-IV critical care dataset (Beth Israel Deaconess Medical Center, Boston, MA). We conducted an external validation study of a previously developed gradient boosting machine (GBM) model without recalibration using data available within the first 6 h of hospital admission. Results: For the primary composite outcome (need for advanced respiratory support [high flow nasal cannula (HFNC), non-invasive mechanical ventilation (NIMV), invasive mechanical ventilation (IMV)] or in-hospital death), the gradient boosting model demonstrated comparable performance in the derivation and external validation cohorts. The area under the receiver operating characteristic curve (AUC) was 0.713 in the Mayo cohort (n = 4379) and 0.689 in the MIMIC-IV cohort. Accuracy was 0.612 (95% confidence interval [CI], 0.595–0.628) versus 0.606 (95% CI 0.600–0.611), specificity 0.574 versus 0.523, sensitivity 0.723 versus 0.754, NPV 0.860 versus 0.842, and PPV 0.364 versus 0.401, respectively. For secondary outcomes, model discrimination was comparable between cohorts. The AUC for in-hospital mortality was 0.727 in the Mayo Cohort versus 0.733 in MIMIC-IV; for IMV, 0.736 versus 0.724; and for NIMV, 0.732 versus 0.708. Conclusions: Our machine learning algorithm demonstrated good discrimination and a high negative predictive value for identifying low-risk hospitalized CAP patients for respiratory deterioration or death in the external MIMIC-IV dataset, supporting its potential utility for prognostic enrichment in pneumonia clinical trials. Full article

Background/Objectives: Intensive care unit (ICU) mortality reflects interactions between baseline vulnerability, acute physiological derangement, ICU-acquired infection, and the intensity of organ-support therapy. Methods: This single-center retrospective cohort study included 3323 adult first ICU hospitalizations at the University Clinical Hospital in Bialystok, Poland, between 1 January 2017 and 1 June 2023. Secondary ICU admissions/readmissions, patients aged <18 years, and one pregnancy admission were excluded. Patients were classified as ICU survivors (n = 1778) or ICU non-survivors (n = 1545). Variables were compared using t-tests, chi-square tests, or Fisher exact tests, and an adjusted logistic regression model was fitted as an exploratory prognostic model. Results: ICU mortality was 46.5%, and 28-day ICU mortality was 40.2%. Non-survivors were older than survivors (66.7 ± 15.1 vs. 60.9 ± 17.2 years; p < 0.001) and more frequently had arterial hypertension, diabetes mellitus, COVID-19, ischemic heart disease, atrial fibrillation, renal failure, and acute myocardial infarction or ischemic stroke. In the adjusted model, ICU mortality was associated with age per 10 years (OR 1.32, 95% CI 1.18–1.47), COVID-19 (OR 3.15, 95% CI 2.07–4.79), ventilator-associated pneumonia (OR 1.68, 95% CI 1.22–2.30), lactate per 1 mmol/L (OR 1.29, 95% CI 1.16–1.43), pH per 0.1-unit decrease (OR 1.79, 95% CI 1.41–2.29), mechanical ventilation (OR 14.74, 95% CI 3.40–63.87), cardiopulmonary resuscitation (OR 9.45, 95% CI 4.67–19.13), renal replacement therapy (OR 2.01, 95% CI 1.39–2.91), and treatment of acidosis or alkalosis (OR 1.95, 95% CI 1.29–2.94). Conclusions: ICU non-survival was associated with older age, COVID-19, cardiovascular and renal vulnerability, ICU-acquired infection, inflammatory and metabolic dysfunction, and early requirement for rescue organ-support interventions. These findings should be interpreted as adjusted associations, not causal effects. Full article

Background/Objectives: Acinetobacter baumannii is a major cause of hospital-acquired and ventilator-associated pneumonia and is associated with high mortality among critically ill patients. Although antimicrobial resistance remains a major therapeutic challenge, the relative contribution of clinical severity, organ dysfunction, and laboratory parameters to patient outcomes requires further clarification. Methods: We conducted a retrospective single-center cohort study including 165 patients with microbiologically confirmed A. baumannii pneumonia admitted to the Clinical Hospital of Pneumology Iași, Romania, between 2019 and 2025. Clinical, laboratory, and outcome data were analyzed, and multivariable logistic regression was performed to identify independent predictors of in-hospital mortality. Results: In-hospital mortality was independently associated with older age (OR: 1.05 per year, 95% CI: 1.01–1.08, p = 0.005), sepsis (OR: 5.23, 95% CI: 1.93–16.5, p = 0.002), and mechanical ventilation (OR: 6.71, 95% CI: 3.02–15.6, p < 0.001). In exploratory analyses restricted to patients with available lactate measurements, lactate levels were not significantly associated with mortality, whereas acute kidney injury and dynamic renal deterioration were associated with increased mortality. Inflammatory markers, particularly neutrophil-to-lymphocyte ratio and C-reactive protein at 72 h, were significantly higher in non-survivors. Conclusions: These findings suggest that mortality in A. baumannii pneumonia is more closely associated with clinical severity, sepsis, respiratory failure, and evolving organ dysfunction than with isolated laboratory parameters. Early recognition of sepsis, acute kidney injury, and respiratory failure, together with serial assessment of inflammatory biomarkers, may support improved risk stratification in this high-risk population. Full article

The increasing prevalence of infections caused by multidrug-resistant (MDR) Gram-negative bacteria represents a major global public health challenge. Among hospital-acquired infections (HAIs), ventilator-associated pneumonia (VAP) caused by non-fermenting Gram-negative pathogens, particularly the Acinetobacter baumannii-calcoaceticus complex, it is associated with limited therapeutic options and high mortality. Sulbactam–durlobactam is a novel combination consisting of sulbactam, a β-lactamase inhibitor with intrinsic activity against Acinetobacter spp., and durlobactam, a diazabicyclooctane β-lactamase inhibitor targeting Ambler class A, C, and D enzymes. This review summarizes current evidence on the pharmacological properties, clinical efficacy, and resistance mechanisms associated with this combination. Clinical trials have demonstrated that sulbactam–durlobactam is non-inferior to colistin in the treatment of infections caused by carbapenem-resistant A. baumannii, with a significantly lower risk of nephrotoxicity. The combination is generally well tolerated and represents a promising therapeutic option for difficult-to-treat infections. However, emerging resistance mechanisms, including PBP3 mutations, metallo-β-lactamase production, and efflux pump overexpression, may limit its long-term effectiveness. Further research is required to better understand resistance development and optimize clinical use. Full article

Objective: To identify risk factors for progression to sepsis in patients with non-ventilator hospital-acquired pneumonia (NV-HAP) and to develop a practical nomogram for individualized risk assessment in this population. Methods: We retrospectively screened 408 hospitalized patients with hospital-acquired pneumonia at Peking University Third Hospital between January 2017 and December 2021. After excluding patients with an unclear diagnosis date or missing critical variables required for SOFA score calculation, 368 eligible patients with NV-HAP were included and randomly divided into a training cohort (n = 260) and an internal validation cohort (n = 108). An independent temporal validation cohort of 68 patients admitted between January 2022 and December 2022 at the same center was further used for temporal validation. Univariable and multivariable logistic regression analyses with backward stepwise selection were performed in the training cohort to identify predictors associated with progression to sepsis. A nomogram was then constructed based on the final model and evaluated by discrimination, calibration, and decision curve analysis. Results: A total of 368 patients were included in the model development dataset. The final multivariable model retained six predictors: male sex (OR = 2.393, 95% CI: 1.333–4.296), diabetes (OR = 2.205, 95% CI: 1.126–4.319), coagulation dysfunction (OR = 3.327, 95% CI: 1.726–6.413), PaO₂/FiO₂ (OR = 0.955 per 10-unit increase, 95% CI: 0.912–1.001), platelet count (OR = 0.900 per 10 × 10⁹/L increase, 95% CI: 0.853–0.949), and bilirubin (OR = 1.176 per 1 μmol/L increase, 95% CI: 1.100–1.258). The nomogram showed acceptable performance, with an apparent C-index of 0.809 and a bootstrap-corrected C-index of 0.792 in the training cohort. The C-index was 0.750 (95% CI: 0.658–0.841) in the internal validation cohort and 0.754 (95% CI: 0.639–0.870) in the temporal validation cohort. Calibration analysis showed acceptable agreement between predicted and observed probabilities, and decision curve analysis indicated a positive net clinical benefit across clinically relevant threshold probabilities. Conclusions: In patients with NV-HAP, male sex, diabetes, coagulation dysfunction, lower PaO₂/FiO₂, lower platelet count, and higher bilirubin were associated with progression to sepsis. The developed nomogram showed acceptable discrimination, calibration, and clinical utility, and may serve as a practical tool for early individualized risk stratification in patients with NV-HAP. Full article

Introduction: The emergence and spread of multidrug-resistant infections has resulted in significant clinical and economic burdens. To address these infections, novel therapy combinations are needed. Ceftolozane/tazobactam is a treatment option that targets multidrug-resistant pathogens and may offer improved patient outcomes compared to traditional antibiotics that are now often ineffective. Objectives: Our objective was to collate findings from comparative efficacy studies to assess the efficacy of ceftolozane/tazobactam for the indications of complex intra-abdominal infection, complex urinary tract infection, ventilated hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. Methods: Two systematic literature reviews were conducted, including randomized controlled trials comparing ceftolozane/tazobactam with other interventions for complex intra-abdominal infection, complex urinary tract infection, ventilated hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia indications. The outcomes of interest were mortality, clinical cure and microbiological eradication. Results: Ceftolozane/tazobactam was determined to be non-inferior to comparators for all outcomes of interest. All-cause mortality for ceftolozane/tazobactam displayed non-inferiority to meropenem, with the largest numerical differences in all-cause mortality displayed in susceptible patients, such as those with severe renal impairment. Similarly, the clinical cure and microbiological eradication for ceftolozane/tazobactam demonstrated non-inferiority compared to meropenem or levofloxacin. Conclusions: These reviews support the role of ceftolozane/tazobactam as an alternative option, particularly when MDR pathogens are suspected or documented. Their findings may contribute to the standardization of treatment guidelines, ultimately helping to reduce the clinical and economic burdens associated with these infections. Full article

Background/Objectives: Community-acquired pneumonia (CAP) remains a major cause of hospitalisation and death, particularly among older and frail adults. Although treatment guidelines exist, adherence to empiric antibiotic recommendations is variable. This study examined whether receiving guideline-concordant antibiotics for CAP was associated with better short- and long-term clinical outcomes. Methods: We conducted a retrospective cohort study of adults admitted with radiologically confirmed CAP to a tertiary hospital in Australia from 1 January to 31 December 2023. Patients with hospital-acquired pneumonia or COVID-19 were excluded. Antibiotic concordance was assessed against local guidelines. Propensity score matching (PSM) accounted for 16 covariates including age, comorbidities (Charlson Index), frailty (Hospital Frailty Risk Score), and pneumonia severity (SMART-COP). Primary outcomes were in-hospital, 30-day, and one-year mortality. Secondary outcomes included ICU admission, invasive ventilation, vasopressor use, hospital length of stay, and 30-day readmissions. Results: Of 241 patients, 51.4% received guideline-concordant antibiotics. Mean age was 73.5 years; 50.2% were male; 42.2% had severe pneumonia (SMART-COP ≥ 5); 36.5% were frail. In unadjusted analysis, in-hospital mortality was higher in the concordant group (5.6% vs. 0.9%, p = 0.038). After PSM (n = 105 matched pairs), concordant treatment was associated with significantly lower 30-day mortality (coefficient = –0.12; 95% CI: –0.23 to –0.02; p = 0.018) and there was a non-significant trend towards reduced 1-year mortality (p = 0.058). Other outcomes, including in-hospital mortality, were not significantly different. Conclusions: Guideline-concordant antibiotics were associated with reduced 30-day mortality in CAP. These results support adherence to evidence-based treatment guidelines to improve patient outcomes. Full article

Determining the optimal duration of antibiotic therapy for infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) is a critical challenge in clinical medicine, balancing therapeutic efficacy against the risks of adverse effects and antimicrobial resistance. This narrative review synthesises current evidence and guidelines regarding antibiotic duration for MDR-GNB infections, emphasising bloodstream infections (BSI), hospital-acquired and ventilator-associated pneumonia (HAP/VAP), complicated urinary tract infections (cUTIs), and intra-abdominal infections (IAIs). Despite robust evidence supporting shorter courses (3–7 days) in uncomplicated infections caused by more susceptible pathogens, data guiding optimal therapy duration for MDR-GNB remain limited, particularly concerning carbapenem-resistant Enterobacterales (CRE), difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), and carbapenem-resistant Acinetobacter baumannii (CRAB). Current guidelines from major societies, including IDSA and ESCMID, provide explicit antimicrobial selection advice but notably lack detailed recommendations on the duration of therapy. Existing studies demonstrate non-inferiority of shorter versus longer antibiotic courses in specific clinical contexts but frequently exclude critically ill patients or those infected with non-fermenting MDR pathogens. Individualised duration decisions must integrate clinical response, patient immunologic status, infection severity, source control adequacy, and pharmacologic considerations. Significant knowledge gaps persist, underscoring the urgent need for targeted research, particularly randomised controlled trials assessing optimal antibiotic duration for the most challenging MDR-GNB infections. Clinicians must navigate considerable uncertainty, relying on nuanced judgement and close monitoring to achieve successful outcomes while advancing antimicrobial stewardship goals. Full article

Objective: This study aimed to assess the effect of antibiotic de-escalation on 30-day mortality, duration of intravenous (IV) antibiotic therapy and length of hospital stay (LOS) in severe community-acquired pneumonia (sCAP). Methods: We performed a retrospective analysis of prospectively collected data from a cohort of adults diagnosed with sCAP and microbiologically confirmed etiology between 1995 to 2022. Two distinct time points of the de-escalation were analyzed: 3 and 6 days post-admission, corresponding, respectively, to the availability of microbiological results and the median time to clinical stability. Inverse propensity score-weighted binary logistic regression was used to adjust for potential confounders. Results: A total of 398 consecutive cases of sCAP were analyzed. No significant differences were observed between the de-escalation and non-de-escalation groups in terms of age, sex, comorbidities, or severity-related variables (such as impaired consciousness, shock, respiratory failure, or multilobar pneumonia). Patients in the de-escalation group had lower rates of leukopenia, bacteremia and empyema, and less need for mechanical ventilation, with variations depending on the timing of de-escalation. After adjusting for confounding factors in an inverse propensity score-weighted analysis, de-escalation within 3 or 6 days after admission was not associated with increased mortality risk (adjusted odds ratio [aOR] 1.48, 95% confidence interval [CI] 0.29–7.4; p = 0.63, and aOR 0.57, 95% CI 0.14–2.31, p = 0.43, respectively). Similar findings were observed for prolonged LOS. However, antibiotic de-escalation was related to a lower risk of prolonged IV antibiotic. Conclusions: Antibiotic de-escalation in microbiologically confirmed sCAP did not negatively impact clinical outcomes, supporting the safety of this strategy for optimizing antibiotic use in this serious infection. Full article

Background/Objectives: Data on multidrug-resistant organism (MDRO) infections in children are scarce, especially in resource-limited regions. This study aimed to estimate the prevalence of MDRO infections in pediatric intensive care units (PICUs) and characterize their epidemiologic and clinical features. Methods: A national, multicenter, point-prevalence study was conducted in 50 PICUs in Argentina over 24 h between 24 and 28 November 2023. The primary study outcome was the prevalence of ICU infections caused by MDROs. Secondary outcomes included the prevalence of carbapenemase-producing Enterobacterales (CPE) colonization, ICU mortality, and ICU length of stay (LOS_ICU). Results: 304 patients were included. The overall prevalence of infection was 45.1% (137/304); of these, 50.3% (69/137) were hospital-acquired. Among the 137 patients with reported infections, 49.6% (n = 68) were classified as definite (microbiologically confirmed) and 50.4% (n = 69) as probable (no confirmatory microbiology). Among definite infections, 20.6% (n = 14) were due to MDROs. The overall prevalence of MDRO infections was 4.6% (14/304). Extended-spectrum β-lactamase (ESBL)-producing organisms were the most commonly identified microorganisms (42.9%), followed by CPE (28.6%). Ventilator-associated pneumonia (VAP) was the most frequent location of MDRO infections. The prevalence of CPE colonization was 13.2%. Mortality was low (5.3%) and similar in patients with MDRO and non-MDRO infections. LOS_ICU was longer in patients with MDRO infections compared to patients with non-MDRO infections (81 [22–150] vs. 25 [12–27] days, respectively, p = 0.0007). Conclusions: Among 304 PICU patients, the prevalence of MDRO infections and colonization was relatively low. MDRO infections were not associated with increased mortality but were associated with longer ICU stays, compared to patients with non-MDRO infections. Full article

Background: Nosocomial lower respiratory tract infections (nLRTIs) are associated with unfavorable clinical outcomes and significant healthcare costs. nLRTIs include hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and other ICU-acquired pneumonia phenotypes. While risk factors for mortality in these infections are critical to guide preventive strategies, it remains unclear whether they vary based on their requirement of invasive mechanical ventilation (IMV) at any point during the hospitalization. Objectives: This study aims to identify risk factors associated with short- and long-term mortality in patients with nLRTIs, considering differences between those requiring IMV and those who do not. Methods: This multinational prospective cohort study included ICU-admitted patients diagnosed with nLRTI from 28 hospitals across 13 countries in Europe and South America between May 2016 and August 2019. Patients were selected based on predefined inclusion and exclusion criteria, and clinical data were collected from medical records. A random forest classifier determined the most optimal clustering strategy when comparing pneumonia site acquisition [ward or intensive care unit (ICU)] versus intensive mechanical ventilation (IMV) necessity at any point during hospitalization to enhance the accuracy and generalizability of the regression models. Results: A total of 1060 patients were included. The random forest classifier identified that the most efficient clustering strategy was based on ventilation necessity. In total, 76.4% of patients [810/1060] received IMV at some point during the hospitalization. Diabetes mellitus was identified to be associated with 28-day mortality in the non-IMV group (OR [IQR]: 2.96 [1.28–6.80], p = 0.01). The 90-day mortality-associated factor was MDRP infection (1.98 [1.13–3.44], p = 0.01). For ventilated patients, chronic liver disease was associated with 28-day mortality (2.38 [1.06–5.31] p = 0.03), with no variable showing statistical and clinical significance at 90 days. Conclusions: The risk factors associated with 28-day mortality differ from those linked to 90-day mortality. Additionally, these factors vary between patients receiving invasive mechanical ventilation and those in the non-invasive ventilation group. This underscores the necessity of tailoring therapeutic objectives and preventive strategies with a personalized approach. Full article

Introduction: Nosocomial lower respiratory tract infections (nLRTIs), including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), remain significant challenges due to high mortality, morbidity, and healthcare costs. Implementing accurate and timely diagnostic strategies is pivotal for guiding optimized antimicrobial therapy and addressing the growing threat of antimicrobial resistance. Areas Covered: This review examines emerging microbiological diagnostic methods for nLRTIs. Although widely utilized, traditional culture-based techniques are hindered by prolonged processing times, limiting their clinical utility in timely decision-making. Advanced molecular tools, such as real-time PCR and multiplex PCR, allow rapid pathogen identification but are constrained by predefined panels. Metagenomic next-generation sequencing (mNGS) provides comprehensive pathogen detection and resistance profiling yet faces cost, complexity, and interpretation challenges. Non-invasive methods, including exhaled breath analysis using electronic nose (e-nose) technology, gene expression profiling, and biomarker detection, hold promise for rapid and bedside diagnostics but require further validation to establish clinical applicability. Expert Opinion: Integrating molecular, metagenomic, biomarker-associated, and traditional diagnostics is essential for overcoming limitations. Continued technological refinements and cost reductions will enable broader clinical implementation. These innovations promise to enhance diagnostic accuracy, facilitate targeted therapy, and improve patient outcomes while contributing to global efforts to mitigate antimicrobial resistance. Full article