Search Results (190)

Background/Objectives: Pseudomonas aeruginosa is one of the leading causes of ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT), with a worldwide spread of difficult-to-treat high-risk clones. This study aimed to investigate the virulence potential and to characterize phenotypic and genotypic antimicrobial resistance (AMR) in P. aeruginosa causing VAP/VAT in the Intensive Care Unit (ICU), University Hospital of Split, Croatia. Methods: The study included P. aeruginosa isolates obtained from ICU patients who met the criteria for VAP or VAT, between January 2023 and January 2024. Isolates were identified using MALDI-TOF MS and tested for antimicrobial susceptibility (AST). A subset of phenotypically multidrug-resistant (MDR) isolates was further analyzed using whole-genome sequencing (WGS) and multilocus sequence typing. Results: A high rate of resistance was detected to ceftazidime (23.4%), imipenem (39.6%), and meropenem (43.8%). WGS confirmed the presence of multiple AMR genes, including the bla_VIM-2 gene, whose genetic environment highlights a complex MDR locus integrating multiple AMR determinants and mobile genetic elements. All tested isolates possessed genes for class C (bla_PDC34, bla_PDC374 or bla_PDC16) and class D (bla_OXA-2, bla_OXA-10 or bla_OXA-50) β-lactamases, fosA, aph(3′)-IIb and crpP genes. Additionally, WGS analysis revealed the presence of numerous virulence genes including those for adherence (Type IV pili and Fap protein production), motility (such as flgF), biofilm formation (e.g., algE and mucE), quorum sensing (lasI, lasR, rhlI and rhlR), exotoxin (toxA and plcH) and exoenzyme activity (exoU, exoT, exoS, exoY, pcrV, hcp1 and lasA). The isolates belonged to four different sequence types: ST235, ST446, the high-risk ST253 and the widely distributed ST395. Phylogenomic comparison demonstrated that the isolates from this study do not originate from a single clonal source, but instead represent multiple globally distributed high-risk P. aeruginosa lineages introduced into the clinical setting. Conclusions: Due to the emergence of high-risk clones with broad AMR and strong virulence potential, ineffectiveness of standard empirical therapy may be anticipated, highlighting the urgent need for new therapeutic approaches (including those targeting major virulence factors). Full article

Ventilator-associated pneumonia (VAP) remains the most frequent ICU-acquired infection and a major driver of antimicrobial exposure. Historically, clinicians treated patients for 10–14 days or longer, particularly when multidrug-resistant organisms were suspected. Current evidence from randomized trials and meta-analyses now supports shorter-course therapy (~7 days) for most immunocompetent patients with VAP who demonstrate clinical improvement. Mortality and treatment failure are not increased when compared with longer regimes. The REGARD-VAP trial demonstrated the non-inferiority of individualized ≤7-day therapy compared with conventional longer courses. This remained true even in cohorts rich in non-fermenting Gram-negative bacilli (NF-GNB) and carbapenem-resistant organisms while markedly reducing antibiotic-related toxicity. North American and European guidelines recommend 7–8 days as the default duration, with individualized extension for slow clinical response, bacteremia, uncontrolled foci, or profound immunosuppression. Additionally, biomarker-guided discontinuation, particularly serial procalcitonin (PCT), may reduce antibiotic days when used to enrich clinical assessment. This narrative review synthesizes guideline recommendations, trial evidence, biomarker-guided stewardship, and pathogen- and patient-specific scenarios to provide a practical framework for intensivists: treat until infection is controlled and the patient is improving, usually about 1 week, and extend therapy only with clear justification. Full article

Background/Objectives: We investigated multimodal strategies to reduce neonatal ventilator-associated pneumonia (VAP) and antimicrobial use across three periods: period 1 (2014–2017), environmental cleaning with sodium hypochlorite, installation of heat and moisture exchangers, elective high frequency oscillatory ventilation (HFOV) as the primary invasive mode, and nasal HFOV after extubation; period 2 (2018–2020), oral care with maternal milk; and period 3 (2021–2024), nasal synchronized intermittent positive pressure ventilation after extubation. Methods: We conducted a quasi-experimental study of all neonates admitted to a neonatal intensive care unit in Thailand. We compared the trends in VAP and antimicrobial use rates using interrupted time-series analysis with segmented regression. Results: During the 11-year study period, 45.6% of neonates were intubated (2470/5414), and the ventilator utilization ratio was 0.19 (17,820 ventilator days/95,151 patient days). The overall VAP incidence was 4.55 per 1000 ventilator days. The yearly VAP incidence density ratio was significantly lower than in 2014. The baseline trend of VAP incidence and colistin use decreased significantly during period 1; nonetheless, the level and slope did not differ significantly between periods 1, 2, and 3. Conclusions: Tailored implementations, namely environmental decontamination, ventilator circuit care, elective HFOV, and nasal HFOV, reduced VAP and colistin use during period 1. Moreover, additive interventions, including oral care in period 2 and nasal synchronized intermittent positive pressure ventilation in period 3, achieved sustained VAP reduction and limited colistin prescriptions in period 1. Full article

Acinetobacter baumannii is a leading intensive care unit (ICU) pathogen associated with high rates of carbapenem resistance and poor clinical outcomes. This narrative review synthesizes recent clinical, microbiological, and pharmacokinetic/pharmacodynamic (PK/PD) evidence regarding resistance mechanisms and therapeutic strategies. A literature review was performed in PubMed, Scopus, and Web of Science (January 2015–August 2025), focusing on multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, ICU-acquired infections, and pivotal trials involving cefiderocol and sulbactam–durlobactam. Resistance is driven by OXA-type carbapenemases (notably OXA-23/24/58), efflux systems (AdeABC/IJK/FGH), porin alterations (CarO, Omp33–36), and lipopolysaccharide (LPS) modifications conferring colistin resistance. Management options include polymyxins, optimized tigecycline dosing, β-lactam/β-lactamase inhibitors, and newer agents such as cefiderocol and sulbactam–durlobactam, though mortality and safety outcomes vary across trials. A comparative table is included, summarizing antimicrobial mechanism coverage, PK/PD parameters, and adverse effects to support regimen selection in ventilator-associated pneumonia (VAP) and bacteremia. Optimized, multimodal approaches integrating timely diagnostics, targeted combination therapies, infection prevention, and antimicrobial stewardship are essential to improve outcomes and limit the spread of MDR and XDR A. baumannii. Full article

Patients with multiple traumas, particularly those with traumatic brain injury (TBI), are among the most challenging cases in intensive care medicine. Although early orotracheal intubation and invasive mechanical ventilation (IMV) are essential for airway protection and neurological treatment, they significantly increase the risk of lower respiratory tract infection (LRTI), including ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT). These complications are particularly prevalent among neurocritical patients due to the distinctive interaction between the brain, lungs and immune system. This narrative review examines the current evidence on the mechanisms underlying the brain–lung–immune axis; the diagnostic challenges in identifying respiratory infections in mechanically ventilated TBI patients; and optimal approaches to empirical or quasi-targeted antimicrobial therapy based on diagnostic algorithms and rapid molecular techniques. Severe TBI induces neurogenic inflammation, autonomic dysregulation, and immunosuppression, thereby increasing susceptibility to pulmonary infections. The ‘triple hit hypothesis’ best explains this cascade: sympathetic hyperactivity (first hit), iatrogenic ventilatory injury (second hit), and intestinal dysbiosis with systemic immune dysregulation (third hit). VAP diagnosis remains challenging due to the lack of universal criteria, the overlap with systemic inflammatory response syndrome, and the low specificity of radiological and clinical signs. VAT may represent an intermediate stage within a continuum of ventilator-associated infection. Recent evidence supports the selective use of nebulized antibiotics for VAT, advocating an individualized, locally adapted empirical approach to VAP treatment. Syndromic molecular panels can accelerate the identification of pathogens, enabling the earlier and more appropriate selection of antimicrobials and improving outcomes while preserving stewardship. Understanding the brain–lung–immune axis and improving diagnostic accuracy are essential to enhancing the treatment of respiratory infections in neurocritical care. Integrating clinical assessment, biomarkers and rapid microbiological testing enables timely, targeted therapy and reduces the misuse of antimicrobials. Full article

Background: Ventilator-associated pneumonia (VAP) is a prevalent and serious complication of invasive mechanical ventilation (MV), contributing to significant mortality and increased healthcare resource utilization. While numerous oropharyngeal interventions exist, their comparative efficacy across critical outcomes remains uncertain due to a lack of direct comparisons in clinical trials. Methods: We conducted a systematic review and network meta-analysis (NMA) with a comprehensive search of MEDLINE, EMBASE, and Cochrane CENTRAL up to September 2025 for randomized and non-randomized studies comparing topical oral interventions in intubated patients. The primary outcome was VAP incidence; secondary outcomes were intensive care unit (ICU) mortality, duration of MV, and ICU length of stay (LOS). Pairwise and network meta-analyses were performed, and the certainty of evidence was assessed. The effect estimates were odds ratios (OR) for categorical outcomes and mean difference (MD) for numerical outcomes represented with 95% confidence intervals (95% CI). Results: Ninety-six studies (20,650 patients) were included, evaluating 44 interventions. For VAP prevention, several interventions were superior to reference/control, including Antimicrobial combinations (OR: 0.21, 95% CI: 0.05–0.39), Povidone-iodine (OR: 0.47, 95% CI: 0.21–0.98), and Chlorhexidine (OR 0.61, 95% CI 0.39–0.95). However, only Chlorhexidine plus toothbrushing significantly reduced mortality (OR: 0.74, 95% CI: 0.58–0.93). For resource utilization, only antimicrobial combinations significantly reduced the duration of MV (MD: −5.55 days, 95% CI: −10.75–−1.7) and ICU LOS (MD: −7.74 days, 95% CI: −13–−4). Evidence certainty (GRADE) was moderate for chlorhexidine and very low for other comparisons. Conclusions: This NMA demonstrates that while multiple oropharyngeal interventions are effective for VAP prevention, their benefits are outcome specific. The choice of intervention should be guided by clinical priorities, as the most effective strategy for preventing VAP may not concurrently reduce mortality or resource use. These findings can inform guideline development and underscore the need for standardized, multi-faceted oral care protocols in the ICU. Full article

Ventilator-associated pneumonia (VAP) is one of the most common hospital-acquired infections. Several studies have explored the potential role of the lung microbiome as a biomarker for identifying and predicting the prognosis of VAP. However, research on the respiratory microbiome in individuals with VAP caused by carbapenem-resistant Acinetobacter baumannii (CRAB) remains limited. Therefore, we aimed to analyze the respiratory microbiome of patients with CRAB VAP. Respiratory specimens were collected from patients who developed CRAB VAP. Microbiome diversity and composition were analyzed using 16S rRNA gene pyrosequencing. Patients were categorized into two groups based on mortality outcomes: intensive care unit (ICU) mortality or 28-day mortality after ICU discharge. Twenty patients with CRAB VAP were enrolled, including nine in the mortality group. No significant differences were observed in α-diversity indices between the study groups. However, multivariable Firth’s logistic regression revealed a significant association between a relative abundance of the Enterococcus genus ≥ 1% and mortality outcomes (odds ratio: 0.06; 95% confidence interval: 0.00–0.771; p = 0.029). This study characterized the respiratory microbiome of patients with CRAB VAP and highlighted the potential role of microbiome analysis in predicting disease prognosis. Further studies with larger sample sizes are warranted to validate these findings. Full article

Background: Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in intensive care units (ICUs), particularly in low- and middle-income countries (LMICs). Evidence-based practice (EBP) bundles have shown effectiveness in reducing VAP; however, the implementation in Bangladesh remains limited. This study aimed to evaluate the effectiveness of EBP to reduce the incidence rate of VAP among adult ICU patients in Bangladesh. Methods: A quasi-experimental study with a historical control group was conducted among 347 eligible ICU patients from October 2024 to April 2025. The intervention included nurse training on VAP bundle practices with advanced equipment support. Data on VAP incidence as a primary endpoint and VAP-related patients’ outcomes were analyzed. Results: The clinically suspected VAP incidence was 30.1 and 51.1 per 1000 ventilator-days, and the prevalence decreased significantly in the intervention group compared to the control group (26.9% vs. 46.1%; p < 0.001), respectively. Logistic regression indicated VAP bundle implementation was associated with reduced VAP (Exp(B) = 0.417, 95% CI: 0.262–0.666), while ventilation ≥96 h was a significant risk factor (Exp(B) = 2.6, 95% CI: 1.385–4.881). Early-onset VAP was reduced (25.0% vs. 10.2%), though late-onset predominated in the intervention group (75.0% vs. 89.8%). Conclusion: Implementation of an EBP-based VAP bundle by trained nurses significantly reduced VAP incidence. However, increased overall ICU mortality highlights the need for broader critical care improvements, including advanced comorbidity management and comprehensive ICU services. This study underscores the feasibility and effectiveness of VAP bundle implementation in the ICU of an LMIC. Full article

Background: Ventilator-associated pneumonia (VAP) is a frequent complication in neurosurgical intensive care patients. This leads to prolonged mechanical ventilation, increased 30-day mortality rates, and extended hospital stays. However, early diagnosis remains a challenge. Biomarkers, such as IL-6, PCT, and CRP, are considered a cornerstone for recognizing VAP and initiating early treatment. Only a very limited number of studies have compared IL-6, PCT, and CRP, focusing on day-to-day dynamics and their albumin ratios. Therefore, we investigated whether, compared with their daily levels, the day-to-day dynamics and albumin-adjusted ratios of IL-6, PCT, and CRP offer improved diagnostic value for VAP. Second, we investigated these biomarkers in patients treated for VAP who did not meet the criteria for VAP. Methods: In this exploratory, matched case–control study, we investigated 171 neurosurgical ICU patients. Daily biomarker levels, their dynamics, and ratios to serum albumin were assessed beginning four days before VAP. Logistic regression and receiver operating curve (ROC) analyses were performed to evaluate the association between each biomarker and VAP. Results: IL-6 and its day-to-day dynamics demonstrated the largest differences between VAP patients and nonVAP patients (r = 0.631; r = 0.452) and were associated with VAP, yielding AUCs of 0.816 and 0.726, respectively. In contrast, for PCT, we did not demonstrate any associative utility, whereas CRP showed a significant, moderate effect size on the day of VAP occurrence (p = 0.015 *; r = 0.351). We could not demonstrate any superiority in the day-to-day dynamics or the albumin-adjusted ratios compared to the daily values. For patients who were treated for VAP without fulfilling the criteria for biomarkers, we did not observe any significant difference from nonVAP patients. Full article

Objectives: This systematic review aimed to evaluate the association between oral health—particularly dental caries and dysbiosis of the oral microbiome—and respiratory diseases across different age groups and clinical settings, with emphasis on microbial overlap, clinical outcomes, and preventive strategies. Methods: A systematic search was conducted in PubMed, Scopus, Embase, Web of Science, and the Cochrane Library up to June 2025. Eligible studies included randomized controlled trials, cohort, case–control, and cross-sectional investigations examining the relationship between oral diseases or microbiome alterations and respiratory outcomes. Data on study design, population, oral health parameters, microbial taxa, and respiratory endpoints were extracted. Study quality was assessed using the Mixed Methods Appraisal Tool (MMAT, 2018). Results: Twenty studies met the inclusion criteria, encompassing pediatric, adult, and elderly populations. Poor oral health, reflected by higher caries indices and periodontal inflammation, was consistently associated with increased risk of lower respiratory tract infections (LRTI), aspiration events, ventilator-associated pneumonia (VAP), and impaired pulmonary function. Oral microbiome analyses revealed enrichment of Veillonella, Prevotella, Klebsiella, and Pseudomonas species in both oral and airway samples, supporting the oral cavity as a reservoir for respiratory pathogens. Interventional evidence from intensive care and nursing home settings demonstrated that structured oral care—particularly daily toothbrushing and chlorhexidine-based plaque control—significantly reduced pneumonia incidence. Conclusions: This review confirms a clinically relevant and biologically plausible link between oral dysbiosis, dental caries, and respiratory disease. Oral biofilms contribute to infection risk through microaspiration and microbial seeding of the lower airways. Integrating oral screening, hygiene maintenance, and treatment of active oral disease into respiratory care pathways may reduce respiratory morbidity and mortality, particularly among high-risk populations such as ICU patients, older adults, and individuals with chronic lung disease. Full article

Microfluidic paper-based analytical devices (µPADs) are ideal for point-of-care diagnostics due to their low cost, compact size, and ease of use. However, current designs have limited multiplexing capabilities, making it difficult to simultaneously detect pathogens and biomarkers in the same sample. In this work, we introduce NanoArrayPAD−X, a novel µPAD design that combines wax-printed microfluidic networks with an array of nanoprobes for the simultaneous detection of multiple targets. This is achieved by distributing the sample through the microfluidic network containing X detection areas. There, targets are captured through physical interactions and recognized by specific antibody-coated nanoprobes released from the nanoprobe array. This generates X dots whose color depends on the concentration of the targets in the sample. A NanoArrayPAD−5 platform capable of detecting five targets was developed to aid in the diagnosis of ventilator-associated pneumonia (VAP). The sensor array could detect Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Escherichia coli, and the inflammatory biomarker myeloperoxidase (MPO) with a total turnaround time of 25 min, which is faster than waiting for an overnight culture and the results of an ELISA. Notably, our prototype successfully detected the targets in 87 bronchial aspirate (BAS) specimens, thus demonstrating the suitability of the platform for analyzing complex samples with sputum-like qualities. These findings establish NanoArrayPAD−X as a promising tool for the rapid, multiplexed screening of respiratory pathogens and biomarkers, with potential for guiding personalized antimicrobial therapy in suspected cases of nosocomial pneumonia. Full article

Background/Objectives: Lower respiratory tract infections (LRTIs) are frequent in the intensive care unit (ICU) and drive empiric broad-spectrum antibiotic use. Rapid multiplex PCR assays may improve pathogen detection and stewardship compared with conventional culture. We evaluated the real-world impact of the BioFire^® FilmArray^® Pneumonia Panel Plus (FA-PNEU^®) on antimicrobial management in suspected nosocomial LRTI. Methods: This was a single-centre, prospective observational cohort study conducted in a tertiary ICU (Madrid, Spain) between April 2021 and March 2025. Adult patients with suspected hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), or ventilator-associated tracheobronchitis (VAT) were included if paired respiratory samples underwent FA-PNEU^® and conventional culture (CC). Diagnostic accuracy and prescribing changes were analysed. Results: A total of 344 samples from 236 patients were included. FA-PNEU^® demonstrated high sensitivity (93.4%) and negative predictive value (97.9%) but moderate specificity (65.0%) and low positive predictive value (36.5%). False positives occurred in 85.8% of patients with prior antibiotic therapy targeting the detected organism. Antibiotic management was considered directly influenced by FA-PNEU^® when any prescribing decision (initiation, escalation, de-escalation, or discontinuation) explicitly followed the panel’s results rather than other clinical or microbiological information. Using this definition, FA-PNEU^® directly influenced antibiotic therapy in 57.6% of cases, while in 17.7%, prescribing was instead guided by a suspected alternative infection. In patients without prior antibiotics, treatment initiation or withholding was fully concordant with FA-PNEU^® results, while in those already receiving therapy, 60.8% underwent modification, two-thirds in agreement with the panel. Conclusions: In critically ill patients with suspected nosocomial LRTI, FA-PNEU^® provided rapid, high-sensitivity diagnostics that substantially influenced antimicrobial prescribing. Its greatest value lies in ruling out bacterial infection and guiding stewardship, though results must be interpreted within the full clinical and microbiological context. Full article

Burn injury triggers a complex inflammatory cascade in which the interplay between pro- and anti-inflammatory mediators determines recovery or progression to sepsis, ventilator-associated pneumonia (VAP) or multi-organ dysfunction, and mortality. We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus for studies published between 2006 and 2024, identifying 1883 records. We conducted a comprehensive systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After screening and eligibility assessment, 24 studies covering both pediatric and adult populations met the inclusion criteria. Data on cytokines, acute-phase proteins, complement fragments, and systemic inflammatory indices were synthesized narratively. The evidence indicates that the inflammatory response to burn injury is not a linear sequence of events but a dynamic and unstable equilibrium, where outcomes are determined less by the initial magnitude of cytokine release and more by the persistence of dysregulated inflammation or failure of compensatory mechanisms. Full article

Background: Intensive Care Unit (ICU) readmission and in-hospital mortality are critical indicators of patient outcomes following ICU discharge. Patients readmitted to the ICU often face worse prognosis, higher healthcare costs, and prolonged hospital stays. Identifying high-risk patients is essential for optimizing post-ICU care and resource allocation. Methods: This two-phase study included the following: (1) a retrospective analysis of ICU survivors in a mixed medical–surgical ICU to identify risk factors associated with ICU readmission and in-hospital mortality, and (2) a prospective validation of a newly developed predictive model: the Worse Outcome Score (WOScore). Data collected included demographics, ICU admission characteristics, severity scores (SAPS II, SAPS III, APACHE II, SOFA), interventions, complications and discharge parameters. Results: Among 1.190 ICU survivors, 126 (10.6%) were readmitted to the ICU, and 192 (16.1%) died in hospital after ICU discharge. Key risk factors for ICU readmission included Diabetes Mellitus, SAPS III on admission, and ICU-acquired infections (Ventilator-Associated Pneumonia (VAP) and Catheter-Related Bloodstream Infection, (CRBSI)). Predictors of in-hospital mortality were identified: medical admission, high SAPS III score, high lactate level on ICU admission, tracheostomy, reduced GCS at discharge, blood transfusion, CRBSI, and Acute Kidney Injury (AKI) during ICU stay. The WOScore, developed based on the results above, demonstrated strong predictive ability (AUC: 0.845 derivation, 0.886 validation). A cut-off of 20 distinguished high-risk patients (sensitivity: 88.1%, specificity: 73.0%). Conclusions: ICU readmission and in-hospital mortality are influenced by patient severity, underlying comorbidities, and ICU-related complications. The WOScore provides an effective, easy-to-use risk stratification tool that can guide clinicians in identifying high-risk patients at ICU discharge and guide post-ICU interventions, potentially improving patients’ outcomes and optimizing resource allocation. Further multi-center studies are necessary to validate the model in diverse healthcare settings. Full article

Background/Objectives: Causal inference requires validating the stable unit treatment variance assumption (SUTVA). Whilst antimicrobial-based interventions, being topical chlorhexidine and topical antibiotics prophylaxis (TAP), appear effective in preventing ventilator-associated pneumonia (VAP) among ICU patients receiving mechanical ventilation (MV) within randomized concurrent controlled trials (RCCT), SUTVA has never been tested for this inference. Methods: Caterpillar plots of the VAP incidence proportions for control and intervention groups within RCCTs obtained from recent Cochrane reviews of antimicrobial-based VAP prevention interventions were derived using random effects methods to enable comparison versus the expert VAP incidence reference range (5 to 40%). Results: The summary VAP prevention effect size derived from three categories of 57 RCCTs of antimicrobial-based interventions was recapitulated. The VAP incidences of 24 control groups and 6 intervention group incidences were above, whereas only 1 and 6, respectively, were below the expert VAP incidence reference range (5 to 40%) (p < 0.001; chi-square = 17.42; df = 2). The results after excluding 18 low-quality studies were similar. Paradoxically, the 90% prediction limits in association with the summary control group incidences are each approximately 20 percentage points wider than for those associated with the intervention group summaries. Conclusions: Control group VAP incidences above and more dispersed versus the expert opinion VAP range are common within the Cochrane reviews of antimicrobial-based VAP prevention interventions. Recognition requires an arms-based analysis using caterpillar plots. The SUTVAs that underlie the inference of prevention from the effect size estimates are not valid. Full article