Search Results (168)

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

Ventilator-associated pneumonia (VAP) develops in patients who stay on mechanical ventilation for more than 48 h. In the presence of causative pathogens, the patient develops clinical signs such as purulent tracheal discharge, fever, and respiratory distress. A prospective observational study was carried out in the Intensive Care Unit (ICU) of Max Healthcare Centre, New Delhi, from 2020 to 2023. The study comprised 70 samples from patients diagnosed with VAP. This study thoroughly examined VAP-associated microorganisms and resistance in the hospital ICU. Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa were the most commonly reported pathogens. Significant drug resistance was seen in P. aeruginosa, K. pneumoniae, A. baumannii and Staphylococcus aureus. The heatmap also supported the antibiotic resistance data patterns obtained from conventional and automated systems of determination. Notably, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, Ralstonia insidiosa, and Ralstonia mannitolilytica, showed 60 to 100% of resistance to a number of antibiotics. Among all VAP patients, 31.42% early-onset and 68.57% late-onset VAP cases were detected. Out of 70 patients, 43 patients died (mortality rate 61.4%); majority of them suffered from late-onset VAP. The study goal was to describe the antibiotic resistance patterns and microbial ecology of the pathogens that were isolated from VAP patients. According to the heatmap analysis, a varied VAP microbiome with high prevalences of MDR in A. baumannii, P. aeruginosa, K. pneumoniae, and S. aureus was identified. To address the increasing prevalence of MDR VAP, the study highlights the critical need for improved VAP monitoring, strong infection control, and appropriate antibiotic usage. Full article

Background: During the influenza A(H1N1) and COVID-19 pandemics, empirical antibiotic treatment (EAT) was widely administered to critically ill patients despite low rates of confirmed bacterial co-infection (COI). The clinical benefit of this practice remains uncertain and may contradict antimicrobial stewardship principles. Objective: To evaluate whether EAT at ICU admission reduces ventilator-associated pneumonia (VAP) incidence or ICU mortality in critically ill patients with pandemic viral pneumonia, stratified by presence of COI. Methods: This retrospective analysis combined two national multicentre ICU registries in Spain, including 4197 adult patients requiring invasive mechanical ventilation for influenza A(H1N1) or COVID-19 between 2009 and 2021. Primary outcomes were ICU mortality and VAP incidence. Analyses were stratified by microbiologically confirmed bacterial COI. Propensity score matching, Cox regression, General Linear (GLM), and random forest models were applied. Results: Among patients without COI (n = 3543), EAT was not associated with lower ICU mortality (OR = 1.02, 95%CI 0.81–1.28, p = 0.87) or VAP (OR = 1.02, 95%CI 0.79–1.39, p = 0.89). In patients with confirmed COI (n = 654), appropriate EAT was associated with reduced VAP (17.4% vs. 36.3%, p < 0.001) and ICU mortality (38.4% vs. 49.6%, OR = 1.89, 95%CI 1.13–3.14, p = 0.03) compared to inappropriate EAT. Conclusions: EAT was not associated with a lower incidence of VAP or higher survival rates and could be harmful if administered incorrectly. These findings support a more targeted approach to antibiotic use, guided by microbiology, biomarkers and stewardship principles. Full article

Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter species, and Candida species are common ventilator-associated pneumonia (VAP) isolates. Whilst the clinical significance of Candida as a VAP isolate is unclear, evidence is emerging that Candida interacts with bacteria, contributing to colonization susceptibility. Indirectly, VAP isolate data reflect patient colonization within cohorts. The objective here is to estimate the association between these three bacteria and Candida as VAP isolates. ICU cohorts were obtained by searching the literature for mechanically ventilated (MV) patient cohorts in which Candida was listed as an isolate among patients with VAP. Regression models of the associated VAP incidence per 100 MV patients, using random effects methods, incorporated group-level factors such as the year of publication, mode of VAP diagnosis, and ICU stay length. The median VAP incidence proportions for Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter species were 3.3 (IQR: 1.2–6.9), 3.6 (IQR: 1.8–5.7), and 1.2 (IQR: 0.4–4.1), respectively. Among 84 cohorts from 67 publications, Staphylococcus aureus (correlation coefficient = 0.759) and Pseudomonas aeruginosa (0.749), and less so Acinetobacter species (0.53), each show correlation with the isolation of Candida species among these ICU populations. These associations may underlie the poor prognosis with Candida colonization. Full article

Background: Ventilator-associated pneumonia (VAP) is a common and serious ICU complication, affecting up to 40% of mechanically ventilated patients. The diagnosis of VAP currently relies on retrospective clinical, radiological, and microbiological criteria, which often delays targeted treatment and promotes the overuse of broad-spectrum antibiotics. The early prediction of VAP is crucial to improve outcomes and guide antimicrobial use related to this disease. This study aimed to develop and validate PREDICT (Pneumonia Risk Evaluation and Diagnostic Intelligence via Computational Technology), a deep learning algorithm for early VAP prediction that is based solely on vital signs. Methods: We conducted a retrospective cohort study using the MIMIC-IV database, which includes ICU patients who were ventilated for at least 48 h. Five vital signs (respiratory rate, SpO₂, heart rate, temperature, and mean arterial pressure) were structured into 24 h temporal windows. The PREDICT model, based on a long short-term memory neural network, was trained to predict the onset of VAP 6, 12, and 24 h in the future. Its performance was compared to that of conventional machine learning models (random forest, XGBoost, logistic regression) using their AUPRC, sensitivity, specificity, and predictive values. Results: PREDICT achieved high predictive accuracy with AUPRC values of 96.0%, 94.1%, and 94.7% at 6, 12, and 24 h before the onset of VAP, respectively. Its sensitivity and positive predictive values exceeded 85% across all horizons. Traditional ML models showed a drop in performance over longer timeframes. Analysis of the model’s explainability highlighted the respiratory rate, SpO₂, and temperature as key predictive features. Conclusions: PREDICT is the first deep learning model specifically designed for early VAP prediction in ICUs. It represents a promising tool for timely clinical decision-making and improved antibiotic stewardship. 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

Despite the increased reporting of Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) in Egypt, there is a paucity of information regarding the molecular characteristics of such strains. Herein, we present the genome sequence of two CR-hvKp strains, K22 and K45, which were isolated from VAP (ventilator-associated-pneumonia) patients admitted to pediatric ICU at Assiut University Children’s Hospital, Egypt. K22 and K45 isolates were subjected to antimicrobial susceptibility testing and whole-genome sequencing. Genomic analysis was performed to characterize each strain, determining their plasmids, antimicrobial resistance (AMR) genes, and virulence determinants. K22 possessed an extensive drug resistance phenotype (XDR), whilst K45 exhibited a multidrug resistance phenotype (MDR), with genome sequencing revealing the presence of a diverse array of AMR genes. Both strains were resistant to the carbapenem antibiotic imipenem, carrying the OXA-48 carbapenemase, with K22 additionally possessing an NDM-1 carbapenemase. Each strain was considered high-risk, with K22 and K45 respectively belonging to sequence types ST383 and ST14 and possessing virulence genes implicated in hypervirulence (e.g., iucABCD-iutA and rmpA). Importantly, both strains carried multiple plasmid replicons, including an AMR/virulence IncHI1B/FIB hybrid plasmid and MDR IncL/M plasmids. This report highlights the critical role of plasmids in the evolution of virulent K. pneumoniae strains and suggests the circulation of an IncHI1B/FIB hybrid plasmid, simultaneously disseminating AMR and hypervirulence, amongst K. pneumoniae strains within Assiut University Children’s Hospital. Full article

Background: Active nasal surveillance culture (ANSC) is recognized to enable rapid detection of antibiotic-resistant bacteria in the intensive care unit (ICU), which can contribute to the prevention of Ventilator-associated pneumonia (VAP). This study aims to evaluate the usefulness of ANSC in assessing the development of VAP in ICU patients. Methods: Patients admitted to the Yamagata Prefectural Central Hospital ICU from January 2017 to 2018 (Term 1) or January 2020 to December 2021 (Term 2) and underwent invasive mechanical ventilation supports were eligible for this study. Nasal swab samples were collected from the patients upon their admission to the ICU. The diagnosis of VAP was made according to the criteria set by the Centers for Disease Control and Prevention. Results: A total of 467 patients (156 women) in term 1, and 312 patients (113 women) in term 2 were enrolled. The incidence of VAP in term 2 was higher than in term 1 (7.1% vs. 12.8%, respectively). ANSC isolated several causative pathogens from the patients on admission who later developed VAP. Haemophilus influenza, Streptococcus pneumoniae, Stenotrophomonas maltophilia, and Pseudomonas aeruginosa had a 100% match rate with the sputum culture, indicating a perfect relation between ANSC results and sputum culture in VAP (+) cases. Conclusions: The isolation of high-risk bacterial species by ANSC could foresee the development of VAP in ICU patients and efficiently prevent VAP in critically ill patients. Full article

Ventilator-associated pneumonia (VAP) remains a significant concern in intensive care units (ICUs), contributing to increased morbidity, mortality, and healthcare costs. Probiotics and synbiotics have been explored as potential preventive measures due to their ability to modulate gut microbiota, reduce pathogenic colonization, enhance immune responses, and maintain intestinal barrier integrity. While some randomized controlled trials (RCTs) suggest that specific strains, such as Lactobacillus rhamnosus GG and Bifidobacterium breve, may reduce VAP incidence, larger trials have not confirmed significant benefits. Systematic reviews and meta-analyses indicate a potential 28–38% relative risk reduction in VAP, but evidence quality remains low due to methodological limitations and study heterogeneity. Economic evaluations also question the cost effectiveness of probiotic use in ICU settings. Future research should focus on large-scale, multicenter RCTs to determine the optimal strains, dosages, and administration methods, along with standardized diagnostic criteria. Until stronger evidence emerges, probiotics should be considered an adjunctive rather than a primary VAP prevention strategy. Full article

Background. Ventilator-associated tracheobronchitis (VAT) and pneumonia (VAP) are the most frequent nosocomial infections in the critical care setting and are associated with increased morbidity. At the same time, VAP is also associated with attributable mortality, especially when caused by difficult-to-treat (DTR) Gram-negative bacteria (GNB) that have limited treatment options. Studies have assessed the impact of nebulized aminoglycosides or colistin to improve VAT and VAP outcomes or as an adjunct to intravenous antimicrobial treatment or as a preventive approach. Objective. This overview aimed to assess systematic reviews that examine the efficacy and safety of antimicrobial nebulization for preventing and treating ventilator-associated infections in the critically ill. Methods. Systematic reviews, meta-analyses, and original randomized controlled trials and prospective observational studies were included. Searches were conducted in MEDLINE (via PubMed), the Cochrane, Epistemonikos, and PROSPERO. The methodological quality assessment was performed using standardized tools. Results. Regarding VAP treatment, the included systematic reviews presented critically low quality. The clinical response effect size to amikacin and colistin nebulization were RR 1.23 (95% CI 1.13–1.34), I² = 47% and OR 1.39 (0.87–2.20), I² = 56%. The main safety concern was bronchospasm with RR 2.55 (1.40–4.66), I² = 0% and OR 5.19 (1.05–25.52), I² = 0%. The certainty of evidence was usually very low. For VAT treatment, limited evidence showed a better clinical response and less emergence of resistant bacteria. Regarding VAP prevention, data are limited to two trials; however, only the larger one presented a low risk of bias and resulted in a reduced VAP rate. Conclusions. Delivery via nebulization might be considered in addition to IV antimicrobial treatment of GNB ventilator-associated infections. The available evidence is weak, and more studies focused on infections due to DTR-GNBs should be prioritized. Full article

Mechanically ventilated (MV) patients often develop ventilator-associated pneumonia (VAP) with increased mortality risk, especially in VAP caused by multidrug-resistant (MDR) microorganisms. We evaluated MV patients and monitored VAP presentation, microbiologically confirmed. The patients underwent bronchoalveolar lavage (BAL) and blind bronchial aspiration (AC) at baseline. Systematic bronchial secretion and radiologic assessments were performed daily. The patients were classified as MDR-VAP, non-MDR-VAP, or non-VAP. The APACHE II and SOFA scores, microbiology, inflammatory markers, respiratory system characteristics, and ventilator settings were evaluated. BAL and AC were assessed for total protein levels, cellular number and profile, and IL-1β and TNF-α levels. Of the VAP patients, 46.1% presented with MDR-VAP due to Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, or Stenotrophomonas maltophilia, and 53.8%—with non-MDR-VAP. The VAP patients had higher APACHE II scores and airway pressure but a lower baseline PO₂/FIO₂ compared to the non-VAP patients, while PO₂/FIO₂ was increased in MDR-VAP compared to non-MDR-VAP. BAL protein, IL-1β, and cellular levels were increased in VAP vs. non-VAP and in non-MDR-VAP compared to MDR-VAP. Macrophages and polymorphonuclears were 34.36% and 23.76% in VAP, statistically significant increased compared to non-VAP. Their percentages were also increased in non-MDR-VAP compared to MDR-VAP. These differences imply a different immunological profile in non-MDR-VAP patients. In conclusion, MDR-VAP patients may present significant differences in baseline clinical characteristics and molecular biomarkers, which may help in prompt diagnosis and an improved therapeutic approach. Full article

Background/Objectives: Ventilator-associated pneumonia (VAP) is the main nosocomial infection in intensive care units (ICUs) that causes the highest morbidity and mortality. The aim of our study is to investigate variations in crude ICU mortality among patients with VAP over the past decade. We also wish to identify associated risk factors, evaluate changes in the etiology, and assess the incidence and impact of inappropriate empirical antibiotic treatment (IEAT). Methods: We conducted a retrospective, observational, single-center study over a 10-year period (2014–2024), including critically ill patients who developed VAP. The population was divided into three periods: (P1) from 2014 to 2018 (pre-COVID-19); (P2) from 2019 to 2021 (COVID-19); and (P3) from 2022 to 2024 (post-COVID-19). Binary logistic regression was used to identify which variables were independently associated with ICU mortality. Results: A total of 220 patients were included in the study (P1 = 47, P2 = 96, and P3 = 77 patients). The most prevalent microorganisms identified were P. aeruginosa, Klebsiella spp., and S. aureus. Significant variations in etiology were not observed over the years. The incidence of IEAT was 4.5%, with no observed differences between the study periods. Crude ICU mortality was 33.6%, with higher rates observed in IEAT (40% vs. 33.3%, p = 0.73). In patients with appropriate empiric antibiotic treatment (AEAT), there was a significant decrease in crude mortality over the years from 42.2% in P1 to 22.2% in P3 (p < 0.001). Age (OR = 1.04; 95% CI = 1.01–1.08) and P2 (OR = 2.8; 95% CI = 1.1–7.4) were found to be independently associated with an increased risk of mortality. Conversely, a lower risk of death was associated with mean arterial pressure (OR = 0.94; 95% CI = 0.69–0.99) and the use of syndromic respiratory panel (OR = 0.23; 95% CI = 0.07–0.68). Conclusions: A reduction in crude VAP mortality over the years was observed, with no change in the etiology or rate of IEAT. The implementation of protocols using respiratory syndromic panels could be a measure to implement to reduce VAP mortality. Full article

Background/Objectives: The COVID-19 pandemic has significantly increased the burden of ventilator-associated pneumonia (VAP) in intensive care units (ICUs) globally. However, epidemiological data on VAP in Slovak ICUs, particularly in the context of the pandemic, remain limited. This study aimed to evaluate the incidence, microbial profiles, and risk factors of VAP in Slovak ICU settings, particularly during the COVID-19 pandemic. Methods: A retrospective analysis of VAP data was conducted for respiratory intensive care unit (ICU) patients in a Slovak university hospital, comparing data from the pre-pandemic and pandemic periods. The CDC/NHSN definitions for VAP were applied, and statistical analyses were performed using STATISTICA 13.1. Results: A total of 803 patients were analyzed, representing 8385 bed days and 5836 mechanical ventilator days. VAP rates increased significantly during the pandemic by 111%, from 8.46 to 17.86 events per 1000 MV days (p < 0.001). VAP rates in non-COVID-19 patients increased by 86% during the pandemic compared to pre-pandemic levels. Pandemic conditions also increased ICU mortality from 25.66% to 40.52% (p < 0.001). VAP was identified as a critical determinant of ICU mortality, contributing to a 21.62% higher mortality rate among patients during the pandemic. Younger age, prolonged mechanical ventilation, and medical (vs. surgical) hospitalizations were associated with higher VAP incidence. Gram-negative bacteria dominated the pathogen profiles, with significant increases observed in Pseudomonas aeruginosa (183%), Klebsiella pneumoniae (150%), and Acinetobacter spp. (100%). Conclusions: The COVID-19 pandemic has significantly affected the incidence and epidemiology of VAP in Slovak ICUs, highlighting systemic vulnerabilities in HAI surveillance and IPC practices. 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

Background/Objectives: Ventilator-associated pneumonia (VAP) remains a critical challenge in ICU settings, often driven by the biofilm-mediated bacterial colonization of endotracheal tubes (ETTs). This study investigates antimicrobial resistance patterns and biofilm dynamics in ICU patients, focusing on microbial colonization and resistance trends in tracheal aspirates and endotracheal tube biofilms at a county emergency hospital in Romania. Methods: We conducted a longitudinal analysis of ICU patients requiring mechanical ventilation for more than 48 h. Tracheal aspirates and ETT biofilms were collected at three key time points: T1 (baseline), T2 (48 h post-intubation with ETT replacement), and T3 (92–100 h post-T2); these were analyzed using sonication and microbiological techniques to assess microbial colonization and antimicrobial resistance patterns. Results: In a total of 30 patients, bacteria from the ESKAPEE group (e.g., Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus) dominated the microbiota, increasing their prevalence over time. Resistance to carbapenems, colistin, and vancomycin was notably observed, particularly among K. pneumoniae and A. baumannii. Biofilm analysis revealed high persistence rates and the emergence of multidrug-resistant strains, underscoring the role of ETTs as reservoirs for resistant pathogens. The replacement of ETTs at T2 correlated with a shift in microbial composition and reduced biofilm-associated contamination. Conclusions: This study highlights the temporal evolution of antimicrobial resistance and biofilm-associated colonization in a limited number of ICU patients (30 patients). The findings support implementing routine ETT management strategies, including scheduled replacements and advanced biofilm-disruption techniques, to mitigate VAP risk and improve patient outcomes. Full article