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Patients with COVID-19 under invasive mechanical ventilation are at higher risk of developing ventilator-associated pneumonia (VAP), associated with increased healthcare costs, and unfavorable prognosis. The underlying mechanisms of this phenomenon have not been thoroughly dissected. Therefore, this study attempted to bridge this gap by performing a lung microbiota analysis and evaluating the host immune responses that could drive the development of VAP. In this prospective cohort study, mechanically ventilated patients with confirmed SARS-CoV-2 infection were enrolled. Nasal swabs (NS), endotracheal aspirates (ETA), and blood samples were collected initially within 12 h of intubation and again at 72 h post-intubation. Plasma samples underwent cytokine and metabolomic analyses, while NS and ETA samples were sequenced for lung microbiome examination. The cohort was categorized based on the development of VAP. Data analysis was conducted using RStudio version 4.3.1. In a study of 36 COVID-19 patients on mechanical ventilation, significant differences were found in the nasal and pulmonary microbiome, notably in Staphylococcus and Enterobacteriaceae, linked to VAP. Patients with VAP showed a higher SARS-CoV-2 viral load in respiratory samples, elevated neutralizing antibodies, and reduced inflammatory cytokines, including IFN-δ, IL-1β, IL-12p70, IL-18, IL-6, TNF-α, and CCL4. Metabolomic analysis revealed changes in 22 metabolites in non-VAP patients and 27 in VAP patients, highlighting D-Maltose-Lactose, Histidinyl-Glycine, and various phosphatidylcholines, indicating a metabolic predisposition to VAP. This study reveals a critical link between respiratory microbiome alterations and ventilator-associated pneumonia in COVID-19 patients with higher SARS-CoV-2 viral loads in respiratory samples, elevated neutralizing antibodies, and reduced inflammatory cytokines, including IFN-δ, IL-1β, IL-12p70, IL-18, IL-6, TNF-α, and CCL4. These findings provide novel insights into the underlying mechanisms of VAP, with potential implications for management and prevention. [ABSTRACT FROM AUTHOR]

Introduction: International guidelines recommend definitive combination antibiotic therapy for the management of serious infections involving carbapenem-resistant Acinetobacter (CRAB) species. The commonly available combination options include high-dose sulbactam, polymyxins, tetracyclines, and cefiderocol. Scanty prospective data exist to support this approach. Methods: Patients with CRAB bacteraemia, ventilator-associated pneumonia (VAP), or both were categorized based on whether they received combination therapy or monotherapy. The 30-day mortality was compared between the two groups. Inverse probability treatment weighting (IPTW) was done using propensity score (PS) for a balanced comparison between groups. Results: Between January 2021 and May 2023, of the 161 patients with CRAB bacteraemia (n = 55, 34.2%), VAP (n = 46, 28.6%), or both (n = 60, 37.3%) who received appropriate intravenous antibiotic therapy, 70% (112/161) received monotherapy, and the rest received combination therapy. The overall 30-day mortality was 62% (99/161) and not different (p = 0.76) between the combination therapy (31/49, 63.3%) and monotherapy (68/112, 60.7%) groups. The propensity score matching using IPTW did not show a statistical difference (p = 0.47) in 30-day mortality for receiving combination therapy with an adjusted odds ratio (OR) P of 1.29 (0.64, 2.58). Conclusion: Combination therapy for CRAB infections needs further study in a randomised controlled trial, as this observational study showed no difference in 30-day mortality between monotherapy and combination therapy. [ABSTRACT FROM AUTHOR]

Nosocomial pneumonia is defined as pneumonia occurring ≥ 48 h after hospital admission in a patient without severe immunosuppression. It can occur in spontaneously breathing patients or with noninvasive ventilation (NIV) and mechanically ventilated patients. In patients with suspected ventilator-associated pneumonia (VAP) (semi)quantitative cultures of tracheobronchial aspirates or bronchoalveolar lavage fluid should be perfomed. The initial empirical antimicrobial treatment is determined by the risk for multidrug-resistant pathogens (MDRP). The advantage of combination treatment increases with the prevalence of MDRPs. The antibiotic treatment should be adapted when the microbiological results are available. After 72 h a standardized re-evaluation including the response to treatment and also checking of the suspected diagnosis of pneumonia in a structured form is mandatory. Treatment failure can occur as a primary or secondary failure and in the case of primary progression necessitates another comprehensive diagnostic work-up before any further antibiotic treatment. [ABSTRACT FROM AUTHOR]

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Background: Antimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP) in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) carriers is challenging. BioFire® FilmArray® Pneumonia plus Panel (mPCR) can detect bacteria and antibiotic resistance genes, including blaCTX-M, the most common ESBL-encoding gene. Methods: This monocentric, prospective study was conducted on a group of ESBL-E carriers from March 2020 to August 2022. The primary objective was to evaluate the concordance between the results of mPCR and conventional culture performed on respiratory samples of ESBL-E carriers to investigate suspected VAP/vHAP. The secondary objective was to appraise the impact of performing or not mPCR on initial antibiotic therapy adequacy in ESBL-E carriers with confirmed VAP/vHAP. Results: Over the study period, 294 patients with ESBL-E carriage were admitted to the ICU, of who 168 (57%) were mechanically ventilated. (i) Diagnostic performance of mPCR was evaluated in suspected 41 episodes of VAP/vHAP: blaCTX-M gene was detected in 15/41 (37%) episodes, where 9/15 (60%) were confirmed ESBL-E-induced pneumonia. The culture and blaCTX-M were concordant in 35/41 (85%) episodes, and in all episodes where blaCTX-M was negative (n = 26), the culture never detected ESBL-E. (ii) The impact of mPCR on initial antibiotic therapy adequacy was assessed in 95 episodes of confirmed VAP/vHAP (22 episodes were tested with mPCR and 73 without); 47 (49%) episodes were ESBL-E-induced, and 24 (25%) were carbapenem-resistant bacteria-induced. The use of mPCR was significantly associated with higher prescription of adequate empirical antibiotic therapy in the multivariable logistic regression (adjusted odds ratio (aOR) (95% CI) of 7.5 (2.1–35.9), p = 0.004), propensity-weighting (aOR of 5.9 (1.6–22.1), p = 0.008), and matching-cohort models (aOR of 5.8 (1.5–22.1), p = 0.01). Conclusion: mPCR blaCTX-M showed an excellent diagnostic value to rule out the diagnosis of ESBL-E related pneumonia in ESBL-E carriers with suspected VAP/vHAP. In addition, in patients with confirmed VAP/vHAP, a mPCR-based antibiotic therapy was associated with an increased prescription of adequate empirical antibiotic therapy. Performing mPCR on respiratory samples seems to be a promising tool in ESBL-E carriers with suspected vHAP/VAP. However, if mPCR is used in very low pre-test clinical probability of pneumonia, due to the high sensitivity and the rate of overdiagnosed pneumonia, the risk of overconsumption of carbapenem may prevail. Further studies are warranted. [ABSTRACT FROM AUTHOR]

Ventilator-associated pneumonia (VAP) affects up to 20% of critically ill patients and induces significant antibiotic prescription pressure, accounting for half of all antibiotic use in the ICU. VAP significantly increases hospital length of stay and healthcare costs yet is also associated with long-term morbidity and mortality. The diagnosis of VAP continues to present challenges and pitfalls for the currently available clinical, radiological and microbiological diagnostic armamentarium. Biomarkers and artificial intelligence offer an innovative potential direction for ongoing future research. In this Review, we summarise the pathobiological heterogeneity and diagnostic challenges associated with VAP. Ventilator-associated pneumonia (VAP) is a nosocomial infection that significantly affects critically ill patients undergoing mechanical ventilation in the Intensive Care Unit (ICU). This review presents the diagnostic challenges associated with VAP in ICU. [ABSTRACT FROM AUTHOR]

Intensive care unit-acquired infections are complicating events in critically ill patients. In this study we analyzed the incidence, microbiological patterns, and outcome in patients with COVID-19 versus influenza in the intensive care unit (ICU). We included all adult patients treated with invasive mechanical ventilation due to (1) COVID-19 between January 2020 and March 2022, and (2) influenza between January 2015 and May 2023 at Sahlgrenska University Hospital, Sweden. Of the 480 participants included in the final analysis, 436 had COVID-19. The incidence rates of ICU-acquired infections were 31.6/1000 and 9.9/1000 ICU-days in the COVID-19 and influenza cohorts, respectively. Ventilator-associated lower respiratory tract infections were most common in both groups. In patients with COVID-19, corticosteroid treatment was associated with an increased risk of ICU-acquired infections and with higher 90-day mortality in case of infection. Furthermore, ICU-acquired infection was associated with a prolonged time in the ICU, with more difficult-to-treat gram-negative infections in late versus early ventilator-associated lower respiratory tract infections. Further research is needed to understand how the association between corticosteroid treatment and incidence and outcome of ICU-acquired infections varies across different patient categories. [ABSTRACT FROM AUTHOR]

Severe acute respiratory infections, such as community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia, constitute frequent and lethal pulmonary infections in the intensive care unit (ICU). Despite optimal management with early appropriate empiric antimicrobial therapy and adequate supportive care, mortality remains high, in part attributable to the aging, growing number of comorbidities, and rising rates of multidrug resistance pathogens. Biomarkers have the potential to offer additional information that may further improve the management and outcome of pulmonary infections. Available pathogen-specific biomarkers, for example, Streptococcus pneumoniae urinary antigen test and galactomannan, can be helpful in the microbiologic diagnosis of pulmonary infection in ICU patients, improving the timing and appropriateness of empiric antimicrobial therapy since these tests have a short turnaround time in comparison to classic microbiology. On the other hand, host-response biomarkers, for example, C-reactive protein and procalcitonin, used in conjunction with the clinical data, may be useful in the diagnosis and prediction of pulmonary infections, monitoring the response to treatment, and guiding duration of antimicrobial therapy. The assessment of serial measurements overtime, kinetics of biomarkers, is more informative than a single value. The appropriate utilization of accurate pathogen-specific and host-response biomarkers may benefit clinical decision-making at the bedside and optimize antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

Introduction: Ceftazidime-avibactam (CAZ-AVI) is a combination of the third-generation cephalosporin ceftazidime and the novel, non-β-lactam β-lactamase inhibitor avibactam that is approved for the treatment of pediatric (≥ 3 months) and adult patients with complicated infections including hospital-acquired and ventilator-associated pneumonia (HAP/VAP), and bacteremia. This systematic literature review and meta-analysis (PROSPERO registration: CRD42022362856) aimed to provide a quantitative and qualitative synthesis to evaluate the effectiveness of CAZ-AVI in treating adult patients with bacteremia or nosocomial pneumonia caused by carbapenem-resistant Enterobacterales (non metallo-β-lactamase-producing strains) and multi-drug resistant (MDR) Pseudomonas aeruginosa infections. Methods: The databases included in the search, until November 7, 2022, were Embase and PubMed. A total of 24 studies (retrospective: 22, prospective: 2) with separate outcomes for patients with bacteremia or pneumonia were included. Results: The outcomes assessed were all-cause mortality, clinical cure, and microbiological cure. Qualitative (24 studies) and quantitative (8/24 studies) syntheses were performed. The quality of the studies was assessed using the MINORS checklist and the overall risk of bias was moderate to high. Conclusions: In studies included in the meta-analysis, lower all-cause mortality for patients with bacteremia (OR = 0.30, 95% CI 0.19–0.46) and improved rates of clinical cure for patients with bacteremia (OR = 4.90, 95% CI 2.60–9.23) and nosocomial pneumonia (OR = 3.20, 95% CI 1.55–6.60) was observed in the CAZ-AVI group compared with the comparator group. Data provided here may be considered while using CAZ-AVI for the treatment of patients with difficult-to-treat infections. Systematic Review Registration: PROSPERO CRD42022362856. [ABSTRACT FROM AUTHOR]

Cefepime/enmetazobactam (EXBLIFEP®), an intravenous (IV) antibacterial fixed-dose combination of a 4th generation cephalosporin and an extended-spectrum β-lactamase (ESBL) inhibitor, is being developed by Allecra Therapeutics and ADVANZ PHARMA for the treatment of infections caused by multi-drug-resistant (MDR) Gram-negative bacteria. In February 2024, cefepime/enmetazobactam was approved in the USA for use in adults with complicated urinary tract infections (cUTI) including pyelonephritis, caused by susceptible strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Enterobacter cloacae complex. In March 2024, cefepime/enmetazobactam was approved in the EU for use in adults for the treatment of cUTI, including pyelonephritis, and hospital-acquired pneumonia, including ventilator associated pneumonia, and the treatment of patients with bacteraemia occurring in association with or suspected to be associated with any of these infections. This article summarizes the milestones in the development of cefepime/enmetazobactam leading to this first approval for the treatment of adults with infections caused by MDR Gram-negative bacteria. [ABSTRACT FROM AUTHOR]

Purpose: Ventilator care bundles are effective in the prevention of ventilator-associated pneumonia (VAP). However, the compliance of these bundles in intensive care units (ICUs) remains poorly studied. This study investigates the Medical Information Mart for Intensive Care (MIMIC)-IV cohort’s compliance with the Institute for Healthcare Improvement (IHI) bundle and its resulting association with VAP incidence. Methods: This is a retrospective cohort study of the MIMIC-IV database. Patients with > 48 h of invasive mechanical ventilation (IMV) were included. Diagnosis of VAP was identified with the International Classification of Diseases (ICD)-9 and ICD-10 codes. Compliance rates to the IHI bundle were extracted. The association of the IHI bundle and its individual interventions with VAP incidence was analyzed with univariate and multivariate analysis. Results: 8270 patients were included, of which 1328 (16.1%) had VAP. 25 patients (0.3%) had full compliance to the IHI bundle. 137 patients (1.7%) received no interventions from the bundle. Gastroprophylaxis had the lowest (2.1%) while head elevation had the highest (89.3%) compliance rates. In patients receiving the IHI bundle, each additional intervention was associated with lower VAP incidence (OR [odds ratio] = 0.906, 95% CI [confidence interval] 0.847–0.969). Appropriate sedation levels (OR = 0.765, 95% CI 0.661–0.885) and the use of heat and moisture exchanger (HME) filters (OR = 0.862, 95% CI 0.745–0.998) were individually associated with reduced VAP incidence, while active humidification was individually associated with increased VAP incidence (OR = 1.139, 95% CI 1.001–1.296). Conclusion: The use of the IHI bundle was associated with a lower incidence of VAP, but compliance with the bundle was poor. Appropriate sedation and HME filters were individually associated with reduced VAP incidence. Better compliance with the IHI bundle may reduce VAP rates in mechanically ventilated patients. [ABSTRACT FROM AUTHOR]

Introduction: Oral chlorhexidine has been widely used for ventilator-associated pneumonia prevention in the critical care setting; however, previous studies and evidence synthesis have generated inconsistent findings. Our study aims to investigate if different concentrations of oral chlorhexidine may be effective in preventing such complication in intensive care unit patients. Methods: After pre-registration (Open Science Framework: 8CUKF), we conducted a network meta-analysis with the following PICOS: adult patients (age > 18 years old) undergoing invasive mechanical ventilation admitted in ICU (P); any concentration of chlorhexidine used for oral hygiene (I); placebo, sham intervention, usual care, or no intervention (C); rate of VAP (primary outcome), mechanical ventilation length, ICU length of stay (LOS), hospital LOS, mortality (secondary outcomes) (O); randomized controlled trials (S). We used the following database: PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and EMBASE without any limitation in publication date or language. Results: Chlorhexidine did not demonstrate any significant advantage over the control group in preventing ventilator-associated pneumonia or reducing mortality, duration of mechanical ventilation, length of stay in the intensive care unit, or overall mortality. Conclusions: Chlorhexidine oral decontamination does not reduce the rate of ventilator-associated pneumonia in critically ill adult patients and its routine use could not be recommended. Trial registration: Registration number: Open Science Framework: 8CUKF. [ABSTRACT FROM AUTHOR]

Background: Multiple randomized controlled studies have compared numerous antibiotic regimens, including new, recently commercialized antibiotics in the treatment of nosocomial pneumonia (NP). The objective of this Bayesian network meta-analysis (NMA) was to compare the efficacy and the safety of different antibiotic treatments for NP. Methods: We conducted a systematic search of PubMed, Medline, Web of Science, EMBASE and the Cochrane Library databases from 2000 through 2021. The study selection included studies comparing antibiotics targeting Gram-negative bacilli in the setting of NP. The primary endpoint was 28 day mortality. Secondary outcomes were clinical cure, microbiological cure and adverse events. Results: Sixteen studies encompassing 4993 patients were included in this analysis comparing 13 antibiotic regimens. The level of evidence for mortality comparisons ranged from very low to moderate. No significant difference in 28 day mortality was found among all beta-lactam regimens. Only the combination of meropenem plus aerosolized colistin was associated with a significant decrease of mortality compared to using intravenous colistin alone (OR = 0.43; 95% credible interval [0.17–0.94]), based on the results of the smallest trial included. The clinical failure rate of ceftazidime was higher than meropenem with (OR = 1.97; 95% CrI [1.19–3.45]) or without aerosolized colistin (OR = 1.40; 95% CrI [1.00–2.01]), imipemen/cilastatin/relebactam (OR = 1.74; 95% CrI [1.03–2.90]) and ceftazidime/avibactam (OR = 1.48; 95% CrI [1.02–2.20]). For microbiological cure, no substantial difference between regimens was found, but ceftolozane/tazobactam had the highest probability of being superior to comparators. In safety analyses, there was no significant difference between treatments for the occurrence of adverse events, but acute kidney failure was more common in patients receiving intravenous colistin. Conclusions: This network meta-analysis suggests that most antibiotic regimens, including new combinations and cefiderocol, have similar efficacy and safety in treating susceptible Gram-negative bacilli in NP. Further studies are necessary for NP caused by multidrug-resistant bacteria. Registration PROSPERO CRD42021226603 [ABSTRACT FROM AUTHOR]

Objectives: To assess the incidences of Herpes Simplex-1 and 2 (HSV-1, HSV-2), Cytomegalovirus (CMV), Epstein–Barr Virus (EBV) reactivations in critically ill COVID-19 patients. To determine the association between viral reactivation and in-hospital mortality, Intensive Care Unit Bloodstream infection (ICU–BSI), ventilator-associated pneumonia (VAP). Design: Observational retrospective cohort study. Setting: COVID-19 Intensive Care Unit. Patients: From November 2020 to May 2021, one hundred and twenty patients with COVID-19 severe pneumonia were enrolled and tested for HSV-1, HSV-2, CMV and EBV at the admission in ICU and weekly until discharge or death. The presence of VAP and ICU–BSI was evaluated according to clinical judgement and specific diagnostic criteria. Measurements and main results: One hundred and twenty patients were enrolled. Multiple reactivations occurred in 75/120 (63%) patients, single reactivation in 27/120 patients (23%). The most reactivated Herpesvirus was EBV, found in 78/120 (65%) patients. The multivariate analysis demonstrated that viral reactivation is a strong independent risk factor for in-hospital mortality (OR = 2.46, 95% CI 1.02–5.89), ICU–BSI (OR = 2.37, 95% CI 1.06–5.29) and VAP (OR = 2.64, 95% CI 1.20–5.82). Conclusions: Human Herpesviruses reactivations in critically ill patients with COVID-19 severe Pneumonia are associated with mortality and with a higher risk to develop both VAP and ICU–BSI. Key points: Question: The impact of Human Herpesviruses reactivations on the morbidity and mortality of COVID-19 critically ill patients is controversial. Findings: Critically ill patients with COVID-19 are at high risk for both EBV, HSV and CMV reactivations. Meanings: Further large prospective studies will be necessary to clarify if the presence of active viral replication must be considered causal agent affecting mortality or the indirect manifestation of immune paralysis in the worst patients. [ABSTRACT FROM AUTHOR]

Acinetobacterbaumannii is without a doubt one of the most problematic bacteria causing hospital-acquired nosocomial infections in today's healthcare system. To solve the high prevalence of multi-drug resistant (MDR) in A.baumannii, we investigated one of the medicinal plants traditionally used as antibacterial agent; namely Murrayakoenigii (L.) Sprengel. The total methanolic extracts of seeds and pericarps were prepared and their anti-bacterial activity was assessed using the agar diffusion method and minimum inhibitory concentration (MIC) was then calculated as compared to tigecycline. Then, an in-vivo murine model was established which confirmed the promising activity of M.koenigii seeds in demonstrating anti-bacterial and anti-inflammatory actions. The histopathological study of lungs, scoring of pulmonary lesions, counting of bacterial loads after infection by multi-drug resistant A.baumannii all provided evidence to support these findings. LC–MS/MS profiling coupled to molecular networking and chemometrics detected the presence of carbazole alkaloids, and coumarins as dominate metabolites of the active seed extracts. Positively correlated metabolites to antibacterial potential were 6-(2ʹ,3ʹ-dihydroxy-3-methylbutyl)-8-prenylumbelliferone, scopoline, and 5-methoxymurrayatin. An in-silico study was also performed on the crystal structure of MurF from A.baumannii (PDB ID: 4QF5), the studied structures of the mentioned extracts revealed good docking interaction at the active site suggestive of competition with the ATP ligand. These collective findings suggest that extracts of Murrayakoenigii (L.) Sprengel seed is a novel prospective for the discovery of drug candidates against infections caused by MDR A.baumannii. [ABSTRACT FROM AUTHOR]

Immunocompromised patients account for an increasing proportion of the typical intensive care unit (ICU) case-mix. Because of the increased availability of new drugs for cancer and auto-immune diseases, and improvement in the care of the most severely immunocompromised ICU patients (including those with hematologic malignancies), critically ill immunocompromised patients form a highly heterogeneous patient population. Furthermore, a large number of ICU patients with no apparent immunosuppression also harbor underlying conditions altering their immune response, or develop ICU-acquired immune deficiencies as a result of sepsis, trauma or major surgery. While infections are associated with significant morbidity and mortality in immunocompromised critically ill patients, little specific data are available on the incidence, microbiology, management and outcomes of ICU-acquired infections in this population. As a result, immunocompromised patients are usually excluded from trials and guidelines on the management of ICU-acquired infections. The most common ICU-acquired infections in immunocompromised patients are ventilator-associated lower respiratory tract infections (which include ventilator-associated pneumonia and tracheobronchitis) and bloodstream infections. Recently, several large observational studies have shed light on some of the epidemiological specificities of these infections—as well as on the dynamics of colonization and infection with multidrug-resistant bacteria—in these patients, and these will be discussed in this review. Immunocompromised patients are also at higher risk than non-immunocompromised hosts of fungal and viral infections, and the diagnostic and therapeutic management of these infections will be covered. Finally, we will suggest some important areas of future investigation. [ABSTRACT FROM AUTHOR]

This article discusses the use of lung ultrasonography (LUS) for diagnosing and managing adult respiratory distress syndrome (ARDS). LUS is a non-invasive and bedside technique that can be used in both high- and low-resource settings. The article explains the technique and utility of LUS in ARDS patients, including the examination process and the different patterns that can be observed. It also discusses the use of LUS for diagnosing ARDS and monitoring its progression and treatment response. Additionally, LUS has the potential to classify subphenotypes of ARDS, which can help in targeting treatment for individual patients. Overall, LUS is an essential tool for diagnosing and managing ARDS due to its accessibility and availability across different resource settings. [Extracted from the article]

Background: Ventilator-associated pneumonia (VAP) is the leading nosocomial infection in critical care and is associated with adverse outcomes. When VAP is suspected, starting antibiotic therapy (AT) immediately after pulmonary sampling may expose uninfected patients to unnecessary treatment, whereas waiting for bacteriological confirmation may delay AT in infected patients. As no robust data exist to choose between these strategies, the decision must balance the pre-test diagnostic probability, clinical severity, and risk of antimicrobial resistance. The objective of this study in patients with suspected non-severe VAP was to compare immediate AT started after sampling to conservative AT upon receipt of positive microbiological results. The outcomes were antibiotic sparing, AT suitability, and patient outcomes. Methods: This single-center, before–after study included consecutive patients who underwent distal respiratory sampling for a first suspected non-severe VAP episode (no shock requiring vasopressor therapy or severe acute respiratory distress syndrome). AT was started immediately after sampling in 2019 and upon culture positivity in 2022 (conservative strategy). The primary outcome was the number of days alive without AT by day 28. The secondary outcomes were mechanical ventilation duration, day-28 mortality, and AT suitability (active necessary AT or spared AT). Results: The immediate and conservative strategies were applied in 44 and 43 patients, respectively. Conservative and immediate AT were associated with similar days alive without AT (median [interquartile range], 18.0 [0–21.0] vs. 16.0 [0–20.0], p = 0.50) and without broad-spectrum AT (p = 0.53) by day 28. AT was more often suitable in the conservative group (88.4% vs. 63.6%, p = 0.01), in which 27.9% of patients received no AT at all. No significant differences were found for mechanical ventilation duration (median [95%CI], 9.0 [6–19] vs. 9.0 [6–24] days, p = 0.65) or day-28 mortality (hazard ratio [95%CI], 0.85 [0.4–2.0], p = 0.71). Conclusion: In patients with suspected non-severe VAP, waiting for microbiological confirmation was not associated with antibiotic sparing, compared to immediate AT. This result may be ascribable to low statistical power. AT suitability was better with the conservative strategy. None of the safety outcomes differed between groups. These findings would seem to allow a large, randomized trial comparing immediate and conservative AT strategies. [ABSTRACT FROM AUTHOR]

Background: TREM-1 (setting off receptor imparted on myeloid cells-1) is an immunoreceptor. Neutrophils, monocytes/macrophages, and endothelial cells all express TREM-1. This work aimed to evaluate the role of STREM-1 in ventilator-associated pneumonia (VAP) early prediction in pediatrics. Methods: This case–control research involved 56 children aged from 1 month to 5 years old, who were admitted to the pediatric intensive care unit (PICU) and needed mechanical ventilation (MV), from January 2023 to June 2023. Subjects were equally allocated into two groups: VAP group and non-VAP group. Results: There was significantly elevated serum STREM-1 after 72 h than at admission between both groups. There was significantly elevated STREM-1, procalcitonin (PCT), and C-reactive protein (CRP) after 72 h in the VAP group compared to the non-VAP group. There was a positive correlation between PCT and CRP after 72 h. STREM-1 at admission and after 72 h area under the curve (AUC) was 0.641 (0.502 to 0.765), 1.000 (0.936 to 1.000), with best cut-off value for prediction of VAP was > 185, > 230 with sensitivity 53.6%, 100% and specificity 67.9%, 100%, respectively. Conclusion: Serum sTREM-1 concentration is a reliable biomarker for predicting VAP in pediatrics received MV. [ABSTRACT FROM AUTHOR]

Objective: To determine the utility of microscopic examination and culture of endotracheal aspirate (ETA) in the early diagnosis of ventilator-associated pneumonia (VAP) in preterm neonates. Methods: We enrolled 80 consecutive neonates (both inborn and out-born) with gestational age of < 37 weeks admitted in Special Newborn Care Unit (SNCU) and requiring mechanical ventilation (MV) for > 48 hours. The diagnosis of VAP was made using the criteria laid down by the Centers for Disease Control (CDC). Results: 47 preterm neonates (58.5%) developed VAP; the overall incidence was 74.7/1000 ventilator-days. The mean (SD) time (hours) to ETA culture was less as compared to diagnosis based on CDC criteria [108.9 (8.00 hrs) vs 132.4 (53.24); P = 0.004] with sensitivity and specificity of 80.8% and 72.7%, respectively. Outborn delivery was the single most important risk factor for VAP. Multidrug resistant (MDR) Klebsiella pneumoniae (63.9%) was the most prevalent organism. Conclusions: We noticed a very high incidence of VAP among preterm neonates in SNCU. ETA culture can aid in early diagnosis. [ABSTRACT FROM AUTHOR]

Background: Early-onset ventilator-associated pneumonia (VAP) is associated with poor outcomes in patients with severe traumatic brain injury (TBI). The primary aim of this study was to describe VAP, including the microbiology of VAP and differences in frequency of VAP when various definitions are applied. The secondary aim was to determine the clinical variables associated with the development of VAP in children with severe TBI. Methods: This is a retrospective cohort study at a quaternary referral children's hospital with a level I trauma center designation. Inclusion criteria were patients aged 0–18 years admitted to the pediatric intensive care unit between 2015 and 2020 with severe TBI requiring at least 2 days of invasive ventilation. VAP was defined by using Center of Disease Control (CDC) definition or clinical VAP, based on physician diagnosis. We compared general demographics, reviewed trauma and injury data, and outcomes to assess any differences between patients with VAP and non-VAP patients. Associations were tested with regression models. Results: After applying all inclusion and exclusion criteria, 90 patients were included in the analysis. Patients with VAP were older (8.5 vs. 5.6 years, P = 0.03). Patients with VAP were less likely to have suffered from abusive head trauma (P = 0.01). Patients who received continuous neuromuscular blockade or targeted temperature management did not have different frequencies of VAP. CDC-defined VAP was diagnosed in 27% of patients. Number of patients with VAP increased to 41% for physician-diagnosed or clinical VAP. Methicillin-sensitive Staphylococcus aureus was the most common isolate grown, followed by Hemophilus influenza, with most VAP occurring on days 2–5 of intubation. VAP was not associated with mortality but was associated with worse functional status scale in patients who survived to discharge (8 vs. 7.5, P = 0.048). Over a cumulative period of days, nebulized 3% and albuterol were associated with decreased incidence of VAP. Conclusions: Ventilator-associated pneumonia occurs commonly in children with severe TBI, with rates of 27–41%, depending on CDC-defined VAP or clinical VAP. The discrepancy between clinical VAP and CDC-defined VAP further illustrates the need for a standardized definition for VAP. Although most interventions were not associated with VAP, nebulized 3% saline and albuterol were associated with reduced incidence of VAP; future investigation is needed to determine whether mucolytic agents can decrease the rate of VAP in children with severe TBI. [ABSTRACT FROM AUTHOR]

This document is a comment on a review article about intensive care unit (ICU)-acquired infections in immunocompromised patients. The authors disagree with the review's view on the role of multiplex polymerase chain reaction (mPCR)-based tests in ventilator-associated lower respiratory tract infections (VA-LRTIs). They argue that mPCR tests are useful for ICU-acquired infections and can improve antibiotic stewardship in the ICU. The authors also discuss the strengths and limitations of mPCR-based tests based on their own study. They suggest that while waiting for further trials, physicians should be aware of the strengths and limitations of these tests. [Extracted from the article]

Klebsiella pneumoniae is associated with a variety of infections, such as pneumonia, urogenital infection, liver abscess, and bloodstream infection. It is especially dangerous for patients in medical facilities, where it can cause ventilator-associated pneumonia or intensive care unit-acquired pneumonia. The emergence of multidrug-resistant and hypervirulent strains as well as the ability to form biofilms on various medical devices complicates the treatment of such infections and makes the use of antibiotics ineffective. The application of bacteriophages is a promising alternative for combating Klebsiella pneumoniae biofilms. In the present study a cocktail of 3 bacteriophages with depolymerase activity was used to control antibiotic resistant Klebsiella pneumoniae biofilms in vitro. Biofilms were examined using optical and scanning electron microscopy. The obtained results demonstrate that the studied bacteriophage cocktail can effectively disrupt Klebsiella pneumoniae biofilms. [ABSTRACT FROM AUTHOR]

Background: Predictors of ICU-acquired pulmonary aspergillosis (IPA) are not well-established in critically ill patients with ventilator-associated pneumonia (VAP), making IPA commonly misdiagnosed and anti-fungal therapy delayed. We aimed to develop a clinical score for prediction of IPA among patients with VAP. Methods: Mechanically ventilated patients who developed VAP in 4 ICUs in Bretagne, Western France, were included. The score was constructed in a learning cohort, based on predictors of IPA in logistic regression model, and validated in a validation cohort. Results: Among 1636 mechanically ventilated patients, 215 developed VAP but only 39 developed IPA (4 possible and 35 probable/putative) (18%). Most cases (31/39) were documented through a positive broncho-alveolar sample culture. Independent predictors of IPA were immunodepression (including onco-hematological disorder, immunomodulatory treatment, solid organ transplant, neutropenia < 0.5G/L and high-dose steroids ≥ 1 mg/kg/day of prednisolone equivalent) (p = 0.001; score = 1 point) and lymphocyte count at admission < 0.8 G/L (p = 0.019; score = 1 point). Operational values of the predictive score in the learning/validation cohort were 50%/52% sensitivity and 90%/87% specificity, respectively, for high PiPa score (score = 2) and 94%/91% sensitivity and 44%/46% specificity, respectively, for moderate PiPa score (score = 1). Finally, the AUC for the prediction of IPA was 0.783 in the learning cohort and 0.770 in the validation cohort. Conclusions: We evaluated a clinical score with good predictive value which may help to predict IPA in patient with VAP. External validation will be needed to confirm our preliminary findings. [ABSTRACT FROM AUTHOR]

Background: Data on ventilator associated pneumonia (VAP) in COVID-19 and influenza patients admitted to intensive care units (ICU) are scarce. This study aimed to estimate day-60 mortality related to VAP in ICU patients ventilated for at least 48 h, either for COVID-19 or for influenza, and to describe the epidemiological characteristics in each group of VAP. Design: Multicentre retrospective observational study. Setting: Eleven ICUs of the French OutcomeRea™ network. Patients: Patients treated with invasive mechanical ventilation (IMV) for at least 48 h for either COVID-19 or for flu. Results: Of the 585 patients included, 503 had COVID-19 and 82 had influenza between January 2008 and June 2021. A total of 232 patients, 209 (41.6%) with COVID-19 and 23 (28%) with influenza, developed 375 VAP episodes. Among the COVID-19 and flu patients, VAP incidences for the first VAP episode were, respectively, 99.2 and 56.4 per 1000 IMV days (p < 0.01), and incidences for all VAP episodes were 32.8 and 17.8 per 1000 IMV days (p < 0.01). Microorganisms of VAP were Gram-positive cocci in 29.6% and 23.5% of episodes of VAP (p < 0.01), respectively, including Staphylococcus aureus in 19.9% and 11.8% (p = 0.25), and Gram-negative bacilli in 84.2% and 79.4% (p = 0.47). In the overall cohort, VAP was associated with an increased risk of day-60 mortality (aHR = 1.77 [1.36; 2.30], p < 0.01), and COVID-19 had a higher mortality risk than influenza (aHR = 2.22 [CI 95%, 1.34; 3.66], p < 0.01). VAP was associated with increased day-60 mortality among COVID-19 patients (aHR = 1.75 [CI 95%, 1.32; 2.33], p < 0.01), but not among influenza patients (aHR = 1.75 [CI 95%, 0.48; 6.33], p = 0.35). Conclusion: The incidence of VAP was higher in patients ventilated for at least 48 h for COVID-19 than for influenza. In both groups, Gram-negative bacilli were the most frequently detected microorganisms. In patients ventilated for either COVID-19 or influenza VAP and COVID-19 were associated with a higher risk of mortality. [ABSTRACT FROM AUTHOR]

Introduction: The timing of tracheostomy in traumatic brain injury is controversial. The benefits of early tracheostomy are early weaning from ventilation, and reduction in pneumonia. But some studies demonstrated increase in intracranial pressure during tracheostomy. Aim and Methods: The aims of the audit are to analyse the timing, benefits, complications, and the results of tracheostomy in patients with traumatic brain injury in the hospital in the period of 2012–2021. Results: The number of patients was 34. The maximum number of tracheostomies(24) were between 6th to 14th days of admission. The complications were: worsening of Glasgow coma scale score − 3 (in the early group), bleeding − 2, subglottic stenosis-1, tracheocutaneous fistula-1. The main benefits obtained form tracheostomy were the easiness of weaning and tracheobronchial toilet. Twelve patients had pneumonia. Nine patients survived out of twelve. Six patients had acute respiratory distress syndrome. Five of them succumbed. The weaning time corresponded to the severity of injury and pulmonary status. The mortality according to the timing of tracheostomy were: 1/6(16.67%) in the group of first week, 9/19(47%) in the group of second week, and 3/8(37.5%) in the group of the third and fourth week. The mortality was less in the group of first week. Conclusions: The timing of tracheostomy in traumatic brain injury should be at the earliest after the control of raised intracranial tension. There was reversible worsening of Glasgow coma scale score for 2 points in 3 cases after early tracheostomy. Mortality was less in the group of early tracheostomy. [ABSTRACT FROM AUTHOR]

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Selective digestive decontamination (SDD) is a controversial technique proposed to prevent infections, particularly ventilator-associated pneumonia (VAP), in critically ill patients in the intensive care unit (ICU). The technique involves the use of topical and non-absorbable antibiotics in the oro-pharynx and stomach, along with a short course of systemic antibiotics. The use of systemic antibiotics in SDD has been a point of contention, with concerns about antimicrobial resistance and the quality of some studies. While studies have shown a decrease in ICU-acquired bacteremia and VAP with SDD, the effect on mortality remains uncertain. An international consensus conference is needed to determine the safety and effectiveness of SDD in the ICU context and address ethical considerations. [Extracted from the article]

Background: Sedation is an integral part in the management of critical patients in the pediatric intensive care unit (PICU). Optimum sedation is when the child is asleep but easily arousable. The patient should be able to breathe synergistically with the ventilator and should tolerate or be compliant with other therapeutic procedures. Undersedation can make the children hypertensive, tachycardic, and agitated. Conversely, oversedation can cause increased tolerance and prolonged ventilation. Both undersedation and oversedation have negative impacts on patient outcomes such as prolonged mechanical ventilation and ICU stay and increased risk of contracting ventilator-associated pneumonia, thus contributing to significant morbidity and mortality. This study aims to assess sedation levels in ventilated children using RASS in the first 48hrs of ventilation and study their correlation with patient outcomes. Results: Of the 111 children enrolled in the study, 2 were excluded because the sedation was discontinued before 48 h, and 9 were excluded because they were ventilated for more than 7 days. Majority of the children receiving ventilation in PICU were oversedated (40%). Adequately sedated children were observed to have significantly lesser duration of mechanical ventilation (p-value: 0.022) and PICU stay (p-value: 0.01). Undersedated children were noted to have significantly higher incidence of self extubation (p-value: < 0.001), reintubation (p-value: < 0.001), and higher requirement of restraints (p-value: < 0.001). Oversedated had a higher incidence of VAP and mortality (p-value: < 0.001). Conclusion: The findings of this study highlight the importance of achieving adequate sedation in PICU which is associated with better outcomes with respect to duration of ventilation, PICU stay, hospital stay, and mortality. This study also reflects the impact of absence of sedation protocols and emphasizes the need for monitoring of sedation and having protocols to guide clinical practice in order to improve patient outcome. [ABSTRACT FROM AUTHOR]

Background Hospital‑acquired pneumonia (HAP) and ventilator‑associated pneumonia (VAP) represent a major health problem among hospitalized patients leading to consequent morbidity and mortality specially after Covid‑19 era and spread of multidrug‑resistance organisms)MDRO) in hospitals. Aim This study aimed to analyze the commonest microorganisms responsible for HAP and VAP at Tanta University Chest Hospital. Methods This prospective observational study was done at Chest Department, Faculty of Medicine, started from June 2022 to February 2023. Fifty HAP patients’ sputum samples and 50 VAP patients (25 endotracheal aspirates and 25 bronchoalveolar lavages) were included. All collected samples were submitted to standard microbiological tests at Microbiology Department, Tanta Faculty of Medicine. Results A total number of 50 HAP and 50 VAP cases were included. Microbial isolates were relatively the same in both groups, where Klebsiella pneumoniae was the predominant isolates (56) followed by Staphylococcus aureus (25), Escherichia coli (14), Pseudomonas aeruginosa (13), Acinetobacter baumannii (5), Streptococcus pneumoniae (4), Enterococci (3), Stenotrophomonas maltophilia (2), Citrobacter freundii (2), Streptococcus pyogenes (2), Providencia stuartii (1), and 7 isolates of Candida. Antimicrobial susceptibility showed predominance of drug‑resistance organisms in VAP (78%) versus HAP (28%), P‑value: < 0.001. Klebsiella pneumonia showed higher rates of resistance (37 out of 56 isolates, P‑value = 0.020). Four out of 5 Acinetobacter baumannii isolates were multidrug resistant, and 2 isolates of Stenotropho- monas maltophilia were polydrug resistant. Multivariate logistic regression analysis showed that intravenous antibiotic administration within last 3 months was associated with risk for MDR‑HAP, while univariate regression analysis showed that intravenous antibiotic administration within the last 3 months was the strongest predictor for MDR‑VAP. A higher mortality rate was recorded in VAP group (66%), versus (14%) in HAP group (P‑value: < 0.001). Conclusion Microbial isolates were relatively the same in both HAP and VAP, but VAP showed significant predomi‑ nance of drug‑resistant organisms. The most significant predictor for risk of MDRO infection in HAP and VAP was intra‑ venous antibiotic administration within last 3 months; so, raising attention towards antibiotic choice may improve the outcome. Finally, VAP was associated with higher mortality compared to HAP. [ABSTRACT FROM AUTHOR]

Introduction: Nosocomial pneumonia has poor prognosis in hospitalized trauma patients. Croce et al. published a model to predict post-traumatic ventilator-associated pneumonia, which achieved high discrimination and reasonable sensitivity. We aimed to externally validate Croce's model to predict nosocomial pneumonia in patients admitted to a Dutch level-1 trauma center. Materials and methods: This retrospective study included all trauma patients (≥ 16y) admitted for > 24 h to our level-1 trauma center in 2017. Exclusion criteria were pneumonia or antibiotic treatment upon hospital admission, treatment elsewhere > 24 h, or death < 48 h. Croce's model used eight clinical variables—on trauma severity and treatment, available in the emergency department—to predict nosocomial pneumonia risk. The model's predictive performance was assessed through discrimination and calibration before and after re-estimating the model's coefficients. In sensitivity analysis, the model was updated using Ridge regression. Results: 809 Patients were included (median age 51y, 67% male, 97% blunt trauma), of whom 86 (11%) developed nosocomial pneumonia. Pneumonia patients were older, more severely injured, and underwent more emergent interventions. Croce's model showed good discrimination (AUC 0.83, 95% CI 0.79–0.87), yet predicted probabilities were too low (mean predicted risk 6.4%), and calibration was suboptimal (calibration slope 0.63). After full model recalibration, discrimination (AUC 0.84, 95% CI 0.80–0.88) and calibration improved. Adding age to the model increased the AUC to 0.87 (95% CI 0.84–0.91). Prediction parameters were similar after the models were updated using Ridge regression. Conclusion: The externally validated and intercept-recalibrated models show good discrimination and have the potential to predict nosocomial pneumonia. At this time, clinicians could apply these models to identify high-risk patients, increase patient monitoring, and initiate preventative measures. Recalibration of Croce's model improved the predictive performance (discrimination and calibration). The recalibrated model provides a further basis for nosocomial pneumonia prediction in level-1 trauma patients. Several models are accessible via an online tool. Level of evidence: Level III, Prognostic/Epidemiological Study. [ABSTRACT FROM AUTHOR]

Regarding pathophysiology, VAT might represent an intermediate process between colonisation and pneumonia and prevention strategies to VAP applies to VAT [[2]]. VAT and ventilator associated pneumonia (VAP) showed similar microbiology and C-reactive protein and procalcitonin have shown a marked overlap in both VAP and VAP not allowing adequate discrimination [[4]]. A course of 7 to 10 days of antibiotics has been successfully implemented for the treatment of VAP and probably shorter courses and nebulised antibiotics could represent a treatment for VAT. Pneumonia is not a black or white disease; there is a continuum between colonisation and pneumonia that results from the interplay between host, bacteria and iMV. [Extracted from the article]

Background: Ventilator acquired pneumonia (VAP) is a frequent and serious complication in ICU. Second episodes of VAP are common in trauma patients and may be related to severity of underlying conditions, treatment or bacterial factors of the first VAP. The aim of this study was to identify risk factors of second VAP episodes in trauma injured patients (defined as the development of a new pulmonary infection during or remotely following the first episode). Design: This is a single-center, retrospective cohort study of trauma injured patients who underwent a first episode of VAP between January 1, 2013 and December 31, 2020 at Beaujon Hospital. Results: A total of 533 patients with a first episode of VAP were analyzed, mostly with head and/or thoracic traumatic injury. A second episode of VAP occurred in one hundred sixty-seven patients (31.3%). The main risk factors found was the degree of hypoxemia at the time of the first episode [PaO2/FiO2 ratio 100–200, OR 3.12 (1.77–5.69); < 100, OR 5.80 (2.70–12.8)] and severe traumatic brain injury characterized by an initial GCS ≤ 8 [OR 1.65 (1.01–2.74)]. Conclusion: Depth of hypoxemia during the first VAP episode and severity of the initial brain injury are the main risk factors for VAP second episode in trauma injured patients. [ABSTRACT FROM AUTHOR]

Objectives: Ventilator-associated pneumonia (VAP) is one of the most common nosocomial infections in intensive care units (ICUs), and the use of mouthwash is the most widely used method to prevent its incidence. The aim of this study was to investigate effect of clove mouthwash on the incidence of VAP in the ICU. Materials and methods: This comparative, randomized, triple-blind, clinical trial was conducted on 168 eligible ICU patients at Kosar Hospital in Semnan, Iran, during 2021–2022, who were divided into intervention and control groups using random blocks. The intervention group received clove extract mouthwash at 6.66% concentration, and the control group received chlorhexidine 0.2% twice a day for 5 days (routine care). Data were collected using a demographic questionnaire, and disease severity was measured based on the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, oral health status was examined using the Beck Oral Assessment Scale (BOAS), and VAP diagnosis was made based on the Modified Clinical Pulmonary Infection Score (MCPIS). Results: Before the intervention, there was no significant difference in disease severity (p = 0.412) and oral health status (p = 0.239) between the patients in the two groups. After the intervention, 20.2% of the patients in the intervention group and 41.7% of those in the control group acquired VAP. The risk of VAP was 2.06 times higher in the control group than in the intervention group (p = 0.005, 95% CI: 1.26–3.37, RR = 2.06), but the severity of VAP did not differ significantly between the patients in the two groups (p = 0.557). Conclusion: The findings showed that clove mouthwash reduces the incidence of VAP significantly. Clinical relevance: Clove mouthwash can be used as a simple and low-cost method to prevent VAP in ICU patients. [ABSTRACT FROM AUTHOR]

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the most common healthcare-associated infections, with rates varying between countries. Antimicrobial resistance (AMR) among common HAP/VAP pathogens has been reported, and multidrug resistance (MDR) is of further concern across Middle Eastern countries. This narrative review summarizes the incidence and pathogens associated with HAP/VAP in hospitals across Gulf Cooperation Council (GCC) countries. A PubMed literature search was limited to available data on HAP or VAP in patients of any age published within the past 10 years. Reviews, non-English language articles, and studies not reporting HAP/VAP data specific to a GCC country were excluded. Overall, 41 articles, a majority of which focused on VAP, were selected for inclusion after full-text screening. Studies conducted over multiple years showed a general reduction in VAP rates over time, with Gram-negative bacteria the most commonly reported pathogens. Gram-negative isolates reported across GCC countries included Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Rates of AMR varied widely among studies, and MDR among A. baumannii, K. pneumoniae, Escherichia coli, P. aeruginosa, and Staphylococcus aureus isolates was commonly reported. In Saudi Arabia, between 2015 and 2019, rates of carbapenem resistance among Gram-negative bacteria were 19–25%; another study (2004–2009) reported antimicrobial resistance rates in Acinetobacter species (60–89%), P. aeruginosa (13–31%), and Klebsiella species (100% ampicillin, 0–13% other antimicrobials). Although limited genotype data were reported, OXA-48 was found in ≥ 68% of patients in Saudi Arabia with carbapenem-resistant Enterobacteriaceae infections. Ventilator utilization ratios varied across studies, with rates up to 0.9 reported in patients admitted to adult medical/surgical intensive care units in both Kuwait and Saudi Arabia. VAP remains a burden across GCC countries albeit with decreases in rates over time. Evaluation of prevention and treatment measures and implementation of a surveillance program could be useful for the management of HAP and VAP. [ABSTRACT FROM AUTHOR]

Ventilator-associated pneumonia (VAP) is a serious intensive care unit (ICU)-related infection in mechanically ventilated patients that is frequent, as more than half of antibiotics prescriptions in ICU are due to VAP. Various risk factors and diagnostic criteria for VAP have been referred to in different settings. The estimated attributable mortality of VAP can go up to 50%, which is higher in cases of antimicrobial-resistant VAP. When the diagnosis of pneumonia in a mechanically ventilated patient is made, initiation of effective antimicrobial therapy must be prompt. Microbiological diagnosis of VAP is required to optimize timely therapy since effective early treatment is fundamental for better outcomes, with controversy continuing regarding optimal sampling and testing. Understanding the role of antimicrobial resistance in the context of VAP is crucial in the era of continuously evolving antimicrobial-resistant clones that represent an urgent threat to global health. This review is focused on the risk factors for antimicrobial resistance in adult VAP and its novel microbiological tools. It aims to summarize the current evidence-based knowledge about the mechanisms of resistance in VAP caused by multidrug-resistant bacteria in clinical settings with focus on Gram-negative pathogens. It highlights the evidence-based antimicrobial management and prevention of drug-resistant VAP. It also addresses emerging concepts related to predictive microbiology in VAP and sheds lights on VAP in the context of coronavirus disease 2019 (COVID-19). [ABSTRACT FROM AUTHOR]

Background: Placement of a tracheostomy for patients requiring prolonged mechanical ventilation (PMV) improves patients' comfort, decreases dead space ventilation, allows superior airway hygiene, and reduces the incidence of ventilator-associated pneumonia. Controversy still exists regarding the role of standard tracheostomy (ST) as opposed to the less frequently done Björk flap tracheostomy (BFT). This study compares the functional outcomes of these two techniques. Study design: Seventy-nine patients receiving tracheostomy in a 12-month period: 38 BFT vs. 41 ST. Data included demographics, indications for PMV, ventilator days before tracheostomy, time to and a number of patients who passed the fiberoptic endoscopic evaluation of swallowing (FEES), time to and a number of patients decannulated. Results: Indications in both groups were PMV from trauma (18/38 vs 15/41), pneumonia (13/38 vs 13/41), and ARDS (7/38 vs 11/4), respectively (p > 0.05). Patients in both groups did not differ with regard to age, sex, GCS, duration of PMV before tracheostomy, the time to and a number of patients who passed the 1st FEES. However, the number of days and the number of FEES required before the next successful FEES in the 20 BFT and 21 ST patients who failed the 1st was 9 (4) vs. 16 (5), and 2 (1) vs. 4 (1), respectively (p < 0.05). Additionally, the number of intraoperative complications in aggregate were 0/38 in the BFT as opposed to 6/41 in the ST group (p < 0.05). Conclusion: We conclude that BFT may be associated with an overall shorter time to restoration of normal swallowing when compared to ST. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa (PA) is a leading cause of hospital-acquired and ventilator-associated pneumonia. The multidrug-resistance (MDR) rate of PA is increasing making the management of PA a global challenge. Messenger RNA (mRNA) vaccines represent the most promising alternative to conventional vaccines and are widely studied for viral infection and cancer immunotherapy while rarely studied for bacterial infections. In this study, two mRNA vaccines encoding PcrV– the key component of the type III secretion system in Pseudomonas and the fusion protein OprF-I comprising outer membrane proteins OprF and OprI were constructed. The mice were immunized with either one of these mRNA vaccines or with the combination of both. Additionally, mice were vaccinated with PcrV, OprF, or the combination of these two proteins. Immunization with either mRNA-PcrV or mRNA-OprF-I elicited a Th1/Th2 mixed or slighted Th1-biased immune response, conferred broad protection, and reduced bacterial burden and inflammation in burn and systemic infection models. mRNA-PcrV induced significantly stronger antigen-specific humoral and cellular immune responses and higher survival rate compared with the OprF-I after challenging with all the PA strains tested. The combined mRNA vaccine demonstrated the best survival rate. Moreover, the mRNA vaccines showed the superiority over protein vaccines. These results suggest that mRNA-PcrV as well as the mixture of mRNA-PcrV and mRNA-OprF-I are promising vaccine candidates for the prevention of PA infection. [ABSTRACT FROM AUTHOR]

Background: Subglottic secretion had been proven as one of the causes of microaspiration and increased risk of ventilator-associated pneumonia (VAP). The role of ultrasound to detect subglottic secretion has not yet been established. Purpose: The purpose of this study is to determine the sensitivity and specificity of upper airway ultrasound (US) in the detection of subglottic secretions as compared to computed tomography (CT) scanning. Material and methods: A prospective observational study was carried out in adult trauma patients requiring mechanical ventilation and cervical CT scan. All patients had an endotracheal tube cuff-pressure maintained between 20 and 30 cm H2O. Airway US was performed at the bedside immediately before the patient was transferred to the CT scan suite. The sensitivity, specificity, and positive/negative predictive values (PPV, NPV) of the upper airway US detection of subglottic secretions were then calculated and compared with CT findings. Results: Fifty participants were consecutively included. Subglottic secretions were detected in 31 patients using upper airway US. The sensitivity and specificity of upper airway US in detecting subglottic secretion were 96.7% and 90%, respectively (PPV 93.5%, NPV 94.7%). 18 (58%) patients with subglottic secretions developed VAP during their ICU stay (p = 0.01). The area under the receiver operating curve (AUROC) was 0.977 (95% CI 0.936–1.00). Conclusions: Upper airway US is a useful tool for detecting subglottic secretions with high sensitivity and specificity. Clinical implications: This study shows: Upper airway US may aid in detecting subglottic secretions, which are linked to VAP. Detecting subglottic secretions at the bedside aids in determining the best frequency of subglottic aspiration to clean the subglottic trachea. Upper airway US may also aid in detecting the correct ETT position. Trial registration Clinicaltrials.gov. Clinicaltrials.gov identifier NCT04739878 Date of registration 2nd May 2021 URL of trial registry record https://clinicaltrials.gov/ct2/show/NCT04739878. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to determine whether interferon gamma-1b prevents hospital-acquired pneumonia in mechanically ventilated patients. Methods: In a multicenter, placebo-controlled, randomized trial conducted in 11 European hospitals, we randomly assigned critically ill adults, with one or more acute organ failures, under mechanical ventilation to receive interferon gamma-1b (100 µg every 48 h from day 1 to 9) or placebo (following the same regimen). The primary outcome was a composite of hospital-acquired pneumonia or all-cause mortality on day 28. The planned sample size was 200 with interim safety analyses after enrolling 50 and 100 patients. Results: The study was discontinued after the second safety analysis for potential harm with interferon gamma-1b, and the follow-up was completed in June 2022. Among 109 randomized patients (median age, 57 (41–66) years; 37 (33.9%) women; all included in France), 108 (99%) completed the trial. Twenty-eight days after inclusion, 26 of 55 participants (47.3%) in the interferon-gamma group and 16 of 53 (30.2%) in the placebo group had hospital-acquired pneumonia or died (adjusted hazard ratio (HR) 1.76, 95% confidence interval (CI) 0.94–3.29; P = 0.08). Serious adverse events were reported in 24 of 55 participants (43.6%) in the interferon-gamma group and 17 of 54 (31.5%) in the placebo group (P = 0.19). In an exploratory analysis, we found that hospital-acquired pneumonia developed in a subgroup of patients with decreased CCL17 response to interferon-gamma treatment. Conclusions: Among mechanically ventilated patients with acute organ failure, treatment with interferon gamma-1b compared with placebo did not significantly reduce the incidence of hospital-acquired pneumonia or death on day 28. Furthermore, the trial was discontinued early due to safety concerns about interferon gamma-1b treatment. [ABSTRACT FROM AUTHOR]

We aimed to explore the relationships between specific viral mutations/mutational patterns and ventilator-associated pneumonia (VAP) occurrence in COVID-19 patients admitted in intensive care units between October 1, 2020, and May 30, 2021. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing. In this prospective multicentre cohort study, 259 patients were included. 222 patients (47%) had been infected with pre-existing ancestral variants, 116 (45%) with variant α, and 21 (8%) with other variants. 153 patients (59%) developed at least one VAP. There was no significant relationship between VAP occurrence and a specific SARS CoV-2 lineage/sublineage or mutational pattern. [ABSTRACT FROM AUTHOR]

Background: Secondary bacterial infections are an important cause of mortality in patients with coronavirus disease 2019 (COVID-19). All healthcare providers acted with utmost care with the reflex of protecting themselves during the COVID-19 period. We aimed to compare the rates of ventilator-associated pneumonia (VAP) and bloodstream infections (BSIs) in our intensive care units (ICUs) before and during the COVID-19 outbreak surges. Methods: This multicenter, retrospective, cross-sectional study was performed in six centers in Turkey. We collected the patient demographic characteristics, comorbidities, reasons for ICU admission, mortality and morbidity scores at ICU admission, and laboratory test data. Results: A total of 558 patients who required intensive care from six centers were included in the study. Four hundred twenty-two of these patients (males (62%), whose mean age was 70 [IQR, 58–79] years) were followed up in the COVID period, and 136 (males (57%), whose mean age was 73 [IQR, 61–82] years) were followed up in the pre-COVID period. BSI and VAP rates were 20.7 (19 events in 916 patient days) and 17 (74 events in 4361 patient days) with a −3.8 difference (P = 0.463), and 33.7 (31 events in 919 patient days) and 34.6 (93 events in 2685 patient days) with a 0.9 difference (P = 0.897), respectively. The mortality rates were 71 (52%) in pre-COVID and 291 (69%) in COVID periods. Conclusion: Protective measures that prioritize healthcare workers rather than patients and exceed standard measures made no difference in terms of reducing mortality. [ABSTRACT FROM AUTHOR]

Background: Acute distress respiratory syndrome (ARDS) patients with veno-venous extra corporeal membrane oxygenation (ECMO) support are particularly exposed to ECMO-associated infection (ECMO-AI). Unfortunately, data regarding AI prophylaxis in this setting are lacking. Selective decontamination regimens decrease AI incidence, including ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) in critically ill patients. We hypothesized that a multiple-site decontamination (MSD) regimen is associated with a reduction in the incidence of AI among VV-ECMO patients. Methods: We conducted a retrospective observational study in three French ECMO referral centers from January 2010 to December 2021. All adult patients (> 18 years old) who received VV-ECMO support for ARDS were eligible. In addition to standard care (SC), 2 ICUs used MSD, which consists of the administration of topical antibiotics four times daily in the oropharynx and the gastric tube, once daily chlorhexidine body-wash and a 5-day nasal mupirocin course. AIs were compared between the 2 ICUs using MSD (MSD group) and the last ICU using SC. Results: They were 241 patients available for the study. Sixty-nine were admitted in an ICU that applied MSD while the 172 others received standard care and constituted the SC group. There were 19 ECMO-AIs (12 VAP, 7 BSI) in the MSD group (1162 ECMO-days) compared to 143 AIs (104 VAP, 39 BSI) in the SC group (2376 ECMO-days), (p < 0.05 for all infection site). In a Poisson regression model, MSD was independently associated with a lower incidence of ECMO-AI (IRR = 0.42, 95% CI [0.23–0.60] p < 0.001). There were 30 multidrug resistant microorganisms (MDRO) acquisition in the SC group as compared with two in the MSD group (IRR = 0.13, 95% CI [0.03–0.56] p = 0.001). Mortality in ICU was similar in both groups (43% in the SC group vs 45% in the MSD group p = 0.90). Results were similar after propensity-score matching. Conclusion: In this cohort of patients from different hospitals, MSD appeared to be safe in ECMO patients and may be associated with improved outcomes including lower ECMO-AI and MDRO acquisition incidences. Since residual confounders may persist, these promising results deserve confirmation by randomized controlled trials. [ABSTRACT FROM AUTHOR]

Introduction: Real-life data about cefiderocol use to treat extensively drug-resistant bacteria are scarce. We aim to report our early experience in patients with difficult-to-treat infections and limited therapeutic options. Methods: Patients treated with cefiderocol from March 2018 to April 2022 in a tertiary-care hospital in Spain were included. Demographic, clinical, and microbiological data were collected up to 90 days after the end of treatment or until death. Survival status was recorded at 30 and 90 days. Results: Ten patients were included, seven of them critically ill. Ventilator-associated pneumonia (40%) and bacteremia (40%) were the main infections. Multidrug-resistant or extensively drug-resistant P. aeruginosa was the most frequently isolated pathogen (70%, of which six patients were infected with bacteria with difficult-to-treat resistance), followed by A. baumannii, E. coli, and A. xylosoxidans (10% each). Seven patients received combination therapy. Clinical and microbiological cures were achieved in 90% and 80% of patients, respectively. Two previously susceptible strains (20%) developed resistance to cefiderocol. Overall, 30-day and 90-day mortality rates were 10% and 50%, respectively, although two out of five patients died due to the infection. No serious adverse events were reported, except for one patient who developed thrombocytopenia. Conclusion: Cefiderocol seems to be an effective and safe rescue therapy for patients infected with difficult-to-treat pathogens, although there is a definite risk of the emergence of resistance. [ABSTRACT FROM AUTHOR]

Background: The role of upper airways microbiota and its association with ventilator-associated pneumonia (VAP) development in mechanically ventilated (MV) patients is unclear. Taking advantage of data collected in a prospective study aimed to assess the composition and over-time variation of upper airway microbiota in patients MV for non-pulmonary reasons, we describe upper airway microbiota characteristics among VAP and NO-VAP patients. Methods: Exploratory analysis of data collected in a prospective observational study on patients intubated for non-pulmonary conditions. Microbiota analysis (trough 16S-rRNA gene profiling) was performed on endotracheal aspirates (at intubation, T0, and after 72 h, T3) of patients with VAP (cases cohort) and a subgroup of NO-VAP patients (control cohort, matched according to total intubation time). Results: Samples from 13 VAP patients and 22 NO-VAP matched controls were analyzed. At intubation (T0), patients with VAP revealed a significantly lower microbial complexity of the microbiota of the upper airways compared to NO-VAP controls (alpha diversity index of 84 ± 37 and 160 ± 102, in VAP and NO_VAP group, respectively, p-value < 0.012). Furthermore, an overall decrease in microbial diversity was observed in both groups at T3 as compared to T0. At T3, a loss of some genera (Prevotella 7, Fusobacterium, Neisseria, Escherichia–Shigella and Haemophilus) was found in VAP patients. In contrast, eight genera belonging to the Bacteroidetes, Firmicutes and Fusobacteria phyla was predominant in this group. However, it is unclear whether VAP caused dysbiosis or dysbiosis caused VAP. Conclusions: In a small sample size of intubated patients, microbial diversity at intubation was less in patients with VAP compared to patients without VAP. [ABSTRACT FROM AUTHOR]

Health care–associated infections (HAI) directly influence the survival of children in pediatric intensive care units (PICU), the most common being central line–associated bloodstream infection (CLABSI) 25–30%, followed by ventilator-associated pneumonia (VAP) 20–25%, and others such as catheter-associated urinary tract infection (CAUTI) 15%, surgical site infection (SSI) 11%. HAIs complicate the course of the disease, especially the critical one, thereby increasing the mortality, morbidity, length of hospital stay, and cost. The incidence of HAI in Western countries is 6.1–15.1% and in India, it is 10.5 to 19.5%. The advances in healthcare practices have reduced the incidence of HAIs in the recent years which is possible due to strict asepsis, hand hygiene practices, surveillance of infections, antibiotic stewardship, and adherence to bundled care. The burden of drug resistance and emerging infections are increasing with limited antibiotics in hand, is still a dreadful threat. The most common manifestation of HAIs is fever in PICU, hence the appropriate targeted search to identify the cause of fever should be done. Proper isolation practices, judicious handling of devices, regular microbiologic audit, local spectrum of organisms, identification of barriers in compliance of hand hygiene practices, appropriate education and training, all put together in an efficient and sustained system improves patient outcome. [ABSTRACT FROM AUTHOR]

This article discusses the challenges of differentiating between atelectasis and pneumonia in critically ill patients using regular computed tomography (CT). The study demonstrates the additional value of a 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) scan in distinguishing between the two conditions. The scan was performed on a 61-year-old male patient with multiple organ failure, and the results showed normal physiological uptake in the myocardium, bilateral pleural effusion, and atelectasis with elevated [18F]FDG uptake in the left and right lower lobes. The high [18F]FDG uptake in the right lower lobe indicated an infectious focus, which was confirmed by a subsequent positive sputum culture. The article highlights the potential of [18F]FDG PET/CT in differentiating between infectious and inflammatory pulmonary abnormalities in critically ill patients. [Extracted from the article]

This study aimed to evaluate the effect of closed versus open endotracheal tube suction in reducing ventilator-associated pneumonia in mechanically ventilated neonates. In this open-label, parallel-group, randomized controlled trial with allocation concealment, ventilated neonates (≥ 28 weeks and ≥ 800 g) were either allocated to the closed-suction group (n = 41) or open-suction group (n = 39). The ventilator circuit of the babies enrolled in the closed-suction group was attached to the closed-suction catheter on the requirement of their first suction, and it was changed after every 48 h or earlier if visibly soiled whereas babies enrolled in the open-suction group were suctioned with a new suction catheter each time they require suction. The primary outcome was the incidence of VAP per 1000 days. Baseline maternal and neonatal characteristics were comparable between the two groups. The proportion of neonates with VAP in the closed-suction group was 3 (7.3%) and 1 (2.6%) in the open-suction group with an RR of 2.8 (95% CI: 0.30–26.28) and a p-value of 0.35. The incidence of VAP in the closed-suction group was 3.9 per 1000 ventilator days and 1.3 per 1000 ventilator days in the open-suction group. The incidence of clinical VAP/1000 ventilator days was 33.63 ± 22.96 in the closed-suction group and 28.67 ± 12.32 in the open-suction group with a mean difference of 5 (95% CI: − 3.26 to 13.26) and p-value of 0.24. Conclusion: In a unit with a low incidence of VAP, the effect of the endotracheal suction method alone did not impact the occurrence of VAP in the study population. Clinical trial registration: CTRI/2020/03/023679; Date: 17.02.2020. What is Known: • Better physiological stability of the closed-suctioning method on short-term measures including noticeably fewer episodes of hypoxia, a smaller drop in TcPO2 levels, and less variability in heart rate and bradycardia episodes. What is New: • In a unit with a low incidence of VAP in the neonates, randomized control trial studying the effect of the endotracheal suction method alone did not impact the occurrence of VAP amongst the study population. [ABSTRACT FROM AUTHOR]

COVID-19 patients have often required prolonged endotracheal intubation, increasing the risk of developing ventilator-associated pneumonia (VAP). A preventive strategy is proposed based on an endotracheal tube (ETT) modified by the in situ deposition of eucalyptus-mediated synthesized silver nanoparticles (AgNPs). The surfaces of the modified ETT were embedded with AgNPs of approximately 28 nm and presented a nanoscale roughness. Energy dispersive X-ray spectroscopy confirmed the presence of silver on and inside the coated ETT, which exhibited excellent antimicrobial activity against Gram-positive and Gram-negative bacteria, and fungi, including multidrug-resistant clinical isolates. Inhibition of planktonic growth and microbial adhesion ranged from 99 to 99.999% without cytotoxic effects on mammalian cells. Kinetic studies showed that microbial adhesion to the coated surface was inhibited within 2 h. Cell viability in biofilms supplemented with human tracheal mucus was reduced by up to 95%. In a porcine VAP model, the AgNPs-coated ETT prevented adhesion of Pseudomonas aeruginosa and completely inhibited bacterial invasion of lung tissue. The potential antimicrobial efficacy and safety of the coated ETT were established in a randomized control trial involving 47 veterinary patients. The microbial burden was significantly lower on the surface of the AgNPs-coated ETT than on the uncoated ETT (p < 0.05). Key points: • Endotracheal tube surfaces were modified by coating with green-synthesized AgNPs • P. aeruginosa burden of endotracheal tube and lung was reduced in a porcine model • Effective antimicrobial activity and safety was demonstrated in a clinical trial [ABSTRACT FROM AUTHOR]

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are both associated with significant morbidity and mortality in daily clinical practice, as well as in a critical care setting. It is unclear whether colistin susceptible-only Acinetobacter baumannii (CSO AB) is a unique phenotype separate from or a subset of CRAB-associated pneumonia. The aim of this study is to investigate the prevalence of CSO AB pneumonia and compare the presentation and outcome between CSO AB and CRAB-associated pneumonia in critically ill patients. This multicenter retrospective cohort study initially recruited 955 patients with CR-GNB pneumonia. After exclusion, 575 patients left who were ICU-admitted and had CRAB nosocomial pneumonia remained. Among them, 79 patients had CSO AB pneumonia, classified as the CSO AB group. The other 496 patients were classified as the CRAB group. We compared demographic characteristics, disease severity, and treatment outcomes between the two groups. The prevalence of CSO AB among all cases of CRAB pneumonia was 13.74% (79/575). The CSO AB and CRAB groups had similar demographic characteristics and disease severities at initial presentation. The in-hospital mortality rate was 45.6% and 46.4% for CSO AB and CRAB groups, respectively (p = 0.991). The CSO AB group had significantly better clinical outcomes at day 7 (65.8% vs 52.4%, p = 0.036) but longer length of ICU stay (27 days vs 19 days, p = 0.043) compared to the CRAB group. However, other treatment outcomes, including clinical outcomes at day 14 and 28, mortality, microbiological eradication, ventilator weaning, and newly onset dialysis, were similar. In conclusion, CSO AB accounted for 13.74% of all cases of CRAB pneumonia, and the clinical presentation and treatment outcomes of CSO AB and CRAB pneumonia were similar. [ABSTRACT FROM AUTHOR]