Novel Antibiotics for Gram-Negative Nosocomial Pneumonia.

Nosocomial pneumonia, including hospital-acquired pneumonia and ventilator-associated pneumonia, is the leading cause of death related to hospital-acquired infections among critically ill patients. A growing proportion of these cases are attributed to multi-drug-resistant (MDR-) Gram-negative bacteria (GNB). MDR-GNB pneumonia often leads to delayed appropriate treatment, prolonged hospital stays, and increased morbidity and mortality. This issue is compounded by the increased toxicity profiles of the conventional antibiotics required to treat MDR-GNB infections. In recent years, several novel antibiotics have been licensed for the treatment of GNB nosocomial pneumonia. These novel antibiotics are promising therapeutic options for treatment of nosocomial pneumonia by MDR pathogens with certain mechanisms of resistance. Still, antibiotic resistance remains an evolving global crisis, and resistance to novel antibiotics has started emerging, making their judicious use crucial to prolong their shelf-life. This article presents an up-to-date review of these novel antibiotics and their current role in the antimicrobial armamentarium. We critically present data for the pharmacokinetics/pharmacodynamics, the in vitro spectrum of antimicrobial activity and resistance, and in vivo data for their clinical and microbiological efficacy in trials. Where possible, available data are summarized specifically in patients with nosocomial pneumonia, as this cohort may exhibit 'critical illness' physiology that affects drug efficacy.

Association between anion gap and the 30-day mortality of patients with ventilator-associated pneumonia: a study of the MIMIC-III database.

Background: Serum anion gap (AG) can potentially be applied to the diagnosis of various metabolic acidosis, and a recent study has reported the association of AG with the mortality of patients with coronavirus disease 2019 (COVID-19). However, the relationship of AG with the short-term mortality of patients with ventilator-associated pneumonia (VAP) is still unclear. Herein, we aimed to investigate the association between AG and the 30-day mortality of VAP patients, and construct and assess a multivariate predictive model for the 30-day mortality risk of VAP. Methods: This retrospective cohort study extracted data of 477 patients with VAP from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Data of patients were divided into a training set and a testing set with a ratio of 7:3. In the training set, variables significantly associated with the 30-day mortality of VAP patients were included in the multivariate predictive model through univariate Cox regression and stepwise regression analyses. Then, the predictive performance of the multivariate predictive model was assessed in both training set and testing set, and compared with the single AG and other scoring systems including the Sequential Organ Failure Assessment (SOFA) score, the confusion, urea, respiratory rate (RR), blood pressure, and age (≥65 years old) (CURB-65) score, and the blood urea nitrogen (BUN), altered mental status, pulse, and age (>65 years old) (BAP-65) score. In addition, the association of AG with the 30-day mortality of VAP patients was explored in subgroups of gender, age, and infection status. The evaluation indexes were hazard ratios (HRs), C-index, and 95% confidence intervals (CIs). Results: A total of 70 patients died within 30 days. The multivariate predictive model consisted of AG (HR =1.052, 95% CI: 1.008-1.098), age (HR =1.037, 95% CI: 1.019-1.055), duration of mechanical ventilation (HR =0.998, 95% CI: 0.996-0.999), and vasopressors use (HR =1.795, 95% CI: 1.066-3.023). In both training set (C-index =0.725, 95% CI: 0.670-0.780) and testing set (C-index =0.717, 95% CI: 0.637-0.797), the multivariate model had a relatively superior predictive performance to the single AG value. Moreover, the association of AG with the 30-day mortality was also found in patients who were male (HR =1.088, 95% CI: 1.029-1.150), and whatever the pathogens they infected (bacterial infection: HR =1.059, 95% CI: 1.011-1.109; fungal infection: HR =1.057, 95% CI: 1.002-1.115). Conclusions: The AG-related multivariate model had a potential predictive value for the 30-day mortality of patients with VAP. These findings may provide some references for further exploration on simple and robust predictors of the short-term mortality risk of VAP, which may further help clinicians to identify patients with high risk of mortality in an early stage in the intensive care units (ICUs).

The Clinical Pulmonary Infection Score Combined with Procalcitonin and Lung Ultrasound (CPIS-PLUS), a Good Tool for Ventilator Associated Pneumonia Early Diagnosis in Pediatrics.

Ventilator-associated pneumonia (VAP) is common in Pediatric Intensive Care Units. Although early detection is crucial, current diagnostic methods are not definitive. This study aimed to identify lung ultrasound (LUS) findings and procalcitonin (PCT) values in pediatric patients with VAP to create a new early diagnosis score combined with the Clinical Pulmonary Infection Score (CPIS), the CPIS-PLUS score. Prospective longitudinal and interventional study. Pediatric patients with suspected VAP were included and classified into VAP or non-VAP groups, based on Centers of Disease Control (CDC) criteria for the final diagnosis. A chest-X-ray (CXR), LUS, and blood test were performed within the first 12 h of admission. CPIS score was calculated. A total of 108 patients with VAP suspicion were included, and VAP was finally diagnosed in 51 (47%) patients. CPIS-PLUS showed high accuracy in VAP diagnosis with a sensitivity (Sn) of 80% (95% CI 65-89%) and specificity (Sp) of 73% (95% CI 54-86%). The area under the curve (AUC) resulted in 0.86 for CPIS-PLUS vs. 0.61 for CPIS. In conclusion, this pilot study showed that CPIS-PLUS could be a potential and reliable tool for VAP early diagnosis in pediatric patients. Internal and external validations are needed to confirm the potential value of this score to facilitate VAP diagnosis in pediatric patients.

Unifying Endotracheal Intracuff-Pressure Monitoring in the Intensive Care Unit: Bridging the Gap Between Standardization and Neglect.

Endotracheal cuff-pressure monitoring is a critical component of patient care in the intensive care unit, ensuring the safety and efficacy of mechanical ventilation. Despite its importance, there remains a lack of standardized protocols regarding optimal pressure targets and documentation practices. This editorial examines the significance of endotracheal intracuff-pressure monitoring in enhancing patient outcomes, highlighting the challenges and potential solutions in clinical practice.

Diagnostic Role of Opsonic Activity in Acinetobacter baumannii Ventilator-Associated Pneumonia.

In this study, we investigated the diagnostic value of opsonic activity against Acinetobacter baumannii in Ventilator-Associated Pneumonia (VAP) among 50 patients, compared to 102 negative and positive controls. Out of the 50 patients, only 33 (66 %) were diagnosed with VAP using the Clinical Pulmonary Infection Score (CPIS). The opsonic activity assay demonstrated three key findings: (i) 95 % sensitivity and 91.7 % specificity, with a Receiver Operating Characteristic (ROC) area of 0.976 for distinguishing A. baumannii culture positives from negatives; (ii) 95 % sensitivity and 78.7 % specificity, with a 0.915 ROC area, in differentiating VAP/blood culture positive patients from colonized/negative groups; (iii) An ROC area of 0.553 for VAP and colonization, as identified by CPIS alone, indicating an indeterminate threshold. These results highlight that CPIS, microbiological, and clinical evaluations were not correlated, suggesting that opsonic activity against A. baumannii could be a potential VAP diagnostic tool, with the need for large-scale validations.

Meropenem plus Ertapenem and Ceftazidime-Avibactam plus Aztreonam for the Treatment of Ventilator Associated Pneumonia Caused by Pan-Drug Resistant Klebsiella pneumonia.

INTRODUCTION: Gram-negative bacteria (GNB) account for about 70% of infections in the intensive care unit (ICU) setting and are associated with significant morbidity and mortality. In recent years, pan-drug resistant (PDR) strains, strains that are not susceptible to any antibiotic, have been emerged and new treatment strategies are required. RESULTS: Fifty eligible patients were recruited in the three groups. A statistically significant reduction in the Sequential Organ Failure Assessment (SOFA) score was observed in the control group on day 4 in comparison to day 0 of VAP (p = 0.005). The Clinical Pulmonary Infection Score (CPIS) was also reduced on day 4 (p = 0.0016) and day 7 in comparison to day 0 (p = 0.001). Patients that received combination therapy, CAZ-AVI + ATM and DCT, presented with a lower SOFA score and CPIS on day 7 in comparison to day 0 (p = 0.0288 and p = 0.037, respectively). No differences in the ΔSOFA score and ΔCPIS were found between the groups. The control group presented with a significantly lower ICU stay and duration of mechanical ventilation (p = 0.03 and p = 0.02, respectively). There was no difference in mortality. MATERIALS AND METHODS: This is a retrospective analysis. This study was conducted in a mixed ICU in the University Hospital of Larissa, Thessaly, Greece during a three-year period (2020-2022). Patients suffering from ventilator associated pneumonia (VAP) due to carbapenem-resistant K. pneumonia (CR-KP) were divided in three different groups: the first one was treated using ceftazidime-avibactam plus aztreonam (CAZ-AVI + ATM group), the second was treated using double carbapenems (DCT group), and the last one (control group) received appropriate therapy since the strain was susceptible in vitro to at least to one antibiotic. CONCLUSIONS: Treatment with CAZ-AVI +ATM or DCT may offer a clinical benefit in patients suffering with infections due to PDR K. pneumoniae. Larger studies are required to confirm our findings.

A Path towards Timely VAP Diagnosis: Proof-of-Concept Study on Pyocyanin Sensing with Cu-Mg Doped Graphene Oxide.

In response to the urgent requirement for rapid, precise, and cost-effective detection in intensive care units (ICUs) for ventilated patients, as well as the need to overcome the limitations of traditional detection methods, researchers have turned their attention towards advancing novel technologies. Among these, biosensors have emerged as a reliable platform for achieving accurate and early diagnoses. In this study, we explore the possibility of using Pyocyanin analysis for early detection of pathogens in ventilator-associated pneumonia (VAP) and lower respiratory tract infections in ventilated patients. To achieve this, we developed an electrochemical sensor utilizing a graphene oxide-copper oxide-doped MgO (GO - Cu - Mgo) (GCM) catalyst for Pyocyanin detection. Pyocyanin is a virulence factor in the phenazine group that is produced by Pseudomonas aeruginosa strains, leading to infections such as pneumonia, urinary tract infections, and cystic fibrosis. We additionally investigated the use of DNA aptamers for detecting Pyocyanin as a biomarker of Pseudomonas aeruginosa, a common causative agent of VAP. The results of this study indicated that electrochemical detection of Pyocyanin using a GCM catalyst shows promising potential for various applications, including clinical diagnostics and drug discovery.

Infection in ECMO patients: Changes in epidemiology, diagnosis and prevention.

Patients with prolonged duration of extracorporeal membrane oxygenation support (ECMO) are a vulnerable population for sepsis, particularly ventilator-associated pneumonia and bloodstream infections. Rates differ between venous-arterial and venous-venous ECMO patients and according to the cannulation technique used. The presence of particular organisms depends on local epidemiology, antibiotic exposure, and the duration of the intervention; patients undergoing ECMO for more than three weeks present a high risk of persistent candidemia. Recognizing predisposing factors, and establishing the best preventive interventions and therapeutic choices are critical to optimizing the management of these complications. Infection control practices, including shortening the period of the indwelling devices, and reducing antibiotic exposure, must be followed meticulously. Innovations in oxygenator membranes require an updated approach. Hand hygiene and avoiding breaking the circuit-oxygenator sterility are cornerstones. ECMO management would benefit from clearer definitions, optimization of infection control strategies, and updated infectious clinical practice guidelines.

Risk factors for ventilator-associated lower respiratory tract infection in COVID-19, a retrospective multicenter cohort study in Sweden.

BACKGROUND: Ventilator-associated lower respiratory tract infections (VA-LRTI) increase morbidity and mortality in intensive care unit (ICU) patients. Higher incidences of VA-LRTI have been reported among COVID-19 patients requiring invasive mechanical ventilation (IMV). The primary objectives of this study were to describe clinical characteristics, incidence, and risk factors comparing patients who developed VA-LRTI to patients who did not, in a cohort of Swedish ICU patients with acute hypoxemic respiratory failure due to COVID-19. Secondary objectives were to decipher changes over the three initial pandemic waves, common microbiology and the effect of VA-LTRI on morbidity and mortality. METHODS: We conducted a multicenter, retrospective cohort study of all patients admitted to 10 ICUs in southeast Sweden between March 1, 2020 and May 31, 2021 because of acute hypoxemic respiratory failure due to COVID-19 and were mechanically ventilated for at least 48 h. The primary outcome was culture verified VA-LRTI. Patient characteristics, ICU management, clinical course, treatments, microbiological findings, and mortality were registered. Logistic regression analysis was conducted to determine risk factors for first VA-LRTI. RESULTS: Of a total of 536 included patients, 153 (28.5%) developed VA-LRTI. Incidence rate of first VA-LRTI was 20.8 per 1000 days of IMV. Comparing patients with VA-LRTI to those without, no differences in mortality, age, sex, or number of comorbidities were found. Patients with VA-LRTI had fewer ventilator-free days, longer ICU stay, were more frequently ventilated in prone position, received corticosteroids more often and were more frequently on antibiotics at intubation. Regression analysis revealed increased adjusted odds-ratio (aOR) for first VA-LRTI in patients treated with corticosteroids (aOR 2.64 [95% confidence interval [CI]] [1.31-5.74]), antibiotics at intubation (aOR 2.01 95% CI [1.14-3.66]), and days of IMV (aOR 1.05 per day of IMV, 95% CI [1.03-1.07]). Few multidrug-resistant pathogens were identified. Incidence of VA-LRTI increased from 14.5 per 1000 days of IMV during the first wave to 24.8 per 1000 days of IMV during the subsequent waves. CONCLUSION: We report a high incidence of culture-verified VA-LRTI in a cohort of critically ill COVID-19 patients from the first three pandemic waves. VA-LRTI was associated with increased morbidity but not 30-, 60-, or 90-day mortality. Corticosteroid treatment, antibiotics at intubation and time on IMV were associated with increased aOR of first VA-LRTI.

A Team Approach to Bundle Compliance.

Hospitals are always looking to improve the quality of patient care and avoid hospital-acquired conditions such as ventilator-associated pneumonia (VAP). Currently, there are no set standards regarding interventions to prevent VAP, and there is not a single element that has a direct impact on VAP prevention. By creating an interprofessional team to work together, the quality improvement project was able to evaluate current practice compared with evidence-based practice in the literature to develop a critical care VAP bundle practice, which demonstrated improvement in compliance.

Prevention of Pneumonia due to Ventilator in Critical Patients with U Shape Oral Hygiene Model: A Systematic Review.

In critical patients, generally, microorganisms originating from nasal cause Ventilator-Associated Pneumonia (VAP). This systematic review was aimed to identify the toothbrush U shape model usage, in potentially decrease the prevalence of ventilator-associated pneumonia among patients in intensive care units. Search strategy identified 15 potentially eligible articles, were 7 RCTs, 4 Meta-analysis, and 4 Observational studies. A total of 15 studies demonstrated the use of toothbrushing and chlorhexidine in mechanically ventilator patients in preventing VAP. Ten studies found positive association between toothbrushing and the use of chlorhexidine in preventing VAP. However, there were 5 studies that did not reveal an additional decrease of VAP incidence either of CHX and only toothbrushing or combination thereof. We cautiously assumed that toothbrushing and chlorhexidine might reduce VAP but the implementation of brushing should be taken into reconsideration in the terms of maintaining it.

Multidrug Resistance in Critically Ill Patients: An Unresolved Issue.

Sepsis and septic shock are common in critically ill patients and, as recommended by the Surviving Sepsis Campaign (SSC), early empiric antimicrobial therapy, specifically within the first hour, is crucial for the successful management of these conditions. To be effective, the antimicrobial therapy must also be appropriately administered: the drugs should cover the most probable pathogens and achieve effective concentrations at the site of infection. However, pharmacokinetics are frequently altered in critically ill patients and continuously change since the clinical conditions of these patients quickly and markedly change over time, either improving or deteriorating. Accordingly, optimizing antimicrobial drug dosing is fundamental in intensive care units (ICUs). This Special Issue of Microorganisms examines the epidemiology, diagnostic innovations, and strategies applied in the context of infections in critically ill patients with MDR infections.

Short-term exposure to ambient fine particulate pollution aggravates ventilator-associated pneumonia in pediatric intensive care patients undergoing cardiovascular surgeries.

BACKGROUND: Ambient air pollutants can be hazardous to human health, especially for vulnerable children. The impact of ambient air pollutant exposure before and during intensive care unit (ICU) stays on the development of ventilator-associated pneumonia (VAP) in critically ill children has not been established. We aimed to determine the correlations between short-term exposures to ambient fine particulate matter (PM2.5) and VAP in pediatric cardiac surgery patients in the ICU, and explore the effect of delayed exposure. METHODS: The medical record of 1755 child patients requiring artificial ventilation in the ICU between December 2013 to December 2020, were analyzed. The daily average concentrations of particulate matters (PM2.5 and PM10), sulfur dioxide (SO2), and ozone (O3) were calculated from public data. Interactions between these pollutants and VAP were simulated with the distributed lag non-linear model. RESULTS: Three hundred forty-eight cases (19.829%) of VAP were identified in this study, while the average concentrations of PM2.5, PM10, O3 and SO2 were 58, 118, 98 and 26 µg/m3, respectively. Exposure to increased levels of PM2.5 two days prior (lag 2-day) to VAP diagnosis is significantly correlated with an enhanced risk for VAP development. Even a slight increase of 10 µg/m3 in PM2.5 can translate to a 5.4% increase in VAP incidence (95% CI: 1.4%-9.5%) while the VAP incidence increased to 11.1% (95%CI: 4.5-19.5%) when PM2.5 concentration is well below the National Ambient Air Quality standard (NAAQS) of 50 µg/m3. The association was more pronounced in those aged below 3-months, with low body mass index or suffered from pulmonary arterial hypertension. CONCLUSION: Short-term PM2.5 exposure is a significant risk for development of VAP in pediatric patients. This risk is present even with PM2.5 levels below the NAAQS. Ambient PM2.5 may represent a previously unrecognized risk factor for pneumonia and the current environmental pollution standards need to be reevaluated to consider susceptible populations. TRIAL REGISTRATION: The trial was registered with the National Clinical Trial Center: The correlation between ambient air pollution and the complications in ICU underwent cardiac surgery. TRIAL REGISTRATION NUMBER: ChiCTR2000030507. Date of registration: March 5, 2020. URL of trial registry record: http://www.chictr.org.cn/index.aspx .

Association between ondansetron use and mortality of patients on mechanical ventilation in the intensive care unit: a retrospective cohort study.

Background: Basic studies show that selective 5-hydroxytryptamine type 3 (5-HT3) serotonin-receptor antagonists can protect organs from inflammatory injury and have shown lung protection. Whether 5-HT3 receptor antagonists ondansetron benefits patients with mechanical ventilation is unclear in the intensive care unit (ICU). Methods: The Medical Information Mart for Intensive Care-IV (MIMIC-IV) database was reviewed to identify patients on mechanical ventilation (aged >16 years) in the ICU, which was divided into two groups according to whether ondansetron is used. Demographic characteristics, medical history data, clinical parameters, diagnosis and treatment measures were included as covariates. Ondansetron use was defined as any kind of ondansetron administration regardless of the dose before the induction of mechanical ventilation. The primary outcome was in-hospital death. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated by multivariable Cox regression. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to further adjust for confounding factors. Kaplan-Meier (KM) curves with log-rank test were also performed. Results: A total of 18,566 patients on mechanical ventilation were included (5,735 with ondansetron use). The overall in-hospital mortality rate of patients on mechanical ventilation was 18.9% (3,512/18,566). Approximately 13.0% (746/5,735) and 21.6% (2,766/12,831) in-hospital mortality rates occurred in the ondansetron and non-ondansetron use groups, respectively. Multivariable regression indicated that ondansetron usage was associated with a 33% and 32% lower risk of in-hospital and 60-day death (HR =0.77, 95% CI: 0.70-0.85, P<0.001; HR =0.68, 95% CI: 0.62-0.75, P<0.001) in the whole sample. Multivariable regression post-PSM indicated that ondansetron usage was associated with a 38% and 31% lower risk of in-hospital and 60-day death (HR =0.62, 95% CI: 0.56-0.68, P<0.001; HR =0.69, 95% CI: 0.62-0.77, P<0.001). Log-rank test for the KM curve of ondansetron and 60-day death was statistically significant (P<0.001). The duration of ventilator use pre- and post-PSM was statistically different (P<0.001 and P=0.007) in the two groups. Conclusions: Ondansetron usage was significantly associated with a lower mortality risk of ventilated patients in the ICU. The 5-HT3 receptor antagonist use is may be new potential adjunctive therapeutic strategy for patients on mechanical ventilation in the ICU.

Unintended impact of COVID-19 pandemic on the rate of catheter related nosocomial infections and incidence of multiple drug resistance pathogens in three intensive care units not allocated to COVID-19 patients in a large teaching hospital.

BACKGROUND: The prevalence of resistant hospital infections in the intensive care unit (ICU) increases mortality and antibiotic resistance. COVID-19 pandemic may have unintended impact on nosocomial infections (NI) and the prevalence of resistant microorganism. METHODOLOGY: The present non-interventional study was performed by a pre and a post survey each lasting 8 months before (March-October 2019) and after (March-October 2020) the onset of COVID-19 pandemic in three ICU's, not allocated to COVID-19 patients, in Nemazee Hospital, Shiraz, Iran. The rates of the following nosocomial infections were compared at pre- and post-pandemic period: ventilator associated pneumonia (VAP), central line associated blood stream infection (CLABSI), catheter-associated urinary tract infections (CAUTI) and incidence of multiple drug resistance (MDR) pathogens. RESULTS: Pre-pandemic and pandemic incidence of VAP was 23.5 and 17.2 cases per 1000 device-days, respectively; an absolute decrease of 27%. The main reason for the decrease in the rate of VAP during the pandemic was a significant decrease in the rate of VAP caused by Acinetobacter baumannii; from 39 to 17% in total VAP episodes. The rate of VAP associated with other microorganisms remained relatively unchanged from 14.2 cases in pre-pandemic period to 14.3 cases per 1000 MV-days during the pandemic (P = 0.801). Pre-pandemic incidence of CLABSI was 7.3 cases and, in pandemic period, was 6.5 cases per 1000 device-days (IRR = 0.88, 95% CI 0.43-1.73, P = 0.703). Pre-pandemic incidence of CAUTI was 2 and in pandemic period, was 1.4 cases per 1000 device-days (IRR = 0.70, 95% CI 0.22-1.98, P = 0.469). CONCLUSION: The results of the present study showed a decrease in the incidence of VAP in critically ill non-COVID-19 patients during the pandemic compared to before the pandemic, especially regarding Acinetobacter baumannii.

Device-Associated Nosocomial Infections in Intensive Care Units at Al-Ahsa Hospitals, Saudi Arabia.

Introduction Patients admitted to intensive care units (ICU), especially those with devices used to support their condition, are at a higher risk of getting healthcare-associated infections (HAIs). The aim of the present study was to analyze the surveillance data and assess the device-associated infection (DAI) rates such as central line-associated blood-stream infection (CLABSI), catheter-associated urinary tract infection (CAUTI), ventilator-associated pneumonia (VAP) and ventilator-associated event (VAE) in ICUs of the Ministry of Health (MoH) hospitals in Al-Ahsa region. Methodology The study was conducted retrospectively using the surveillance data of governmental hospitals' intensive care units in the Al-Ahsa region. The surveillance data was collected from 10 ICUs at six MoH hospitals in the Al-Ahsa region during the year 2022. The data from the participating hospitals was entered into the Health Electronic Surveillance Network (HESN) plus program by trained infection prevention control practitioners of the respective hospitals. Results An overall CLABSI rate of 4.29 per 1000 central line days was reported during the study period. The CAUTI rate was 0.55 with a range from 0 to 1.29 cases per 1000 urinary catheter days. VAP rate ranged from 0.33 to 2.21 cases per 1000 ventilator days (average of 1.17). The study reported VAE only for the adult medical-surgical ICU (3.36 per 1000 ventilator days). Conclusion The present study revealed that the most common DAIs in the Al-Ahsa region are CLABSI and CAUTI. DAI rates generated from this study may be used as benchmarks for regional hospitals. An educational program regarding the prevention and control of DAIs targeting all healthcare workers, especially ICU staff, has to be done in the Al-Ahsa region.

Probiotic prophylaxis to prevent ventilator-associated pneumonia in children on mechanical ventilation: A randomized double-blind clinical trial.

Purpose: Ventilator-Associated Pneumonia (VAP) is one of the most common nosocomial infections in the Pediatric Intensive Care Unit (PICU). Using new strategies to prevent nosocomial infections is crucial to avoid antibiotic resistance. One of these strategies is the utilization of probiotics. This study aims to investigate the efficacy of probiotic prophylaxis in preventing VAP in mechanically ventilated children. Method: This study was a randomized, double-blind clinical trial. The study included 72 children under 12 years of age under mechanical ventilation for more than 48 h in the Mofid Children's Hospital. Patients were randomly divided into Limosilactobacillus reuteri DSM 17938 probiotic recipients (n = 38) and placebo groups (n = 34). In addition to the standard treatment, both groups received a sachet containing probiotics or a placebo twice a day. Children were screened for VAP based on clinical and laboratory evidence. Results: The mean age of children in the intervention and placebo groups was 4.60 ± 4.84 and 3.38 ± 3.49 years, respectively. After adjusting the other variables, it was observed that chance of VAP among probiotics compared to the placebo group was significantly decreased (OR adjusted = 0.29; 95% CI: 0.09-0.95). Also, probiotic was associated with a significantly lower chance of diarrhea than the placebo group (OR adjusted = 0.09; 95% CI: 0.01-0.96). Conclusion: Probiotic utilization is effective in preventing the incidence of VAP and diarrhea in children under mechanical ventilation in the PICU.

Effect of ICU quality control indicators on VAP incidence rate and mortality: a retrospective study of 1267 hospitals in China.

PURPOSE: To investigate the effects of ICU quality control indicators on the VAP incidence rate and mortality in China throughout 2019. METHODS: This was a retrospective study. A total of 1267 ICUs from 30 provinces in mainland China were included. Data were collected using the National Clinical Improvement System Data that report ICU information. Ten related quality control indicators were analyzed, including 5 structural factors (patient-to-bed ratio, physician-to-bed ratio, nurse-to-bed ratio, patient-to-physician ratio, and patient-to-nurse ratio), 3 process factors (unplanned endotracheal extubation rate, reintubation rate within 48 h, and microbiology detection rate before antibiotic use), and 2 outcome factors (VAP incidence rate and mortality). The information on the most common infectious pathogens and the most commonly used antibiotics in ICU was also collected. The Poisson regression model was used to identify the impact of factors on the incidence rate and mortality of VAP. RESULTS: The incidence rate of VAP in these hospitals in 2019 was 5.03 (2.38, 10.25) per 1000 ventilator days, and the mortality of VAP was 11.11 (0.32, 26.00) %. The most common causative pathogen was Acinetobacter baumannii (in 39.98% of hospitals), followed by Klebsiella pneumoniae (38.26%), Pseudomonas aeruginosa, and Escherichia coli. In 26.90% of hospitals, third-generation cephalosporin was the most used antibiotic, followed by carbapenem (24.22%), penicillin and beta-lactamase inhibitor combination (20.09%), cephalosporin with beta-lactamase inhibitor (17.93%). All the structural factors were significantly associated with VAP incidence rate, but not with the mortality, although the trend was inconsistent. Process factors including unplanned endotracheal extubation rate, reintubation rate in 48 h, and microbiology detection rate before antibiotic use were associated with higher VAP mortality, while unplanned endotracheal extubation rate and reintubation rate in 48 h were associated with higher VAP mortality. Furthermore, K. pneumoniae as the most common pathogen was associated with higher VAP mortality, and carbapenems as the most used antibiotics were associated with lower VAP mortality. CONCLUSION: This study highlights the association between the ICU quality control (QC) factors and VAP incidence rate and mortality. The process factors rather than the structural factors need to be further improved for the QC of VAP in the ICU.

GC-MS profiling of volatile metabolites produced by Klebsiella pneumoniae.

Currently used methods for diagnosing ventilator-associated pneumonia (VAP) are complex, time-consuming and require invasive procedures while empirical antibacterial therapy applies broad spectrum antibiotics that may promote antimicrobial resistance. Hence, novel and fast methods based on alternative markers are needed for VAP detection and differentiation of causative pathogens. Pathogenic bacteria produce a broad range of volatile organic compounds (VOCs), some of which may potentially serve as biomarkers for microorganism identification. Additionally, monitoring of dynamically changing VOCs concentration profiles may indicate emerging pneumonia and allow timely implementation of appropriate antimicrobial treatment. This study substantially extends the knowledge on bacterial metabolites providing the unambiguous identification of volatile metabolites produced by carbapenem-resistant and susceptible strains of Klebsiella pneumoniae (confirmed with pure standards in addition to mass spectra match) but also revealing their temporary concentration profiles (along the course of pathogen proliferation) and dependence on the addition of antibiotic (imipenem) to bacteria. Furthermore, the clinical strains of K. pneumoniae isolated from bronchoalveolar lavage specimens collected from mechanically ventilated patients were investigated to reveal, whether bacterial metabolites observed in model experiments with reference strains could be relevant for wild pathogens as well. In all experiments, the headspace samples from bacteria cultures were collected on multibed sorption tubes and analyzed by GC-MS. Sampling was done under strictly controlled conditions at seven time points (up to 24 h after bacteria inoculation) to follow the dynamic changes in VOC concentrations, revealing three profiles: release proportional to bacteria load, temporary maximum and uptake. Altogether 32 VOCs were released by susceptible and 25 VOCs by resistant strain, amongst which 2-pentanone, 2-heptanone, and 2-nonanone were significantly higher for carbapenem-resistant KPN. Considerably more metabolites (n = 64) were produced by clinical isolates and in higher diversity compared to reference KPN strains.

Molecular point-of-care testing for lower respiratory tract pathogens improves safe antibiotic de-escalation in patients with pneumonia in the ICU: Results of a randomised controlled trial.

BACKGROUND: Effective treatment of pneumonia requires timely administration of appropriate antimicrobials but standard diagnostic tests take around 48 h to generate results. Highly accurate, rapid molecular tests have been developed for identifying organisms in lower respiratory tract samples, however their impact on antibiotic use is unknown. The aim of this study was to assess the impact of syndromic molecular point-of-care testing compared to conventional diagnostic testing, on antibiotic use. METHODS: In this pragmatic, randomised controlled trial, we enrolled critically ill adults with pneumonia. Patients were assigned (1:1) to molecular testing of samples at the point-of-care or routine clinical care. The primary outcome was the proportion of patients who received results-directed antimicrobial therapy. RESULTS: 200 patients were randomly assigned to point-of-care testing (n = 100) or the control group (n = 100). 85 patients had community acquired pneumonia (42 in the mPOCT group and 43 in the control group), 69 hospital acquired pneumonia (30 in mPOCT and 39 in control) and 46 ventilator associated pneumonia (28 in mPOCT and 18 in control). The median [IQR] time to results was 1.7 [1.6-1.9] hours for point-of-care testing and 66.7 [56.7-88.5] hours for standard diagnostics (difference of -65.0 h, 95%CI -68.0 to -62.0; p < 0.0001). 71 (71%) patients in the point-of-care testing arm had pathogens detected compared to 51 (51%) in the control arm (difference of 20%, 95%CI 7 to 33; p = 0.004). 80 (80%) of patients in the point-of-care group received results-directed therapy, compared with 29 (29%) of 99 in the control group (difference of 51%, 95%CI 39-63; p < 0.0001). Time to results-directed therapy was 2.3 [1.8-7.2] hours in the mPOCT group and 46.1 [23.0-51.5] hours in the control group (difference of -43.8 h, 95% CI -48.9 to -38.6; p < 0.0001). 42 (42%) patients in mPOCT group had antibiotics de-escalated compared with 8 (8%) of 98 in the control group (difference of 34%, 95%CI 23-45; p < 0.0001). Time to de-escalation was 4.8 [2.4-13.0] hours in the mPOCT group compared with 46.5 [26.3-48.6] hours in the control group (difference of -41.4 h, 95%CI -53 to -29.7; p < 0.0001). There was no major difference in antibiotic duration or in clinical or safety outcomes between the two groups. CONCLUSIONS: Use of molecular point-of-care testing in patients with pneumonia returned results more rapidly and identified more pathogens than conventional testing. This was associated with improvements in appropriate antimicrobial use and appeared safe.