Multidrug-resistant pathogens and ventilator-associated pneumonia in critically ill COVID-19 and non-COVID-19 patients: a prospective observational monocentric comparative study.

BACKGROUND: The COVID-19 pandemic has increased the incidence of ventilator-associated pneumonia (VAP) among critically ill patients. However, a comparison of VAP incidence in COVID-19 and non-COVID-19 cohorts, particularly in a context with a high prevalence of multidrug-resistant (MDR) organisms, is lacking. MATERIAL AND METHODS: We conducted a single-center, mixed prospective and retrospective cohort study comparing COVID-19 patients admitted to the intensive care unit (ICU) of the "Città della Salute e della Scienza" University Hospital in Turin, Italy, between March 2020 and December 2021 (COVID-19 group), with a historical cohort of ICU patients admitted between June 2016 and March 2018 (NON-COVID-19 group). The primary objective was to define the incidence of VAP in both cohorts. Secondary objectives were to evaluate the microbial cause, resistance patters, risk factors and impact on 28 days, ICU and in-hospital mortality, duration of ICU stay, and duration of hospitalization). RESULTS: We found a significantly higher incidence of VAP (51.9% - n = 125) among the 241 COVID-19 patients compared to that observed (31.2% - n = 78) among the 252 NON-COVID-19 patients. The median SOFA score was significantly lower in the COVID-19 group (9, Interquartile range, IQR: 7-11 vs. 10, IQR: 8-13, p < 0.001). The COVID-19 group had a higher prevalence of Gram-positive bacteria-related VAP (30% vs. 9%, p < 0.001), but no significant difference was observed in the prevalence of difficult-to-treat (DTR) or MDR bacteria. ICU and in-hospital mortality in the COVID-19 and NON-COVID-19 groups were 71% and 74%, vs. 33% and 43%, respectively. The presence of COVID-19 was significantly associated with an increased risk of 28-day all-cause hospital mortality (Hazard ratio, HR: 7.95, 95% Confidence Intervals, 95% CI: 3.10-20.36, p < 0.001). Tracheostomy and a shorter duration of mechanical ventilation were protective against 28-day mortality, while dialysis and a high SOFA score were associated with a higher risk of 28-day mortality. CONCLUSION: COVID-19 patients with VAP appear to have a significantly higher ICU and in-hospital mortality risk regardless of the presence of MDR and DTR pathogens. Tracheostomy and a shorter duration of mechanical ventilation appear to be associated with better outcomes.

Bacterial profiles detected in ventilator-associated pneumonia in Japan: A systematic review.

The primary objective of this study was to identify the predominant organisms associated with ventilator-associated pneumonia (VAP) in Japan. Studies on VAP conducted in Japan were systematically reviewed, and seven studies with a total of 374 cases were included. The detection rate of each bacterium and multidrug-resistant (MDR) pathogen was analyzed using the inverse variance method. Pseudomonas aeruginosa was identified as the predominant pathogen in 29.2 % of cases, followed by methicillin-resistant Staphylococcus aureus (MRSA) (12.0 %), and Klebsiella spp. (9.5 %). An integrated analysis revealed a detection rate of 57.8 % (95 % confidence interval: 48.7%-66.8 %) for MDR pathogens. This review highlights P. aeruginosa and MRSA as the predominant VAP-associated organisms in Japan, with a significant prevalence of MDR pathogens. This analysis provides valuable insights based on the regional distribution of bacteria detected in VAP, which is critical for selecting appropriate empirical therapy.

Role of soluble urokinase plasminogen activator receptor in critically ill children with hospital-acquired pneumonia: an observational study in hospital with controls.

BACKGROUND: Diagnosing hospital-acquired pneumonia (HAP) (ventilator-associated pneumonia (VAP) and non-ventilator associated pneumonia (Non-VAP)) is still a hot issue. Soluble urokinase plasminogen activator receptor (suPAR) is prognostic in critically ill children with sepsis regarding mortality prediction. Our aim was to evaluate suPAR levels in children with HAP. METHODS: An observational, prospective study was conducted on 45 children diagnosed HAP (VAP and Non-VAP) and 40 healthy controls. Paediatric Sequential Organ Failure assessment Score (pSOFA) was assessed for each patient. Plasma suPAR levels were measured with ELISA on the day of diagnosis. RESULTS: On comparison levels of plasma suPAR for the children with HAP with the healthy control group, no statistically significant difference was observed (148 pg/mL (22.4-1939.7) and 184.4 pg/mL (31.6-1311.7), respectively, (p=0.32). suPAR was significantly increased in children with elevated pSOFA score on the day of diagnosis of pneumonia (p=0.034). suPAR was significantly increased in children with shock (p=0.005). suPAR levels was negatively correlated with oxygen saturation (rs=0.31,p=0.048). suPAR was not significantly correlated with C reactive protein. CONCLUSIONS: suPAR can be used as a predictor for severity of illness in children with HAP. We firmly know that plasma suPAR, a novel marker, could indicate the disease if carried out on larger patient groups.

Ventilator-associated pneumonia by Weeksella virosa: case report.

BACKGROUND: Weeksella virosa pneumonia is an infection that has been described as a healthcare-associated infection. This is a rare gram-negative anaerobic bacterium associated with the use of mechanical ventilation for a long period of time and is more frequent in immunosuppressed patients. This is the first case reported in the state of Veracruz and the second in Mexico. CASE PRESENTATION: We present the case of a 64-year-old female from Veracruz, Mexico who developed an infectious process in the right pelvic limb after a transcatheter aortic valve replacement procedure and subsequently developed sudden cardiorespiratory arrest requiring mechanical ventilation, with subsequent imaging studies demonstrating a pneumonic process associated with a nosocomial infection. DISCUSSION AND CONCLUSIONS: We should take into consideration that this pathogen affects not only adults with multiple comorbidities but also children with renal, hepatic, or oncological pathologies, as well as immunocompromised patients, who should be considered high-risk populations for W. virosa infection.

The Role of Biomarkers in the Diagnosis and Management of Pneumonia.

Biomarkers are used in the diagnosis, severity determination, and prognosis for patients with community-acquired pneumonia (CAP). Selected biomarkers may indicate a bacterial infection and need for antibiotic therapy (C-reactive protein, procalcitonin, soluble triggering receptor expressed on myeloid cells). Biomarkers can differentiate CAP patients who require hospital admission and severe CAP requiring intensive care unit admission. Biomarker-guided antibiotic therapy may limit antibiotic exposure without compromising outcome and thus improve antibiotic stewardship. The authors discuss the role of biomarkers in diagnosing, determining severity, defining the prognosis, and limiting antibiotic exposure in CAP and ventilator-associated pneumonia patients.

Management of Ventilator-Associated Pneumonia: Guidelines.

Two recent major guidelines on diagnosis and treatment of ventilator-associated pneumonia (VAP) recommend consideration of local antibiotic resistance patterns and individual patient risks for resistant pathogens when formulating an initial empiric antibiotic regimen. One recommends against invasive diagnostic techniques with quantitative cultures to determine the cause of VAP; the other recommends either invasive or noninvasive techniques. Both guidelines recommend short-course therapy be used for most patients with VAP. Although neither guideline recommends use of procalcitonin as an adjunct to clinical judgment when diagnosing VAP, they differ with respect to use of serial procalcitonin to shorten the length of antibiotic treatment.

Qualitative and quantitative rapid detection of VOCs differentially released by VAP-associated bacteria using PTR-MS and FGC-PTR-MS.

Ventilator-associated pneumonia (VAP) is a prevalent disease caused by microbial infection, resulting in significant morbidity and mortality within the intensive care unit (ICU). The rapid and accurate identification of pathogenic bacteria causing VAP can assist clinicians in formulating timely treatment plans. In this study, we attempted to differentiate bacterial species in VAP by utilizing the volatile organic compounds (VOCs) released by pathogens. We cultured 6 common bacteria in VAP in vitro, including Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Staphylococcus aureus, which covered most cases of VAP infection in clinic. After the VOCs released by bacteria were collected in sampling bags, they were quantitatively detected by a proton transfer reaction-mass spectrometry (PTR-MS), and the characteristic ions were qualitatively analyzed through a fast gas chromatography-proton transfer reaction-mass spectrometry (FGC-PTR-MS). After conducting principal component analysis (PCA) and analysis of similarities (ANOSIM), we discovered that the VOCs released by 6 bacteria exhibited differentiation following 3 h of quantitative cultivation in vitro. Additionally, we further investigated the variations in the types and concentrations of bacterial VOCs. The results showed that by utilizing the differences in types of VOCs, 6 bacteria could be classified into 5 sets, except for A. baumannii and E. cloacae which were indistinguishable. Furthermore, we observed significant variations in the concentration ratio of acetaldehyde and methyl mercaptan released by A. baumannii and E. cloacae. In conclusion, the VOCs released by bacteria could effectively differentiate the 6 pathogens commonly associated with VAP, which was expected to assist doctors in formulating treatment plans in time and improve the survival rate of patients.

A quasi-experimental study of a bundled diagnostic stewardship intervention for ventilator-associated pneumonia.

OBJECTIVES: Diagnostic error in the use of respiratory cultures for ventilator-associated pneumonia (VAP) fuels misdiagnosis and antibiotic overuse within intensive care units. In this prospective quasi-experimental study (NCT05176353), we aimed to evaluate the safety, feasibility, and efficacy of a novel VAP-specific bundled diagnostic stewardship intervention (VAP-DSI) to mitigate VAP over-diagnosis/overtreatment. METHODS: We developed and implemented a VAP-DSI using an interruptive clinical decision support tool and modifications to clinical laboratory workflows. Interventions included gatekeeping access to respiratory culture ordering, preferential use of non-bronchoscopic bronchoalveolar lavage for culture collection, and suppression of culture results for samples with minimal alveolar neutrophilia. Rates of adverse safety outcomes, positive respiratory cultures, and antimicrobial utilization were compared between mechanically ventilated patients (MVPs) in the 1-year post-intervention study cohort (2022-2023) and 5-year pre-intervention MVP controls (2017-2022). RESULTS: VAP-DSI implementation did not associate with increases in adverse safety outcomes but did associate with a 20% rate reduction in positive respiratory cultures per 1000 MVP days (pre-intervention rate 127 [95% CI: 122-131], post-intervention rate 102 [95% CI: 92-112], p < 0.01). Significant reductions in broad-spectrum antibiotic days of therapy per 1000 MVP days were noted after VAP-DSI implementation (pre-intervention rate 1199 [95% CI: 1177-1205], post-intervention rate 1149 [95% CI: 1116-1184], p 0.03). DISCUSSION: Implementation of a VAP-DSI was safe and associated with significant reductions in rates of positive respiratory cultures and broad-spectrum antimicrobial use. This innovative trial of a VAP-DSI represents a novel avenue for intensive care unit antimicrobial stewardship. Multicentre trials of VAP-DSIs are warranted.

Early Predictors of Ventilator Associated Pneumonia in Preterm Neonates Admitted in a Special Newborn Care Unit.

OBJECTIVES: 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.

Pulmonary superinfection diagnosed with bronchoalveolar lavage at intubation in COVID patients: A Swedish single-centre study.

BACKGROUND: Patients with severe coronavirus disease 2019 (COVID) pneumonia and acute respiratory distress syndrome (C-ARDS) on invasive mechanical ventilation (IMV) have been found to be prone to having other microbial findings than severe acute respiratory syndrome coronavirus 2 (SARS-2)-CoV-19 in the bronchoalveolar lavage (BAL) fluid at intubation causing a superinfection. These BAL results could guide empirical antibiotic treatment in complex clinical situations. However, there are limited data on the relationship between microbial findings in the initial BAL at intubation and later ventilator-associated pneumonia (VAP) diagnoses. OBJECTIVE: To analyse the incidence of, and microorganisms responsible for, superinfections in C-ARDS patients at the time of first intubation through microbial findings in BAL fluid. To correlate these findings to markers of inflammation in plasma and later VAP development. DESIGN: Retrospective single-centre study. SETTING: One COVID-19 intensive care unit (ICU) at a County Hospital in Sweden during the first year of the pandemic. PATIENTS: All patients with C-ARDS who were intubated in the ICU. RESULTS: We analysed BAL fluid specimens from 112 patients at intubation, of whom 31 (28%) had superinfections. Blood levels of the C-reactive protein, procalcitonin, neutrophil granulocytes, and lymphocytes were indistinguishable between patients with and without a pulmonary superinfection. Ninety-eight (88%) of the patients were treated with IMV for more than 48 h and of these patients, 37% were diagnosed with VAP. The microorganisms identified in BAL at the time of intubation are normally found at the oral, pharyngeal, and airway sites. Only one patient had an indistinguishable bacterial strain responsible for both superinfection at intubation and in VAP. CONCLUSIONS: One fourth of the patients with C-ARDS had a pulmonary superinfection in the lungs that was caused by another microorganism identified at intubation. Routine serum inflammatory markers could not be used to identify this complication. Microorganisms located in BAL at intubation were rarely associated with later VAP development.

Early prediction of ventilator-associated pneumonia with machine learning models: A systematic review and meta-analysis of prediction model performance✰.

BACKGROUND: Machine learning-based prediction models can catalog, classify, and correlate large amounts of multimodal data to aid clinicians at diagnostic, prognostic, and therapeutic levels. Early prediction of ventilator-associated pneumonia (VAP) may accelerate the diagnosis and guide preventive interventions. The performance of a variety of machine learning-based prediction models were analyzed among adults undergoing invasive mechanical ventilation. METHODS: This systematic review and meta-analysis was conducted in accordance with the Cochrane Collaboration. Machine learning-based prediction models were identified from a search of nine multi-disciplinary databases. Two authors independently selected and extracted data using predefined criteria and data extraction forms. The predictive performance, the interpretability, the technological readiness level, and the risk of bias of the included studies were evaluated. RESULTS: Final analysis included 10 static prediction models using supervised learning. The pooled area under the receiver operating characteristics curve, sensitivity, and specificity for VAP were 0.88 (95 % CI 0.82-0.94, I2 98.4 %), 0.72 (95 % CI 0.45-0.98, I2 97.4 %) and 0.90 (95 % CI 0.85-0.94, I2 97.9 %), respectively. All included studies had either a high or unclear risk of bias without significant improvements in applicability. The care-related risk factors for the best performing models were the duration of mechanical ventilation, the length of ICU stay, blood transfusion, nutrition strategy, and the presence of antibiotics. CONCLUSION: A variety of the prediction models, prediction intervals, and prediction windows were identified to facilitate timely diagnosis. In addition, care-related risk factors susceptible for preventive interventions were identified. In future, there is a need for dynamic machine learning models using time-depended predictors in conjunction with feature importance of the models to predict real-time risk of VAP and related outcomes to optimize bundled care.