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.

Co-immobilization of Ciprofloxacin and Chlorhexidine as a Broad-Spectrum Antimicrobial Dual-Drug Coating for Poly(vinyl chloride) (PVC)-Based Endotracheal Tubes.

The endotracheal tube (ETT) affords support for intubated patients, but the increasing incidence of ventilator-associated pneumonia (VAP) is jeopardizing its application. ETT surfaces promote (poly)microbial colonization and biofilm formation, with a heavy burden for VAP. Devising safe, broad-spectrum antimicrobial materials to tackle the ETT bioburden is needful. Herein, we immobilized ciprofloxacin (CIP) and/or chlorhexidine (CHX), through polydopamine (pDA)-based functionalization, onto poly(vinyl chloride) (PVC) surfaces. These surfaces were characterized regarding physicochemical properties and challenged with single and polymicrobial cultures of VAP-relevant bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis) and fungi (Candida albicans). The coatings imparted PVC surfaces with a homogeneous morphology, varied wettability, and low roughness. The antimicrobial immobilization via pDA chemistry was still evidenced by infrared spectroscopy. Coated surfaces exhibited sustained CIP/CHX release, retaining prolonged (10 days) activity. CIP/CHX-coated surfaces evidencing no A549 lung cell toxicity displayed better antibiofilm outcomes than CIP or CHX coatings, preventing bacterial attachment by 4.1-7.2 Log10 CFU/mL and modestly distressingC. albicans. Their antibiofilm effectiveness was endured toward polymicrobial consortia, substantially inhibiting the adhesion of the bacterial populations (up to 8 Log10 CFU/mL) within the consortia in dual- and even inP. aeruginosa/S. aureus/C. albicans triple-species biofilms while affecting fungal adhesion by 2.7 Log10 CFU/mL (dual consortia) and 1 Log10 CFU/mL (triple consortia). The potential of the dual-drug coating strategy in preventing triple-species adhesion and impairing bacterial viability was still strengthened by live/dead microscopy. The pDA-assisted CIP/CHX co-immobilization holds a safe and robust broad-spectrum antimicrobial coating strategy for PVC-ETTs, with the promise laying in reducing VAP incidence.

Does organophosphorus poisoning increase the risk of staphylococcal ventilator associated pneumonia? - a retrospective study.

INTRODUCTION: The aim of this study was to determine the clinical predictors of staphylococcal ventilator-associated pneumonia (VAP) and to compare the outcomes of staphylococcal VAP with non-staphylococcal VAP. METHODOLOGY: A retrospective observational study was conducted among adult patients admitted to the medical intensive care unit (MICU) in a tertiary care hospital in India from January 2017 to December 2019. The patients were grouped based on their diagnosis into staphylococcal and non-staphylococcal VAP, and the baseline characteristics, clinical parameters, co-morbidities, and outcome parameters were compared. RESULTS: Out of 2129 MICU admissions, 456 patients with microbiologically confirmed VAP were included, of which 69 (15.1%) had staphylococcal VAP, and the remaining 387 (84.9%) had non-staphylococcal VAP. Organophosphorus (OP) poisoning was identified as an independent predictor of staphylococcal VAP (odds ratio: 2.57; 95% CI: 1.4 to 4.73). The median duration of mechanical ventilation before VAP diagnosis was less in the staphylococcal VAP group (4 vs. 5 days; p = 0.004). The staphylococcal group also showed a better in-hospital outcome. CONCLUSIONS: OP poisoning was an independent predictor of staphylococcal VAP. Staphylococcal VAP was diagnosed earlier in patients than non-staphylococcal VAP. Screening for nasal carriage for Staphylococcus, especially in patients with OP poisoning at the time of MICU admission, may help guide antibiotic therapy.

Understanding the nebulisation of antibiotics: the key role of lung microdialysis studies.

BACKGROUND: Nebulisation of antibiotics is a promising treatment for ventilator-associated pneumonia (VAP) caused by multidrug-resistant organisms. Ensuring effective antibiotic concentrations at the site of infection in the interstitial space fluid is crucial for clinical outcomes. Current assessment methods, such as epithelial lining fluid and tissue homogenates, have limitations in providing longitudinal pharmacokinetic data. MAIN BODY: Lung microdialysis, an invasive research technique predominantly used in animals, involves inserting probes into lung parenchyma to measure antibiotic concentrations in interstitial space fluid. Lung microdialysis offers unique advantages, such as continuous sampling, regional assessment of antibiotic lung concentrations and avoidance of bronchial contamination. However, it also has inherent limitations including the cost of probes and assay development, the need for probe calibration and limited applicability to certain antibiotics. As a research tool in VAP, lung microdialysis necessitates specialist techniques and resource-intensive experimental designs involving large animals undergoing prolonged mechanical ventilation. However, its potential impact on advancing our understanding of nebulised antibiotics for VAP is substantial. The technique may enable the investigation of various factors influencing antibiotic lung pharmacokinetics, including drug types, delivery devices, ventilator settings, interfaces and disease conditions. Combining in vivo pharmacokinetics with in vitro pharmacodynamic simulations can become feasible, providing insights to inform nebulised antibiotic dose optimisation regimens. Specifically, it may aid in understanding and optimising the nebulisation of polymyxins, effective against multidrug-resistant Gram-negative bacteria. Furthermore, lung microdialysis holds promise in exploring novel nebulisation therapies, including repurposed antibiotic formulations, bacteriophages and immunomodulators. The technique's potential to monitor dynamic biochemical changes in pneumonia, such as cytokines, metabolites and inflammation/infection markers, opens avenues for developing theranostic tools tailored to critically ill patients with VAP. CONCLUSION: In summary, lung microdialysis can be a potential transformative tool, offering real-time insights into nebulised antibiotic pharmacokinetics. Its potential to inform optimal dosing regimen development based on precise target site concentrations and contribute to development of theranostic tools positions it as key player in advancing treatment strategies for VAP caused by multidrug-resistant organisms. The establishment of international research networks, exemplified by LUMINA (lung microdialysis applied to nebulised antibiotics), signifies a proactive step towards addressing complexities and promoting multicentre experimental studies in the future.

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.

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.

Combination eravacycline therapy for ventilator-associated pneumonia due to carbapenem-resistant Acinetobacter baumannii in patients with COVID-19: A case series.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia is associated with poor clinical outcomes and increased mortality. Clinical data regarding the optimal treatment of CRAB is limited, and combination therapy is often preferred. Eravacycline has demonstrated in-vitro activity against A. baumannii and has been considered for the treatment of pulmonary infections caused by CRAB. OBJECTIVE: The objective of this case series was to describe clinical outcomes associated with eravacycline when utilized as part of a combination regimen for the treatment of CRAB pneumonia at a county hospital. METHODS: A retrospective chart review was conducted from April 1, 2020, to October 1, 2020, which included hospitalized patients ≥18 years of age, diagnosed with coronavirus disease 2019 (COVID-19), with a sputum culture positive for CRAB, and receipt of at least one dose of eravacycline. The primary outcome studied was clinical resolution of CRAB pneumonia. A key secondary outcome was microbiological resolution. RESULTS: A total of 24 patients received combination eravacycline therapy for a median of 10.5 days. Overall, 17 (71%) patients demonstrated clinical resolution of CRAB pneumonia. Repeat sputum cultures post-treatment were collected in 17 (71%) patients, of which 12 (71%) achieved microbiological resolution. No adverse events attributable to eravacycline were identified. CONCLUSION: With limited viable salvage treatment options, combination eravacycline therapy showed favorable microbiological and clinical outcomes in patients with CRAB pneumonia. In light of this, eravacycline could be considered as a potential treatment option when designing CRAB pneumonia salvage therapy regimens.

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.

Single-drug versus combination antimicrobial therapy in critically ill patients with hospital-acquired pneumonia and ventilator-associated pneumonia due to Gram-negative pathogens: a multicenter retrospective cohort study.

KEY MESSAGES: In this study including 391 critically ill patients with nosocomial pneumonia due to Gram-negative pathogens, combination therapy was not associated with a reduced hazard of death at Day 28 or a greater likelihood of clinical cure at Day 14. No over-risk of AKI was observed in patients receiving combination therapy. BACKGROUND: The benefits and harms of combination antimicrobial therapy remain controversial in critically ill patients with hospital-acquired pneumonia (HAP), ventilated HAP (vHAP) or ventilator-associated pneumonia (VAP) involving Gram-negative bacteria. METHODS: We included all patients in the prospective multicenter OutcomeRea database with a first HAP, vHAP or VAP due to a single Gram-negative bacterium and treated with initial adequate single-drug or combination therapy. The primary endpoint was Day-28 all-cause mortality. Secondary endpoints were clinical cure rate at Day 14 and a composite outcome of death or treatment-emergent acute kidney injury (AKI) at Day 7. The average effects of combination therapy on the study endpoints were investigated through inverse probability of treatment-weighted regression and multivariable regression models. Subgroups analyses were performed according to the resistance phenotype of the causative pathogens (multidrug-resistant or not), the pivotal (carbapenems or others) and companion (aminoglycosides/polymyxins or others) drug classes, the duration of combination therapy (< 3 or ≥ 3 days), the SOFA score value at pneumonia onset (< 7 or ≥ 7 points), and in patients with pneumonia due to non-fermenting Gram-negative bacteria, pneumonia-related bloodstream infection, or septic shock. RESULTS: Among the 391 included patients, 151 (38.6%) received single-drug therapy and 240 (61.4%) received combination therapy. VAP (overall, 67.3%), vHAP (16.4%) and HAP (16.4%) were equally distributed in the two groups. All-cause mortality rates at Day 28 (overall, 31.2%), clinical cure rate at Day 14 (43.7%) and the rate of death or AKI at Day 7 (41.2%) did not significantly differ between the groups. In inverse probability of treatment-weighted analyses, combination therapy was not independently associated with the likelihood of all-cause death at Day 28 (adjusted odd ratio [aOR], 1.14; 95% confidence interval [CI] 0.73-1.77; P = 0.56), clinical cure at Day 14 (aOR, 0.79; 95% CI 0.53-1.20; P = 0.27) or death or AKI at Day 7 (aOR, 1.07; 95% CI 0.71-1.63; P = 0.73). Multivariable regression models and subgroup analyses provided similar results. CONCLUSIONS: Initial combination therapy exerts no independent impact on Day-28 mortality, clinical cure rate at Day 14, and the hazard of death or AKI at Day 7 in critically ill patients with mono-bacterial HAP, vHAP or VAP due to Gram-negative bacteria.

Carbapenem vs. non-carbapenem antibiotics for ventilator-associated pneumonia: A systematic review with meta-analysis.

BACKGROUND: Carbapenem is recommended as one of the first-line regimens for ventilator-associated pneumonia (VAP), but no recent systematic review has fully investigated its efficacy. This systematic review aims to evaluate the efficacy of carbapenem compared with non-carbapenem for VAP treatment. METHODS: We performed a systematic review and meta-analysis of studies comparing the efficacy and the safety between carbapenem and non-carbapenem with activity to Pseudomonas aeruginosa in the treatment for VAP. The main outcome was mortality, and the additional outcomes were the clinical cure of pneumonia, length of intensive care unit stay, recurrence, adverse effects, and the development of resistant bacteria. This study was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Of the initial 1,730 publications, 9 randomized control trials were enrolled. In the meta-analysis, no difference was observed between the carbapenem and non-carbapenem regimens in improving mortality (odds ratio, 0.83; 95 % confidence interval (CI) 0.67-1.02). While the carbapenem regimen was superior to the non-carbapenem regimen in studies reporting the resolution of pneumonia (odds ratio, 1.09; 95 % CI 1.01-1.17), the effectiveness of carbapenem treatment was not evident in studies assessing the other outcomes. CONCLUSIONS: Carbapenem might have no superiority in survival when treating VAP. Moreover, non-carbapenem antibiotics with activities to P. aeruginosa have a potential option to avoid inducing carbapenem-resistant pathogens.

Moving Beyond Mortality: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia.

BACKGROUND: Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are frequently caused by multidrug-resistant organisms. Patient-centered endpoints in clinical trials are needed to develop new antibiotics for HABP/VABP. Desirability of outcome ranking (DOOR) is a paradigm for the design, analysis, and interpretation of clinical trials based on a patient-centered, benefit-risk evaluation. METHODS: A multidisciplinary committee created an infectious diseases DOOR endpoint customized for HABP/VABP, incorporating infectious complications, serious adverse events, and mortality. We applied this to 2 previously completed, large randomized controlled trials for HABP/VABP. ZEPHyR compared vancomycin to linezolid and VITAL compared linezolid to tedizolid. For each trial, we evaluated the DOOR distribution and probability, including DOOR component and partial credit analyses. We also applied DOOR in subgroup analyses. RESULTS: In both trials, the HABP/VABP DOOR demonstrated similar overall clinical outcomes between treatment groups. In ZEPHyR, the probability that a participant treated with linezolid would have a more desirable outcome than a participant treated with vancomycin was 50.2% (95% confidence interval [CI], 45.1%--55.3%). In VITAL, the probability that a participant treated with tedizolid would have a more desirable outcome than a participant treated with linezolid was 48.7% (95% CI, 44.8%-52.6%). The DOOR component analysis revealed that participants treated with tedizolid had a less desirable outcome than those treated with linezolid when considering clinical response alone. However, participants with decreased renal function had improved overall outcomes with tedizolid. CONCLUSIONS: The HABP/VABP DOOR provided more granular information about clinical outcomes than is typically presented in clinical trials. HABP/VABP trials would benefit from prospectively using DOOR.

Assessment of the prognosis, frequency, and isolated bacteria in ventilator-associated pneumonia among patients with severe coronavirus disease 2019 pneumonia: A single-center retrospective observational study.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) due to severe coronavirus disease 2019 (COVID-19) pneumonia is associated with a high incidence of ventilator-associated pneumonia (VAP). We aimed to evaluate the epidemiology of VAP associated with severe COVID-19 pneumonia. METHODS: This retrospective observational study recruited patients with COVID-19-associated ARDS admitted to our center from April 1, 2020, to September 30, 2021. The primary outcome was the survival-to-discharge rate. The secondary outcomes were the VAP rate, time to VAP, length of ICU stay, length of ventilator support, and isolated bacteria. RESULTS: Sixty-eight patients were included in this study; 23 developed VAP. The survival-to-discharge rate was 60.9 % in the VAP group and 84.4 % in the non-VAP group. The median time to VAP onset was 16 days. The median duration of ventilator support and of ICU stay were higher in the VAP group than in the non-VAP group. The VAP rate was 33.8 %. The most common isolated species was Stenotrophomonas maltophilia. On admission, carbapenems were used in a maximum number of cases (75 %). Furthermore, the median body mass index (BMI) was lower and the median sequential organ failure assessment (SOFA) score on admission was higher in the VAP group than in the non-VAP group. CONCLUSIONS: The survival-to-discharge rate in VAP patients was low. Moreover, VAP patients tended to have long ICU stays, low BMI, and high SOFA scores on admission. Unusually, S. maltophilia was the most common isolated bacteria, which may be related to the frequent use of carbapenems.

Metagenomics for the microbiological diagnosis of hospital-acquired pneumonia and ventilator-associated pneumonia (HAP/VAP) in intensive care unit (ICU): a proof-of-concept study.

BACKGROUND: Hospital-acquired and ventilator-associated-pneumonia (HAP/VAP) are one of the most prevalent health-care associated infections in the intensive care unit (ICU). Culture-independent methods were therefore developed to provide faster route to diagnosis and treatment. Among these, metagenomic next-generation sequencing (mNGS) has shown considerable promise. METHODS: This proof-of-concept study describes the technical feasibility and evaluates the clinical validity of the mNGS for the detection and characterization of the etiologic agents causing hospital-acquired and ventilator-associated pneumonia. We performed a prospective study of all patients with HAP/VAP hospitalized in our intensive care unit for whom a bronchoalveolar lavage (BAL) was performed between July 2017 and November 2018. We compared BAL fluid culture and mNGS results of these patients. RESULTS: A total of 32 BAL fluids were fully analyzed. Of these, 22 (69%) were positive by culture and all pathogens identified were also reported by mNGS. Among the culture-positive BAL samples, additional bacterial species were revealed by mNGS for 12 patients, raising the issue of their pathogenic role (colonization versus coinfection). Among BALF with culture-negative test, 5 were positive in mNGS test. CONCLUSIONS: This study revealed concordant results for pneumonia panel pathogens between mNGS and culture-positive tests and identified additional pathogens potentially implicated in pneumonia without etiologic diagnosis by culture. mNGS has emerged as a promising methodology for infectious disease diagnoses to support conventional methods. Prospective studies with real-time mNGS are warranted to examine the impact on antimicrobial decision-making and clinical outcome.

Predicting ventilator-associated pneumonia in elderly patients requiring mechanical ventilation through the detection in tracheal aspirates.

OBJECTIVE: In this study, we evaluated the clinical utility of tracheal aspirates α-amylase (AM), pepsin, and lipid-laden macrophage index (LLMI) in the early diagnosis of ventilator-associated pneumonia (VAP) in elderly patients on mechanical ventilation. METHODS: Within 96 hours of tracheal intubation, tracheal aspirate specimens were collected from elderly patients on mechanical ventilation; AM, pepsin, and LLMI were detected, and we analyzed the potential of each index individually and in combination in diagnosing VAP. RESULTS: Patients with VAP had significantly higher levels of AM, pepsin, and LLMI compared to those without VAP (P < 0.001), and there was a positive correlation between the number of pre-intubation risk factors of aspiration and the detection value of each index in patients with VAP (P < 0.001). The area under a receiver operating characteristic (ROC) curve (AUC) of AM, pepsin, and LLMI in diagnosis of VAP were 0.821 (95% CI:0.713-0.904), 0.802 (95% CI:0.693-0.892), and 0.621 (95% CI:0.583-0.824), the sensitivities were 0.8815, 0.7632, and 0.6973, the specificities were 0.8495, 0.8602, and 0.6291, and the cutoff values were 4,321.5 U/L, 126.61 ng/ml, and 173.5, respectively. The AUC for the combination of indexes in diagnosing VAP was 0.905 (95% CI:0.812-0.934), and the sensitivity and specificity were 0.9211 and 0.9332, respectively. In the tracheal aspirate specimens, the detection rate of AM ≥ cutoff was the highest, while it was the lowest for LLMI (P < 0.001). The detection rates of AM ≥ cutoff and pepsin ≥ cutoff were higher within 48 hours after intubation than within 48-96 hours after intubation (P < 0.001). In contrast, the detection rate of LLMI ≥ cutoff was higher within 48-96 hours after intubation than within 48 hours after intubation (P < 0.001). The risk factors for VAP identified using logistic multivariate analysis included pre-intubation aspiration risk factors (≥3), MDR bacteria growth in tracheal aspirates, and tracheal aspirate AM ≥ 4,321.5 U/L, pepsin ≥ 126.61 ng/ml, and LLMI ≥ 173.5. CONCLUSION: The detection of AM, pepsin, and LLMI in tracheal aspirates has promising clinical utility as an early warning biomarker of VAP in elderly patients undergoing mechanical ventilation.

Bacterial respiratory infections in patients with COVID-19: A retrospective study from a tertiary care center in Lebanon.

BACKGROUND: Despite multiple reports of increased incidence of bacterial respiratory tract infections following COVID-19 globally, the microbiology is not yet fully elucidated. In this study, we describe the microbiology of bacterial infections and the prevalence of multidrug resistant organisms (MDROs) in hospitalized COVID-19 patients with community-acquired pneumonia (CAP), and hospital-acquired pneumonia (HAP) which includes both non-ventilated hospital acquired pneumonia (NVHAP) and ventilator-associated pneumonia (VAP). To our knowledge, this is the first study that compares the microbiology of VAP and NVHAP in COVID-19 patients. METHODS: This is a longitudinal retrospective cohort study conducted at the American University of Beirut Medical Center (AUBMC), a tertiary-care centre in Lebanon. Adult patients with confirmed COVID-19 and concurrent bacterial respiratory infections with an identifiable causative organism who were hospitalized between March 2020 and September 2021 were included. Bacterial isolates identified in hospital-acquired pneumonia (HAP) were divided into 3 groups based on the time of acquisition of pneumonia after admission: hospital day 3-14, 15-28 and 29-42. RESULTS: Out of 1674 patients admitted with COVID-19, 159 (9.5%) developed one or more respiratory infections with an identifiable causative organism. Overall, Gram-negative bacteria were predominant (84%) and Stenotrophomonas maltophilia was the most common pathogen, particularly in HAP. Among 231 obtained isolates, 59 (26%) were MDROs, seen in higher proportion in HAP, especially among patients with prolonged hospital stay (> 4 weeks). Non-fermenter Gram-negative bacilli (NFGNB) (OR = 3.52, p-value<0.001), particularly S. maltophilia (OR = 3.24, p-value = 0.02), were significantly more implicated in VAP compared to NVHAP. CONCLUSIONS: NFGNB particularly S. maltophilia were significantly associated with COVID-19 VAP. A high rate of bacterial resistance (25%), especially among Gram-negative bacteria, was found which may compromise patients' outcomes and has important implications in guiding therapeutic decisions in COVID-19 patients who acquire bacterial respiratory infections.

A metagenomics method for the quantitative detection of bacterial pathogens causing hospital-associated and ventilator-associated pneumonia.

IMPORTANCE: The management of ventilator-associated pneumonia and hospital-acquired pneumonia requires rapid and accurate quantitative detection of the infecting pathogen. To this end, we propose a metagenomic sequencing assay that includes the use of an internal sample processing control for the quantitative detection of 20 relevant bacterial species from bronchoalveolar lavage samples.

Diagnostic accuracy of the BioFire® FilmArray® pneumonia panel in COVID-19 patients with ventilator-associated pneumonia.

BACKGROUND: Ventilator-Associated pneumonia (VAP) is one of the leading causes of morbidity and mortality in critically ill COVID-19 patients in lower-and-middle-income settings, where timely access to emergency care and accurate diagnostic testing is not widely available. Therefore, rapid microbiological diagnosis is essential to improve effective therapy delivery to affected individuals, preventing adverse outcomes and reducing antimicrobial resistance. METHODS: We conducted a cross-sectional study of patients with suspected VAP and COVID-19, evaluating the diagnostic performance of the BioFire® FilmArray® Pneumonia Panel (FA-PP). Respiratory secretion samples underwent standard microbiological culture and FA-PP assays, and the results were compared. RESULTS: We included 252 samples. The traditional culture method detected 141 microorganisms, and FA-PP detected 277, resulting in a sensitivity of 95% and specificity of 60%, with a positive predictive value of 68% and negative predictive value of 93%. In samples with high levels of genetic material (> 10^5 copies/mL), the panel had a sensitivity of 94% and specificity of 86%. In addition, 40% of the culture-negative samples had positive FA-PP® results, of which 35% had > 10^5 copies/mL of genetic material. The most prevalent bacteria were Gram-negative bacilli, followed by Gram-positive cocci. The panel identified 98 genes associated with antimicrobial resistance, predominantly extended-spectrum beta-lactamases (28%). CONCLUSION: The FA-PP is a sensitive assay for identifying bacteria causing VAP in patients with COVID-19, with a greater capacity to detect bacteria than the conventional method. The timely microbiological recognition offered by this panel could lead to optimized decision-making processes, earlier tailored treatment initiation, and improved antibiotic stewardship practices.

A prospective surveillance study of healthcare-associated infections in an intensive care unit from a tertiary care teaching hospital from 2012-2019.

Healthcare-associated infections (HAIs) continue to be the most common adverse event affecting critically ill inpatients in intensive care units (ICUs). Limited data exist in the English literature on the epidemiology of HAIs in ICUs from China. The purpose of this prospective study was to understand the prevalence and trends of HAIs in the ICU to guide clinicians to take effective prevention and control measures. In total, 20 ICU beds in the hospital from January 2012 to December 2019 were selected for surveillance. HAI diagnosis and device-associated infection surveillance were based on the criteria set forth by the original Ministry of Health of the People's Republic of China. The full-time staff for HAI management monitored all patients who stayed in the ICU > 48 hours during the study period and calculated the device utilization ratio and device-associated infection rate. The rate of HAIs and the adjusted rate were 18.78 per 1000 patient-days and 5.17 per 1000 patient-days, respectively. The rates of ventilator-associated pneumonias, catheter-associated urinary tract infections, and central line-associated bloodstream infections were 22.68 per 1000 device-days, 2.40 per 1000 device-days, and 2.27 per 1000 device-days, respectively. A total of 731 pathogenic bacteria were detected in the patients with HAIs. Gram-negative and gram-positive bacteria accounted for 67.44% and 16.83%, respectively. Continuous target monitoring, regular analysis of high-risk factors, and timely intervention measures could effectively reduce HAIs in the ICU. Additionally, these findings could be used for developing new strategies to prevent and control HAIs in ICUs.