Detection of volatile organic compounds as new paradigm to accelerate antimicrobial susceptibility testing: performance evaluation of VITEK® REVEAL™.

OBJECTIVES: The measurement of VOCs release in the headspace of a bacterial culture represents a new approach to rapidly assess antimicrobial susceptibility. Herein, we evaluated the diagnostic performance of the VITEK® REVEAL™ system directly from a collection of Gram-negative positive blood cultures. MATERIALS AND METHODS: One hundred and twenty-eight positive blood cultures were included in the analysis (Enterobacterales, n = 95; Pseudomonas aeruginosa, n = 21; Acinetobacter baumannii complex, n = 12). Samples were processed using VITEK® REVEAL™ according to the manufacturer's recommendations, and MICs of 22 antimicrobials were compared with those obtained using reference methods. Categorical agreement (CA), essential agreement (EA) and categorical errors were calculated. RESULTS: Overall, 2220 strain/antibiotic pair combinations were analysed. Of these, most were classified as resistant by reference antimicrobial susceptibility testing (1091/2220; 48.7%). The overall CA and EA were 97.6% and 97.7%, respectively. CA ranged from 97.5% in Enterobacterales to 97.9% in both P. aeruginosa and A. baumannii complex. The overall number of categorical discrepancies were: 18 very major errors (1.6%), 13 major errors (1.2%) and 22 minor errors (2.4%). EA ranged from 95.2% in P. aeruginosa to 98.1% in Enterobacterales. Screening test for ESBL phenotype was positive, indeterminate and negative in 13.7%, 32.6% and 27.4% of Enterobacterales isolates tested by both VITEK® REVEAL™ and the reference method, showing 100% CA. CONCLUSIONS: VITEK® REVEAL™ represents a reliable tool to obtain antimicrobial susceptibility results of the main Gram-negative species directly from positive blood cultures with time to results of less than 8 h.

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.

First case of Chryseobacterium gallinarum bloodstream infection: a diagnostic and therapeutic challenge for an emerging pathogen.

Chryseobacterium spp. belongs to the Flavobacteriaceae family and is a rod-shaped gram-negative, glucose non-fermenting, non-motile bacterium ubiquitous in the environment. In humans, Chryseobacterium may be responsible for infections such as urinary tract infections (UTI) and ventriculitis with a pathogenic burden increasing in recent years. Chryseobacterium gallinarum was isolated for the first time in 2014 in a pharyngeal scrape sample of chicken and, until now, only one case of human UTI has been described in a pregnant 20-year-old Indian patient. Herein, we report the first case of bloodstream infection caused by C. gallinarum in a 67-year-old female burn patient, correctly identified by 16S-rRNA sequencing and successfully treated with cefepime and fosfomycin.

Disseminated Enterovirus Infection in a Patient Affected by Follicular Lymphoma Treated with Obinutuzumab: A Case Report and a Narrative Review of the Literature.

Background and Objectives: the principal purpose of this literature review is to cluster adults with hematological malignancies after treatment or on maintenance with obinutuzumab who experienced disseminated EV infection to understand clinical characteristics and outcome of this rare condition in these patients. We report the first clinical case of a male affected by follicular lymphoma treated with immune-chemotherapy including obinutuzumab who was affected by disseminated EV infection with cardiovascular involvement. Materials and Methods: this narrative review summarizes all the research about disseminated EV infection in immunosuppressed adult patients treated with obinutuzumab from January 2000 to January 2024 using the Scale for the Assessment of Narrative Review Articles (SANRA) flow-chart. We performed a descriptive statistic using the standard statistical measures for quantitative data. Results: we included six studies, five case reports, and one case report with literature analysis. We collected a total of seven patients, all female, with disseminated EV infection. The most common signs and clinical presentations of EV infection were fever and encephalitis symptoms (N = 6, 85.7%), followed by hepatitis/acute liver failure (N = 5, 71.4%). Conclusions: onco-hematological patients who receive immune-chemotherapy with a combination of treatments which depress adaptative immunity, which includes the antiCD20 obinutuzumab, could be at higher risk of disseminated EV infection, including CNS and cardiac involvement.

Stenotrophomonas maltophilia Infections in Haematological Malignancies and Hematopoietic Stem Cell Transplantation: A Case Series including Cefiderocol-Based Regimens.

Background and Objectives: Stenotrophomonas maltophilia is a ubiquitous, aerobic, Gram-negative bacillus causing increasing concern in patients affected by haematological malignancies. Materials and Methods: We report a case series from two centres in Northern Italy to describe the characteristics, outcome and microbiological response of S. maltophilia infections in patients with haematological malignancies and/or allogenic hematopoietic stem cell transplantation (aHSCT). Results: Ten patients were included. The median age was 67 years, and seven patients (70%) were males. The median Charlson Comorbidity Index was 6 (IQR: 4-8). The most frequent haematological comorbidities were acute myeloid leukaemia (AML; n = 3; 30%) and non-Hodgkin's lymphoma (n = 3; 30%). Three (30%) patients underwent aHSCT before infection, all for AML. All the patients had undergone a recent antibiotics course and had an indwelling central venous catheter before infection. The main clinical presentations were nosocomial pneumonia, with (2; 20%) or without (4; 40%) secondary bloodstream infection and CRBSI (3; 30%). Four patients were treated with cefiderocol in monotherapy or combinations therapy with cotrimoxazole. The rest of the patients were treated with cotrimoxazole or levofloxacin in monotherapy. Conclusions: Despite a high rate of clinical improvement (90%) after starting antimicrobial therapy, we faced high 30-day mortality (30%) and in-hospital mortality (50%) rates in a highly comorbid population.

Synergistic Effect of Essential Oils and Antifungal Agents in Fighting Resistant Clinical Isolates of Candida auris.

Recently, a large number of nosocomial infections have been caused by an emerging pathogen that is rising as a worldwide issue in human health: Candida auris. This yeast is considered resistant to antifungals of the first-line therapies, and consequently it is related to morbidity and mortality. Therefore, the aim of this research was to determine the in vitro anti-C. auris activity against twenty-three resistant clinical strains of different essential oils (EOs), pure or in combination with traditional antifungal agents, mainly caspofungin, fluconazole, micafungin and 5-flucytosine. Broth dilution assay was performed to evaluate the fungistatic and fungicidal effectiveness of fifteen EOs towards all the C. auris isolates. The data demonstrated that EOs were able to prevent C. auris growth, with MIC values ranging from 0.03 to 1% for the efficacious EOs (thyme, cinnamon, geranium, clove bud, lemongrass and mentha of Pancalieri), whereas the MICs were >1% for the ineffective ones. Thereafter, the six most effective EOs were used to perform the checkerboard experiments by assaying simultaneously the activity of EOs and traditional antifungals towards two selected strains. The most promising synergic combinations towards C. auris, depending on the isolate, were those with micafungin and geranium, thyme, cinnamon, lemongrass or clove bud EOs, with fluconazole and mentha of Pancalieri EO, and with 5-flucytosine and mentha of Pancalieri EO. These EOs and their combinations with antifungal drugs may provide a useful therapeutic alternative that could reduce the dose of the individual components, limiting the overall side effects. These associations might be a prospective option for the future treatment of infections, thus helping to overcome the challenging issue of resistance in C. auris.

Risk factors for mortality in Acinetobacter baumannii bloodstream infections and development of a predictive mortality model.

OBJECTIVES: Acinetobacter baumannii (A. baumannii) nosocomial infections represent a serious hazard to public health, given high mortality rates and rapid spread of multidrug-resistance. The primary outcome of this study was to evaluate predictors of 14- and 30-d mortality in bloodstream infections (BSIs) due to both carbapenem-resistant and carbapenem-sensitive Acinetobacter. Secondary end points were to identify risk factors for BSIs due to carbapenem-resistant A. baumannii (CRAB) and to develop a predictive model for mortality in CRAB-related BSIs. METHODS: Between 2019 and 2023, all consecutive hospitalized adult patients with bacteraemia due to A. baumannii were retrospectively enrolled at a single-centre. RESULTS: One hundred twenty-six episodes of BSI caused by A. baumannii were recorded, 89.7% of which were due to CRAB. Recent burn injuries, older age, previous CRAB colonization, and antibiotics exposure were identified as risk factors for acquiring CRAB BSI. Overall, 14-d mortality was observed in 26.1% of the patients and 30-d mortality in 30.9% of the patients. On multivariate analysis, the Sequential Organ Failure Assessment (SOFA) score was associated with both 14- and 30-d mortality, whereas burn injuries correlated with 30-d survival. Concurrent coronavirus disease (COVID) was associated with mortality, although not reaching statistical figures. No major impact of receiving appropriate treatment was observed. Based on these findings, a multivariable model to predict mortality among patients with CRAB BSI was built and internally validated. CONCLUSIONS: A. baumannii BSIs are characterized by poor outcomes and limited therapeutic options. This study aimed to assist physicians in prompt identification of patients who are at greater risk of death, contributing to more informed clinical decision making.

Fourier Transform Infrared Spectroscopy Application for Candida auris Outbreak Typing in a Referral Intensive Care Unit: Phylogenetic Analysis and Clustering Cut-Off Definition.

Recently Candida auris has emerged as a multi-resistant fungal pathogen, with a significant clinical impact, and is able to persist for a long time on human skin and hospital environments. It is a critical issue on the WHO fungal priority list and therefore it is fundamental to reinforce hospital surveillance protocols to limit nosocomial outbreaks. The purpose of this study was to apply Fourier transform infrared spectroscopy (FT-IR) to investigate the phylogenetic relationships among isolated strains from a C. auris outbreak at the University Intensive Care Unit of a Tertiary University hospital in Turin (Italy). To calculate a clustering cut-off, intra- and inter-isolate, distance values were analysed. The data showed the presence of a major Alfa cluster and a minor Beta cluster with a defined C. auris clustering cut-off. The results were validated by an external C. auris strain and Principal Component and Linear Discriminant Analyses. The application of FT-IR technology allowed to obtain important information about the phylogenetic relationships between the analysed strains, defining for the first time a "not WGS-based" clustering cut-off with a statistical-mathematical approach. FT-IR could represent a valid alternative to molecular methods for the rapid and cost-saving typing of C. auris strains with important clinical implications.

Herpes Virus Infection in Lung Transplantation: Diagnosis, Treatment and Prevention Strategies.

Lung transplantation is an ultimate treatment option for some end-stage lung diseases; due to the intense immunosuppression needed to reduce the risk of developing acute and chronic allograft failure, infectious complications are highly incident. Viral infections represent nearly 30% of all infectious complications, with herpes viruses playing an important role in the development of acute and chronic diseases. Among them, cytomegalovirus (CMV) is a major cause of morbidity and mortality, being associated with an increased risk of chronic lung allograft failure. Epstein-Barr virus (EBV) is associated with transformation of infected B cells with the development of post-transplantation lymphoproliferative disorders (PTLDs). Similarly, herpes simplex virus (HSV), varicella zoster virus and human herpesviruses 6 and 7 can also be responsible for acute manifestations in lung transplant patients. During these last years, new, highly sensitive and specific diagnostic tests have been developed, and preventive and prophylactic strategies have been studied aiming to reduce and prevent the incidence of these viral infections. In this narrative review, we explore epidemiology, diagnosis and treatment options for more frequent herpes virus infections in lung transplant patients.