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Keywords = DTR-PA

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22 pages, 848 KiB  
Article
Modeling Prediction of Physical Properties in Sustainable Biodiesel–Diesel–Alcohol Blends via Experimental Methods and Machine Learning
by Kaan Yeşilova, Özgün Yücel and Başak Temur Ergan
Processes 2025, 13(7), 2310; https://doi.org/10.3390/pr13072310 - 20 Jul 2025
Viewed by 451
Abstract
This study investigated the production of biodiesel from canola oil, the formulation of sustainable ternary fuel blends with diesel and alcohol (ethanol or propanol), and the experimental and machine learning-based modeling of their physical properties, including density and viscosity over a temperature range [...] Read more.
This study investigated the production of biodiesel from canola oil, the formulation of sustainable ternary fuel blends with diesel and alcohol (ethanol or propanol), and the experimental and machine learning-based modeling of their physical properties, including density and viscosity over a temperature range of 10 °C to 40 °C. Biodiesel was synthesized via alkali-catalyzed transesterification (6:1 methanol-to-oil molar ratio, 0.5 wt % NaOH of oil) and blended with diesel and alcohols (ethanol and propanol) in varying volume ratios. The experimental results revealed that blend density decreased from 0.8622 g/cm3 at 10 °C to 0.8522 g/cm3 at 40 °C for a blend containing ethanol. Similarly, the viscosity showed a significant reduction with temperature, e.g., the blend exhibited a viscosity decline from 8.5 mPa·s at 10 °C to 7.2 mPa·s at 40 °C. Increasing the alcohol or diesel content further reduced density and viscosity due to the lower intrinsic properties of these components. The machine learning models, Gaussian process regression (GPR), support vector regression (SVR), artificial neural networks (ANN), and decision tree regression (DTR), were applied to predict the properties of these blends. GPR demonstrated the best predictive performance for both density and viscosity. These findings confirm the strong potential of GPR for the accurate and reliable prediction of fuel blend properties, supporting the formulation of alternative fuels optimized for diesel engine performance. These aspects contribute new insights into modelling strategies for sustainable fuel formulations. Full article
(This article belongs to the Section AI-Enabled Process Engineering)
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23 pages, 752 KiB  
Review
Antibiotic Therapy Duration for Multidrug-Resistant Gram-Negative Bacterial Infections: An Evidence-Based Review
by Andrea Marino, Egle Augello, Carlo Maria Bellanca, Federica Cosentino, Stefano Stracquadanio, Luigi La Via, Antonino Maniaci, Serena Spampinato, Paola Fadda, Giuseppina Cantarella, Renato Bernardini, Bruno Cacopardo and Giuseppe Nunnari
Int. J. Mol. Sci. 2025, 26(14), 6905; https://doi.org/10.3390/ijms26146905 - 18 Jul 2025
Viewed by 677
Abstract
Determining the optimal duration of antibiotic therapy for infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) is a critical challenge in clinical medicine, balancing therapeutic efficacy against the risks of adverse effects and antimicrobial resistance. This narrative review synthesises current evidence and guidelines regarding [...] Read more.
Determining the optimal duration of antibiotic therapy for infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) is a critical challenge in clinical medicine, balancing therapeutic efficacy against the risks of adverse effects and antimicrobial resistance. This narrative review synthesises current evidence and guidelines regarding antibiotic duration for MDR-GNB infections, emphasising bloodstream infections (BSI), hospital-acquired and ventilator-associated pneumonia (HAP/VAP), complicated urinary tract infections (cUTIs), and intra-abdominal infections (IAIs). Despite robust evidence supporting shorter courses (3–7 days) in uncomplicated infections caused by more susceptible pathogens, data guiding optimal therapy duration for MDR-GNB remain limited, particularly concerning carbapenem-resistant Enterobacterales (CRE), difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), and carbapenem-resistant Acinetobacter baumannii (CRAB). Current guidelines from major societies, including IDSA and ESCMID, provide explicit antimicrobial selection advice but notably lack detailed recommendations on the duration of therapy. Existing studies demonstrate non-inferiority of shorter versus longer antibiotic courses in specific clinical contexts but frequently exclude critically ill patients or those infected with non-fermenting MDR pathogens. Individualised duration decisions must integrate clinical response, patient immunologic status, infection severity, source control adequacy, and pharmacologic considerations. Significant knowledge gaps persist, underscoring the urgent need for targeted research, particularly randomised controlled trials assessing optimal antibiotic duration for the most challenging MDR-GNB infections. Clinicians must navigate considerable uncertainty, relying on nuanced judgement and close monitoring to achieve successful outcomes while advancing antimicrobial stewardship goals. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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12 pages, 247 KiB  
Article
Restoring Control: Real-World Success with Imipenem–Relebactam in Critical MDR Infections—A Multicenter Observational Study
by Andrea Marino, Giuseppe Pipitone, Emmanuele Venanzi Rullo, Federica Cosentino, Rita Ippolito, Roberta Costa, Sara Bagarello, Ylenia Russotto, Chiara Iaria, Bruno Cacopardo and Giuseppe Nunnari
Pathogens 2025, 14(7), 685; https://doi.org/10.3390/pathogens14070685 - 11 Jul 2025
Viewed by 441
Abstract
Background: Multidrug-resistant (MDR) Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), present a growing global healthcare challenge, especially in critically ill populations. Imipenem–relebactam (I/R), a novel β-lactam/β-lactamase inhibitor combination, has shown efficacy in clinical trials, but [...] Read more.
Background: Multidrug-resistant (MDR) Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), present a growing global healthcare challenge, especially in critically ill populations. Imipenem–relebactam (I/R), a novel β-lactam/β-lactamase inhibitor combination, has shown efficacy in clinical trials, but real-world data remain limited. Methods: We conducted a multicenter, retrospective–prospective observational study across tertiary-care hospitals in Italy between January 2020 and May 2025. Adult patients (≥18 years) treated with I/R for ≥48 h for suspected or confirmed MDR Gram-negative infections were included. Primary endpoints were clinical success at the end of therapy and 30-day all-cause mortality. Secondary endpoints included microbiological eradication, recurrence, safety, and predictors of treatment failure. Statistical analysis involved descriptive methods and correlation analysis for mortality predictors. Results: Twenty-nine patients were included (median age 66 years; 58.6% ICU admission; 71.4% mechanical ventilation). Clinical success was achieved in 22/29 patients (75.9%), while 30-day mortality was 24.1% (7/29). The most common pathogen was Klebsiella pneumoniae (62.1%), with 41.4% of infections being polymicrobial. Microbiological eradication was confirmed in all the BSIs. Parenteral nutrition (p = 0.016), sepsis at presentation (p = 0.04), candidemia (p = 0.036), and arterial catheter use (p = 0.029) were significantly more frequent in non-survivors. Survivors showed significant reductions in CRP, PCT, and bilirubin at 48 h, while non-survivors did not. Parenteral nutrition (rho = 0.427, p = 0.023), sepsis (rho = 0.378, p = 0.043), and arterial catheter use (rho = 0.384, p = 0.04) were significantly correlated with mortality. Conclusions: In this Italian multicenter cohort of critically ill patients, imipenem–relebactam demonstrated high clinical success and acceptable mortality rates in the treatment of severe MDR Gram-negative infections, particularly those caused by KPC-producing K. pneumoniae. Early biomarker dynamics may aid in monitoring treatment response. Larger prospective studies are needed to confirm these findings and define optimal treatment strategies. Full article
8 pages, 618 KiB  
Case Report
The Use of Cefiderocol as Salvage Therapy in an Infant Receiving ECMO and Continuous Renal Replacement Therapy
by Stefania Mercadante, Costanza Tripiciano, Lorenza Romani, Matteo Di Nardo, Gabriella Bottari, Bianca Maria Goffredo, Raffaele Simeoli, Isabella Guzzo, Laura Lancella, Charalampos Antachopoulos and Maia De Luca
Antibiotics 2024, 13(1), 37; https://doi.org/10.3390/antibiotics13010037 - 30 Dec 2023
Cited by 6 | Viewed by 3061
Abstract
Background: Infections caused by antimicrobial-resistant (AMR) pathogens are increasing worldwide, representing a serious global public health issue with high morbidity and mortality rates The treatment of Pseudomonas aeruginosa (PA) infections has become a significant challenge due to its ability to develop resistance to [...] Read more.
Background: Infections caused by antimicrobial-resistant (AMR) pathogens are increasing worldwide, representing a serious global public health issue with high morbidity and mortality rates The treatment of Pseudomonas aeruginosa (PA) infections has become a significant challenge due to its ability to develop resistance to many of the currently available antibiotics, especially in intensive care unit (ICU) settings. Among the very few therapeutic lines available against extensively drug-resistant (XDR)-PA and/or with difficult-to-treat resistance (DTR)-PA, cefiderocol is an injectable siderophore cephalosporin not licensed for use in pediatric patients. There are only a few case reports and two ongoing trials describing the administration of this cephalosporin in infants. Case presentation: This report describes the case of a critically ill 8-month-old girl affected by ventilator-associated pneumonia (VAP) infection complicated by bloodstream infection (BSI) sustained by VIM-producing PA. She was treated with cefiderocol as a salvage therapy during ECMO and CRRT support. Conclusions: In healthcare settings, treating multidrug-resistant, Gram-negative bacteria poses a serious challenge, especially in pediatric patients. Our findings suggest that cefiderocol can be considered as an off-label rescue therapy in selected pediatric cases. Full article
(This article belongs to the Special Issue Antimicrobials Agents: Latest Advances and Prospects)
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19 pages, 6795 KiB  
Article
Deforestation and Its Effect on Surface Albedo and Weather Patterns
by Dalia Lizeth Santos Orozco, José Ariel Ruiz Corral, Raymundo Federico Villavicencio García and Víctor Manuel Rodríguez Moreno
Sustainability 2023, 15(15), 11531; https://doi.org/10.3390/su151511531 - 26 Jul 2023
Cited by 3 | Viewed by 5962
Abstract
Deforestation is an important environmental problem and a key promoter of regional climate change through modifying the surface albedo. The objective of this research was to characterize the impact of deforestation and land use changes on surface albedo (α) and climate patterns in [...] Read more.
Deforestation is an important environmental problem and a key promoter of regional climate change through modifying the surface albedo. The objective of this research was to characterize the impact of deforestation and land use changes on surface albedo (α) and climate patterns in a tropical highland region of Mexico, between the years 2014 and 2021. The main land cover types are coniferous forests (CF), oak and gallery woodlands (OGW), and annual agriculture (AA), which represent more than 88% of the regional territory. We used 2014 and 2021 Landsat 8 OLI images with topographic and atmospheric correction in order to develop an inventory of albedo values for each land cover type in both time scenarios. Albedo images were generated by using the equation proposed by Liang in 2001, which is based on the reflectance of the bands 2, 3, 4, 5, and 7. Differences in albedo values were calculated between the years 2014 and 2021, and those differences were correlated with variations in climate parameters, for which we used climate data derived from the WRF model. In addition, the different land use changes found were classified in terms of triggers for increasing or decreasing surface albedo. We used the Mann–Whitney U Test to compare the 2021 − 2014 climatic deviations in two samples: Sample A, which included sites without albedo change in 2021; and Sample B, including sites with albedo change in 2021. Results showed that between 2014 and 2021, at least 38 events of land use change or deforestation occurred, with albedo increments between 1 and 11%, which triggered an average increment of 2.16% (p < 0.01; Mann–Whitney U Test) of the regional surface albedo in comparison to the 2014 scenario. In this period, the albedo for CF, OGW, and AA also increased significantly (p < 0.001; Mann–Whitney U Test) by +79, +12, and +9%, respectively. In addition, the regional albedo increment was found to be significant and negatively correlated (p < 0.01 Spearman’s coefficient) with relative humidity (RH), maximum temperature (Tmax), and minimum temperature (Tmin), and correlated (p < 0.01) positively with diurnal temperature range (DTR). The Mann–Whitney U Test revealed that 2021 climatic variations in Sample B sites are statistically different (p < 0.05) to 2021 climatic variations in Sample A sites, which demonstrates that albedo changes are linked to a decrease in minimum temperature and relative humidity and an increase in DTR. Conversion of CF and OGW into AA, perennial agriculture (PA), or grassland (GR) always yielded an albedo increment, whilst the conversion of AA to irrigation agriculture (IA) or PA triggered a decrease in albedo, and finally, the pass from GR or AA to protected agriculture (PA) caused albedo to increase or decrease, depending on the greenhouse covers materials. Reducing deforestation of CF and OGW, conversion of AA or GR into PA, and selecting adequate greenhouse covers could help to mitigate regional climate change. Full article
(This article belongs to the Special Issue Global Climate Change: What Are We Doing to Mitigate Its Effects)
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19 pages, 345 KiB  
Review
The Hidden Cost of COVID-19: Focus on Antimicrobial Resistance in Bloodstream Infections
by Giulia Micheli, Flavio Sangiorgi, Francesca Catania, Marta Chiuchiarelli, Federico Frondizi, Eleonora Taddei and Rita Murri
Microorganisms 2023, 11(5), 1299; https://doi.org/10.3390/microorganisms11051299 - 16 May 2023
Cited by 21 | Viewed by 3231
Abstract
Antibiotic resistance is one of the greatest growing public health threats and a worldwide priority. According to the WHO, drug-resistant diseases may cause 10 million deaths a year by 2050 and have a substantial impact on the global economy, driving up to 24 [...] Read more.
Antibiotic resistance is one of the greatest growing public health threats and a worldwide priority. According to the WHO, drug-resistant diseases may cause 10 million deaths a year by 2050 and have a substantial impact on the global economy, driving up to 24 million people into poverty. The ongoing COVID-19 pandemic has exposed the fallacies and vulnerability of healthcare systems worldwide, displacing resources from existing programs and reducing funding for antimicrobial resistance (AMR) fighting efforts. Moreover, as already seen for other respiratory viruses, such as flu, COVID-19 is often associated with superinfections, prolonged hospital stays, and increased ICU admissions, further aggravating healthcare disruption. These events are accompanied by widespread antibiotic use, misuse, and inappropriate compliance with standard procedures with a potential long-term impact on AMR. Still, COVID-19-related measures such as increasing personal and environmental hygiene, social distancing, and decreasing hospital admissions could theoretically help the AMR cause. However, several reports have shown increased antimicrobial resistance during the COVID-19 pandemic. This narrative review focuses on this “twindemic”, assessing the current knowledge of antimicrobial resistance in the COVID-19 era with a focus on bloodstream infections and provides insights into the lessons learned in the COVID-19 field that could be applied to antimicrobial stewardship initiatives. Full article
10 pages, 272 KiB  
Article
Pharmacokinetic/Pharmacodynamic Analysis of Continuous-Infusion Fosfomycin in Combination with Extended-Infusion Cefiderocol or Continuous-Infusion Ceftazidime-Avibactam in a Case Series of Difficult-to-Treat Resistant Pseudomonas aeruginosa Bloodstream Infections and/or Hospital-Acquired Pneumonia
by Milo Gatti, Maddalena Giannella, Matteo Rinaldi, Paolo Gaibani, Pierluigi Viale and Federico Pea
Antibiotics 2022, 11(12), 1739; https://doi.org/10.3390/antibiotics11121739 - 2 Dec 2022
Cited by 28 | Viewed by 3274
Abstract
Objectives: To perform a pharmacokinetic/pharmacodynamic (PK/PD) analysis of continuous-infusion (CI) fosfomycin combined with extended-infusion (EI) cefiderocol or CI ceftazidime-avibactam in a case series of severe difficult-to-treat Pseudomonas aeruginosa (DTR-PA) infections. Methods: A single-center retrospective study of patients who were treated with CI fosfomycin [...] Read more.
Objectives: To perform a pharmacokinetic/pharmacodynamic (PK/PD) analysis of continuous-infusion (CI) fosfomycin combined with extended-infusion (EI) cefiderocol or CI ceftazidime-avibactam in a case series of severe difficult-to-treat Pseudomonas aeruginosa (DTR-PA) infections. Methods: A single-center retrospective study of patients who were treated with CI fosfomycin plus EI cefiderocol or CI ceftazidime-avibactam for severe DTR-PA infections and who underwent therapeutic drug monitoring (TDM), from 1 September 2021 to 30 June 2022 was performed. Concentrations were measured at steady-state (Css) for CI fosfomycin and ceftazidime-avibactam and at trough (Cmin) for EI cefiderocol. Joint PK/PD targets of combination therapy were analyzed (thresholds: area-under-the curve to minimum inhibitory concentration (AUC/MIC) ratio > 40.8 for fosfomycin; ceftazidime Css/MIC ratio ≥ 4 coupled with avibactam Css > 4 mg/L for ceftazidime-avibactam; Cmin/MIC ratio ≥ 4 for cefiderocol). Joint PK/PD targets of the combination therapy were analyzed and defined as optimal when both were achieved, quasi-optimal if only one of the two was achieved, and suboptimal if none of the two was achieved). The relationship between joint PK/PD target attainment and microbiological response was assessed. Results: Six patients (three pneumonia, two BSI + pneumonia, and one BSI) were included. The joint PK/PD targets were optimal in four cases and quasi-optimal in the other two. Microbiological eradication (ME) occurred in 4/4 of patients with optimal joint PK/PD targets and in one of the two patients with quasi-optimal joint PK/PD targets. Conclusions: Attaining optimal joint PK/PD targets with a combo-therapy of CI fosfomycin plus EI cefiderocol or CI ceftazidime-avibactam could represent an effective strategy for granting favorable microbiological outcomes in patients with DTR-PA pneumonia and/or BSI. Full article
18 pages, 4319 KiB  
Article
Activation of Drosophila melanogaster TRPA1 Isoforms by Citronellal and Menthol
by Brett Boonen, Justyna B. Startek, Alina Milici, Alejandro López-Requena, Melissa Beelen, Patrick Callaerts and Karel Talavera
Int. J. Mol. Sci. 2021, 22(20), 10997; https://doi.org/10.3390/ijms222010997 - 12 Oct 2021
Cited by 8 | Viewed by 3650
Abstract
Background: The transient receptor potential ankyrin 1 (TRPA1) cation channels function as broadly-tuned sensors of noxious chemicals in many species. Recent studies identified four functional TRPA1 isoforms in Drosophila melanogaster (dTRPA1(A) to (D)), but their responses to non-electrophilic chemicals are yet to be [...] Read more.
Background: The transient receptor potential ankyrin 1 (TRPA1) cation channels function as broadly-tuned sensors of noxious chemicals in many species. Recent studies identified four functional TRPA1 isoforms in Drosophila melanogaster (dTRPA1(A) to (D)), but their responses to non-electrophilic chemicals are yet to be fully characterized. Methods: We determined the behavioral responses of adult flies to the mammalian TRPA1 non-electrophilic activators citronellal and menthol, and characterized the effects of these compounds on all four dTRPA1 channel isoforms using intracellular Ca2+ imaging and whole-cell patch-clamp recordings. Results: Wild type flies avoided citronellal and menthol in an olfactory test and this behavior was reduced in dTrpA1 mutant flies. Both compounds activate all dTRPA1 isoforms in the heterologous expression system HEK293T, with the following sensitivity series: dTRPA1(C) = dTRPA1(D) > dTRPA1(A) ≫ dTRPA1(B) for citronellal and dTRPA1(A) > dTRPA1(D) > dTRPA1(C) > dTRPA1(B) for menthol. Conclusions: dTrpA1 was required for the normal avoidance of Drosophila melanogaster towards citronellal and menthol. All dTRPA1 isoforms are activated by both compounds, but the dTRPA1(B) is consistently the least sensitive. We discuss how these findings may guide further studies on the physiological roles and the structural bases of chemical sensitivity of TRPA1 channels. Full article
(This article belongs to the Special Issue TRP Channels)
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