Seven-day antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients: toward a new paradigm.

PURPOSE: Data on short courses of antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients are limited. The aim of the study was to describe and compare the frequency of bacteremia relapse, 30-day overall and infection-related mortality, Clostridiodes difficile infection and length of hospital stay since bacteremia among those who received antibiotic therapy for 7 or 14 days. METHODS: This is a multicenter, prospective, observational cohort study in adult high-risk neutropenic patients with hematologic malignancies or hematopoietic stem cell transplant and monomicrobial Enterobacterales bacteremia. They received appropriate empirical antibiotic therapy, had a clinical response within 7 days, and infection source control. Clinical, epidemiological and outcomes variables were compared based on 7 or 14 days of AT. RESULTS: Two hundred patients were included (100, 7-day antibiotic therapy; 100, 14-day antibiotic therapy). Escherichia coli was the pathogen most frequently isolated (47.5%), followed by Klebsiella sp. (40.5%). Among those patients that received 7-day vs. 14-day antibiotic course, a clinical source of bacteremia was found in 54% vs. 57% (p = 0.66), multidrug-resistant Enterobacterales isolates in 28% vs. 30% (p = 0.75), and 40% vs. 47% (p = 0.31) received combined empirical antibiotic therapy. Overall mortality was 3% vs. 1% (p = 0.62), in no case related to infection; bacteremia relapse was 7% vs. 2% (p = 0.17), and length of hospital stay since bacteremia had a median of 9 days (IQR: 7-15) vs. 14 days (IQR: 13-22) (p = < 0.001). CONCLUSIONS: These data suggest that seven-day antibiotic therapy might be adequate for patients with high-risk neutropenia and Enterobacterales bacteremia, who receive appropriate empirical therapy, with clinical response and infection source control.

Effects of pH on the Pathogenicity of Escherichia coli and Klebsiella pneumoniae on the Kidney: In Vitro and In Vivo Studies.

Urine pH reflects the functional integrity of the body and may influence the virulence of uropathogenic Escherichia coli and Klebsiella pneumoniae, the main causes of urinary tract infections (UTIs). This study evaluated the effects of acidic pH on the pathogenicity of uropathogenic E. coli and K. pneumoniae strains, in vitro and in vivo. Four uropathogenic E. coli and four K. pneumoniae strains were used. Biofilm formation, growth competition indices, motility, and adhesion and invasion of human renal cells were analyzed in media with acidic, neutral, and alkaline pH. A murine lower UTI model was used, with urine adjusted to acidic, neutral, or alkaline pH. At acidic pH, E. coli and K. pneumoniae exhibited higher bacterial concentrations in the kidneys and systemic symptoms, including bacteremia. Alkaline urine pH did not affect bacterial concentrations of any strain. In mice with UTIs caused by E. coli Nu14 and K. pneumoniae HUVR42 and acidic urine pH, histopathological studies of the kidneys showed acute inflammation affecting the urothelium and renal parenchyma, which are traits of acute pyelonephritis. These results indicate that acidic pH could increase the pathogenicity of E. coli and K. pneumoniae in murine models of lower UTI, promoting renal infection and acute inflammation.

Engineering of Thermoelectric Composites Based on Silver Selenide in Aqueous Solution and Ambient Temperature.

The direct, solid state, and reversible conversion between heat and electricity using thermoelectric devices finds numerous potential uses, especially around room temperature. However, the relatively high material processing cost limits their real applications. Silver selenide (Ag2Se) is one of the very few n-type thermoelectric (TE) materials for room-temperature applications. Herein, we report a room temperature, fast, and aqueous-phase synthesis approach to produce Ag2Se, which can be extended to other metal chalcogenides. These materials reach TE figures of merit (zT) of up to 0.76 at 380 K. To improve these values, bismuth sulfide (Bi2S3) particles also prepared in an aqueous solution are incorporated into the Ag2Se matrix. In this way, a series of Ag2Se/Bi2S3 composites with Bi2S3 wt % of 0.5, 1.0, and 1.5 are prepared by solution blending and hot-press sintering. The presence of Bi2S3 significantly improves the Seebeck coefficient and power factor while at the same time decreasing the thermal conductivity with no apparent drop in electrical conductivity. Thus, a maximum zT value of 0.96 is achieved in the composites with 1.0 wt % Bi2S3 at 370 K. Furthermore, a high average zT value (zTave) of 0.93 in the 300-390 K range is demonstrated.

Dilute-and-shoot approach for the high-throughput LC-MS/MS determination of illicit drugs in the field of wastewater-based epidemiology.

The determination of illicit drugs in urban influent wastewater (IWW) enables the monitoring of spatial and temporal drug usage trends and assessment of community lifestyle habits. The increasing number of wastewater surveillance studies has emphasized the necessity for the development of rapid, high-throughput methods that maintain high quality data. This work evaluates the use of a dilute-and-shoot methodology, based on direct injection (DI) of centrifuged samples, as an alternative approach to the widely applied sample pre-treatment based on solid-phase extraction, for the liquid chromatography-tandem mass spectrometry determination of seven widely consumed illicit drugs and their metabolites in IWW (amphetamine; cocaine metabolite, benzoylecgonine; ketamine; 3,4-methylenedioxymethamphetamine (MDMA); methamphetamine; cannabis metabolite, 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THCCOOH); heroin metabolite, 6-acetylmorphine (6-MAM)). Comparison of both approaches in terms of matrix effects, sensitivity and accuracy, demonstrates the DI method suitability to correctly quantify these analytes in IWW, with a limit of quantification lower than 30 ng L-1 for most compounds. After validation of the method and participation in an interlaboratory exercise, the DI method was applied to the analysis of 54 IWW samples collected from different Spanish wastewater treatment plants. Additionally, quality controls were incorporated in each analysis batch to support the DI method applicability and robustness. The use of a 10 µL-DI reduces time-consuming sample preparation, analysis time and measurement uncertainty. Moreover, it supports green chemistry by reducing the consumption of organic solvents and it facilitates logistics by collecting, transporting, and storing less sample volume. The methodology is therefore especially appropriate for monitoring illicit drugs in large wastewater-based epidemiology sampling campaigns or when fast near real-time results are needed.

Increased Severity of Mycoplasma pneumoniae Infections in Spanish Children.

BACKGROUND: Since the end of 2023, an elevated incidence and severity of Mycoplasma pneumoniae infections among children in Asia has been noted. Subsequently, this trend was observed in several European countries although limited data are currently available. We conducted a national study to delineate the ongoing M. pneumoniae outbreak in our country. METHODS: A multicenter retrospective observational study was conducted across 32 hospitals in Spain, encompassing patients under 18 years old hospitalized for M. pneumoniae infection from January 2023 to March 2024. Infection was confirmed by positive polymerase chain reaction and/or by 2 serological tests. RESULTS: A total of 623 children were included, with 79% of cases diagnosed in the final 3 months of the study period. Pneumonia was the most common diagnosis (87%). Respiratory symptoms were present in 97% of cases, with 62% requiring oxygen supplementation and 14% requiring admission to the pediatric intensive care unit (PICU). Risk factors for PICU admission included the presence of neurological symptoms, hypoxemia and a history of prematurity. Children admitted to the PICU exhibited significantly higher neutrophil counts upon admission. CONCLUSIONS: We have observed a notable increase in hospital admissions, including PICU support by up to 14%, due to M. pneumoniae infection in our country since November 2023, indicative of a more severe clinical course associated with this pathogen.

Solution-Processed, Surface-Engineered, Polycrystalline CdSe-SnSe Exhibiting Low Thermal Conductivity.

In recent years, solution processes have gained considerable traction as a cost-effective and scalable method to produce high-performance thermoelectric materials. The process entails a series of critical steps: synthesis, purification, thermal treatments, and consolidation, each playing a pivotal role in determining performance, stability, and reproducibility. We have noticed a need for more comprehensive details for each of the described steps in most published works. Recognizing the significance of detailed synthetic protocols, we describe here the approach used to synthesize and characterize one of the highest-performing polycrystalline p-type SnSe. In particular, we report the synthesis of SnSe particles in water and the subsequent surface treatment with CdSe molecular complexes that yields CdSe-SnSe nanocomposites upon consolidation. Moreover, the surface treatment inhibits grain growth through Zenner pinning of secondary phase CdSe nanoparticles and enhances defect formation at different length scales. The enhanced complexity in the CdSe-SnSe nanocomposite microstructure with respect to SnSe promotes phonon scattering and thereby significantly reduces the thermal conductivity. Such surface engineering provides opportunities in solution processing for introducing and controlling defects, making it possible to optimize the transport properties and attain a high thermoelectric figure of merit.

Nanocrystal Assemblies: Current Advances and Open Problems.

We explore the potential of nanocrystals (a term used equivalently to nanoparticles) as building blocks for nanomaterials, and the current advances and open challenges for fundamental science developments and applications. Nanocrystal assemblies are inherently multiscale, and the generation of revolutionary material properties requires a precise understanding of the relationship between structure and function, the former being determined by classical effects and the latter often by quantum effects. With an emphasis on theory and computation, we discuss challenges that hamper current assembly strategies and to what extent nanocrystal assemblies represent thermodynamic equilibrium or kinetically trapped metastable states. We also examine dynamic effects and optimization of assembly protocols. Finally, we discuss promising material functions and examples of their realization with nanocrystal assemblies.

Efficacy of Tamoxifen Metabolites in Combination with Colistin and Tigecycline in Experimental Murine Models of Escherichia coli and Acinetobacter baumannii.

This study aimed to evaluate the potential of tamoxifen and N-desmethyltamoxifen metabolites as therapeutic agents against multidrug-resistant Escherichia coli and Acinetobacter baumannii, using a repurposing approach to shorten the time required to obtain a new effective treatment against multidrug-resistant bacterial infections. Characterisation and virulence studies were conducted on E. coli (colistin-susceptible C1-7-LE and colistin-resistant MCR-1+) and A. baumannii (tigecycline-susceptible Ab#9 and tigecycline-resistant Ab#186) strains. The efficacy of the metabolite mix (33.3% each) and N-desmethyltamoxifen in combination with colistimethate sodium (CMS) or tigecycline was evaluated in experimental models in mice. In the pneumonia model, N-desmethyltamoxifen exhibited significant efficacy against Ab#9 and both E. coli strains, especially E. coli MCR-1+ (-2.86 log10 CFU/g lungs, -5.88 log10 CFU/mL blood, and -50% mortality), and against the Ab#186 strain when combined with CMS (-2.27 log10 CFU/g lungs, -2.73 log10 CFU/mL blood, and -40% mortality) or tigecycline (-3.27 log10 CFU/g lungs, -4.95 log10 CFU/mL blood, and -50% mortality). Moreover, the metabolite mix in combination with both antibiotics decreased the bacterial concentrations in the lungs and blood for both A. baumannii strains. In the sepsis model, the significant efficacy of the metabolite mix was restricted to the colistin-susceptible E. coli C1-7-LE strain (-3.32 log10 CFU/g lung, -6.06 log10 CFU/mL blood, and -79% mortality). N-desmethyltamoxifen could be a new therapeutic option in combination with CMS or tigecycline for combating multidrug-resistant GNB, specifically A. baumannii.

Querión de Celso: a propósito de un caso

Divulgamos el caso de Queiron de Celso del cuero cabelludo en una niña de 6 años, procedente de área urbana con antecedente patológico de tiña capitis. La tiña de la cabeza, tinea capitis o dermatofitosis es una infección fúngica causada por hongos, denominados «dermatofitos». El querión es una manifestación grave de tinea capitis que resulta de una intensa respuesta inmune a la infección y caracteriza por el desarrollo de una placa inflamatoria con pústulas, costras gruesas y/o drenaje.

We report the case of Queiron de Celso of the scalp in a 6-year-old girl from an urban area with a pathologic history of tinea capitis. Tinea capitis or dermatophytosis is a fungal infection caused by fungi called "dermatophytes". Kerion is a severe manifestation of tinea capitis resulting from an intense immune response to infection and characterized by the development of an inflammatory plaque with pustules, thick crusts and/or drainage.

Unveiling Crucial Chemical Processing Parameters Influencing the Performance of Solution-Processed Inorganic Thermoelectric Materials.

Production of thermoelectric materials from solution-processed particles involves the synthesis of particles, their purification and densification into pelletized material. Chemical changes that occur during each one of these steps render them performance determining. Particularly the purification steps, bypassed in conventional solid-state synthesis, are the cause for large discrepancies among similar solution-processed materials. In present work, the investigation focuses on a water-based surfactant free solution synthesis of SnSe, a highly relevant thermoelectric material. We show and rationalize that the number of leaching steps, purification solvent, annealing, and annealing atmosphere have significant influence on the Sn : Se ratio and impurity content in the powder. Such compositional changes that are undetectable by conventional characterization techniques lead to distinct consolidated materials with different types and concentration of defects. Additionally, the profound effect on their transport properties is demonstrated. We emphasize that understanding the chemistry and identifying key chemical species and their role throughout the process is paramount for optimizing material performance. Furthermore, we aim to demonstrate the necessity of comprehensive reporting of these steps as a standard practice to ensure material reproducibility.

Indoor Air Quality and Bioaerosols in Spanish University Classrooms.

A comprehensive study assessed indoor air quality parameters, focusing on relevant air pollutants such as particulate matter (PM10 and PM2.5), gaseous compounds (CO, CO2, formaldehyde, NO2) and volatile/semi-volatile organic chemicals, as well as respiratory viruses (including SARS-CoV-2), fungi and bacteria in Spanish university classrooms. Non-target screening strategies evaluated the presence of organic pollutants inside and outside the classrooms. Saliva samples from teachers and students were collected to explore correlations between respiratory viruses in the air and biological samples. Indoor results revealed the punctual exceedance of recommended guidelines for CO2, formaldehyde (HCHO), volatile organic compounds (TVOCs) and PM in the least naturally ventilated classrooms. Significant differences occurred between the classes, with the least ventilated one showing higher average concentrations of CO2, HCHO, NO2, PM10 and PM2.5. A respiratory virus (rhinovirus/enterovirus) was detected in the medium naturally ventilated classroom, although saliva samples tested negative. Suspect screening tentatively identified 65 substances indoors and over 200 outdoors, with approximately half reporting a high toxicological risk based on the Cramer rules. The study provides a comprehensive overview of indoor air quality, respiratory viruses and organic pollutants in university classrooms, highlighting the variations and potential health risks associated with ventilation differences.

Electron highways are cooler.

Reducing defects boosts room-temperature performance of a thermoelectric device.

Machine learning-based prediction of tear osmolarity for contact lens practice.

PURPOSE: This study addressed the utilisation of machine learning techniques to estimate tear osmolarity, a clinically significant yet challenging parameter to measure accurately. Elevated tear osmolarity has been observed in contact lens wearers and is associated with contact lens-induced dry eye, a common cause of discomfort leading to discontinuation of lens wear. METHODS: The study explored machine learning, regression and classification techniques to predict tear osmolarity using routine clinical parameters. The data set consisted of 175 participants, primarily healthy subjects eligible for soft contact lens wear. Various clinical assessments were performed, including symptom assessment with the Ocular Surface Disease Index and 5-Item Dry Eye Questionnaire (DEQ-5), tear meniscus height (TMH), tear osmolarity, non-invasive keratometric tear film break-up time (NIKBUT), ocular redness, corneal and conjunctival fluorescein staining and Meibomian glands loss. RESULTS: The results revealed that simple linear regression was insufficient for accurate osmolarity prediction. Instead, more advanced regression models achieved a moderate level of predictive power, explaining approximately 32% of the osmolarity variability. Notably, key predictors for osmolarity included NIKBUT, TMH, ocular redness, Meibomian gland coverage and the DEQ-5 questionnaire. In classification tasks, distinguishing between low (<299 mOsmol/L), medium (300-307 mOsmol/L) and high osmolarity (>308 mOsmol/L) levels yielded an accuracy of approximately 80%. Key parameters for classification were similar to those in regression models, emphasising the importance of NIKBUT, TMH, ocular redness, Meibomian glands coverage and the DEQ-5 questionnaire. CONCLUSIONS: This study highlights the potential benefits of integrating machine learning into contact lens research and practice. It suggests the clinical utility of assessing Meibomian glands and NIKBUT in contact lens fitting and follow-up visits. Machine learning models can optimise contact lens prescriptions and aid in early detection of conditions like dry eye, ultimately enhancing ocular health and the contact lens wearing experience.

High resolution mass spectrometry-based screening for the comprehensive investigation of organic micropollutants in surface water and wastewater from Pasto city, Colombian Andean highlands.

The complexity of the aquatic environment scenario, including the impact of urban wastewater, together with the huge number of potential hazardous compounds that may be present in waters, makes the comprehensive characterization of the samples an analytical challenge, particularly in relation to the presence of organic micropollutants (OMPs). Nowadays, the potential of high-resolution mass spectrometry (HRMS) for wide-scope screening in environmental samples is out of question. Considering the physicochemical characteristics of OMPs, the coupling of liquid (LC) and gas chromatography (GC) to HRMS is mandatory. In this work, we have explored the combined use of LC and GC coupled to Quadrupole-Time-of-Flight Mass Spectrometry (QTOF MS) for screening of surface water and wastewater samples from Pasto (Nariño), a town of the Colombian Andean highlands (average altitude 2527 m), located in an important agricultural area. The upper basin of the Pasto River is impacted by phytosanitary products used in different crops, whereas the domestic wastewater is directly discharged into the river without any treatment, enhancing the anthropogenic impact on the water quality. The OMP searching was made by target (standards available) and suspect (without standards) approaches, using home-made databases containing >2000 compounds. Up to 15 pesticides (7 insecticides, 6 fungicides and 2 herbicides) were identified in the sampling point of the Pasto River up to the town, while no pharmaceuticals were found at this site, illustrating the impact of agriculture practices. On the contrary, 14 pharmaceuticals (7 antibiotics and 3 analgesics, among others) were found in river samples collected in the middle and down to the town sites, revealing the impact of the urban population. Interestingly, some transformation products, including metabolites, such as carbofuran-3-hydroxy and 4-acetylamino antipyrine were identified in the screening. Based on these data, future monitoring will apply target quantitative LC-MS/MS methods for the most relevant compounds identified.

Acidic Urine pH and Clinical Outcome of Lower Urinary Tract Infection in Kidney Transplant Recipients Treated with Ciprofloxacin and Fosfomycin.

Different factors, including antimicrobial resistance, may diminish the effectiveness of antibiotic therapy, challenging the management of post-transplant urinary tract infection (UTI). The association of acidic urine pH with microbiological and clinical outcomes was evaluated after fosfomycin or ciprofloxacin therapy in 184 kidney transplant recipients (KTRs) with UTI episodes by Escherichia coli (N = 115) and Klebsiella pneumoniae (N = 69). Initial urine pH, antimicrobial therapy, and clinical and microbiological outcomes, and one- and six-month follow-up were assessed. Fosfomycin was prescribed in 88 (76.5%) E. coli and 46 (66.7%) K. pneumoniae UTI episodes in the total cohort. When the urine pH ≤ 6, fosfomycin was prescribed in 60 (52.2%) E. coli and 29 (42.0%) K. pneumoniae. Initial urine pH ≤ 6 in E. coli UTI was associated with symptomatic episodes (8/60 vs. 0/55, p = 0.04) at one-month follow-up, with a similar trend in those patients receiving fosfomycin (7/47 vs. 0/41, p = 0.09). Acidic urine pH was not associated with microbiological or clinical cure in K. pneumoniae UTI. At pH 5, the ciprofloxacin MIC90 increased from 8 to >8 mg/L in E. coli and from 4 to >8 mg/L in K. pneumoniae. At pH 5, the fosfomycin MIC90 decreased from 8 to 4 mg/L in E. coli and from 512 to 128 mg/L in K. pneumoniae. Acidic urine is not associated with the microbiological efficacy of fosfomycin and ciprofloxacin in KTRs with UTI, but it is associated with symptomatic UTI episodes at one-month follow-up in E. coli episodes.

Endoscopic management of pancreatic collections. Endoscopic Ultrasound Group from the Spanish Society of Digestive Endoscopy (GSEED-USE) Clinical Guidelines.

Acute pancreatitis is associated with significant morbidity and mortality. It can develop complications such as fluid collections and necrosis. Infection of necrosis occurs in about 20-40% of patients with severe acute pancreatitis, and is associated with organ failure and worse prognosis. In the past years, the treatment of pancreatic collections has shifted from open surgery to minimally invasive techniques, such as endoscopic ultrasound guided drainage. These guidelines from a selection of experts among the Endoscopic Ultrasound Group from the Spanish Society of Gastrointestinal Endoscopy (GSEED-USE) have the purpose to provide advice on the management of pancreatic collections based on a thorough review of the available scientific evidence. It also reflects the experience and clinical practice of the authors, who are advanced endoscopists or clinical pancreatologists with extensive experience in managing patients with acute pancreatitis.

Navigating job satisfaction in family firms during crisis.

Occupational health is one of the aspects significantly affected during crisis periods. It is essential to learn about the factors that improve organizational capacity in coping with such shocks. This study investigates how the working environment of a family business influences job satisfaction during crises. Conducting a survey with 516 employees at the peak of the pandemic, the research utilizes structural equation analysis, revealing that family business environments can mitigate burnout, enhance affective commitment, and consequently, boost job satisfaction. The study highlights the need to manage burnout and utilize resources, such as employee commitment, for family firms to sustain job satisfaction amidst disruptions. It deepens the comprehension of family businesses' crisis response, emphasizing the significance of human resource commitment and management. The investigation illuminates the dynamic interplay between the work environment, employee well-being, and organizational resilience, providing valuable insights for both theoretical understanding and practical application.

Muscle mass loss measured with portable ultrasound in hospitalized older adults: The ECOSARC study.

OBJECTIVES: The main objective was to analyze the evolution of muscle of the Quadriceps Rectus Femoris (QRF) between admission and discharge, in older adults hospitalized with an acute medical disease in Acute Geriatric Units (AGUs). DESIGN: Prospective multicentric observational cohort study. SETTING: Seven AGUs from University Hospitals in Spain. PARTICIPANTS: Hospitalized adults ≥ 70 years old, able to ambulate and without severe dementia. MEASUREMENTS: Ultrasound measurements of QRF were acquired at 2/3 distal between anterior-superior iliac spine and patella in both legs by trained Geriatricians. Ultrasound Chison model ECO2 was used. QRF area, thickness, edema, echogenicity, and fasciculations were measured. RESULTS: From the complete sample (n = 143), in 45 (31.5%) participants, ultrasound images were classified as non-valid by an expert radiologist. Mean age was 87.8 (SD 5.4). Mean hospital stay 7.6 days (SD 4.3). From those with valid images, 36 (49.3%), 2 (2.7%), and 35 (47.9%) presented a decrease, equal values, or an increase in QRF area from baseline to discharge, respectively, and 37 (50.0%), 2 (2.7%), and 35 (47.3%) presented a decrease, equal values, or an increase in QRF thickness, respectively. 26 (35.6%) presented a decrease in more than 0.2 cm2 of QRF area, and 23 (31.1%) a decrease in more than 0.1 cm of QRF thickness. Only 4 (5.4%) patients presented new edema, while 13 (17.6%) worsened echogenicity. CONCLUSION: One third of older adults develop significant muscle loss during a hospitalization for acute medical diseases. TRIAL REGISTRATION NUMBER: NCT05113758.

A Suitable HPLC-MS/MS Methodology for the Detection of Oxytetracycline, Enrofloxacin, and Sulfachloropyridazine Residues in Lettuce Plants.

Oxytetracycline (OTC), enrofloxacin (EFX), and sulfachloropyridazine (SCP) are critically important antimicrobials (AMs) in both human and veterinary medicine, where they are widely used in farm animals. Lettuce has become a matrix of choice for studying the presence of residues of these AMs in plants, as the concentrations of residues detected in lettuce can range from ng to mg. While several analytical methodologies have been developed for the purpose of detecting AMs in lettuce, these currently do not detect both the parent compound and its active metabolites or epimers, such as in the case of ciprofloxacin (CFX) and 4-epi-oxitetracycline (4-epi-OTC), which also pose a risk to public health and the environment due to their AM activity. In light of this situation, this work proposes an analytical method that was developed specifically to allow for the detection of OTC, 4-epi-OTC, EFX, CFX, and SCP in a lettuce matrix. This method uses acetonitrile, methanol, 0.5% formic acid, and McIlvaine-EDTA buffer as extraction solvents, and dispersive solid-phase extraction (dSPE) for the clean-up. The analytes were detected using a liquid chromatography technique coupled to mass spectrometry (HPLC-MS/MS). Parameters such as the specificity, linearity, recovery, precision, limit of detection, and limit (LOD) of quantification (LOQ) were calculated according to the recommendations established in the European Union decision 2021/808/EC and VICH GL2: Validation of analytical procedures. The LOQ for the analytes OTC, 4-epi-OTC, CFX, and SCP was 1 µg·kg-1, whereas for EFX, it was 5 µg·kg-1 dry weight. All calibration curves showed a coefficient of determination (R2) of >0.99. The recovery levels ranged from 93.0 to 110.5% and the precision met the acceptance criteria, with a coefficient of variation of ≤14.02%. Therefore, this methodology allows for the precise and reliable detection and quantification of these analytes. The analysis of commercial samples confirmed the suitability of this method.

Ceftazidime-Avibactam Improves Outcomes in High-Risk Neutropenic Patients with Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales Bacteremia.

Few studies have evaluated the efficacy of ceftazidime-avibactam (CA) for Klebsiella pneumoniae carbapenemase-producing Enterobacterales bacteremia (KPC-PEB) in high-risk neutropenic patients. This is a prospective multicenter observational study in high-risk neutropenic patients with multi-drug resistant Enterobacterales bacteremia. They were compared according to the resistance mechanism and definitive treatment provided: KPC-CPE treated with CA (G1), KPC-CPE treated with other antibiotics (G2), and patients with ESBL-producing Enterobacterales bacteremia who received appropriate definitive therapy (G3). Thirty-day mortality was evaluated using a logistic regression model, and survival was analyzed with Kaplan-Meier curves. A total of 238 patients were included: 18 (G1), 52 (G2), and 168 (G3). Klebsiella spp. (60.9%) and Escherichia coli (26.4%) were the Enterobacterales most frequently isolated, and 71% of the bacteremias had a clinical source. The resistance profile between G1 and G2 was colistin 35.3% vs. 36.5%, amikacin 16.7% vs. 40.4%, and tigeclycline 11.1% vs. 19.2%. The antibiotics prescribed in combination with G2 were carbapenems, colistin, amikacin, fosfomycin, tigecycline, and fluoroquinolones. Seven-day clinical response in G1 vs. G2 vs. G3 was 94.4% vs. 42.3% vs. 82.7%, respectively (p < 0.001). Thirty-day overall mortality in G1 vs. G2 vs. G3 was 22.2% vs. 53.8% vs. 11.9%, respectively (p < 0.001), and infection-related mortality was 5.5% vs. 51.9% vs. 7.7% (p < 0.001). The independent risk factors for mortality were Pitt score > 4: OR 3.63, 95% CI, 1.18-11.14 (p = 0.025) and KPC-PEB treated with other antibiotics: OR 8.85, 95% CI, 2.58-30.33 (p = 0.001), while 7-day clinical response was a protective factor for survival: OR 0.02, 95% CI, 0.01-0.08 (p < 0.001). High-risk neutropenic patients with KPC-CPE treated with CA had an outcome similar to those treated for ESBL-producing Enterobacterales, with higher 7-day clinical response and lower overall and infection-related mortality than those treated with other antibiotics. In view of these data, CA may be considered the preferred therapeutic option for KPC-PEB in high-risk neutropenic patients.