Antibiotics-Basel最新文献

Background/Objectives: Animals destined for human consumption play a key role in potentially transmitting bacteria carrying antibiotic resistance genes. However, there is limited knowledge about the carriage of antibiotic-resistant bacteria in native breeds. We aimed to characterize the phenotypic profiles and antibiotic resistance genes in Escherichia coli isolated from bovines, including three native Portuguese bovine breeds. Methods: Forty-nine E. coli isolates were selected from 640 fecal samples pooled by age group (eight adult or eight calf samples) from each farm, representing both dairy cattle raised in intensive systems and meat cattle raised in extensive systems in Northern Portugal. The presumptive E. coli colonies plated onto MacConkey agar were confirmed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The antibiotic resistance profiles were screened by antimicrobial susceptibility testing (EUCAST/CLSI guidelines), and the antibiotic resistance genes by PCR. Results: Most isolates showed resistance to ampicillin (69%), tetracycline (57%), gentamicin (55%), and trimethoprim + sulfamethoxazole (53%), with no resistance to imipenem. Resistance to at least one antibiotic was found in 92% of isolates, while 59% exhibited multidrug resistance. Most calf isolates, including those from native breeds, showed a multidrug-resistant phenotype. Among the adults, this was only observed in Holstein-Friesian and Barrosã cattle. None of the Holstein-Friesian isolates were susceptible to all the tested antibiotics. ESBL-producing E. coli was identified in 39% of isolates, including those from Holstein-Friesian calves and adults, Cachena calves and Minhota adults. The sul2 gene was detected in 69% of isolates, followed by bla_CTX-M (45%), aac(3')-IV (41%), and aac(6')-Ib-cr (31%), with a higher prevalence in adults. Conclusions: This pioneering study highlights the concerning presence of multidrug-resistant E. coli in native Portuguese cattle breeds.

Background: L2 is formed by combining the pheromone of Streptococcus agalactiae (S. agalactiae) and a cell-penetrating peptide (CPP) with cell-penetrating selectivity. L2 has more significant penetration and better specificity for killing S. agalactiae. However, the production of AMPs by chemical synthesis is always a challenge because of the production cost.

Methods: This study was devoted to the heterologous expression of the cell-penetrating peptide L2 in Pichia pastoris using SUMO and a short acidic fusion tag as fusion partners, and the high-density expression of SUMO-L2 was achieved in a 5 L fermenter.

Results: The results showed that SUMO-L2 expression in the 5 L fermenter reached 629 mg/L. The antibacterial activity of recombinant L2 was examined; the minimum inhibitory concentration (MICs) and minimum bactericidal concentration (MBCs) of purified L2 were 4-8 μg/mL and 8-16 μg/mL against S. agalactiae after 84 h of lysis with 50% formic acid.

Conclusions: The findings suggest that SUMO is a suitable fusion tag to express cell-penetrating peptide L2.

Introduction: Despite the advancements in diagnostic methods and antibiotic treatment, empyema is a critical respiratory infection, showing a high mortality rate of 10-25%. Patients and Methods: To evaluate the bacterial etiology and prognostic factors of acute empyema, we conducted this long-term retrospective cohort study at our institute between 2008 and 2022. Results: A total of 80 patients were enrolled in this cohort. The median age was 72 years (range 19 to 93 years), and 61 (76%) were male. The most common underlying disease was malignancy, seen in 28 (35%). The mean Charlson comorbidity index (CCI) was 2.7 (±2.4). The 30-day and in-hospital mortality were 9 (11%) and 15 (19%), respectively. Univariate analysis revealed that healthcare-associated infection, inappropriate treatment, high CCI score, performance status (PS) of 2-4, and isolation of potentially drug-resistant (PDR) pathogens were poor prognostic factors. Finally, multivariate analysis showed that high CCI score (p = 0.009) and isolation of PDR pathogens (p = 0.011) were independent poor prognostic factors for in-hospital death in acute empyema. Conclusions: We found that higher CCI scores and isolation of PDR pathogens were independent poor prognostic factors for in-hospital mortality among empyema patients.

Background. Urinary tract infections (UTIs) and asymptomatic bacteriurias (ABU) represent a large field of interest for antimicrobial stewardship programmes especially after 2020 EUCAST update in antimicrobial susceptibility testing interpretation and the possible related increase in carbapenems' prescription rate. The aim of this study was to evaluate the impact of the 2020 EUCAST update on antibiotic prescription in UTI due to Pseudomonas aeruginosa organism and their characteristics. Methods. A retrospective observational study. We enrolled all the patients with P. aeruginosa isolation from urine, admitted to our hospital from 2018 to 2021. We compared demographic, clinical, and microbiological characteristics and treatment between cases before 2020 EUCAST update (period A, 2018-2019) and after it (period B, 2020-2021). Results. A total of 643 cases was analysed, 278 in period A and 365 in period B; 65% were ABU. Carbapenems' prescription rate significantly increased in period B when considering ABU alone (21.4% vs. 41%, p = 0.016) and all the treated cases (treated ABU and UTI; 27.8% vs. 41.4%, p = 0.013); anti-Pseudomonas cephalosporins prescription significantly decreased in period B when considering ABU alone (15.7% vs. 3.6%, p = 0.021), UTI alone (20.7% vs. 5.9%, p = 0.009) and all the treated cases (18.5% vs. 5.9%, p = 0.001). Conclusions. The 2020 EUCAST update could have contributed to an increase in carbapenem prescriptions. UTI and ABU represent a large field of interest for stewardship interventions both from a diagnostic and therapeutic point of view.

Background/Objectives: Evaluating antimicrobial use (AMU) is essential in the investigation and implementation of antimicrobial resistance (AMR) prevention measures. Here, we examined AMU using an index (mg/kg biomass) that considers the antimicrobial sales volume and livestock biomass in Japan from 2011 to 2022. Methods: Antimicrobial sales volumes were obtained from JVARM data, and biomass data were obtained from reliable statistics. Beef cattle, dairy cattle, pigs, broiler chickens, layer chickens, fish raised in freshwater, and fish raised in seawater were targeted in this study. Results: Tetracycline accounted for 39%, macrolides for 18%, penicillins for 12%, and sulfonamides for 11% of the sales in 2022. The peak antimicrobial sales volume was 847 tons in 2017, and then declined to 766 tons by 2022 with fluctuations in the interim. From the perspective of mg/kg biomass, AMU tended to increase in beef cattle, dairy cattle, and fish raised in seawater, while pigs, broilers, layers, and fish raised in freshwater showed a decreasing trend. In broilers, the decreasing trend that could not be confirmed by sales amount alone was detected using the newly established index. Conclusions: By calculating the mg/kg biomass, it became possible to create an interpretation that is different from that of the simple sales quantity data. We believe that this indicator is stable, transparent, and easily understandable for national monitoring.

Background/Objectives: Previously, we reported that 3-O-alkyl difluoroquercetins (di-F-Q) potentiates the antimicrobial activity of aztreonam (ATM) against metallo-β-lactamase (MBL)-producing P. aeruginosa through simultaneous inhibition of MBLs and efflux pumps. However, the ATM-potentiating activity of the 3-O-alkyl di-F-Q was observed only at high and potentially toxic concentrations (32 mg/L). Methods: As both MBLs and efflux pumps reside in the periplasm of Gram-negative bacteria, their inhibitors should accumulate in the periplasmic space. However, the outer membrane porins, the major entry pathway in Gram-negative bacteria, allow the passive diffusion of hydrophilic polar molecules across the outer membrane. Thus, we reasoned that the introduction of a polar substituent at 7-OH position of 3-O-alkyl di-F-Q would enhance its periplasmic concentration to result in potentiation of ATM at lower concentrations. Results: The title compound 5 exhibited inhibitory activity against NDM-1 as well as the efflux pump of P. aeruginosa, which resulted in synergistical potentiation of ATM. A combination of ATM (8 mg/L) and 5 (8 mg/L) inhibited 80% of the ATM-resistant CPPA, while ATM alone did not show any inhibition. In addition, only 4 mg/L of 5 was needed to reduce the MIC₉₀ of ATM four-fold in ATM-resistant CPPA (n = 15). The time-kill data further supported the effectiveness of the combined treatment of ATM with 5, and the combination of ATM (1xMIC) with 8 mg/L of 5 showed bactericidal effects in every bacterial strain tested (PA-002, bla_IMP, PA-003, bla_VIM, PA-014, bla_GES, and PA-017, bla_NDM) by reducing the bacterial loads by 5.1 log₁₀~8.9 log₁₀. Conclusions: The title compound 5 exhibited inhibitory activity against NDM-1 as well as the efflux pump of P. aeruginosa, and the combined inhibitory activity resulted in synergistical potentiation of ATM. It should be noted that most CPPA isolates tested were sensitized to 8 mg/L of ATM upon combination with 4~8 mg/L of 5.

The antimicrobial concentration-time profile in humans affects antimicrobial activity, and as such, it is critical for preclinical infection models to simulate human-like dynamic concentration-time profiles for maximal translatability. This review discusses the setup, principle, and application of various dynamic in vitro PK/PD infection models commonly used in the development and optimisation of antimicrobial treatment regimens. It covers the commonly used dynamic in vitro infection models, including the one-compartment model, hollow fibre infection model, biofilm model, bladder infection model, and aspergillus infection model. It summarises the mathematical methods for the simulation of the pharmacokinetic profile of single or multiple antimicrobials when using the serial or parallel configurations of in vitro systems. Dynamic in vitro models offer reliable pharmacokinetic/pharmacodynamic data to help define the initial dosing regimens of new antimicrobials that can be developed further in clinical trials. They can also help in the optimisation of dosing regimens for existing antimicrobials, especially in the presence of emerging antimicrobial resistance. In conclusion, dynamic in vitro infection models replicate the interactions that occur between microorganisms and dynamic antimicrobial exposures in the human body to generate data highly predictive of the clinical efficacy. They are particularly useful for the development new treatment strategies against antimicrobial-resistant pathogens.

Background and Objectives: The use of artificial intelligence (AI) and, in particular, machine learning (ML) techniques is growing rapidly in the healthcare field. Their application in pharmacokinetics is of potential interest due to the need to relate enormous amounts of data and to the more efficient development of new predictive dose models. The development of pharmacokinetic models based on these techniques simplifies the process, reduces time, and allows more factors to be considered than with classical methods, and is therefore of special interest in the pharmacokinetic monitoring of antibiotics. This review aims to describe the studies that use AI, mainly oriented to ML techniques, for dose prediction and analyze their results in comparison with the results obtained by classical methods. Furthermore, in the review, the techniques employed and the metrics to evaluate the precision are described to improve the compression of the results. Methods: A systematic search was carried out in the EMBASE, OVID, and PubMed databases and the results obtained were analyzed in detail. Results: Of the 13 articles selected, 10 were published in the last three years. Vancomycin was monitored in seven and none of the studies were performed on new antibiotics. The most used techniques were XGBoost and neural networks. Comparisons were conducted in most cases against population pharmacokinetic models. Conclusions: AI techniques offer promising results. However, the diversity in terms of the statistical metrics used and the low power of some of the articles make the overall assessment difficult. For now, AI-based ML techniques should be used in addition to classical population pharmacokinetic models in clinical practice.

Objectives: The early identification of infection-causing microorganisms through multiplex PCR panels enables prompt and targeted antibiotic therapy. This study aimed to assess the performance of the BioFire^® Joint Infection Panel (BF-JIP) in analysing non-synovial fluid samples. Methods: We conducted a retrospective cohort study at Trieste University Hospital, Italy, on hospitalised adults with non-synovial fluid samples tested by both BF-JIP and traditional culture methods (November 2022-April 2024). Results: We evaluated 48 samples from 45 patients, including 24 abscess drainage fluids and 10 tissue samples. The BF-JIP showed high concordance (85.4%) and enhanced detection (4.3%) compared to culture methods. The BF-JIP excelled in cerebrospinal fluid (CSF) (100% accuracy and concordance) and in abscess drainage fluid (accuracy: 95.8%; concordance: 91.7%) identification and maintained high performance rates in patients under antibiotics. Conclusions: These findings suggest that BF-JIP is a valuable tool for accurate pathogen detection in various clinical samples, offering the additional advantage of being a rapid method.

The utilization of nano-sized drug delivery systems in herbal drug delivery systems has a promising future for improving drug effectiveness and overcoming issues connected with herbal medicine. As a consequence, the use of nanocarriers as novel drug delivery systems for the improvement of traditional medicine is critical to combating infectious diseases globally. In line with this, we herein report the biosynthesis of silver nanoparticles (AgNPs), gold nanoparticles (AuNPs), and bimetallic nanoparticles (BMNPs) as antibacterial agents against pathogenic bacterial strains using Annona squamosa L. leaf extract as a bio-reductant and bio-stabilizing agent. The as-synthesized metal nanoparticles were characterized by transmission electron microscopy (TEM), ultraviolet-visible (UV-Vis) absorption spectroscopy, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and the dynamic light scattering (DLS) method. The as-synthesized MNPs had an average particle size of 6.98 nm ± 2.86 nm (AgNPs), 21.84 ± 8.72 nm (AuNPs), and 2.05 nm ± 0.76 nm (BMNPs). The as-synthesized AgNPs and BMNPs showed good antibacterial activity against pathogenic bacterial strains of Gram-positive Staphylococcus aureus (ATCC 25923) and Gram-negative Escherichia coli (ATCC 25922). The obtained results offer insight into the development of benign nanoparticles as safe antibacterial agents for antibiotic therapy using Annona squamosa L. leaf extract.