Antibiotics-Basel最新文献

Objectives: In 2022, the World Health Organization highlighted the necessity for the development of new antifungal agents. Polyene antibiotics are characterized by a low risk of drug resistance; however, their use is limited by low solubility and severe side effects. Methods: A series of N-alkylated derivatives of amphotericin B and nystatin A₁ as well as their N-(2-hydroxyethyl)amides were synthesized. Their antifungal activity was evaluated against various Candida strains and Aspergillus fumigatus using the broth microdilution method. Cytotoxicity was assessed using an MTT assay on human embryonic kidney cells HEK293 and human skin fibroblast cells hFB-hTERT6, as well as a hemolysis assay on erythrocytes. Membrane activity was analyzed by fluorimetric measurement of calcein leakage from model liposomes. Results: Derivatives containing the N-(hydroxyethyl)amino)ethyl fragment (compounds 3 and 4) exhibited relatively high antifungal activity, as did N-(2-hydroxyethyl)amides 5 and 9. Bis-modified compounds 6 and 10 did not outperform their mono-modified analogues in terms of activity or cytotoxicity. The mono-N-alkylated compound 3 showed the highest activity/toxicity ratio, which correlated well with its selectivity for ergosterol-containing model membranes. Discussion: Combining two successful modifications does not necessarily improve the activity/toxicity ratio of polyenes. Further studies can be performed for the optimization of carboxyl group of 3.

Background/Objectives: Antifungal resistance to azoles, coupled with the increasing prevalence of Candida albicans infections, represents a significant public health challenge and has driven the search for new natural compounds that can act as alternatives or adjuvants to the current antifungals. Ellagic acid (EA) has demonstrated antifungal activity; however, its effects are not fully understood. In this study, we investigated the in vitro anti-Candida activity of EA and its ability to potentiate the effects of fluconazole (FLZ) on C. albicans.Methods: The Minimum Inhibitory Concentration (MIC) of EA was determined by broth microdilution and its interaction with FLZ was assessed using a checkerboard assay. Additionally, we examined the effects of EA on yeast-to-hypha transition, inhibition of biofilm formation, time-kill kinetics, hemolytic activity, and cytotoxicity in HeLa ATCC^® CCL-2™ cells. Results: EA exhibited MIC values ranging from 250 to 2000 µg/mL and showed synergistic and additive interactions with FLZ, resulting in a marked reduction in the MIC values of FLZ (up to 32-fold) and EA (up to 16-fold). In the time-kill assay, the most effective combinations were 4× EA MIC, 2× EA MIC, and FIC EA + FLZ, which showed fungicidal activity. Furthermore, EA did not show hemolytic activity and demonstrated low and dose-dependent cytotoxicity in HeLa cells, with no cytotoxic effects observed in combination with FLZ. EA and the synergistic combination of EA and FLZ interfered with both the yeast-to-hypha transition process in C. albicans cells and biofilm formation. In addition to its antifungal efficacy, EA demonstrated a favorable safety profile at the concentrations used. Conclusions: This study presents promising results regarding the potential use of EA in combination with FLZ for the treatment of C. albicans infections.

Background: Widespread use of antibiotics has led to a global increase in resistance. The Escherichia coli bacterium is a facultative pathogen that often develops antibiotic resistance and is easily transmitted, not only in animal health but also in public health. Within the poultry sector, domestic fowl is widespread and one of the most dynamically growing sectors, which is why regular, extensive monitoring is crucial. Among economically important livestock, poultry as a major source of animal protein for humans is a frequent carrier of Escherichia coli, also with sporadically detected clinical disease. Methods: Our research evaluates the susceptibility of commensal Escherichia coli strains, isolated from large domestic fowl flocks in Hungary, to antibiotics of animal and public health importance, by determining the minimum inhibitory concentration value. Results: A total of 410 isolates were tested, with the highest level of resistance being found for florfenicol (62.7%). Particularly alarming are the resistance rates to enrofloxacin (52.9%), colistin (30.7%), and ceftriaxone (23.9%). We also found a resistance of 56.1% to amoxicillin and 22.2% to amoxicillin-clavulanic acid, which suggests that the majority of strains are β-lactamase-producing. When compared with the national human resistance data, we found with similar values for amoxicillin and amoxicillin-clavulanic acid, but the resistance rates of aminoglycosides, fluoroquinolones, and potency sulfonamide were worse in animal health. Conclusions: In conclusion, our results suggest that periodic surveys should be carried out and that long-term trends can be established that allow the monitoring of resistance patterns over time. For multidrug-resistant strains, new generation sequencing can be used to investigate the genetic background of resistance.

Background: The optimal antimicrobial treatment duration for diabetes-related foot osteomyelitis (DFO) currently needs to be determined. We systematically reviewed the effects of short and long treatment durations on outcomes of DFO. Methods: We performed a systematic review searching Cochrane, CENTRAL, MEDLINE, Embase, and CINAHL Plus from inception up to 19 January 2024. Two independent reviewers screened the titles and abstracts of the studies. Studies comparing short (<6 weeks) and long (>6 weeks) treatment durations for DFO were included. The primary outcome was amputation; the secondary outcomes were remission, mortality, costs, quality of life, and adverse events. Risk of bias and GRADE were assessed. Results: We identified 2708 references, of which 2173 remained after removing duplicates. Two studies were included. Differences in methodology precluded a meta-analysis. The primary outcome, major amputation, was reported in one study, with a rate of 10% in both the intervention and comparison groups (p = 1.00), regardless of treatment duration. For the secondary outcome, remission rates, the first study reported 60% in the intervention group versus 70% in the comparison group (p = 0.50). In the second study, remission rates were 84% in the intervention group versus 78% in the comparison group (p = 0.55). Data for the outcomes mortality, costs, and quality of life were not available. Short treatment duration may lead to fewer adverse events. The risk of bias was assessed as low to moderate, and the level of evidence ranged from very low to moderate. Conclusions: Our findings suggest that for DFO, there is no difference between a shorter and more prolonged duration of antimicrobial treatment regarding amputation and remission, with potentially fewer adverse events with shorter treatment durations. However, the uncertainty stems from limited, heterogeneous studies and generally low-quality evidence marred by moderate biases, imprecision, and indirectness. More high-quality studies are needed to substantiate these findings.

Background: Phytol is a diterpene from the long-chain unsaturated acyclic alcohols, known for its diverse biological effects, including antimicrobial and anti-inflammatory activities. Present in essential oils, phytol is a promising candidate for various applications in the pharmaceutical and biotechnological sectors. This study aimed to evaluate the in vitro antibacterial and drug-potentiating effects of phytol against multidrug-resistant bacteria and to evaluate its in silico properties: ADME and molecular docking. Methods: The in vitro antibacterial activity of phytol and the phytol combined with conventional drugs was evaluated by microdilution tests against standard and resistant bacterial strains. Finally, the SwissADME platform was employed to analyse the physicochemical and pharmacokinetic characteristics of phytol. Results: Phytol significantly reduced the Minimum Inhibitory Concentration (MIC) of norfloxacin and gentamicin required to inhibit multidrug-resistant strains of Escherichia coli and Staphylococcus aureus, respectively. Additionally, ADME analysis revealed that phytol exhibits low toxicity and favourable pharmacokinetic properties; in addition, it is revealed through molecular docking that phytol showed a relevant affinity with the proteins 6GJ1 and 5KDR, however, with values lower than the drugs gentamicin and ampicillin. Conclusions: Collectively, these findings suggest that phytol holds potential as an effective adjuvant in combating antimicrobial resistance.

Background/Objectives: Antimicrobial resistance is considered one of the foremost global public health challenges, and its prevalence is increasing. In Jordan, particularly in Al-Karak Governorate, there is a lack of sufficient data on antimicrobial resistance to make accurate assessments. The main aim of the current study was to evaluate antibiotic resistance trends in clinical specimens from 2022 and assess antibiotic resistance patterns. The emphasis on the WHO antibiotic classification as Access, Watch, and Reserved (AWaRe) was adopted in the current study. Results: Among Gram-positive bacteria, Enterococcus faecalis exhibited 100% susceptibility to nitrofurantoin and 96% to vancomycin, Streptococcus viridans exhibited 100% susceptibility to teicoplanin, while CoNS (coagulase-negative Staphylococci) showed moderate resistance to Trimethoprim + Sulfamethoxazole (63%) and clindamycin (47%). Among Gram-negative bacteria, Escherichia coli and Klebsiella pneumoniae displayed high susceptibility to fosfomycin (E. coli: 95%, K. pneumoniae: 80%) and amikacin (E. coli: 93%, K. pneumoniae: 81%). Resistance was notable for trimethoprim + sulfamethoxazole (E. coli: 47%, K. pneumoniae: 53%) and nitrofurantoin (K. pneumoniae: 30%). Pseudomonas aeruginosa exhibited the highest proportion of XDR strains (15%), followed by K. pneumoniae (11%) and E. coli (4%), while PDR strains were found in P. aeruginosa (6%), K. pneumoniae (3%), and E. coli (0.6%). XDR was observed in 4% of CoNS and 3% of S. viridans (α), with Staphylococcus aureus exhibiting both XDR and PDR at 1%. Methods: A cross-sectional retrospective study of bacterial species and their antimicrobial susceptibility was carried out at a hospital in Al Karak, Jordan, from January to December of 2022, the study included 1187 isolates from all locations in Al-Karak Governmental Hospital. Conclusions: The significant prevalence of XDR and PDR strains in key pathogens, particularly P. aeruginosa and K. pneumoniae, underscores the need for a robust Antimicrobial Stewardship Program (ASP) and infection control measures at Al-Karak Governmental Hospital. High susceptibility in several Access group antibiotics (e.g., amikacin and nitrofurantoin) supports their prioritization in empirical therapy, while the emergence of resistance in Watch and Reserved antibiotics highlights the necessity for rational use. These findings are very important for adjusting the local strategies to lower the spread of resistant strains and improve clinical outcomes.

Antibiotics, widely used medications that have significantly increased life expectancy, possess a broad range of effects beyond their primary antibacterial activity. While some are recognized as adverse events, others have demonstrated unexpected benefits. These adjunctive effects, which have been defined as "pleiotropic" in the case of other pharmacological classes, include immunomodulatory properties and the modulation of the microbiota. Specifically, macrolides, tetracyclines, and fluoroquinolones have been shown to modulate the immune system in both acute and chronic conditions, including autoimmune disorders (e.g., rheumatoid arthritis, spondyloarthritis) and chronic inflammatory pulmonary diseases (e.g., asthma, chronic obstructive pulmonary disease). Azithromycin, in particular, is recommended for the long-term treatment of chronic inflammatory pulmonary diseases due to its well-established immunomodulatory effects. Furthermore, antibiotics influence the human microbiota. Rifaximin, for example, exerts a eubiotic effect that enhances the balance between the gut microbiota and the host immune cells and epithelial cells. These pleiotropic effects offer new therapeutic opportunities by interacting with human cells, signaling molecules, and bacteria involved in non-infectious diseases like spondyloarthritis and inflammatory bowel diseases. The aim of this review is to explore the pleiotropic potential of antibiotics, from molecular and cellular evidence to their clinical application, in order to optimize their use. Understanding these effects is essential to ensure careful use, particularly in consideration of the threat of antimicrobial resistance.

Introduction: This study explores the bioactive properties of extracts obtained from Robin's pincushion (Diplolepis rosae) collected in Sokobanja, Serbia. Results: Comprehensive in vitro assessments reveal high concentrations of total phenolics (186.37 mg GAE/g), along with significant levels of carotenoids (44.10 μg β-car/g). Robin's pincushion exhibited superior antioxidant capacities across DPPH, ABTS, and reducing power assays, significantly outperforming comparable extracts from rosehip (Rosa canina) and black rosehip (Rosa spinosissima) in these activities. Additionally, high inhibitory effects were observed in antimicrobial assays, with the extract demonstrating minimal inhibitory concentrations (MIC) as low as 1.56 mg/mL against the Staphylococcus species. Notably, the extract achieved full bactericidal effect within 24 h in time-kill kinetic studies which additionally highlight its potent antistaphylococcal potential. Materials and methods: Analyzing their phytochemical profiles and evaluating their potential as antioxidant, anti-inflammatory, antihyperglycemic, and antimicrobial agents, wide-ranging evaluation of bioactivity of Robin's pincushion was conducted. Conclusions: These findings highlight Robin's pincushion as a promising natural source of bioactive compounds with potential applications in traditional and modern medicine for managing oxidative stress, inflammation, hyperglycemia, and microbial infections.

Introduction: The emergence of carbapenem-resistant pathogenic bacteria is a growing global public health concern. Carbapenem-resistant uropathogenic strains of Klebsiella pneumoniae can cause uncomplicated or complicated urinary tract infections, leading to a high risk of treatment failure and the spread of resistance determinants. The objectives of this 24-month study were to identify the prognostic characteristics of patients who were infected with carbapenem-resistant Klebsiella pneumoniae (CRKpn) and to create a tool to estimate the probability of a CRKpn infection before having the complete results of a patient's antibiogram. Results: We found that 41.6% of all urinary infections with Kpn were caused by CRKpn. Factors such as male gender, the presence of upper urinary tract infections, invasive urinary maneuvers, recent infection with or carriage of the germ, and the nosocomial occurrence of UTIs with Kpn were predictive for CRKpn infection. Based on these factors, we proposed a model to estimate the presence of CRKpn. Methods: A retrospective case-control study including all hospitalized patients with urinary tract infections (UTIs) caused by Klebsiella pneumoniae was carried out. We reported data as percentages, identified independent predictors of the presence of CRKpn, and proposed a tool to evaluate the probability through multivariate analysis. Conclusions: Through this study, we aim to provide clinicians with a tool to support decision making regarding first-line antibiotic treatment.

Background: The development of broad-range polymerase chain reaction (BR-PCR) and next-generation sequencing techniques has significant implications for antimicrobial stewardship by increasing clinicians' ability to provide a tailored antimicrobial regimen. We sought to explore the clinical utility of BR-PCR testing and its impact on antimicrobial treatment among an adult cohort in a large hospital system. Methods: We retrospectively evaluated samples that underwent BR-PCR testing between 2017 and 2021 and summarized their clinical characteristics and impact on antimicrobial therapy. We identified BR-PCR testing as having clinical utility if the results led to adjustment of antimicrobial choice or duration or to confirmation of the initial empiric regimen, while no clinical utility was assigned to results that were negative or clinically insignificant, unavailable due to loss to follow-up, or lacking clinical indication (treatment completed before the test results returned or conventional cultures revealed the causative pathogen). Results: Among 359 specimens, BR-PCR was positive for 107 (30%). Clinical utility was identified for 106 (29.5%) specimens, including 45 with negative BR-PCR results. The rates of clinical utility varied based on the type of sample tested, with the highest clinical utility associated with cranial samples (60%), followed by body fluid (56%) and endovascular (54%) samples, and the lowest with CSF (15%) and bone and joint (19%) samples. We also identified many BR-PCR tests that were not clinically indicated (23.4%). Conclusions: This study highlights the utility of BR-PCR testing to support antimicrobial stewardship initiatives. Further studies are needed to identify clinical scenarios in which it is appropriate to order BR-PCR testing and for a careful interpretation of negative BR-PCR results.