Antibiotics-Basel最新文献

Background/Objectives: Metallo-β-lactamase (MBL)-producing Gram-negative bacteria represent a growing global health threat due to their broad resistance to β-lactam antibiotics, including carbapenems, which severely limits treatment options. This study aimed to evaluate the in vitro synergistic activity of fosfomycin (FOS) in combination with selected older and newer antimicrobials against MBL-producing Klebsiella pneumoniae and Pseudomonas aeruginosa. Methods: Synergistic interactions were assessed using agar dilution checkerboard on 42 MBL-producing clinical isolates (22 K. pneumoniae, 20 P. aeruginosa) and confirmed using time-kill assays with selected isolates. FOS was tested in combination with colistin (COL), ceftazidime-avibactam (CAZ-AVI), meropenem (MER), amikacin (AMI), aztreonam (AZT), aztreonam-avibactam (AZT-AVI), or cefiderocol (FDC). Results: Most FOS combinations exhibited additive or synergistic effects against clinical isolates. Synergy rates reached 72.7% for the FOS+CAZ-AVI combination (K. pneumoniae) and 65.0% for the FOS+COL combination (P. aeruginosa). An asymmetric synergistic interaction was identified for FOS+CAZ-AVI, with FOS enhancing the activity of CAZ-AVI more markedly than vice versa, especially in K. pneumoniae. Time-kill assays on selected isolates confirmed synergistic and bactericidal activity of FOS+CAZ-AVI and FOS+COL, and showed that bacterial regrowth observed with FOS, CAZ-AVI, and COL alone was suppressed in combination therapy. Conclusions: FOS-based combinations, particularly with CAZ-AVI and COL, demonstrated potent synergistic activity against MBL-producing K. pneumoniae and P. aeruginosa, supporting their potential utility in rational combination therapies for infections due to MBL-producing bacteria.

The rapid rise of antimicrobial resistance (AMR) has emerged as a critical global health crisis, driven by the widespread emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens. This growing threat, coupled with the stagnation in the development of novel antibiotics, necessitates the investigation of alternative antimicrobial strategies. Plant-derived essential oils (EOs) have emerged as promising candidates due to their broad-spectrum antibacterial activity, multi-targeted mechanisms, and capacity to enhance the efficacy of existing antibiotics. Recent studies have underscored the potential of EOs in disrupting biofilms, inhibiting quorum sensing, modulating efflux pumps, and reversing resistance in a variety of bacterial pathogens, including those listed as priorities by the World Health Organization. Notably, many of these effects have been demonstrated against resistant strains isolated directly from clinical samples, thereby enhancing the translational significance of EOs. In addition to their antimicrobial properties, advances in analytical, omics-based, and microfluidic technologies have further elucidated the mechanisms of EOs and may accelerate their therapeutic development. Nevertheless, challenges such as variability in composition, lack of standardized testing protocols, and limited in vivo data continue to impede clinical application. Therefore, the aim of this scoping review is to critically examine the advances over the past decade in the antibacterial activity of plant EOs against clinical isolates, with a particular focus on their efficacy against resistant bacterial pathogens and their potential role in combating AMR.

Background: Pediatric urinary tract infections (UTIs) are increasingly complicated to treat due to antimicrobial resistance (AMR). The coronavirus disease 2019 (COVID-19) pandemic has led to substantially reduced pediatric antibiotic prescribing, but its impact on resistance trends remains unclear. This study aimed to investigate the AMR trends in urinary pathogens from children under 24 months of age hospitalized with febrile UTI during the pre-, during-, and post-COVID-19 pandemic periods.

Methods: We conducted a retrospective study of children aged <24 months who were hospitalized at a tertiary center in Korea between 2008 and 2023 for first febrile UTI. The patients were stratified by age (<100 days vs. 100 days to 24 months) and pandemic period (pre-, during-, and post-COVID-19). Interrupted time-series (ITS) analysis and multivariable logistic regression were used to assess the temporal trends and predictors of ciprofloxacin nonsusceptibility.

Results: Ciprofloxacin susceptibility decreased significantly during the pandemic, especially among infants < 100 days. ITS analysis demonstrated an immediate 12.1% increase in ciprofloxacin nonsusceptibility at pandemic onset, which persisted thereafter. Extended-spectrum β-lactamase production was the strongest predictor of ciprofloxacin resistance.

Conclusions: These findings suggest that adult antibiotic use and clonal dissemination may contribute to the persistence and spread of AMR, highlighting the need for integrated stewardship and genomic surveillance.

Background. The establishment and diversity of the gut microbiota during early childhood are fundamental for immune regulation and metabolic processes, with factors such as prematurity, delivery method, antibiotic treatment, and breastfeeding significantly impacting microbiome development and potential health outcomes. Objectives/Methods. This comparative study examined the gut microbiota composition in children aged 6-8 and 9-12 months, born via spontaneous labor at ≥38 weeks' gestation, who either did not receive antibacterial therapy or required beta-lactam antibiotics. The composition of the colonic microbiota was analyzed in these fecal samples using a quantitative real-time PCR (qRT-PCR). Results. Significant differences in microbiota composition were observed between groups. Children treated with antibiotics exhibited a statistically significant reduction in alpha diversity indices (Shannon and Simpson), along with decreased colonization of key functionally important microorganisms, including obligate anaerobic bacteria such as Faecalibacterium prausnitzii, Clostridium leptum, Bacteroides spp., and metabolically active Bifidobacteria (B. bifidum, B. breve, B. longum). Conclusions. These microbiota alterations may adversely affect child health by diminishing microbial balance and functional potential, especially during this critical period of immune and metabolic development. The decline in anti-inflammatory, short-chain fatty acid-producing bacteria elevates the risk for allergic, atopic, dysbiotic, and metabolic conditions. Recognizing these impacts underscores the importance of strategies to supports microbiota restoration after antibiotic use, such as probiotics, prebiotics, and dietary interventions. Further research should focus on microbiota recovery dynamics to facilitate early intervention and optimize pediatric health outcomes. Overall, understanding antibiotic effects on gut microbiota can guide more judicious treatment approaches, reducing long-term health risks.

Background/Objective: Sewage sludge (biosolids) is increasingly reused as a fertilizer to recycle nutrients and close material cycles; however, concerns persist regarding antibiotics and antimicrobial resistance. This study evaluated the agronomic safety and microbiological integrity of biosolid fertilization in soybean and maize systems, with particular attention to grain quality and food safety. Methods: Soybean and maize were cultivated in greenhouse microcosms under biosolid or mineral fertilization. Soil, roots, shoots, and grains were analyzed for antibiotic residues using LC-MS/MS and antibiotic-resistant bacteria (ARB) using culture-based assays. Minimum inhibitory concentrations for isolates from grains were compared with clinical breakpoints to verify phenotypic susceptibility. Multivariate analyses (PCA) integrating real-time antibiotic concentrations and updated resistance indicators were performed using centered and scaled data. Results: Fluoroquinolones were the predominant residues introduced by biosolids and exhibited consistent time-dependent declines across all treatments, although low concentrations remained detectable at 90 d in several soil-fertilizer-crop combinations. Tetracyclines, macrolides, and sulfonamides showed similar decreasing trends, with planted soils displaying faster dissipation than bulk control soils. Biosolid fertilization increased shoot biomass by 1.5-2.3-fold and nitrogen, phosphorus, and potassium uptake by 30-60% without impairing soybean nodulation or nitrogenase function. ARB was observed in all soils, including mineral and plant-free controls, indicating a natural background resistome. Ciprofloxacin-resistant isolates were detected in one simple sampling point, and MDR proportions were transient (67%), returning to their background levels by 45-90 days. PCA showed that crop presence, not fertilizer type, was the primary driver of microbial ordination, and that antibiotic concentrations and resistance indicators were only weakly aligned, indicating a limited selective pressure. No antibiotic residues or phenotypically resistant bacteria were detected in the soybean or maize grains. Conclusions: Updated residue, resistance, and multivariate data confirmed that biosolids did not induce, amplify, or transfer antibiotic resistance and maintained complete grain safety. Properly treated biosolids function as safe, agronomically beneficial fertilizers aligned with One Health goals, enhancing crop productivity without compromising food quality or increasing antimicrobial resistance.

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Background/Objectives:Providencia stuartii is intrinsically resistant to several antibiotic classes, and acquisition of bla_NDM further restricts treatment options. This study aimed to characterize NDM-producing P. stuartii isolates from a small hospital cluster in Russia and to place them within the global genomic context. Methods: Four isolates recovered between June and July 2023 from a single hospital were analyzed using Illumina and Oxford Nanopore sequencing to assess genetic relatedness and plasmid content. Results: The isolates showed identical extensively drug-resistant profiles and were closely related genomically. All carried nearly identical IncC plasmids harboring multiple antimicrobial resistance genes, including bla_NDM. Comparative analysis indicated that these genomes clustered with recent European isolates but differed in the bla_NDM allele and its genomic location. Highly similar IncC plasmids were also found in our previous Klebsiella pneumoniae dataset, demonstrating that this plasmid backbone occurs in multiple bacterial species in the region. Conclusions: The study highlights the role of IncC plasmids in carbapenemase dissemination and underscores the value of genomic surveillance integrating chromosomal and plasmid analyses to track extensively drug-resistant pathogens.

Background/Objectives:Staphylococcus aureus is a well-known opportunistic pathogen that causes a wide range of infections, from cutaneous blemishes to potentially fatal systemic diseases. The increasing prevalence of antibiotic-resistant bacteria highlights the critical need for alternative therapeutic methods that target virulence factors rather than growth. Methods: The antibacterial activity of 3-fluorocatechol (3-FC) against bacterial and fungal pathogens (e.g., Candida albicans) was determined by broth microdilution to establish the lowest inhibitory concentration. The antibiofilm impact of 3-FC against S. aureus was evaluated using crystal violet staining and viable colony counts, followed by scanning electron microscopy to visualize the biofilm architecture. The methanol extraction method was used to quantify staphyloxanthin synthesis in S. aureus cells. Furthermore, in silico molecular docking was used to evaluate 3-FC binding interactions and provide mechanistic insight into its impacts on S. aureus biofilms and virulence-associated factors. Results: Although the study showed that 3-FC exhibits weak antibacterial activity against S. aureus (MIC > 2048 µg/mL), it shows effective inhibition of up to 86.5% at sub-inhibitory doses during the initial stage of biofilm formation. The CFU enumeration also confirms the significant reduction of viable cell count of S. aureus in the presence of sub-MIC of 3-FC. The SEM analysis confirms disruption of the S. aureus biofilm architecture in the presence of a sub-MIC of 3-FC. Furthermore, the eradication of mature S. aureus biofilm at a sub-MIC dose of 3-FC was 60.6%. 3-FC significantly reduced staphyloxanthin formation, a vital antioxidant pigment that contributes to bacterial pathogenicity, with a maximal suppression of 66.3% at 2048 µg/mL. Molecular docking analyses provide further insight into the molecular basis of 3-FC activity, revealing strong binding affinities with numerous S. aureus virulence regulators and enzymes, suggesting interference with quorum-sensing, adhesion, and oxidative-stress response pathways. Conclusions: Collectively, our findings indicate that 3-FC has antibiofilm and antivirulence properties against S. aureus. Furthermore, this study suggests 3-FC as a viable structural scaffold for the development of a novel anti-infective agent to treat chronic staphylococcal infections.

Background: Hearing loss (HL) affects more than 1.5 billion people worldwide and represents a major global health concern. Recent evidence suggests that alterations in gut microbial composition and antimicrobial resistance (AMR) may be linked to inflammatory and metabolic pathways that could influence auditory physiology. Objectives: This study aimed to explore the relationship between auditory function and the antimicrobial resistance in the gut microbiome of young adults. Methods: Fecal and auditory data were collected from young adults. Auditory function was assessed through pure-tone audiometry, and participants were classified according to the presence or absence of HL based on the American Speech-Language-Hearing Association (ASHA) criteria. Bacterial resistance was analyzed under aerobic and anaerobic conditions using disk diffusion and E-test methods to determine minimum inhibitory concentrations (MICs) for a panel of antibiotics. Gut microbiota composition was further characterized using quantitative polymerase chain reaction (qPCR) to quantify 15 key microbial taxa. Results: Overall, 40.9% of participants presented some degree of HL, with mild or slight HL being more frequent in women (53.3%) than in men (14.3%). Participants with HL exhibited significantly higher MICs for nalidixic acid, amoxicillin, and ciprofloxacin, as well as trends toward increased MIC variability for several other agents. Principal component analysis demonstrated distinct clustering of individuals without HL and greater dispersion among those with HL, suggesting higher interindividual variability in resistance profiles. These findings suggest potential associations between antimicrobial resistance and auditory function, possibly mediated through gut microbiome alterations. qPCR analyses demonstrated that Faecalibacterium prausnitzii abundance was significantly higher in individuals with HL and in those exhibiting greater resistance to amoxicillin. Conclusions: These findings provide preliminary evidence connecting the gut resistome with auditory function, supporting the emerging concept of a gut-ear-brain axis and underscoring the need for further research into microbiome-related mechanisms underlying HL.

Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections (UTIs) and a major contributor to the global antimicrobial resistance crisis. The increasing prevalence of multidrug-resistant (MDR) strains, including expanded-spectrum β-lactamases (ESBL) and carbapenemase-producing isolates, severely limits treatment options. This review provides an overview on the key molecular mechanisms of UPEC antibiotic resistance, such as enzymatic inactivation, target-site mutations, efflux pump activity, and biofilm formation. Beyond conventional antibiotics, special emphasis is placed on phytochemical strategies as promising alternatives. Flavonoids, alkaloids, terpenoids, and essential oils exhibit antibacterial, anti-adhesive, and antibiofilm properties. These natural bioactive compounds modulate motility, suppress fimbrial expression, inhibit quorum sensing, and enhance antibiotic efficacy, acting both as standalone agents and as adjuvants. Current in vitro and in vivo studies highlight the potential of plant-derived compounds and biologically based therapies to combat UPEC. However, challenges related to standardization, bioavailability, and clinical validation remain unresolved. Integrating molecular mechanistic insights with advanced phytochemical research may offers a sustainable and effective strategy for mitigating UPEC antibiotic resistance.