Antibiotics-Basel最新文献

Objective: The current gold standard for detection of implant-related infections is the intraoperative collection of tissue samples. However, false-negative results frequently occur, particularly in infections caused by biofilm-forming bacteria. As a complementary method, sonication has therefore been established for detecting implant-associated infections, especially in periprosthetic joint infections. In trauma surgery, this technique is still rarely used. The aim of this study is to evaluate the diagnostic significance of sonication after osteosynthesis. Methods: A retrospective single-center analysis was conducted on all patients who underwent plate osteosynthesis removal between 1 January 2019, and 1 May 2021, with both sonication and intraoperative tissue sampling performed. Patients with inlying arthroplasties or nail-less osteosynthesis systems were excluded. Pre- and postoperative infection parameters (leukocytes, CRP) were recorded, and preoperative clinical findings were used to classify suspected infection. Results: A total of 57 patients (30 men, 27 women; mean age 57.6 years, range 12-91) were included. The mean treatment duration was 20.1 days (range 1-152). Sonication was positive in 33 patients, tissue samples in 28, with 31 cases (54%) showing concordant results. In cases with preoperative suspicion of infection, sonication was positive in 21 of 26 cases (80.7%) and tissue samples in 18 of 26 (69.2%), whereas without suspicion, positivity rates were 38% and 31%, respectively. Sonication and tissue results matched in 14 of 26 cases; in the remainder, results were different or incomplete. Preoperative CRP elevation and the presence of an infection membrane influenced sensitivity: sonication generally detected more bacteria (59-81%) than tissue samples (49-73%), though discrepancies remained. Conclusions: Sonication represents a valuable complementary method for detecting implant-related infections. Due to its high sensitivity but limited specificity, it should not be used as a standalone diagnostic method.

Background/Objectives: Staphylococcus (S.) aureus is a major pathogen causing bovine mastitis and is often refractory to antibiotic therapies due to virulence factors and resistance mechanisms. In this pilot study, the safety and efficacy of an intramammary phage cocktail, in naturally S. aureus-infected dairy cows, were investigated. Methods: The initial part of the study on farm 1 confirmed tolerability and safety, as there were no observed systemic side effects of treatment. The subsequent efficacy study on farm 2 included 23 with S. aureus infected udder quarters, which were randomly divided into a treatment group (n = 16) and a control group (n = 7). The quarters in the treatment group received five intramammary infusions of the phage cocktail at 12-h intervals. Results: This resulted in a bacteriological cure rate of 81.3% (13/16) for the treatment group, compared to 28.6% (2/7) in the control group (p = 0.026). Conclusions: These results indicate that phage therapy is well-tolerated and may be a promising alternative to antibiotics for treating S. aureus mastitis, although confirmation in larger-scale, multicenter studies is required.

Background: The global incidence of multidrug-resistant and extensively drug-resistant tuberculosis continues to rise. The ribosome serves as a target for multiple antimicrobials, making functional research on it hold great significance. Methods: Using homologous recombination combined with a multiple serine integrase-mediated site-specific recombination system, we replaced the two endogenous rRNA operons in Mycobacterium smegmatis MC² 155 with a single copy of the single rRNA operon from Mycobacterium tuberculosis H37Rv, constructing the M. smegmatis BRkoA strain. We assessed growth kinetics at 37 °C, cold sensitivity at lower temperatures, transcriptional levels by RT-qPCR, 70S ribosome integrity through cryo-EM, and antimicrobial susceptibility by microdilution assays. Results: The BRkoA strain was successfully constructed. It exhibited markedly slower growth compared to the wild-type strain. Cold-sensitivity assays indicated potential ribosome assembly defects, while transcriptional analysis suggested altered rRNA processing and modification. Cryo-EM analysis further demonstrated the absence of specific ribosomal proteins in the BRkoA 70S ribosome. Moreover, BRkoA displayed reduced susceptibility tendency to several ribosome-targeting antibiotics, including kanamycin, amikacin, paromomycin, gentamicin, and linezolid. Conclusions: Replacement of the two endogenous rrn operons in M. smegmatis with a single copy of the single M. tuberculosis rrn operon using a serine integrase-mediated recombination system caused growth impairment and decreased sensitivity tendency to several ribosome-targeting antimicrobials. These findings suggest that ribosome structural variation contributes to intrinsic drug resistance mechanisms.

Background/objectives: Plasmids are autonomous DNA molecules that can replicate independently and transfer horizontally between bacterial cells. They play a key role in disseminating adaptive traits, such as antimicrobial resistance and virulence. Our study investigates the fundamental differences between plasmid populations originating from clinical/isolates and environmental/metagenomes.

Methods: We compare three distinct plasmid genome datasets-the NCBI Reference Sequence Database (RefSeq), the Integrated Microbial Genomes & Microbiomes system (IMG/PR) from bacterial isolates (I) and microbiomes (M)-to assess how plasmid origin shapes their characteristics, including mobility types, antimicrobial resistance genes (ARGs), virulence genes (VGs) and host taxonomy.

Results: We show that plasmids originating from bacterial isolates, more enriched in clinical samples, are fundamentally distinct from recovered from metagenomic data. Plasmids from isolates are larger, enriched in conjugative plasmids and display a higher frequency of ARGs and VGs than the ones assembled from metagenomes. Furthermore, ARGs are more frequently associated with highly mobile plasmids, particularly pCONJ.

Conclusions: These findings highlight the importance of plasmid origins in studies of plasmid epidemiology, functional potential and mobility.

Background: Catheter-related bloodstream infections (CRBSIs) caused by environmental organisms are uncommon, and polymicrobial cases are even rarer. Methods: We describe the first case of catheter-related bloodstream infection caused by two infrequent environmental organisms-Rhizobium radiobacter and Pseudomonas oryzihabitans-occurring as a co-infection. Results: The patient's occupation involved frequent exposure to moist, soil-contaminated environments. Although these bacteria are often considered contaminants, they are capable of causing invasive infections such as bacteremia, which can be life-threatening. Conclusions: This case underscores the emerging pathogenic potential of R. radiobacter and P. oryzihabitans co-infection, particularly in patients with underlying malignancies or end-stage renal disease who have indwelling vascular devices, and highlights the importance of considering occupational and environmental exposures in the differential diagnosis of unusual pathogens.

Background:Aeromonas hydrophila is a common bacterial pathogen that causes hemorrhagic septicaemia in several farmed aquaculture species. Phage therapy is considered a promising and feasible alternative to antibiotic treatment. Methods: In this study, an A. hydrophila-infecting jumbo phage Z90 was isolated from an aquaculture pond. The biological characteristics, genomic features, and in vitro and in vivo experiments were investigated to evaluate its application potential. Results: Phage Z90 was a myovirus with distinctive curled tail fibers. Additionally, phylogenetic and genomic analyses found that the phage Z90 was a novel virus belonging to the genus Ferozepurvirus of the family Chimalliviridae. One-step growth curve analysis revealed that the phage Z90 was a lytic phage, exhibiting a short latency period of 20 min and a relatively large burst size of 270 ± 42 PFU/cell. The phage Z90 particles were stable at psychrotrophic and mesophilic temperatures (10-50 °C) and a wide range of pH (pH 3-12). Genomic analysis revealed that the phage Z90 did not contain any genes encoding toxins, virulence factors, or antibiotic resistance factors. In vivo analysis demonstrated that the phage Z90 protected American eels from A. hydrophila infection, greatly increasing eel survival rates and alleviating symptoms caused by bacterial infections. The comparison of different phage administration methods suggested that phage Z90 was better administered through intraperitoneal injection than immersion in aquaculture water. Moreover, the combination of phage Z90 and ampicillin improved the bactericidal effect and reduced the treatment dosage compared to antibiotics or phage alone. Conclusions: Altogether, the findings of this study indicate that the phage Z90 can serve as a promising biocontrol agent for the treatment of A. hydrophila infection in aquaculture.

Background/objectives: Multidrug-resistant tuberculosis remains a critical public health challenge in Kazakhstan, yet the genomic determinants contributing to its emergence are still insufficiently understood. Although the quantity of genomic studies from Central Asia and the wider post-Soviet region has increased in recent years, the involvement of DNA repair and genome maintenance pathways in the development of resistance within Kazakhstan has not been comprehensively explored.

Methods: In this study, we performed whole-genome analysis of 175 Mycobacterium tuberculosis clinical isolates collected across Kazakhstan between 2010 and 2022 to evaluate the contribution of single-nucleotide polymorphisms in DNA replication, repair, and recombination (3R) genes to the evolution of drug resistance.

Results: Alongside well-established resistance mutations in gyrA, we identified recurrent variants in 3R-associated loci (genes involved in DNA replication, repair, and recombination)-including polA, uvrC and ligC-that were enriched among drug-resistant isolates, suggesting a broader role for genome maintenance pathways in facilitating resistance evolution under treatment pressure.

Conclusions: These findings provide the first region-specific genomic insights into 3R gene variation in Kazakhstani M. tuberculosis isolates.

Background: Periprosthetic joint infections (PJI) represent a serious complication following joint arthroplasty and require, in addition to surgical intervention, a targeted antibiotic therapy. The aim of this study was to compare microbiological recommendations for the antibiotic treatment of fictitious PJI patients generated by an artificial intelligence (AI) system with those of an interdisciplinary team (IT) consisting of microbiologists and orthopedic surgeons. The differences between the recommendations suggested by AI and the IT were analyzed with regard to the suggested agents and duration of antibiotic therapy. Methods: Based on meta-analyses, a cohort of 100 fictitious patients with acute early- and acute late-onset PJI was created, reflecting the typical demographic data, comorbidities and pathogen profiles of such a population. This information was input into the AI system ChatGPT (OpenAI, GPT-5 "Thinking mode" accessed via ChatGPT Plus, San Francisco, CA, USA) to generate corresponding recommendations. The objective was to use these profiles to obtain recommendations for definitive antibiotic therapy, including daily dosage, intravenous and oral treatment durations. Simultaneously, the same fictitious patient data were reviewed by the IT to produce their own recommendations. Results: The results revealed both concordances and discrepancies in the selection of antibiotics. Notably, in cases involving multidrug-resistant organisms and more complex clinical scenarios, the AI-generated recommendations were incongruent with those of the IT, with estimated percentage agreement ranging from 0-33%. In straightforward clinical scenarios with monomicrobial infections, AI reached an estimated percentage agreement of up to 57% (95%-CI [0.47-0.67]). Furthermore, AI consistently recommended 12 weeks of therapy duration vs. six weeks usually recommended by the IT. Conclusions: The study provides important insights into the potential and limitations of AI-assisted decision-making models in orthopedic infection treatments. Consultation of AI is universally accessible at all times of day, which may offer a significant advantage in the future for the treatment of PJI. This kind of application will be of particular interest for institutions without in-house microbiology services. However, from our perspective, the current level of incongruence between the AI-generated recommendations and those of an experienced interdisciplinary team remains too high for this approach to be clinically implemented at this time. Furthermore, AI lacks transparency regarding the sources it uses to inform about its decision-making and therapeutic recommendations, currently carries no legal weight and clinical implementation is severely hindered by restrictive privacy laws regarding health care data.

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Background: Amoxicillin, clindamycin and azithromycin are the most frequently prescribed antibiotics for odontogenic infections, but their comparative effects on gut microbiota and intestinal homeostasis remain insufficiently understood. Disruption of gut microbiota, short-chain fatty acid (SCFA) production, and mucosal barrier integrity may contribute to gastrointestinal symptoms. We aimed to compare the impacts of these antibiotics on gut microbiota, SCFA levels, and colonic goblet cells. Methods: C57BL/6N mice were treated with oral amoxicillin, clindamycin, or azithromycin at clinically relevant dosages. Cecal index, fecal water content, and diarrhea index were assessed during treatment and recovery. Gut microbiota composition and absolute bacterial abundance were determined using 16S rRNA amplicon absolute quantification sequencing. SCFAs in cecal contents were quantified by gas chromatography-mass spectrometry. Goblet cell abundance and Muc2 mRNA expression in colon tissues were evaluated using Alcian blue staining and RT-PCR. Results: Amoxicillin caused moderate increases in cecal index, reduced Ligilactobacillus abundance, increased Escherichia-Shigella, lowered SCFA levels, and decreased goblet cells and Muc2 expression, with partial recovery after two weeks. Clindamycin induced more severe dysbiosis, including sustained Proteobacteria expansion, persistent loss of beneficial taxa, 86-90% reduction in SCFA production, and lasting decreases in goblet cells and Muc2 expression without recovery during the observation period. Azithromycin caused mild and reversible changes across all parameters. Conclusions: Among the three antibiotics, azithromycin had the least detrimental effects on gut microbiota, SCFA production, and mucosal barrier function, whereas clindamycin caused profound and persistent intestinal disruption. These findings provide comparative evidence to inform antibiotic selection in clinical practices.