Search Results (3,531)

Peritoneal dialysis (PD)-associated peritonitis remains a major cause of treatment failure, hospitalisation, catheter loss and transition to haemodialysis despite reductions in incidence over the decades. This narrative review examines the global evolution of microbiological epidemiology and pharmacological management of PD-associated peritonitis, looking at global trends in microbiological epidemiology and exploring how treatment recommendations have evolved in response to changing pathogen distribution, antibiotic resistance patterns and associated clinical outcomes. Although Gram-positive organisms remain the predominant pathogens in most PD programmes, recent evidence demonstrates marked geographical and centre-level heterogeneity with rising clinical importance of Gram-negative, polymicrobial, fungal and culture-negative infections in certain regions. Antibiotic resistance has emerged as an additional challenge, including methicillin-resistant staphylococci, vancomycin-resistant enterococci, extended-spectrum β-lactamase-producing Enterobacterales and multidrug-resistant non-fermenting Gram-negative organisms. These changes challenge conventional empirical regimens and emphasise the importance of programme-specific microbiological surveillance. In parallel, pharmacological management has evolved considerably from relatively standardised empirical antibiotic combinations towards an individualised approach incorporating intraperitoneal administration, local susceptibility profiles, organism-directed therapy, pharmacokinetic optimisation, therapeutic drug monitoring and antifungal prophylaxis. However, substantial evidence gaps remain, particularly regarding antibiotic resistance patterns globally, optimal dosing in automated PD, intraperitoneal stability and clinical efficacy of newer antimicrobial agents. Full article

The options for controlling agricultural plant-pathogenic bacterial diseases with antibiotics are rather limited. Applications of naturally derived antimicrobial peptides may offer an alternative. Objectives. The cell-free conditioned media of Xenorhabdus budapestensis and X. szentirmaii bacteria inactivate Erwinia amylovora, the causative agent of fire blight in Rosaceae, both in vitro and in planta. The working hypothesis was that the active ingredient was fabclavine. To test this hypothesis, inducible fabclavine-producing strains were constructed in both Xenorhabdus species. The anti-Erwinia potential of non-induced and induced fabclavine-producing cultures was compared in vitro and in planta. Methods. Promoter exchange mutants known to exclusively produce the fabclavine antibiotic were generated and their fabclavine production was confirmed by LC-HRMS, and in vitro bioassays. Finally, apple blossoms in an incubator were subjected to antimicrobial and control treatments before experimental inoculation of the buds with Erwinia amylovora strain Ea1. Results. Cell-free medium from both induced fabclavine-producing Xenorhabdus species exerted strong antagonistic effects on Ea1 cells in vitro, whereas the non-induced ones showed substantially reduced antibacterial activity. Similarly, both induced culture media prevented fire blight symptoms in experimentally inoculated flowers in a dose-dependent manner. The non-induced X. szentirmaii mutant strain was completely inactive in planta, whereas the X. budapestensis strain exhibited some protective activity. Conclusions. The results support the hypothesis that the fermentation product of the inducible Xenorhabdus mutants producing only fabclavines can be used for protection against E. amylovora. Some aspects of the application perspectives are discussed in comparison with conventional streptomycin and kasugamycin treatments. Full article

Bacterial-infected skin wounds, especially those caused by drug-resistant pathogens accompanied by persistent inflammation, remain a major clinical therapeutic challenge. Rising antimicrobial resistance compromises the therapeutic effect of conventional single-agent antibiotics, creating an urgent demand for novel wound therapeutics that integrate bactericidal potency, immunomodulation and tissue regeneration capacity. In this work, an injectable multifunctional chitosan-based hydrogel (C@MC) was developed, which simultaneously incorporates metformin hydrochloride (as a potential antibiotic adjuvant) and cefazolin sodium (as a β-lactam class antibacterial drug). The optimized C@MC possesses interconnected three-dimensional pores with an initial storage modulus of ~0.83 kPa (C@MC₃₆₀), featuring desirable mechanical strength, injectability, tissue adhesion and dual pH/glucose-responsive sustained drug release. In vitro evaluations revealed the dose-dependent bactericidal activity of C@MC against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and New Delhi metallo-β-lactamase-1-producing E. coli (NDM-1 E. coli, resistant bacteria). The highest drug-laden group nearly eliminated all wound bacteria in vitro. It scavenged reactive oxygen species (ROS) to lower cellular MDA levels and suppress pro-inflammatory TNF-α and IL-6 in LPS-stimulated RAW 264.7 macrophages. In full-thickness mouse wounds infected with NDM-1 E. coli, C@MC₃₆₀ achieved nearly complete wound closure, with only a 4.2% residual wound area on day 14, accompanied by suppressed inflammatory infiltration and accelerated wound regeneration. This dual-drug hydrogel integrates antibiotic potentiation, anti-inflammation and antioxidation, providing an intervention regimen for skin wounds infected with drug-resistant bacteria. Full article

Xenorhabdus species are prolific producers of diverse bioactive natural products. However, the genomic characteristics, biosynthetic potential, and biological activities of Xenorhabdus thuongxuanensis remain poorly characterized. This study aimed to characterize the genomic features and biosynthetic potential of X. thuongxuanensis strains KLK17.5 and KLK18.1 through comparative genomic analyses and to evaluate the antibacterial, antifungal, and cytotoxic activities of their crude extracts. Both strains had genome sizes and GC contents comparable to those of other Xenorhabdus species, with average nucleotide identity (ANI) values of 96–98% supporting their classification as X. thuongxuanensis. Functional annotation identified genes involved in secondary metabolism, while antiSMASH predicted diverse biosynthetic regions showing similarity to known BGCs, including those associated with holomycin, putrebactin, avaroferrin, and aryl polyenes. The crude extracts exhibited antibacterial activity against several antibiotic-resistant bacteria with minimum inhibitory concentration (MIC) values ranging from 0.2 to 6.25 mg/mL. They also inhibited Candida albicans and Cryptococcus neoformans, with inhibition zones ranging from 7.5 to 12 mm and from 10 to 42.5 mm, respectively. The crude extract from KLK18.1 exhibited cytotoxicity against HepG2 cells, with an IC₅₀ value of 10.85 µg/mL. These findings expand the current knowledge of the genomic, biosynthetic, and biological potential of X. thuongxuanensis and provide a basis for future characterization of its BGC-associated metabolites. Full article

Background: Most acute gastrointestinal infections are self-limiting, but antibiotics remain essential for selected patients with severe, invasive, or high-risk disease. This narrative review examines when antibiotics should be started or withheld in adults and children with suspected or confirmed bacterial gastrointestinal infection, which regimens should be selected, and how treatment should be reassessed after diagnostic and susceptibility results become available. Methods: PubMed and Scopus were searched for relevant English-language evidence published from 1 January 2014 through 28 August 2026. Google Scholar was used for supplementary citation tracking, and landmark earlier studies and major international guidelines were also considered. The search informed a narrative synthesis and was not conducted as a systematic review. Sixty-one sources were included. Results: The evidence base is uneven. Recommendations concerning rehydration, avoidance of antibiotics in Shiga toxin-producing Escherichia coli infection, and treatment of Clostridioides difficile infection (CDI) are comparatively consistent. By contrast, treatment thresholds and durations for several enteric infections rely largely on observational evidence, indirect evidence, or expert consensus. Antibiotics should generally be withheld in uncomplicated watery diarrhea and used selectively for dysentery, severe travelers’ diarrhea, cholera, enteric fever, invasive salmonellosis, and CDI. Regimen selection should reflect host risk, illness severity, travel exposure, and local susceptibility data. Therapy should be narrowed or discontinued after diagnostic clarification whenever appropriate. Conclusions: The principal stewardship priorities are appropriate patient selection, culture and susceptibility testing when the results may change management, and use of the shortest effective regimen supported by the available evidence. Full article

Veterinary practice faces rising antimicrobial resistance, driving interest in plant-derived alternatives. Purslane (Portulaca oleracea L.), a medicinal edible herb with antimicrobial, anti-inflammatory, and immunomodulatory properties, is a promising candidate. This narrative review synthesizes 160 studies into a unified framework linking chemical composition (flavonoids, alkaloids, polysaccharides, organic acids), pharmacological activities (12 major effects), and veterinary applications. Mechanistically, polysaccharides act as immunomodulators via the TLR4/MyD88 pathway; flavonoids (quercetin, kaempferol) exert antioxidant/anti-inflammatory effects through NF-κB/MAPK inhibition and Nrf2 activation; organic acid extracts show potent anti-MRSA activity (MIC 0.5–1.0 mg/mL); and alkaloids enhance insulin secretion. In vivo, dietary purslane at 2–3% improves broiler growth performance and feed conversion, while supplementation enriches omega-3 fatty acids in eggs and meat. However, translational barriers persist, including limited pharmacokinetic data, lack of large-scale field trials, and insufficient safety and residue-depletion information for food-producing animals. We outline future priorities, including species-specific pharmacokinetic studies, field efficacy trials, and quality-control standards, positioning purslane as a mechanism-rich, antibiotic-sparing candidate for further investigation in veterinary therapeutics and functional feed additives. Full article

Klebsiella pneumoniae can cause a wide array of infections and exhibit substantial phenotypic heterogeneity depending on the infection site. However, less is known about phenotypic heterogeneity among bacteria isolated from the same infection site. We screened K. pneumoniae clinical isolates taken from various infection sites and found that 4 of 29 isolates produced two colony morphologies on antibiotic-supplemented chromogenic agar, which we classified as solid and gelatinous based on their appearance. The paired colony phenotypes exhibited similar growth in rich and chemically defined media and comparable carbon-source utilization, but differed in antimicrobial susceptibility and virulence-associated traits. Gelatinous colonies tended to produce more capsular polysaccharide, and displayed greater colony spreading, whereas solid colonies produced more biofilm. To determine whether the divergent phenotypes could occur in a closely related genomic background, we performed Oxford Nanopore whole-genome sequencing of the solid and gelatinous colonies from MCFM21. Mapping of solid-colony reads to the gelatinous-colony assembly demonstrated 99.86% primary-read mapping with genome-wide coverage across the 5.29 Mb chromosome and 198 kb circular contig. Haploid variant calling identified one strongly supported single-nucleotide variant and 30 candidate indels. Together, these findings demonstrate that differences in K. pneumoniae colony morphology, capsule, biofilm, colony spreading, and antimicrobial susceptibility can occur between closely related populations recovered from the same clinical specimen. Full article

Vermicomposting has been shown to be a cost-effective and sustainable approach for improving the environmental safety of sewage sludge, yet it remains comparatively understudied at the industrial scale. This study investigates how vermicomposting with the earthworm Eisenia andrei alters the taxonomic and functional diversity of bacterial and fungal communities in sewage sludge, including human-associated pathogens. Using 16S rRNA and ITS metabarcoding, we compared fresh sludge and sludge aged for 13 months without earthworms to vermicomposted sludge after 13 months. The study included one pilot-scale vermireactor and one control pilot-scale reactor with ten spatial subsamples per sampled layer (30 subsamples). Bioinformatic and statistical analyses showed that vermicomposting may produce significant shifts in taxonomic composition, reduce the abundance of baseline taxa, and enrich decomposer-associated bacteria and fungi. Both bacterial and fungal alpha diversity (e.g., Shannon) increased over time, while beta diversity (e.g., Bray–Curtis) analyses indicated heterogeneous changes in community structure across treatments and time points. Vermicomposting also seemed to activate the prediction of pathways associated with nitrogen metabolism, amino acid biosynthesis, and pollutant degradation, while reducing the prevalence of predicted antibiotic resistance. Human bacterial pathogens exhibited persistence but also temporal variation, suggesting compositional shifts during vermicomposting. Fungal communities transitioned from pathogen-associated taxa to predominantly saprotrophic and multifunctional groups, particularly in vermicompost. Overall, these findings suggest that vermicomposting may contribute to restructuring microbial communities in sewage sludge, with potential implications for the sustainability and safety of this biosolid. Full article

Antimicrobial peptides (AMPs) are regarded as promising candidates for the post-antibiotic era because of their broad-spectrum bactericidal activity and low propensity to induce bacterial resistance. However, their small molecular weight and intrinsic cytotoxicity toward the expression host result in poor soluble expression and low yields when unmodified AMPs are produced directly in prokaryotic systems. In this study, the coding sequences of three AMPs (Swine_2, P3-3R-8I, and QLX-3DV-1) were assembled by primer-complementary PCR, and nine recombinant expression vectors covering three fusion-tag systems were constructed by restriction digestion and ligation, namely pET32a-Swine_2, pET32a-P3-3R-8I, pET32a-QLX-3DV-1, pET32a-GSHHW-Swine_2, pET32a-GSHHW-P3-3R-8I, pET32a-GSHHW-QLX-3DV-1, pET3C-SUMO-Swine_2, pET3C-SUMO-P3-3R-8I, and pET3C-SUMO-QLX-3DV-1. The resulting plasmids were transformed into Escherichia coli BL21(DE3), and the nine fusion proteins were expressed under IPTG induction and auto-induction. The fusion proteins were purified by Ni-NTA affinity chromatography; the target AMPs were released by enterokinase digestion, SNAC-mediated chemical cleavage, or SUMO protease digestion, and the peptides were recovered by ultrafiltration. The antibacterial activity of the recovered peptides against E. coli and Staphylococcus aureus was systematically compared using the agar diffusion assay and the broth microdilution method. All three strategies yielded bioactive AMPs. For a given peptide backbone, the three preparations showed identical MIC values, whereas the peptides released by SUMO protease produced the largest inhibition zones. Because the three preparations of any one backbone share an identical primary sequence and an identical MIC, this difference cannot be attributed to a higher intrinsic potency of the peptide; it is treated here as a semi-quantitative observation. This study provides a complete technical workflow and a methodological reference for the engineered production of AMPs. Full article

Background/Objectives: Antimicrobial resistance has renewed interest in bacteriophage cocktails as antibacterial and adjunctive agents, but the global research landscape and the bacterial determinants that constrain cocktail performance have not been mapped within a single framework. We quantified global phage-cocktail research and tested whether antibiotic-resistance, phage-receptor, and biofilm gene sets converge on shared genes in three Gram-negative pathogens representing three bacterial orders. Methods: The Web of Science Core Collection was searched on 5 July 2026 (query “phage” and “cocktail”). After deduplication and screening, 1598 articles and reviews (1992–2026) were analyzed with bibliometric workflows, citation-burst and co-citation analyses, and a focused China–United States comparison. Because these are the two leading producers and represent the dominant biocontrol and clinical research models, the comparison is deliberately restricted to them and is not presented as a global ranking. Resistance (R), phage receptor/defense (P), and biofilm (B) gene sets were curated for Pseudomonas aeruginosa PAO1, Escherichia coli K-12, and Acinetobacter baumannii ATCC 17978; overlaps were tested by one-sided hypergeometric tests with Benjamini–Hochberg correction and against size-matched control gene sets, followed by STRING protein–protein interaction and KEGG/GO enrichment. Orthologous conservation was assessed with KEGG Orthology in addition to gene-symbol matching. Results: Annual output grew from 2 records (1992–1996) to 873 (2022–2026; 54.6% of the corpus), led by the USA (322 records) and China (292). Phage-receptor–biofilm overlaps were strongly enriched in all three species (29, 7, and 28 genes; odds ratios 47.0, 8.1, and 31.7; all P ≤ 7.6 × 10⁻⁵), whereas resistance–phage-receptor overlaps were strongly enriched in PAO1 (18 genes; odds ratio 17.7) and K-12 (26 genes; odds ratio 30.2) but not in A. baumannii (9 genes; odds ratio 1.8; P = 0.088). Four unrelated control gene sets showed no enrichment in any species (odds ratios 0–1.9; P ≥ 0.42). Candidate networks formed alginate, Psl–Pel, lipopolysaccharide-modification, and SOS/porin modules; KEGG enrichment converged on biofilm formation and cationic antimicrobial peptide resistance; 14 of the 18 symbol-level conserved genes were corroborated by shared KEGG Orthology assignments. Conclusions: Phage-cocktail research has entered a phase of rapid growth, with hotspots converging on combination therapy and formulation. Biofilm-matrix synthesis and surface-appendage assembly form a transferable interface between phage adsorption and biofilm formation across three bacterial orders, whereas the coupling between antibiotic resistance and phage-receptor genes is lineage-restricted. Because the R, P, and B sets overlap by construction, these convergences are hypothesis-generating and require experimental validation before they can be used as design rules. Full article

Infective endocarditis (IE) is a rare but life-threatening infection of the endocardial surface of the heart, usually arising when circulating microorganisms colonise the cardiac valves; it carries an in-hospital mortality of roughly 15–30%. Because oral viridans group streptococci cause a substantial proportion of community-acquired cases, antibiotic prophylaxis (AP) before invasive dental procedures has historically been central to prevention, placing dental practitioners at the centre of a long-standing and unsettled debate. This narrative review synthesises the contemporary evidence and the divergence between major guideline bodies. The 2023 European Society of Cardiology (ESC) guidelines raised AP for high-risk patients to a Class I recommendation, and the 2021 American Heart Association (AHA) statement remains closely aligned, restricting AP to those at highest risk of adverse outcome. The United Kingdom’s National Institute for Health and Care Excellence (NICE), by contrast, has advised against AP since 2008 (and, since a 2016 amendment, against its routine use). This divergence has produced an international discordance that leaves clinicians and patients facing conflicting advice. This review examines the pathogenesis and microbiology of oral-origin IE, the conditions and procedures that define risk, and the contested epidemiological evidence, including population-level data linking reduced prescribing to rising IE incidence. It then discusses the implications for clinical practice and the central role of oral health. The evidence base remains observational and associative rather than causal; definitive randomised data are lacking. The review argues that, pending stronger evidence, dentists should identify the framework governing their jurisdiction, apply it consistently, prioritise oral health, and share documented decisions with patients. Full article

Antimicrobial resistance is nowadays a global health issue, mainly related to antibiotic overuse and misuse in different sectors. In veterinary medicine, it is essential to understand farmers’ knowledge and awareness of this serious problem in order to minimize it. In Spain, there are virtually no studies on this issue. A cross-sectional online study was carried out among Spanish farmers to identify their knowledge and awareness of antibiotic use and antimicrobial resistance (AMR). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated, and logistic regression analysis was also performed. 217 farmers took part in the study, and 215 surveys were analyzed. Farmers were mainly men (60%), middle-aged (76.8%), and with more than 15 years of professional experience (41.4%). They worked mostly in extensive systems of production (53.5%), usually with only one species (54%), with ruminants being found in most farms (70.2%). Most participants showed a satisfactory knowledge of this topic, a positive attitude towards reducing the use of antibiotics, and a growing awareness of their importance for public health, although for almost a fifth of them the meaning of AMR is unclear. Respondents were more likely to achieve satisfactory scores if they were between 31 and 45 years (OR = 2.42, p < 0.05) and rearing only ruminant species (OR = 2.51, p < 0.05). Spanish livestock farmers have an acceptable level of knowledge about antibiotics and AMR, although there are still gaps related to the adequate use of these drugs. Full article

Staphylococcus epidermidis biofilms are inherently tolerant to antimicrobial treatment, contributing to the persistence and recurrence of biofilm-associated infections. In this study, we examined the phenotypic and proteomic responses of S. epidermidis ATCC 35984 biofilms following exposure to subinhibitory concentrations (1/8× MIC) of levofloxacin, rifampicin, and their combination. Phenotypic analyses revealed clear differences among the treatments. Rifampicin significantly reduced the number of viable biofilm-associated cells, whereas levofloxacin alone had little effect. The combination of rifampicin and levofloxacin produced the most pronounced antibiofilm activity, significantly reducing both biofilm biomass and viability. These findings were supported by confocal laser scanning microscopy, which showed the greatest loss of viable cells and biofilm integrity in the combination-treated biofilms. Label-free quantitative proteomic analysis demonstrated distinct treatment-specific adaptive responses. Rifampicin, either alone or in combination with levofloxacin, triggered broadly increased abundance of proteins involved in translation, energy production, amino acid and nucleotide metabolism, ATP-binding cassette transport, and quorum sensing. In contrast, levofloxacin predominantly suppressed proteins associated with central metabolism, transcription, translation, and biosynthetic pathways. Hierarchical clustering further showed that the proteomic profile of the combination treatment closely resembled that of rifampicin alone, suggesting that rifampicin was the dominant driver of proteomic remodeling. Expression pattern network analysis identified a conserved stress-response signature comprising Fhs, YdaG, PerR, and YcsE across all treatment conditions. Notably, the multidrug efflux pumps NorA and NorC showed decreased protein abundance across all treatment conditions, indicating a potential reduction in efflux-mediated resistance under sub-MIC antibiotic exposure. Taken together, these findings demonstrate that rifampicin retains substantial antibiofilm activity at subinhibitory concentrations and elicits extensive metabolic adaptation, whereas levofloxacin primarily induces a metabolically repressed state. The enhanced activity of the rifampicin–levofloxacin combination appears to arise from complementary effects on biofilm viability and cellular physiology. This study provides new insights into the adaptive responses of S. epidermidis biofilms to sublethal antibiotic stress and highlights the potential of rifampicin-based combination therapies for the management of biofilm-associated infections. Full article

Background/Objectives: The growing global burden of antimicrobial resistance highlights the need for whole-animal screening platforms that better reflect in vivo determinants of antimicrobial efficacy. A Caenorhabditis elegans infection–rescue model previously developed for antibiotic screening against Enterococcus faecalis was adapted to evaluate additional clinically relevant Gram-positive and Gram-negative bacteria. Methods: L4-stage AU37 worms were infected with Staphylococcus aureus 2406, E. faecalis ATCC51299, Escherichia coli CFT073, and Pseudomonas aeruginosa PAO1. Pathogen-specific infection durations were optimized using conventional antibiotic treatments, including vancomycin for S. aureus and gentamicin for E. faecalis, E. coli, and P. aeruginosa. Following antibiotic treatment, pathogen-specific mean rescue rates (MRR) were determined. Assay performance was then validated using positive- and negative-control antibiotics selected based on contrasting susceptibility profiles. Results: Optimized antibiotic-mediated rescue occurred at pathogen-specific time points following treatment with vancomycin for S. aureus and gentamicin for the remaining pathogens, 48 h for S. aureus (MRR, 92.6% ± 3.5%), 72 h for E. faecalis (89.4% ± 3.6%), 4 h for E. coli (94.5% ± 3.6%), and 72 h for P. aeruginosa (85.5% ± 9.1%) following treatment with conventional antibiotics, with all treated groups differing significantly from controls (p < 0.001). Positive-control antibiotics, including chloramphenicol, tetracycline, and amikacin, produced strong rescue at the optimized infection time points. In contrast, negative-control antibiotics, including erythromycin and chloramphenicol, produced minimal rescue. Conclusions: These data show that the C. elegans infection–rescue model can distinguish effective from ineffective antibiotic treatment across the four tested bacterial infection conditions and may serve as a useful early-stage platform for antimicrobial screening. Full article

Antipsychotic drugs are essential for the treatment of schizophrenia-spectrum disorders and other severe psychiatric conditions, but several agents produce clinically important metabolic and gastrointestinal adverse effects. Increasing evidence suggests that these outcomes may involve bidirectional interactions between antipsychotics and the gut microbiota. This structured narrative review integrates human, animal, gnotobiotic, in vitro, pharmacokinetic, and multi-omic evidence to examine drug-specific microbiome effects and microbiota-dependent modulation of host responses. Olanzapine has the strongest mechanistic evidence, with germ-free, antibiotic-depletion, colonization, and vagotomy studies supporting a contributory role of the microbiota in weight gain, adiposity, inflammation, altered microbial metabolites, and lipid dysregulation. Risperidone also shows microbiota-dependent metabolic and neurobiological effects, whereas findings for clozapine, quetiapine, aripiprazole, lurasidone, and amisulpride remain more heterogeneous or limited. Across agents, no universal taxonomic pattern has emerged. Functional pathways involving short-chain fatty acids, bile acids, epithelial barrier integrity, immune and neuroendocrine signaling, vagal pathways, and microbial drug metabolism appear more informative than individual taxa or the Firmicutes/Bacteroidota ratio. Current evidence remains limited by methodological heterogeneity, small cohorts, confounding, and predominantly preclinical mechanistic data. Prospective, treatment-naive, drug-specific longitudinal multi-omic studies are required. Full article