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When a population of bacteria is exposed to a bactericidal antibiotic, most cells die rapidly. However, a subpopulation of antibiotic-tolerant cells known as 'persister cells' can survive for prolonged periods. In addition, antibiotic tolerance can be broadly induced throughout the population by stresses such as nutrient deprivation. However, the pathways required to maintain viability in this setting and how stress induces antibiotic tolerance are both poorly understood. To identify genetic determinants of antibiotic tolerance in mycobacteria, we carried out transposon insertion sequencing (Tn-Seq) screens in Mycobacterium abscessus (Mabs) exposed to bactericidal translation-inhibiting antibiotics. This analysis identified genes essential for the survival of both spontaneous persister cells, as well as for stress-induced tolerance, allowing the first genetic comparison of these states in mycobacteria. Pathway analysis identified multiple genes involved in the detoxification of reactive oxygen species (ROS), including the catalase-peroxidase katG, which contributed to survival in both unstressed and nutrient-starved cells. In addition, we found that endogenous ROS were generated by translation-inhibiting antibiotics, and that hypoxia impaired bacterial killing. KatG specifically contributed to survival following exposure to transcription or translation inhibitors, but not other antibiotic classes tested. Thus, the lethality of some antibiotics is amplified by toxic ROS accumulation, and antibiotic-tolerant cells require detoxification systems in order to remain viable. These findings further demonstrate that antibiotic-induced ROS plays a broad role in mediating antibiotic lethality across diverse organisms.
The inappropriate use of antibiotics leads to a range of clinical and administrative problems. Understanding antibiotic use in different contexts is therefore essential. This study aims to describe antibiotic use among hospitalized patients in a specialized pediatric center in Peru. This was a descriptive cross-sectional study. Data were collected using the WHO methodology for point prevalence surveys of antimicrobial use. All patients hospitalized during November 2023 were included. Demographic data, antibiotic use, and types of infections were recorded. A total of 252 patients were evaluated, of whom 127 (50.4%) received 186 antibiotic treatments. Most patients (58.7%) received only one antibiotic prescription. Most infections treated were healthcare-associated infections, with empirical treatment initiated based on a diagnosis of clinical sepsis. The most used antibiotics were vancomycin (21.5%), meropenem (15.6%), and piperacillin/tazobactam (10.8%). Most antibiotics were prescribed empirically at the discretion of the treating physician. Ongoing evaluation of antibiotic use patterns is essential to develop targeted interventions aimed at improving infection control and reducing antimicrobial resistance. El uso inadecuado de antibióticos genera una serie de problemas tanto clínicos como administrativos, por lo que conocer su comportamiento en diversas situaciones se vuelve relevante. Por dicho motivo el objetivo del presente estudio es describir el uso de antibióticos en pacientes hospitalizados en un centro pediátrico especializado en Perú. Estudio transversal descriptivo. Se recolectaron datos utilizando la metodología propuesta por la OMS para la prevalencia puntual de uso de antimicrobianos. Se incluyeron todos los pacientes hospitalizados durante noviembre del 2023, registrando información demográfica, el uso de antibióticos y tipos de infecciones. Se evaluaron 252 pacientes, de los cuales 127 (50.4%) recibieron 186 tratamientos antibióticos. La mayoría (58.7%) recibía una sola prescripción con un antibiótico. Asimismo, la mayoría de las infecciones tratadas fueron infecciones asociadas a la atención de la salud, recibiendo tratamiento empírico por un diagnóstico de sepsis clínica. Los antibióticos más usados fueron vancomicina, meropenem y piperacilina/tazobactam (21.5, 15.6 y 10.8% respectivamente). La mayoría de los antibióticos se recetaron en la primera prescripción bajo responsabilidad del médico tratante. Es necesario realizar una evaluación continua de los patrones de uso de antibióticos para desarrollar estrategias de intervención específicas que mejoren el control de infecciones y la resistencia antibiótica.
Robot-assisted radical cystectomy (RARC) is a growingly preferred minimally invasive technique for bladder extraction and urinary reconstruction. Postoperative urinary tract infections (UTIs) remain one of the most common complications. This narrative review examines the role of prophylactic antibiotics in reducing UTIs following RARC, with attention to risk factors, antimicrobial resistance patterns, and emerging non-antibiotic preventive strategies. A literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar for English-language articles published between January 2014 and October 2025. Search terms included "urinary tract infection," "radical cystectomy," "antibiotic prophylaxis," "drug resistance," and "non-antibiotic strategies." Clinical trials, meta analysis, and randomized controlled trials were prioritized. Key themes included UTI prevalence, bacterial resistance trends, prophylactic approaches, and the potential applicability of adjunctive non-antibiotic measures. UTI incidence after RARC ranges from 14% to 39%, typically within 30 days but occasionally up to 90 days. Risk is influenced by patient factors such as age, female sex, and obesity, as well as surgical variables. Prophylactic antibiotics are associated with reduced UTI rates, though optimal duration remains uncertain. Evidence suggests short-course regimens are often effective, while extended prophylaxis may benefit selected high-risk patients. However, rising resistance, particularly to fluoroquinolones and cephalosporins, complicates empirical treatment. Prophylactic antibiotics after RARC reduce postoperative UTIs and related complications. However, conflicting RCT evidence and lack of consensus on duration require balancing benefits against risks of antimicrobial resistance and Clostridioides difficile infection. A comprehensive strategy-including culture-guided therapy, protocol adherence, and non-antibiotic preventive measures-may optimize outcomes.
The escalating antimicrobial resistance crisis demands innovative strategies for antibiotic discovery. Conventional approaches for identifying antibiotic-producing microorganisms from environmental samples are often laborious and low-throughput, requiring prior isolation and purification of individual strains. Here, we developed a high-throughput screening platform integrating a microbial whole-cell biosensor into a double-layer plate assay, enabling rapid identification of bacteria producing cell wall-targeting antibiotics from environmental samples. The biosensor is based on the PghKR two-component system from the gram-negative bacterium Shewanella oneidensis MR-1. Upon exposure to cell wall-targeting antibiotics, PghKR activates the promoter of blaA, driving expression of the luxCDABE reporter and generating luminescence. A highly sensitive biosensor was engineered through the synergistic deletion of blaA and ampG, which greatly improved its responsiveness. The method was then applied to screen soil samples. From the primary screen, 103 colonies producing distinct luminescent signals were identified. Of these, 36 isolates consistently activated the biosensor in a confirmation assay, and 5 exhibited antibacterial activity against a multidrug-resistant indicator strain. This integrated approach combines microbial separation with immediate biosensor-based detection, thereby accelerating the discovery of novel antibiotic producers from complex environmental communities. The rise of antimicrobial resistance calls for faster, more efficient ways to discover new antibiotics from environmental microbes. Traditional methods are slow because they require laborious, one-by-one isolation and purification of individual strains before any activity testing. To overcome this bottleneck, we developed a simple double-layer plate assay that directly identifies bacteria producing cell wall-targeting antibiotics while they grow. This "grow-and-detect" strategy bypasses traditional isolation steps, dramatically speeding up the initial discovery pipeline. Our platform enables large-scale, low-cost screening of environmental samples for antibiotic producers.
The effect of perioperative antibiotics covering bacteriobilia on organ/space surgical site infection (SSI) after pancreaticoduodenectomy (PD) with preoperative biliary drainage (PBD) remains unclear. This study aimed to evaluate the effect of prophylactic antibiotics covering bacteriobilia on postoperative complications of patients undergoing PD with PBD. Clinicopathological data of patients who underwent PD with PBD between May 2019 and December 2024 were analyzed retrospectively. Risk factors of organ/space SSI were identified using univariate and multivariate analysis. Propensity score matching (PSM) with a ratio of 1:1 was conducted to minimize bias from baseline characteristics between the sufficient and insufficient antibiotic coverage groups. Based on coverage of cultured biliary bacteria, 210 (55.6%) patients received sufficient perioperative antibiotics. Organ/space SSI occurred in 204 (54.0%) patients, and perioperative antibiotics (OR = 4.353, 95%CI = 2.803-6.761, P < 0.001) were the only independent risk factor. Both before and after PSM, the group receiving sufficient antibiotics exhibited a significantly lower incidence of organ/space SSI (P < 0.05) compared to those with insufficient coverage. Postoperative cholangitis was also significantly reduced in the sufficient group (pre-PSM: 2.9% vs. 8.9%, P = 0.008; post-PSM: 3.0% vs. 7.6%, P = 0.045). Perioperative antibiotics regimens specifically targeting bile cultures reduce the risk of organ/space SSI in patients undergoing PD with PBD. Therefore, bile cultures in PBD patients can guide the optimal choice of perioperative prophylactic antibiotics to minimize organ/space SSI.
Ophthalmic infections, including conjunctivitis and keratitis, caused by Streptococcus pneumoniae may lead to significant ocular morbidity. Rising antibiotic resistance among ocular pathogens has reduced the efficacy of conventional treatments highlighting the need for alternative antimicrobial strategies. This study aimed to evaluate the antimicrobial potential of bacteriocins produced by lactic acid bacteria (LAB) against antibiotic-resistant Streptococcus pneumoniae isolated from clinical ophthalmic samples and to compare their efficacy with conventional antibiotics. A total of 230 eye swab samples were collected from patients attending Rashid Latif Medical Complex (RLMC), Lahore, Pakistan. S. pneumoniae isolates were identified using morphological, biochemical, and 16 S rRNA gene sequencing methods. Antibiotic susceptibility was performed using the agar well diffusion method. LAB strains from milk, curd, and pickle samples were identified by 16 S rRNA sequencing and screened for bacteriocin-mediated inhibitory activity against S. pneumoniae. Bacteriocin concentrations were quantified using the Bradford assay, and molecular weight was determined by SDS-PAGE. Four S. pneumoniae isolates exhibited varying resistance patterns, including resistance to ciprofloxacin and gentamicin. LAB strains, particularly Enterococcus faecium and Ligilactobacillus salivarius, demonstrated inhibitory activity against S. pneumoniae, with inhibition zones of up to 8.6 mm. Bacteriocin concentrations ranged from 3.55 to 7.17 µg/mL, with an estimated molecular weight of ~ 3.5 kDa. LAB-derived bacteriocins exhibit promising antibacterial activity against antibiotic-resistant S. pneumoniae, suggesting their potential as cost-effective and sustainable alternatives to conventional antibiotics for ophthalmic infections. Further studies on purification, formulation, and in vivo evaluation are required to advance bacteriocin-based therapeutics toward clinical application.
Actinomycetoma is a chronic infectious disease recognized by the World Health Organization as a neglected tropical disease. In the Americas, the most common etiologic agent is the Gram-positive bacterium, Nocardia brasiliensis. This pathogen is a facultative intracellular organism that can multiply and survive within macrophages, evading microbicidal mechanisms by inducing an immunosuppressive environment. Current antibiotic treatments are expensive, prolonged and toxic, and bacterial resistance has been reported. Host defense peptides, known for their bactericidal and immunomodulatory properties, represent a promising new therapeutic approach. Recently, DMS-DA6, a dermaseptin isolated from the Mexican tree frog, Pachymedusa dacnicolor, has been shown to exert strong activity against Gram-positive bacteria, including multidrug-resistant strains. Our study evaluated the effects of DMS-DA6 in a mouse model of actinomycetoma caused by N. brasiliensis, comparing it with the conventional antibiotic linezolid. Infected mice were treated either twice a week with this peptide at a dose of 12.5 mg/kg or every 12 h with linezolid at a dose of 25 mg/kg over a four-week period. Our results suggest that DMS-DA6 is more effective at resolving the disease than linezolid, as it achieves a similar reduction in inflammation and bacterial load of the footpad at a lower dose and with fewer injections. Furthermore, DMS-DA6 modulates IL-10, IL-1α, and IL-6 levels at the chronic stage of actinomycetoma infection and increases the abundance of CD4 + and CD8 + T lymphocytes in the infected footpad. These findings highlight the potential of DMS-DA6 as an innovative addition to current treatments.
Wastewater released from hospitals acts as environmental reservoir of antibiotic-resistant genes (ARGs) harbouring bacteria and act as disseminators of antimicrobial resistance (AMR). To determine the mechanism of horizontal gene transfer (HGT) conjugation assay was performed. The present study focuses on environmental plasmid mediated HGT of multidrug resistant (MDR) Aeromonas spp. recovered from hospital effluents to bacteria such as Escherichia coli and Salmonella enterica serovar Typhimurium. Broth mating conjugation assays exhibited variation in the conjugation frequency across the strains. Molecular analyses verified the transmissibility of the plasmids from the donor strains conferring clinically relevant resistance genes (tet(A), OXA-513, KPC-2, mexC and vanA) to recipient strains. The study also revealed selective plasmid mobilization, as no conjugative transfer was observed from two donor strains. The remaining donor strains demonstrated transferability, supported by the presence of genes required for conjugative transfer, mobilization and integrase activity. Plasmid curing under non-selective conditions demonstrated progressive plasmid segregation. The persistence and acquisition of ARGs post-transfer was confirmed by quantitative PCR (qPCR), with highest abundance of tet(A) gene across all transconjugants. Conjugation assays demonstrated laboratory-based horizontal transferability of ARGs, and plasmid curing assays support the plasmid-associated nature of the detected resistance determinants. Understanding these gene transfer mechanisms offer insights crucial for developing effective surveillance and mitigation strategies.
Listeriosis caused by Listeria monocytogenes is an important emerging foodborne disease worldwide and possesses remarkable environmental adaptability, enabling its evolution under diverse host and environmental conditions. To address this, the present study investigated the occurrence, virulence potential, biofilm-forming ability, and antimicrobial resistance profiles of L. monocytogenes isolated from animal- and plant-derived foods collected from four states of India during 2023-2025. A total of 941 food samples, comprising animal-derived foods (n = 690) and plant-derived foods (n = 251), were analyzed using EN ISO 11290-1:2017 protocols, VITEK® 2 identification, and duplex PCR confirmation. Overall, 21 isolates (2.23%) were confirmed as L. monocytogenes, with higher positivity observed in plant-derived foods (3.59%) compared to animal-derived foods (1.74%). All isolates harboured major virulence-associated genes (plcA, prfA, hlyA, actA, and inlC). Animal-derived isolates exhibited significantly higher virulence characteristics, including stronger hemolytic activity, earlier PI-PLC expression, and greater lethality in the G. mellonella larvae compared to plant-derived isolates. Biofilm biomass also increased significantly with incubation time in both groups of isolates; however, the magnitude of biofilm formation differed significantly (p = 0.001) between the two groups of isolates. Antimicrobial susceptibility testing revealed multidrug resistance among isolates from both sources; however, plant-derived isolates exhibited a more uniform resistance pattern, while animal-derived isolates showed greater variability. The findings highlight that the source of isolation of L. monocytogenes plays a significant role in shaping the virulence, biofilm formation, and antimicrobial resistance characteristics of the isolates, and hence warrant studies to understand how environmental and host-specific conditions can influence the adaptive evolution and pathogenic potential of microbial isolates.
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Antibiotics can be released into the environment when used to treat bacterial infections in humans and animals. These residues are poorly removed by wastewater treatment processes, leading to the selection of bacterial antibiotic resistance that impacts human, animal, and environmental health. To combat antibiotic resistance, photopharmacology is a promising emerging technology. Based on the coupling of an antibiotic with a photochromic unit, it enables the spatiotemporal control of the drug's antibacterial activity by modulating the conformation of the molecules using light. Couplings between ciprofloxacin and photochromic nuclei have led to the synthesis of the Triazole-Ciprofloxacin (TC) compound families. The antibacterial activity of the compounds was evaluated through an initial screening at a concentration of 50 mg/L in the absence and presence of UVA exposure, using the microdilution technique, to select the compounds with the highest antibacterial potency. The determination and comparison of the MIC50 values of the selected TC compounds identified molecules exhibiting increased activity resulting from a conformational change under UVA exposure.
Sulfate-reducing microbiomes (SRMs) have shown strong potential for antibiotic remediation, yet the active microorganisms and community-level strategies associated with sulfamethoxazole (SMX) biotransformation remain poorly understood. In this study, long-term bioreactor operation (269 days; 500-1500 μg/L SMX), DNA-stable isotope probing (DNA-SIP), and metagenomic analyses were integrated to investigate the microbial contributors and functional organization underlying SRM-driven SMX biotransformation. Desulfobacterium, a key SRM member, was co-enriched with Geobacter and Leptolinea in the 13C-labeled heavy fraction, suggesting potential metabolic complementarity during community-level SMX biotransformation. Genome-resolved analyses further revealed structured patterns of inferred horizontal gene transfer (HGT) and predicted metabolite exchange among keystone taxa. The transferred genes were mainly associated with energy conservation, transport, sulfur-associated metabolism, and stress-response functions, whereas the predicted exchanged metabolites included carbon metabolites, amino acid-related sulfur compounds, purine-related intermediates, and cofactor-associated metabolites. Together, these findings suggest that HGT-associated functional redistribution and metabolic complementarity may contribute to the persistence and coordinated activity of sulfate-reducing microbiomes under high SMX stress. This study links SIP-identified active populations with genome-inferred interaction patterns in a sulfate-reducing system and provides new insight into microbiome-based anaerobic strategies for antibiotic-containing wastewater treatment.
Digital dermatitis (DD) is the leading cause of lameness in cattle, posing major animal welfare and economic concerns. Effective prevention strategies are increasingly important given emerging antimicrobial resistance associated with common DD treatments. Supplementation with Saccharomyces cerevisiae fermentation postbiotics (SCFP) has been shown to enhance innate immunity and reduce DD lesion development. This study evaluated the effect of a commercial SCFP supplement on the microbial composition of DD lesions using shotgun metagenomic sequencing to characterize microbial communities and associated antimicrobial resistance genes. Beta diversity analysis revealed that stage M4 DD lesions from SCFP-supplemented cows had a trend for different microbial compositions compared with controls (P = 0.051). At the genus level, M2 lesions were found to have statistically significant lower abundance of the genera Desulfovibrio, Pseudomonas, Staphylococcus, Anaerotignum, Caproicibacterium, and Bacteroides in the SCFP treatment group compared with the control (P < 0.05). M2 lesions from the SCFP treatment group were also found to have statistically significant higher abundance of the genera Fusobacterium, Citricoccus, Listeria, and Fundicoccus as compared with the control (P < 0.05). M4 lesions were found to have statistically significant lower abundance of the genera Blautia and Petrimonas in the SCFP treatment group compared with the control (P < 0.05). At the species level, M2 lesions were found to have statistically significant lower abundance of the species Desulfovibrio sp. G11, Anaerotignum sp. MB30-C6, Caproicibacterium argilliputei, and Prevotella intermedia in the SCFP treatment group compared with the control (P < 0.05). M2 lesions from the SCFP treatment group were also found to have statistically significant higher abundance of the species Fundicoccus culcitae and Helcococcus ovis as compared with the control (P < 0.05). Metagenomic analysis identified antimicrobial resistance genes associated with multiple antibiotics commonly used for DD treatment, including tetracyclines, lincosamides, and pleuromutilins. These findings demonstrate the potential for SCFP supplementation to alter the microbial composition of DD lesions while highlighting the ongoing concerns regarding antimicrobial resistance in DD management.IMPORTANCEDigital dermatitis (DD) causes substantial economic loss and welfare concerns in cattle production systems worldwide. Our findings show that dietary supplementation with Saccharomyces cerevisiae fermentation postbiotics (SCFP) has the potential to alter the microbial ecology of DD lesions. Importantly, this work identifies antimicrobial resistance genes within DD lesions, underscoring the limitations of antibiotic-based control strategies. By linking nutritional supplementation to changes in microbial communities and resistance gene profiles, this study advances understanding of non-antibiotic approaches to disease mitigation and supports the development of sustainable, microbiome-informed management practices in food animal production.
Introduction an objective:Urinary tract infections (UTIs) are a significant health concern with high costs and poor quality of life (QoL) impact. Managing recurrent UTIs (rUTI) in women requires effective treatments that relieve symptoms and reduce recurrence, while also sparing antibiotics due to rising resistance. This study evaluates the efficacy of a nutritional supplement in reducing UTI recurrences and improving QoL compared to antibiotic therapy.Materials and methods:The study compared the effectiveness of a dietary supplement (containing D-mannose, Palmitoylethanolamide, N-acetylcysteine, Lactobacillus rhamnosus, and Hibiscus extract) with a low dose of Fosfomycin in treating recurrent urinary tract infections (rUTI) in women. Both treatments were administered for 6 months, with clinical and microbiological evaluations at 3 and 6 months. Quality of life and patient satisfaction were assessed using specific questionnaires. Fosfomycin was given every 10 days, while the supplement was taken for 14 days each month.Results:The study involved 55 patients in the nutritional supplement group (NGroup) and 34 in the Fosfomycin group (FGroup). In the NGroup, the average age was 62.2 years, with a BMI of 27.2. UTIs significantly decreased from 1.87 at baseline to 0.51 at 3 months and 0.28 at 6 months (p < 0.001). Few mild gastrointestinal side effects were reported. Quality of life (QoL) and satisfaction both improved significantly. In the FGroup, the average age was 62.9 years, with a lower BMI of 23.5. UTIs also decreased from 2.68 at baseline to 0.87 at 3 months and 0.67 at 6 months (p < 0.001). No side effects were reported. QoL improved, but satisfaction declined significantly. Both groups showed similar improvements in UTI frequency and QoL, but the Fosfomycin group had lower satisfaction overall.
Cell population data (CPD) from the Sysmex XN-Series hematology analyzer have attracted attention as a new leukocyte biomarker in the field of infectious diseases. For CPD, we focused on the fluorescent light distribution of the neutrophil area (NE-WY) and recently reported that it is useful for the early diagnosis of bacteremia. In clinical practice, the rapid assessment of the effectiveness of antibiotic treatment is as important as the early recognition of bacteremia, but it is still unclear whether NE-WY is useful. We compared the time-dependent changes in NE-WY with parameters commonly used in 54 patients with bacteremia who responded well to initial antibiotic treatment. NE-WY peaked approximately 1 day earlier than C-reactive protein (CRP) and returned to baseline levels significantly earlier. Additionally, NE-WY fluctuated in a similar manner as white blood cells (WBCs) and neutrophils (Neut), but NE-WY had narrower error bars and tended to reach a plateau at the reference value more quickly. This is the first report to demonstrate that NE-WY is a highly useful biomarker not only for diagnosing bacteremia but also for assessing the therapeutic efficacy of antibiotics. NE-WY changes more rapidly over time than other biomarkers during the treatment of bacteremia. Thus, NE-WY has the potential to become a key biomarker in the field of infectious diseases.
The skin, the body's largest organ, acts as the primary barrier against infections, but this function can be compromised by wounds. While antibiotics are commonly used for treating skin infections, their misuse has led to antibiotic-resistant pathogens, emphasizing the need for safer alternatives. Fucoidan has shown antibacterial and anti-inflammatory properties. However, its biological activity can vary due to differences in species and geographical origin. In this study, fucoidan was isolated from Sargassum polycystum collected in the intertidal zone of South Sulawesi, Indonesia, and its wound-healing potential was tested in Staphylococcus aureus-infected rats. Fucoidan was extracted using hot ethanol-water extraction and CaCl₂-ethanol precipitation, and characterized by FTIR, ¹H NMR, and ¹³C NMR. Toxicity was assessed with a hemolysis assay, and wound healing was evaluated in rats with 6 mm excision wounds infected with Staphylococcus aureus (0.1 mL, 10⁷ CFU/mL). Results showed that fucoidan was non-toxic and that a 2.4% topical application significantly reduced bacterial load and accelerated healing within 9 days. Histological analysis revealed enhanced fibroblast proliferation, granulation tissue formation, re-epithelialization, and thicker collagen deposition compared to the control group (Vaseline only) (P < 0.05). These findings suggest that fucoidan from Sargassum polycystum is safe and effective in promoting wound healing, supporting its potential as an alternative therapy for infected wounds and providing a validated molecular candidate for future sustainable marine synthetic biology applications.
Staphylococcus aureus is the predominant cause of acute hematogenous osteoarticular infection (AHOAI, osteomyelitis or bacterial arthritis) in children and is commonly associated with bacteremia. Current guidelines suggest that persistent bacteremia may warrant more aggressive treatment. We evaluated the outcomes of children with S. aureus AHOAI with respect to bacteremia duration. Children ≤18 years old with AHOAI secondary to S. aureus from 2011 to 2021 were identified through prospective surveillance studies at Texas Children's and St. Louis Children's Hospitals. Orthopedic complications included pathologic fractures, avascular necrosis, angular deformity and chronic osteomyelitis. Five hundred four cases were included, of which 65% had a positive blood culture. The median duration of bacteremia was 1 day (interquartile range: 1-3 days). Children with prolonged bacteremia (≥3 days) had a longer duration of fever in the hospital, more often had methicillin-resistant S. aureus, pyomyositis and venous thromboses, and were less often transitioned to oral therapy. Duration of bacteremia was independently associated with nonmusculoskeletal foci of infection (adjusted odds ratio 2.07, 95% confidence interval: 1.28-3.32). However, the duration of bacteremia was not directly associated with orthopedic complications. Within the subset of patients with prolonged bacteremia, those who were transitioned to oral therapy had similar rates of readmission and orthopedic complications as those treated with prolonged intravenous antibiotics. Prolonged bacteremia in the setting of S. aureus AHOAI should prompt evaluation for other foci of infection. At least a subset of children with S. aureus AHOAI and prolonged bacteremia can be safely transitioned to oral antibiotics after a period of intravenous therapy with good outcomes.
Antimicrobial resistance and inadequate sanitation, particularly in developing nations such as Pakistan, exacerbate the impact of Salmonella, a leading cause of foodborne and clinical infections worldwide. Effective surveillance and source tracking are hindered by a lack of comprehensive analyses linking clinical and environmental strains, despite increasing reports of resistant variants. This study uses disk diffusion, conventional PCR, and ERIC-PCR to compare clinical and environmental Salmonella strains from Karachi, with an emphasis on antibiotic resistance, virulence factors, and genetic relatedness. Multidrug resistance is highly prevalent, with 63% of clinical strains (41/65) (MARi: 0.3-0.8) and 34.5% of environmental strains (22/55) (MARi: 0.4-0.7) exhibiting resistance to multiple antibiotics. All strains were capable of forming biofilms, and the correlation between MARi and biofilm formation in both sources was weak and non-significant (p > 0.05). All strains from both sources harbored core virulence genes; however, three genes, fimA, spvR, and acrA, were significantly more prevalent in clinical than in environmental strains (p < 0.001 and p = 0.023). ERIC-PCR showed low to moderate DI (0.45 to 0.75) across different clinical Salmonella serovars and moderate DI across different environmental serovars, indicating heterogeneous and homogeneous genetic relatedness. These results suggest a crucial and underexplored connection between environmental and clinical Salmonella reservoirs, implying potential environmental contamination from clinical sources. The coexistence of multidrug resistance and virulence highlights the critical need for integrated surveillance strategies to minimize the risk of widespread outbreaks.
Aflatoxin B1 (AFB1) is a potent hepatotoxin that poses significant health risks to both livestock and humans. β-Nicotinamide mononucleotide (NMN) has potential therapeutic benefits for liver diseases. However, its mechanism against AFB1-induced liver injury remains unclear. This study investigates whether NMN supplementation reduces AFB1-induced liver injury through the modulation of the gut-liver axis and elucidates the underlying molecular mechanism. Mice were exposed to AFB1 (0.75 mg·kg-1, p.o.) for 2 weeks to induce liver injury, with or without NMN (300 mg·kg-1, p.o.). Changes in gut microbiota were assessed via 16S rRNA sequencing, while bile acids (BAs) profiles were quantified using targeted metabolomics. The farnesoid X receptor (FXR/NR1H4) pathway was analysed using qPCR, western blot and immunofluorescence. To establish causality, antibiotic depletion, faecal microbiota transplantation (FMT) and intestine-specific FXR knockout (FXRΔIE) mice were utilized. NMN supplementation attenuated AFB1-induced liver injury, inflammation and oxidative stress, while restoring intestinal barrier integrity and reducing hepatic bile acids accumulation. Mechanistically, NMN reshaped the gut microbiota, increased bile salt hydrolase (BSH) activity and lowered intestinal conjugated bile acids, which correlated with activation of intestinal FXR/fibroblast growth factor 15 (FGF-15) signalling and suppression of hepatic Cyp7a1 expression. Importantly, antibiotic depletion of gut microbiota abolished NMN protection, whereas FMT from NMN-treated donors conferred resistance. Importantly, NMN failed to protect FXRΔIE mice, demonstrating that intestinal FXR is essential. NMN alleviates AFB1-induced liver injury via a gut microbiota-bile acid-FXR axis, highlighting a novel mechanism for its hepatoprotective effects.
Osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms presents significant therapeutic challenges due to antibiotic resistance and persistent bacterial presence. Inspired by the natural periosteum structure, we developed an injectable biomimetic periosteum through thiol-click chemistry-a hydrogel loaded with NiSr MOF@Mem nanocomposites(NiSr MOF@Mem Gel). This system not only serves as a physical barrier covering bone defects but also, under alternating magnetic field (MF) activation, synergistically executes chemodynamic therapy, controlled antibiotic release, and immunomodulation. In vitro studies demonstrated that this biomimetic periosteum activates NADPH oxidase-dependent ROS bursts under MF, driving PAD4-mediated histone H3 citrullination and thereby inducing neutrophil extracellular trap (NET) formation. This process relies on the classical ROS/PAD4 signaling axis, as confirmed by the PAD4 inhibitor Cl-Amidine significantly suppressing NETosis. Functional assays verified that the system, via NET induction, exerts potent synergistic antibacterial effects against both planktonic and biofilm-embedded MRSA. In a rat osteomyelitis model, the biomimetic periosteum combined with MF treatment significantly reduced bacterial load in bone tissue and effectively promoted bone repair by modulating the immune microenvironment. This study presents a novel strategy of using a magnetically responsive biomimetic periosteum to remotely regulate innate immunity for biofilm eradication, offering an integrated solution for the synergistic treatment of osteomyelitis.