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Background: Antibiotic resistance and recurrent infections, driven by increased antibiotic use, represent a global health problem. This study aims to evaluate the effect of probiotics and synbiotics consumption on antibiotic resistance in common infections. Methods: A systematic search was performed on international electronic databases (PubMed/Medline, Scopus, and Web of Science) using predefined keywords to identify relevant clinical trials published prior to 1 March 2025. Study quality was assessed, and the PRISMA 2020 guideline was followed. Results: In our systematic review, 47 studies were included. Twenty studies reported positive effects on antibiotic resistance, eradication rates, and recurrence, particularly in gastrointestinal infections. In contrast, 10 studies reported no effect, and 2 indicated a negative effect of these interventions on infection recurrence and antibiotic resistance. In three studies focusing on children, probiotics significantly lowered the risk of urinary tract infection (UTI) recurrence and antibiotic resistance. However, an adult study found that probiotics had minimal effect on UTI recurrence. Four studies examined the effect of probiotics on respiratory infections in both children and adults, showing improvements in antibiotic resistance outcomes. Three studies involving preterm infants found that probiotics could modify their gut microbiome composition, with two studies confirming this effect. Conclusion: Our study indicates that incorporating probiotics and synbiotics into common infection therapy could improve antibiotic resistance, eradicate rates, minimize side effects, and boost treatment compliance. However, concerns remain regarding the potential transfer of antibiotic resistance genes via probiotics.
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Chronic suppurative otitis media is an easily managed condition with potential for severe sinus thrombophlebitis complications secondary to cholesteatoma, if not diagnosed and treated promptly. Diagnosis relies on the culture and sensitivity of the drained suppuration, computed tomography (CT), and magnetic resonance imaging (MRI). Treatment entails a combination of all or some surgical, antibiotic, and anticoagulant use with postoperative follow-up. Our 8-year-old female patient presented with chronic left postauricular swelling with foul-smelling otorrhea and associated otalgia. More recently, she developed fever, headache, and vomiting. Fundoscopy noted papilledema. After ear examination, emergency incision and drainage were conducted with the suppuration sent for culture analysis. Tuberculosis was also ruled out. The patient had no history of dental caries. Contrast CT scan of the brain revealed features suggestive of partial thrombosis of the superior sagittal, left transverse sinus and sigmoid sinus extending up to the jugular vein. MRI and magnetic resonance venography (MRV) also indicated left otomastoiditis. Surgical treatment involved left-sided tympanomastoidectomy and otomastoidectomy. Anticoagulant Rivaroxaban was used 15 mg twice daily for 21 days. Postoperatively, the dosage was increased to 20 mg once daily for 3 months. Antibiotic vancomycin was administered preoperatively. Postoperative CT showed good prognosis. Postoperatively there was gradual improvement in headache and vision deterioration of right eye; fundoscopy showed improvement in papilledema, patient leukocyte counts also declined significantly, eventually to 13.4/µL. Anticoagulant and antibiotic therapy was continued. Some authors advocate only blood-brain barrier crossing antibiotics, while others employ surgical treatment. The risks involved with using anticoagulants must be carefully weighed before use. Our case presents classic clinical signs and symptoms.
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BACKGROUND: Optimising antimicrobial use during surgery is essential for preventing surgical site infections, ensuring patient safety and minimising the risk of antimicrobial resistance. To investigate the management, use and documentation of 'off-label' antimicrobials in Australian operating theatres (OT). METHODS: A cross-sectional online survey of hospital pharmacists with expertise in antimicrobial stewardship, surgery or and/or medication safety. Demographic and quantitative questions were analysed using descriptive statistics. Free-text responses underwent reflexive thematic analysis. RESULTS: Responses from 61 Australian hospital pharmacists were analysed. 83 % of survey participants reported that ceftriaxone was stocked in OT, with 70 % and 62 % stocking IV amoxicillin-clavulanate and piperacillin-tazobactam respectively. Vancomycin (34 %), rifampicin (18 %) and gentamicin (16 %) were the most commonly used antimicrobials for wound irrigation. Over half (51 %) of participants reported seeing vancomycin powder applied directly to surgical sites. Thematic analysis of free-text responses generated three dominant themes: surgical staff work-arounds, risks to patient safety, and detached or unclear pharmacist role in OT. CONCLUSION: Broad-spectrum antimicrobials are used topically as washes, soaks, and applied directly to surgical sites, however the extent of this practice is unclear due to poor documentation. There is wide variation between hospitals regarding which antimicrobials are kept in OT, with inconsistent compliance to systems restricting use in this setting. Opportunities to improve the use of broad-spectrum antimicrobials include: better utilisation of automated dispensing cabinets to track use and facilitate audits, embedding of pharmacists in OT to improve management, and policies to ensure documentation and patient consent for use outside of evidence-based guidelines.
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Cytoplasmic pentapeptide repeat proteins (PRPs) protect bacterial DNA gyrase from quinolone antibiotics. While some secreted PRPs are essential upon quinolone exposure, their role in the regulation of antibiotic resistance remains to be fully characterized. We show that a YjbI-type secreted PRP regulates antibiotic sensitivity, bimodally for small or large molecules, via modulation of the Caulobacter crescentus outer membrane (OM). YjbI silences two converging envelope-stress pathways that globally reprogram the OM proteome via TonB-dependent receptors (TBDRs), periplasmic proteases, and AcrAB-NodT, a multidrug efflux pump whose induction by small molecules and antibiotics is lethal to yjbI mutant cells. Loss of YjbI also confers sensitivity to vancomycin and bacitracin, two large peptidoglycan-targeting and zinc-binding antibiotics that permeate the outer membrane via the previously uncharacterized TBDR BugA and its orthologs. Zinc stress triggers rapid proteolytic removal of Yjbl, activates expression of TBDRs, including BugA, and ultimately leads to replenishment of YjbI. Molecular dynamics simulations and reactive thiol probing imply an asymmetric surface disposition of YjbI, explaining the differential accessibility of its conserved cysteine pairs that flank the quadrilateral ß-helix. Taken together, our findings identify a role of YjbI as a cell surface-regulator of outer membrane composition and antibiotic sensitivity in a Gram-negative bacterium.
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The rapid emergence and dissemination of bacterial antibiotic resistance pose serious threats to global public health and ecological systems. While antibiotics are traditionally considered the primary drivers of resistance evolution, emerging evidence indicates that pesticides also play a critical role in promoting bacterial antibiotic resistance. However, comprehensive reviews integrating current findings on the mechanisms by which pesticides influence resistance development are lacking. This review systematically examines the effects of pesticides on bacterial antibiotic resistance, with a focus on both direct and indirect pathways. Pesticides can directly induce vertical transferable resistance via gene mutations associated or elicit adaptive resistance by modulating bacterial gene expression. Indirectly, pesticides facilitate the horizontal transfer of antibiotic resistance genes (ARGs) by promoting reactive oxygen species (ROS) generation, increasing membrane permeability, and upregulating genes related to conjugation and natural transformation. Additionally, pesticide exposure can reshape environmental microbial communities, selectively enriching ARG-carrying populations. Under co-exposure conditions with other environmental pollutants, pesticides exhibit synergistic effects that further accelerate resistance development. Notably, current evidence suggests that the predominant role of pesticides lies in indirectly enhancing the propagation of antibiotic resistance or synergistically amplifying its development. These findings offer a novel perspective on the ecological risks associated with pesticide use and underscore the urgent need to incorporate bacterial antibiotic resistance into pesticide risk assessment frameworks.
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Background: Empirical antibiotic therapy (EAT) in febrile neutropenia (FN) remains challenging due to multidrug-resistant (MDR) Gram-negative bacteria, often leading to inappropriate empirical antibiotic therapy (IEAT). Objective: To demonstrate that risk stratification based on machine learning (ML) and prior colonisation with MDR bacteria may support the tailoring of EAT in patients with haematological malignancies. Design: Retrospective proof-of-concept cohort study. Methods: All consecutive FN episodes in patients with haematological malignancies were retrospectively included from January 2020 to March 2023 at a tertiary-level university hospital. We compared real-world, clinician-driven empirical antibiotic use with a simulated approach guided by an ML-based risk stratification model combined with prior colonisation data. The main outcomes were antibiotic selection and rates of IEAT. Results: A total of 553 FN episodes in 398 haematological patients were analysed. Bloodstream infection (BSI) occurred in 141/553 episodes (25.5%). Anti-pseudomonal (PsA) beta-lactams were prescribed in 515/553 episodes (93.1%), with carbapenems in 406/553 (73.4%). The clinician-driven approach resulted in 16/70 (22.9%) GNB-BSI episodes receiving IEAT. The ML plus colonisation-guided approach would have reduced the use of meropenem by 29.7% (-2.08 days; 95% CI, -2.42 to -1.73; p < 0.001) and anti-PsA beta-lactams by 6.7% (-0.47 days; 95% CI, -0.76 to -0.19; p = 0.001), and would also have led to a reduction in the rate of IEAT from 16/70 (22.9%) to 6/70 (8.6%) (p = 0.035). Conclusion: ML-based risk stratification combined with colonisation status would allow for personalised antibiotic therapy in FN, potentially reducing IEAT and improving antimicrobial use. These results support integrating these tools into clinical practice.
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Objective: The optimum duration of prophylactic antibiotics after pancreaticoduodenectomy following preoperative biliary drainage to prevent surgical site infections remains controversial. We evaluate whether a prolonged course of prophylactic antibiotics reduces surgical site infection after pancreaticoduodenectomy following biliary drainage more than that within the standard duration. Methods: We enrolled 352 consecutive patients from one hospital who underwent pancreaticoduodenectomy following biliary drainage between 2010 and 2023. The patients were prospectively assigned to two groups according to prophylactic antibiotic duration. In the standard duration group (2010-2013; 112 patients), the duration was within 24 h postoperatively. In the prolonged duration group (2014-2023; 240 patients), it was 3 days postoperatively. The primary endpoint was the incidence of surgical site infection between these groups. We performed 1:1 propensity score matching to balance baseline characteristics, which yielded 77 patients per group. Results: There was significantly less surgical site infection in the longer duration group (13%) than in the standard duration group (29%) (p = 0.0010). After matching, the prolonged duration group maintained significantly lower rates of all surgical site infection (32% vs. 14%, p = 0.0126), organ/space surgical site infection (27% vs. 13%, p = 0.0433), incisional surgical site infection (18% vs. 3%, p = 0.0026), superficial incisional surgical site infection (13% vs. 3%, p = 0.0314). In the multivariate analysis, independent risk factors for surgical site infection after pancreaticoduodenectomy following biliary drainage were elevated drain fluid amylase on postoperative day 1 (p < 0.0001) and 1-day prophylactic antibiotics (p = 0.00012). Conclusions: Prolonged prophylactic antibiotics significantly reduced surgical site infection incidence after pancreaticoduodenectomy in patients undergoing preoperative biliary drainage.
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INTRODUCTION: Urinary tract infections (UTIs) are common among women, and approximately 20-30% experience recurrent episodes (rUTIs). The increasing prevalence of antimicrobial resistance highlights the need for non-antibiotic preventive strategies. D-mannose and proanthocyanidins (PAC) have shown potential in reducing rUTIs. The aim of this study was to evaluate the efficacy of a combination of D-mannose and PAC in preventing postcoital UTIs over a 6-month period. MATERIALS AND METHODS: We conducted a prospective, single-center pilot study including 26 women aged 18-45 years with a history of recurrent postcoital UTIs. Participants received a daily prolonged-release formulation containing D-mannose (2000 mg) and PAC (140 mg) for 6 months. The primary outcome was the incidence of postcoital UTI episodes. Secondary outcomes included treatment adherence, episode severity, microbiological findings, safety, quality of life, and patient-reported improvement. Analyses were performed on both the intention-to-treat (ITT) and per-protocol (PP) populations. RESULTS: At 6 months, 53.6% of participants had no new UTI episodes. A total of 24 episodes were recorded in 12 women, with more than two-thirds concentrated in a small subgroup. Overall, UTI incidence decreased significantly (p = 0.01), and 76.2% of participants remained infection-free at the final visit. Adherence was high (90.9% at 3 months and 85.7% at 6 months). Positive urine cultures most frequently identified Klebsiella aerogenes and Escherichia coli. Sexual function remained stable, and 80.9% of women reported subjective improvement. Only one withdrawal occurred due to vaginal dryness. CONCLUSIONS: The combination of D-mannose and PAC in a prolonged-release formulation appears to be a promising, safe, and well-tolerated strategy for the prevention of postcoital rUTIs in young women. Larger randomized controlled trials are warranted to confirm these preliminary findings.
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PURPOSE: Fever in neutropenia (FN) is a potentially lethal complication of chemotherapy for cancer. Prompt administration of broad-spectrum antibiotics is standard of care. Despite conflicting results on the association of time to antibiotics (TTA) with outcomes, TTA limits are used as FN quality measure both in adult and pediatric oncology. This individual patient data (IPD) meta-analysis studied the association between TTA and outcomes in pediatric patients with FN. PATIENTS AND METHODS: IPD on TTA in pediatric patients with FN receiving chemotherapy for any malignancy was collected internationally. Three-level mixed binomial logistic regression analyzed the association of TTA with safety relevant events (SRE; death, admission to intensive care unit [ICU], bacteremia), primarily in patients with severe disease at presentation and secondarily in all patients. RESULTS: Data on 4006 FN episodes in 2073 patients, diagnosed 2016-2023, were reported from 15 study sites in eight countries. Median TTA was 61 min overall and 53 min in the 345 (8.6%) episodes with severe disease at presentation. Among these with severe disease, an SRE was reported in 119 (34%) episodes. Longer TTA (> 60 vs. ≤ 60 min) was associated with less SRE (odds ratio, 0.41; 95% CI, 0.24-0.70). This primary finding was confirmed in secondary and additional exploratory analyses. CONCLUSION: This large, international and adequately powered IPD meta-analysis found no association between shorter TTA and improved clinical outcomes in pediatric patients with FN. This finding was consistent across analyses. These results challenge the continued use of TTA limits as a quality measure for pediatric oncology centers.
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Antibacterianos , Antineoplásicos , Neutropenia Febril Inducida por Quimioterapia , Neutropenia Febril , Fiebre , Neoplasias , Neutropenia , Tiempo de Tratamiento , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Niño , Preescolar , Femenino , Masculino , Adolescente , Neutropenia/inducido químicamente , Neutropenia/tratamiento farmacológico , Tiempo de Tratamiento/estadística & datos numéricos , Fiebre/tratamiento farmacológico , Antineoplásicos/efectos adversos , Resultado del Tratamiento , Lactante , Neutropenia Febril Inducida por Quimioterapia/tratamiento farmacológico , Neutropenia Febril/tratamiento farmacológicoRESUMEN
BACKGROUND: Paediatric cancer patients are highly susceptible to bloodstream infections (BSIs), which are a leading cause of morbidity and mortality in this population. However, data focusing on BSI pathogens and resistance profiles in paediatric oncology patients in Ghana are lacking. This study aimed to characterize the spectrum of bacterial pathogens and their antibiotic susceptibility patterns among paediatric cancer patients with BSIs at the national tertiary referral centre, to inform empiric therapy and infection control strategies. METHODS: A prospective cross-sectional study was conducted at Korle Bu Teaching hospital from April to September 2023. Paediatric cancer patients (ages 1-18) presenting with fever on admission were consecutively sampled and enrolled, excluding those on antibiotics for BSI. Blood cultures were performed using standard microbiological techniques, and isolates were identified by conventional biochemical tests. Antimicrobial susceptibility testing was done using the modified Kirby-Bauer disk diffusion method on Mueller-Hinton agar, interpreted according to Clinical and Laboratory Standards Institute (CLSI) 2021 guidelines. Patient demographics and clinical data were collected, and infection prevalence was calculated. Associations were analysed by chi-square tests, with significance at p < 0.05. RESULTS: BSIs were confirmed in 22% of patients (22/100). Gram-positive organisms predominated (59.1% of isolates), chiefly Staphylococcus aureus (31.8%), coagulase-negative staphylococci (22.7%) and Streptococcus pneumoniae (4.5%). Gram-negatives (40.9%) included Klebsiella pneumoniae (18.2%), Pseudomonas aeruginosa (13.6%), and Escherichia coli (9.1%). No significant difference in BSI occurrence was observed by gender (p > 0.5). All Gram-negative isolates were susceptible to meropenem and amikacin, whereas over half of all isolates were resistant to gentamicin. For Gram-positives, cefoxitin susceptibility was 85.7% and S. aureus showed high resistance to penicillin (71.4% resistant) and gentamicin (85.7% resistant). Overall, 18.2% of isolates were multi-drug resistant (MDR) bacteria which were more common in Gram-negatives (75%) than Gram-positives (25%). CONCLUSION: BSIs constitute a significant complication in paediatric cancer patients in this Ghanaian centre. Meropenem and amikacin were highly effective against Gram-negative bacteria, whereas substantial resistance was observed to gentamicin and ceftriaxone. There is the need to revise the empiric fever protocol at the centre to consider amikacin instead of gentamicin, The emergence of MDR organisms underscores the need for robust antibiotic stewardship and infection control measures at the oncology clinic.
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BACKGROUND: Perioperative antibiotic prophylaxis (PAP) is one of the key measures for preventing surgical site infections (SSI). In total joint replacement (TJA), infection prevention is crucial due to the risk of bacterial biofilm formation in the event of infection. OBJECTIVE: The study's goal was to analyze the current clinical practise in German tertiary TJA centers (EPZmax), assess adherence to the currently valid German AWMF-S3 guideline, and present the contemporary literature on PAP in revision and tumor TJA. MATERIALS AND METHODS: In 2023, a nationwide survey on PAP practices was conducted among 100 EPZmax institutions. In addition, a comprehensive review of the relevant literature and guidelines was performed, and an interdisciplinary institutional standard operating procedure (SOP) was developed. RESULTS: A total of 45 centers participated in the survey. First- and second-generation cephalosporins are used in 98% of primary and 95% of revision arthroplasties. In 98% of primary and 67% of revision procedures, PAP is administered as a single dose with 95% and 77% given within 30 minutes prior to incision, respectively. The evidence level for PAP was rated by the participating centers as high in primary and low to moderate in revision arthroplasty. CONCLUSION: The survey findings demonstrate guideline-conform implementation of PAP in primary TJA but reveal a heterogeneous situation in revision TJA. The interdisciplinary SOP written by the authors is based on the recommendations of the currently valid German guideline regarding the choice of antibiotic, dosing, and timing of PAP administration as well as on the differentiated approach in patients with a documented penicillin allergy. In deviation from the currently valid German guideline, and taking into account the available evidence and international expert consensus, an extended PAP for up to 24 hours is recommended for revision and tumor TJA, in order to adequately address the particular risk profile of these procedures (increased risk of infection and the potentially very severe consequences in the event of infection).
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To analyse the trends in drug susceptibility patterns (DSP) of gram- negative bacilli (GNB) in setting of febrile neutropenia in hematology-oncology patients. This retrospective study (done from April 2019-April 2024) compares clinical (Charlson co-morbidity index [CCI], Sequential organ functional assessment [SOFA] score, Pitts bacteraemia score, and all cause 30 day mortality) parameters and trends in DSP of GNBs isolated from blood cultures of hematology-oncology patients. Various AMS activities, including restriction on use of high end antibiotics, cessation of antibiotics in patients with pre-neutropenic fever, involvement of an infectious diseases physician for management of multi-drug resistant (MDR) infections and improvement in diagnostics, among others, were done during this time period. In 535 patients, 601 different GNB bacteraemia episodes were identified. Time series analysis showed that carbapenem resistance in Klebsiella pneumoniae and Escherichia coli decreased from 90.3 to 48.1% (r = -0.961, p = 0.0006) & 54.5-27.7% (r = -0.882, p < 0.001) respectively, DTR (difficult to treat) rates in Pseudomonas aeroginosa fell from 83.3 to 10% (r = -0.716, p- 0.036). This study provides evidence that resistance in GNB can be curtailed by AMS activities even in highly vulnerable population like hematology-oncology.
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The role of reactive oxygen species (ROS) in antibiotic-mediated bacterial killing and the emergence of resistance remains incompletely understood, particularly the identities and functional impacts of specific protein targets. To address this, we employed a site-centric chemoproteomics approach to map dynamic changes in the Escherichia coli cysteinome upon treatment with eight diverse antibiotics. Functional annotation revealed that these redox-sensitive proteins are enriched in crucial cellular processes such as amino acid biosynthesis and redox homeostasis. We further demonstrated that antibiotic-induced ROS directly regulate specific cysteine residues, C102 in MnmA, C116 in NemR, and C337 in TyrR, altering their functions through mechanisms including impaired enzymatic activity, induced dimerization, and modulated gene expression. These redox-mediated functional changes ultimately dictate E. coli's susceptibility to antibiotics. Our findings establish a direct molecular link between antibiotic-triggered ROS, specific cysteine modifications in key proteins, and bacterial survival, offering a new framework for strategies aimed at enhancing antibiotic efficacy.
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CONTEXT: The growing multidrug resistance (MDR) of Pseudomonas aeruginosa presents a pressing global health challenge and demands novel solutions. Medicinal plants offer a largely untapped reservoir of structurally diverse compounds with promising antibacterial and adjuvant potential. OBJECTIVE: This study investigated Sida acuta Burm.f. (Malvaceae) as a reservoir of dual-target phytochemicals capable of modulating resistance. MATERIALS AND METHODS: An integrated workflow combining LC/Q-TOF-MS metabolomic profiling, molecular docking (MD), dynamics simulations (MDS), and microbiological assays was applied to the ethyl acetate fraction of the aerial parts (SAAP-EA). RESULTS: Metabolomic analysis identified 35 compounds, including biochanin A (BCA), resveratrol (RSV), methyl gallate (MG), 3-hydroxycinnamic acid (3-HCA), and azelaic acid (AZA), with favorable drug-likeness. Their toxicity predictions indicated low risks of acute toxicity (LD50 >900 mg/kg), mutagenicity, and carcinogenicity, but flagged a potential nephrotoxicity risk requiring further investigation. MD and MDS revealed stable RSV and BCA binding to both BamB (outer membrane biogenesis) and OprM (efflux), while 3-HCA and AZA preferentially targeted OprM with higher affinities than reference inhibitors. Hydrogen-bonding supported specificity and complex stability. Experimentally, SAAP-EA showed potent bactericidal activity against clinical MDR P. aeruginosa (MIC 32-256 µg/mL) and synergized with ß-lactams, fluoroquinolones, and tetracyclines, achieving up to 64-fold MIC reductions at sub-inhibitory doses. The dual inhibition of membrane assembly and efflux likely underlies the observed resistance-breaking effects, facilitating intracellular antibiotic accumulation. DISCUSSION AND CONCLUSIONS: These findings establish a mechanistic basis for translating ethnopharmacology into therapeutic strategies against MDR Gram-negative pathogens. Future work should prioritize in vivo validation and preclinical optimization of lead dual-target adjuvants.
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Antibacterianos , Malvaceae , Extractos Vegetales , Pseudomonas aeruginosa , Pseudomonas aeruginosa/efectos de los fármacos , Metabolómica/métodos , Antibacterianos/farmacología , Antibacterianos/aislamiento & purificación , Simulación del Acoplamiento Molecular , Extractos Vegetales/farmacología , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Malvaceae/química , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Animales , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Simulación de Dinámica Molecular , Componentes Aéreos de las PlantasRESUMEN
Background: Vancomycin-resistant Enterococcus faecium (VRE) is a major cause of healthcare-associated infections, especially in immunocompromised hosts. Linezolid is a key therapeutic agent due to its oral bioavailability and activity against resistant Gram-positive bacteria. While rare in U.S. pediatric patients, linezolid resistance can severely limit treatment options. Case Summary: We describe a 16-year-old female with high-risk B-cell acute lymphoblastic leukemia whose hospitalization was complicated by urinary tract infection with VRE. Serial isolates tested on multiple antimicrobial susceptibility testing platforms yielded discordant results for linezolid susceptibility. Minimum inhibitory concentrations to linezolid and chloramphenicol increased together, suggesting potential ribosomal-target-mediated resistance. She ultimately required daptomycin therapy for linezolid-resistant VRE urinary tract infection treatment. Conclusion: This case underscores the diagnostic challenges in detecting emerging linezolid resistance in E. faecium, particularly in immunocompromised patients. Accurate, timely susceptibility testing and improved access to confirmatory or molecular diagnostics are essential to guide therapy for VRE where linezolid remains one of the few viable therapeutic options.
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BACKGROUND: Preirradiated patients undergoing microvascular head and neck reconstruction for tumor recurrence or osteoradionecrosis (ORN) face surgical site infection (SSI) rates exceeding 30%. The impact of perioperative extended-spectrum antibiotic coverage remains unclear. This study hypothesizes that calculated prophylaxis with piperacillin/tazobactam reduces early-onset SSI in this high-risk population. METHODS: From a microvascular reconstructed cohort, 161 with prior irradiation were retrospectively identified (tumor, N = 101; ORN, N = 60). SSI risk reduction was compared between patients receiving piperacillin/tazobactam (N = 39) and standard prophylaxis (N = 122). RESULTS: With underlying SSI incidence of 36%, piperacillin/tazobactam showed a fourfold SSI risk reduction (HR 0.24; p = 0.002) across the entire cohort and a fivefold reduction in patients with bone resection (HR 0.17; p = 0.01). Subgroup analyses confirmed this effect with a sevenfold reduction in tumor patients (HR 0.14; p = 0.008) and a threefold reduction in ORN patients (HR 0.29; p = 0.04). Extended coverage did not significantly prolong antibiotic treatment times. CONCLUSION: In summary, calculated use of piperacillin/tazobactam in previously irradiated patients requiring microvascular reconstruction appears effective in reducing early-onset SSI.
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Foodborne pathogenic bacterial infections pose significant challenges to global food safety and public health, while the issue of antimicrobial resistance (AMR) has worsened in recent years, creating an urgent need for safe, natural alternatives to combat foodborne pathogens and associated intestinal diseases. This study focuses on the Protease-Resistant Antimicrobial Peptide R7I, composed of natural amino acids, elucidating its mechanisms of action as a functional food ingredient in modulating intestinal health, thereby offering novel strategies for antibiotic alternatives. The results showed a 13.52 % increase in average daily weight gain in the R7I group compared to the control group. Average daily feed intake was significantly lower (P < 0.05) in the control group than in both the normal and R7I groups. Additionally, serum and jejunal lipopolysaccharide (LPS) content, as well as serum D-lactic acid levels (P < 0.05), were reduced in the R7I group, indicating markedly alleviated intestinal permeability. Compared to the control group, the R7I group significantly reduced serum levels of lactate dehydrogenase and total bile acids, while increasing high-density lipoprotein levels (P < 0.05). R7I treatment significantly elevated (P < 0.05) serum levels of anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10), while suppressing production of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17). Furthermore, multi-omics analyses revealed that R7I alleviated Enterotoxigenic Escherichia coli (ETEC)-induced intestinal damage through synergistic mechanisms involving modulation of gene expression regulatory pathways, restructuring of gut microbiota composition, and improvement of metabolite profiles. These findings substantiate the potential of R7I as a promising antibiotic-alternative functional food ingredient, offering new strategies for preventing foodborne diseases and managing intestinal health.
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Aminoácidos , Péptidos Antimicrobianos , Alimentos Funcionales , Intestinos , Animales , Péptidos Antimicrobianos/farmacología , Aminoácidos/farmacología , Masculino , Intestinos/efectos de los fármacos , Intestinos/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Lipopolisacáridos/sangre , Citocinas/sangre , Ratas , Ratas Sprague-DawleyRESUMEN
Sulfonamides (SNs) are a well-known class of antibiotics that have been explored in many areas of medicinal chemistry. Their broad spectrum of biological and medicinal properties, which includes antibacterial, anticancer, antifungal, anti-inflammatory, and enzyme inhibitory activities, has sustained continuous scientific interest. This review offers a thorough overview of the biological activities of SNs and their derivatives, with particular emphasis on their antibacterial and anticancer effects, as well as their role as carbonic anhydrase inhibitors. Additionally, we summarize some structure-activity relationship (SAR) studies that clarify how different substituents modulate potency and selectivity. By integrating insights from recent literature, this work, which is divided into five categories (antibacterial activity, anticancer activity, carbonic anhydrase inhibitory activity, and toxicity), highlights the pharmacological relevance of SNs, their structural diversity, and their continuing potential as scaffolds for creating new antibiotics.
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Antibacterianos , Antineoplásicos , Inhibidores de Anhidrasa Carbónica , Sulfonamidas , Relación Estructura-Actividad , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Sulfonamidas/farmacología , Sulfonamidas/química , Sulfonamidas/síntesis química , Inhibidores de Anhidrasa Carbónica/farmacología , Inhibidores de Anhidrasa Carbónica/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Estructura Molecular , Animales , Bacterias/efectos de los fármacosRESUMEN
Biofilms, structured communities of microbial cells embedded in extracellular polymeric substances, are notorious for their resilience against conventional antimicrobial treatments. They contribute significantly to chronic infections and industrial biofouling, necessitating innovative strategies for their eradication. Magnetic iron oxide nanoparticles have emerged as a promising tool in combating biofilms due to their biocompatibility and unique physicochemical properties, which enable magnetic delivery of antibacterial agents, magnetic hyperthermia, magneto-mechanical actuation including mechanical biofilm disruption, and reversible dynamic magnetic assembly into hierarchical structures. This review describes developing stages of magnetic nanoscale weapons against biofilms ranging from individual iron oxide nanoparticles to complex hierarchical nanoparticle assemblies in the form of magnetic robots and their swarms. A vast array of possible antibiofilm and antibacterial functionalities originating from iron ions, individual iron oxide nanoparticles, spherical nanoparticle assemblies, magnetic robots, and swarms of robots are presented. Magnetic nanotools offer significant improvements and advantages over conventional methods for biofilm eradication, yet their successful future applications depend on addressing and overcoming critical material, biological, and engineering challenges.