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Transformation of antibiotics mediated by iron-bearing minerals: A review.

Iron-bearing minerals are ubiquitous in water, sediments and soil, where their surface chemical properties and redox activity can play an important role in degradation of trace antibiotics. This review systematically summarizes the roles of various iron-bearing minerals in chemical transformation and microbial degradation of antibiotics and reaction mechanisms involved, and refines the critical idea for iron-driven control of antibiotics with trace level in natural environment. Overall, antibiotics removal in the presence of iron-bearing minerals involves combination of adsorption, surface oxidative degradation, photo-induced degradation, Fenton-like reaction and microbial degradation. Adsorption of antibiotics by Fe(III)-minerals involves electrostatic interaction, complexation, H-bonding, π-π interaction and hydrophobic interaction. Adsorbed antibiotics form complexes with Fe(III)-minerals, undergoing electron transfer to generate radical intermediates, subsequently generating final products through hydroxylation, dealkylation, and deamination. Additionally, Fe(III)-minerals can be excited to produce electrons and holes under sunlight and to produce antibiotics-degrading hydroxyl radical through O2 reduction, H2O oxidation and ligand-to-metal charge transfer. Reduced iron minerals can activate oxygen to participate in Fenton-like degradation reactions. Finally, antibiotics are mainly removed by bio-driven Fenton reaction and direct enzyme biodegradation. The presence of iron-bearing minerals can promote antibiotics microbial degradation by providing nutrients for microorganisms or by changing microbial activity and microbial community structure. Existing problems and future research directions are identified. New insights for application of iron-bearing minerals in transformation of antibiotics are proposed. The work aims to suggest new methods and insights for pollution control and remediation of emerging contaminants including trace antibiotics in the natural environment.

Anti-Bacterial Agents

Efficacy of Oral Baicalin in Canine Atopic Dermatitis: A Randomised Placebo Controlled Trial.

BACKGROUND: Baicalin has shown efficacy in various dermatitis models in animals. However, its therapeutic effects on naturally occurring canine atopic dermatitis (cAD) have not been evaluated. OBJECTIVE: To evaluate the efficacy and safety of baicalin in dogs with cAD. ANIMALS: 56 client-owned dogs were enrolled. MATERIALS AND METHODS: All dogs were randomly divided to receive oral baicalin or placebo over a 90day period. All subjects had veterinary evaluations using the Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) during the trial and owners were requested to evaluate itching using the pruritus Visual Analog Scale (PVAS) and to complete a quality-of-life (QoL) questionnaire at Day (D)0 and D90. Additionally, the transepidermal water loss (TEWL), total serum IgE levels (IgE), complete blood count and serum biochemical results were measured at D0 and D90. RESULTS: The significant decreases in CADESI-04 (p&#x2009;<&#x2009;0.001), PVAS (p&#x2009;<&#x2009;0.001), TEWL (p&#x2009;=&#x2009;0.014), IgE (p&#x2009;<&#x2009;0.001) and QoL scores (p&#x2009;<&#x2009;0.001) were observed in the baicalin group D90 compared to baseline. When compared to placebo, the baicalin group had significantly lower scores in CADESI-4 and PVAS (p&#x2009;<&#x2009;0.001). A significantly higher proportion of subjects in the baicalin group showed a good-to-excellent treatment response (82.1%) compared to those in the placebo group (35.7%). The treatment was well tolerated. CONCLUSIONS AND RELEVANCE: Baicalin had a significant benefit in alleviating pruritus and reducing clinical signs in dogs with mild-to-moderate cAD and was well tolerated.

Animals

Cost-effectiveness analysis of omeprazole for preventing esophageal stricture in patients with Zargar grade 2b and 3a corrosive esophageal injuries: A trial-based economic evaluation.

BACKGROUND: Corrosive esophageal injury frequently results in esophageal stricture requiring repeated endoscopic dilatation and substantial healthcare expenditure. This study evaluated the cost-effectiveness of omeprazole plus standard treatment compared with standard treatment alone for preventing esophageal stricture in adult patients with Zargar grade 2b and 3a corrosive esophageal injuries. METHODS: A trial-based economic evaluation was conducted alongside a randomized controlled trial from the healthcare provider and patient perspectives. Twenty patients were randomized to receive either standard treatment alone (n&#x2005;=&#x2005;10) or standard treatment plus omeprazole (n&#x2005;=&#x2005;10). Direct medical costs were analyzed using the incremental cost-effectiveness ratio. Deterministic one-way sensitivity analysis and probabilistic sensitivity analysis using Monte Carlo simulation were performed. RESULTS: The incidence of corrosive esophageal stricture was 20% (2/10) in the omeprazole group and 70% (7/10) in the standard treatment group (relative risk, 0.29; 95% confidence interval, 0.08-1.05; Fisher's exact test, P&#x2005;=&#x2005;.070). Omeprazole plus standard treatment reduced healthcare costs by THB 4642.30 per patient from the provider perspective and THB 5476.60 per patient from the patient perspective. The intervention remained the dominant strategy across all deterministic sensitivity analyses. Probabilistic sensitivity analysis demonstrated that 68.3% and 78.8% of simulations favored omeprazole from the provider and patient perspectives, respectively. CONCLUSION: Omeprazole plus standard treatment may represent a cost-effective strategy for adult patients with Zargar grade 2b and 3a corrosive esophageal injuries. However, these findings should be considered preliminary and require confirmation in larger multicenter randomized controlled trials.

Humans

Ceftriaxone for methicillin-susceptible Staphylococcus aureus bloodstream infections is associated with increased short-term mortality: a systematic review and meta-analysis.

BACKGROUND: Bloodstream infections (BSIs) by methicillin-susceptible Staphylococcus aureus (MSSA) are a significant cause of morbidity and mortality, traditionally treated with antistaphylococcal penicillins (ASPs) or cefazolin. Ceftriaxone has emerged as an alternative due to its once-daily dosing regimen and favourable safety profile; however, its efficacy compared to the standard of care (SoC) remains controversial. This evidence synthesis aimed to assess the role of ceftriaxone in treating MSSA-BSIs. METHODS: A systematic literature search was conducted in PubMed, Embase, and Scopus up to December 31, 2025 (PROSPERO protocol CRD42024595748). Studies comparing ceftriaxone to ASPs or cefazolin for MSSA-BSIs were included. Primary outcomes were 30-day and 90-day all-cause mortality . Pooled effect sizes with their 95% confidence intervals (CIs), were calculated using random-effects models, odds ratios (ORs) and mean differences (MDs) according to the type of outcome. RESULTS: Eleven studies totalling 2,568 patients were included. Ceftriaxone was associated with significantly increased 30-day mortality (OR 3.33; 95% CI: 2.17-5.10), although differences at 90&#x2009;days were not significant (OR 1.71; 95% CI: 0.75-3.90). No significant differences were noted for clinical success (OR 0.49; 95% CI: 0.19-1.26), microbiological clearance (OR 1.66; 95% CI: 0.73-3.82). Adverse event rates were similar between groups. CONCLUSION: Given the availability of various alternatives and the consistent short-term mortality signal observed, routine use of ceftriaxone for MSSA-BSIs, especially as initial therapy, is not supported by current evidence. Only novel findings from randomized studies may change the place in therapy of the drug in this context.

Humans

Genomic epidemiology of clinically critical antibiotic resistance in Salmonella enterica causing bloodstream infections across six Chinese provinces, 1994-2023.

Clinically critical antibiotic-resistant Salmonella enterica (S. enterica) causing bloodstream infections remains a public health challenge. Here, we aim to reveal the emergence and trends of clinically important antibiotic resistance in S. enterica causing bloodstream infections using 833 isolates from six Chinese provincial-level administrative areas during 1994-2023. We identified 48 serovars and 64 sequence types (STs). Overall, 8.52% of 833 isolates were resistant or had decreased susceptibility to ciprofloxacin, 4.32% and 6.84% reported resistance or decreased susceptibility to third- and fourth-generation cephalosporins (3GCs and 4GCs), 1.80% reported resistance to fosfomycin, and 2.16% reported resistance to azithromycin. Across these six regions, azithromycin and fosfomycin resistance is increasing, as is decreased susceptibility or resistance to ciprofloxacin, 3GCs, and 4GCs, especially among younger children and elderly people. Clinically prioritized antibiotic resistance also varies by region, serovar, and age group. S. Paratyphi A genotype 2.3.3 strains are mainly divided into 2 lineages distributed in Guangxi and Shanghai. Within the scope of this passive surveillance dataset, S. Typhi genotype 4.3.1.2.1 was identified as the earliest documented case among the collected isolates. Our retrospective and longitudinal genomic epidemiology study provides critical data for the formulation of treatment guidelines and policies for bloodstream infections and for the monitoring and control of antimicrobial resistance.

Humans

Intentions to use different modalities of long-acting HIV PrEP among men who have sex with men and transgender and gender diverse persons in the Netherlands.

Insight into intentions to use long-acting HIV pre-exposure prophylaxis (PrEP) is essential for successful implementation. We assessed intention to use three hypothetical long-acting PrEP modalities (oral, intramuscular and subdermal) among HIV-negative men who have sex with men (MSM) and transgender and gender diverse persons in Amsterdam, recruited through the Amsterdam Cohort Studies (ACS-participants) and social media (survey-participants). Intention was measured per modality using a 7-point Likert scale. We modeled the probability of high intention to use long-acting PrEP using relative risk regression. Of 1258 participants [1231 (97.9%) MSM; 557 ACS and 701 survey; median age 40 years (IQR 32-50)], 76% had ever used oral short-acting PrEP. Intention to use was highest for monthly oral long-acting PrEP [ACS: median 4.5 (IQR 2-6), 38% high intention; survey: median 7 (IQR 6-7), 81% high intention], followed by 2-monthly intramuscular PrEP [ACS: median 3 (IQR 2-5), 19% high intention; survey: median 5 (IQR 3-7), 47% high intention], and implants [ACS: median 2 (IQR 1-4), 9% high intention; survey: median 4 (IQR 2-7), 37% high intention]. PrEP-experienced participants had higher intention to use oral long-acting PrEP and injectables than PrEP-na&#xef;ve participants. Offering multiple PrEP modalities may improve the acceptability of HIV prevention strategies and increase PrEP uptake and retention in PrEP care.

Humans

From commensal to pathobiont: The emergence of virulence-enhanced Escherichia coli in China's food-animal systems - insights with future implications.

A fundamental shift in Escherichia coli epidemiology is being driven by convergence of virulence determinants and antimicrobial resistance within linked human-animal-environment systems. In China, the rapid growth of food-animal production, extensive antimicrobial use, and complex food networks are accelerating the emergence and dissemination of virulence-enhanced E. coli pathobionts. This review synthesizes recent epidemiological, genomics, and outbreak data to characterize China's evolving landscape of food-animal-associated E. coli. We highlight a significant shift from classical pathotypes to hybrid lineages that simultaneously carry virulence factors and last-resort antibiotic resistance determinants, including mcr-1, tet(X4), and blaNDM. These traits disseminate rapidly via plasmid-mediated horizontal gene transfer, facilitating rapid adaptation and enabling cross-sectoral One Health transmission. National surveillance, foodborne outbreak investigations, and whole-genome sequencing data show that food-animal reservoirs are active evolutionary niches that drive pathogen diversity and fitness, rather than serving merely as contamination sources. Whole-genome sequencing also pinpoints high-risk clones (e.g., ST394) and plasmid-mediated co-selection of virulence and AMR. The emergence of hybrid pathotypes (e.g., STEC/ETEC) and AMR-virulence co-selection challenges traditional classification and limits the effectiveness of conventional surveillance approaches. The 2017 colistin ban reduced mcr-1, yet ongoing resistance and emerging tet(X4) demand integrated surveillance. Collectively, these findings call for reconceptualizing E. coli as a dynamic genomic entity embedded within a unified ecological network. Addressing this threat requires an integrated One Health strategy including genomic surveillance, agricultural antimicrobial stewardship, and coordinated food-environment-clinical monitoring to prevent high-risk clone emergence and global spread.

Animals

A randomized study of antibiotic prophylaxis after hypospadias repair in children.

BACKGROUND AND OBJECTIVE: Antibiotic resistance is a challenge in contemporary world. Urethroplasty for hypospadias is one of the most common urological surgeries performed around the world, yet, there is still no consensus on the use of antibiotics pre- and post-operatively. Our objective was to analyze the effectiveness of antibiotic prophylaxis and therapy before, during, and after hypospadias repair in children. METHODS: A prospective randomized trial was carried out including patients with coronal hypospadias who underwent urethroplasty performed by one surgeon. Urethral catheters were used in all cases for 10 days. Study participants were randomly assigned in a 1:1:1 ratio to receive a single intraoperative administration of antibiotics (Group I); an intraoperative antibiotic prophylaxis and antibiotic therapy for 10 days until the removal of urethral catheter (Group II); no antibiotic administration (Group III). Randomization was performed using computer-generated permuted blocks with randomly varying block sizes, prepared by an independent statistician. The results were analyzed using the analysis of variance (ANOVA). The following criteria were compared: postoperative functional complications, such as: urethral fistula, stenosis, diverticulum; wound infection symptoms: hyperemia of surgical site, pain during palpation, and symptomatic urinary tract infection. RESULTS: A total of 300 patients were included in the study. Two patients (2%) in Group I, two patients (2%) in Group II, and four patients (4%) in Group III had urethral fistulas, requiring surgery 6 months after primary repair, yet without statistical difference between groups. We found no significant difference in frequency of symptomatic UTIs between three groups (p = 0.182). CONCLUSION: There is no effect of antibiotic prophylaxis and therapy on the frequency of postoperative surgical and infectious complications after urethroplasty for coronal hypospadias repair in children.

Humans

Ruling out pediatric bacterial epididymo-orchitis with urinalysis - The case for minimizing unnecessary antibiotic prescription.

INTRODUCTION: Epididymo-orchitis in pediatric patients is predominantly non-bacterial, often stemming from viral or reactive etiologies. Despite guidelines recommending conservative management for non-bacterial cases, antibiotic overtreatment remains prevalent in the outpatient setting. We evaluated the diagnostic accuracy of urinalysis in ruling out bacterial infection to support antibiotic stewardship in this population. METHODS: We conducted a cross-sectional diagnostic accuracy study using electronic health records from a large health maintenance organization in Israel. The cohort included patients younger than 18 years with a diagnosis of epididymo-orchitis or clinically overlapping entities (acute scrotum, appendage torsion) who had paired urinalysis and urine culture results within one week of diagnosis. Logistic regression and ROC curve analysis were performed to assess the ability of urinalysis parameters to predict positive urine cultures. RESULTS: Of 682 eligible cases, confirmed bacterial infection was rare, occurring in only 17 patients (2.5%). Nitrite positivity was the strongest independent predictor of infection (OR 43.98; p < 0.001). A prediction model incorporating all urinalysis parameters yielded an area under the curve (AUC) of 0.825 and achieved a 97.7% classification accuracy for correctly predicting negative cultures. Despite the low prevalence of infection, antibiotics were prescribed in 237 cases (34.7%). Urinary anatomic abnormalities were significantly associated with culture positivity. CONCLUSIONS: Bacterial coinfection in pediatric epididymo-orchitis is uncommon. Urinalysis serves as a highly accurate screening tool to rule out bacterial etiology. A negative urinalysis supports withholding antibiotics in this setting, reserving treatment for children with positive markers or known anatomic abnormalities. This evidence-based approach This evidence-based approach has the potential to reduce unnecessary antibiotic exposure, however prospective studies are needed to validate these findings before broad implementation.

Humans

Cefoxitin versus cefotaxime as empirical treatment of spontaneous bacterial peritonitis in liver cirrhotic patients: randomized controlled clinical trial.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a severe complication of cirrhosis requiring immediate empirical antibiotic therapy. Third-generation cephalosporins are the traditional agents of choice; however, increasing clinical failure rates necessitate the evaluation of alternative antibiotics to ensure optimal therapeutic outcomes. The aim was to investigate the efficacy of cefoxitin versus cefotaxime for SBP treatment. METHODS: A randomized clinical trial was conducted on 140 cirrhotic patients with community-acquired SBP at Al-Rajhy Liver University Hospital, Assiut, Egypt. Patients were randomized to receive either cefotaxime (n&#x200a;=&#x200a;70) or cefoxitin (n&#x200a;=&#x200a;70), 2&#x2005;g every 8&#x2005;h for 5&#x2005;days. Polymorphonuclear neutrophil (PMN) counts were measured upon admission, on Day 2 and on Day 5. Clinical response rates at Days 2 and 5, development of hepatorenal syndrome, length of stay and mortality were assessed. RESULTS: According to intention-to-treat analysis, clinical response rates at Day 2 were 74.2% in the cefotaxime group and 80% in the cefoxitin group, while at Day 5, they were 71.4% and 74.3%, respectively (P&#x200a;=&#x200a;0.704). The PMN counts at Days 0, 2 and 5 showed no significant differences between the cefotaxime and cefoxitin groups (P&#x200a;=&#x200a;0.889, 0.909 and 0.360, respectively). The incidence of hepatorenal syndrome was 7.1% in the cefotaxime group compared with 8.6% in the cefoxitin group (P&#x200a;=&#x200a;0.753), and mortality was 15.7% and 12.9%, respectively (P&#x200a;=&#x200a;0.629). CONCLUSIONS: Cefoxitin showed comparable effectiveness to cefotaxime but may be utilized in selected clinically stable SBP patients.

Humans

Comparative Efficacy of Tirzepatide Versus Semaglutide for Weight Loss in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis of Head-to-Head Studies.

This systematic review and meta-analysis aimed to compare&#xa0;the efficacy and safety of tirzepatide versus semaglutide for weight reduction in adults with overweight or obesity. We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with &#x2265;&#x2009;24&#x2009;weeks of follow-up. The primary outcome was percentage weight change from baseline. Secondary outcomes included absolute weight change, weight-loss thresholds, HbA1c and safety outcomes. Ten studies including 41&#x2009;381 participants were analysed. Tirzepatide was associated with greater percentage weight reduction than semaglutide (MD -4.28 percentage points; 95% CI -5.28 to -3.28; p&#x2009;<&#x2009;0.00001) and greater absolute weight loss (MD -4.43&#x2009;kg; 95% CI -5.56 to -3.30; p&#x2009;<&#x2009;0.00001). Tirzepatide was also associated with a higher likelihood of achieving &#x2265;&#x2009;10%, &#x2265;&#x2009;15% and &#x2265;&#x2009;20% weight loss, with no difference at &#x2265;&#x2009;5%. HbA1c reduction was greater with tirzepatide (MD -0.29%; p&#x2009;=&#x2009;0.0002). Subgroup analyses by study design and type 2 diabetes status yielded consistent findings. There was no significant difference in treatment discontinuation due to adverse events (RR 1.28; p = 0.54), whereas serious adverse events were more frequent with tirzepatide (RR 1.83; p&#x2009;=&#x2009;0.007). Overall and gastrointestinal adverse events were similar between groups. Tirzepatide was associated with greater weight reduction, greater glycaemic benefit and a higher likelihood of achieving weight-loss thresholds than semaglutide, but with a higher risk of serious adverse events.

Humans

Natural products alleviate exercise-induced fatigue by modulating gut microbiota: a systematic review.

BACKGROUND: Exercise-induced fatigue critically impairs athletic performance and training quality. The gut microbiota, as a key regulator of the "gut-muscle axis," has emerged as a promising anti-fatigue target. Natural products - owing to their diverse sources, structural complexity, and favorable safety profiles - have attracted growing research interest. However, a systematic synthesis comparing their anti-fatigue effects via gut microbiota modulation across different sources is lacking. SCOPE AND APPROACH: We systematically searched PubMed, Web of Science, the Cochrane Library, and CNKI for original studies that administered natural products and concurrently assessed gut microbiota changes and anti-fatigue outcomes. Twenty-six studies (25 animal experiments and 1 human trial) were included and categorized into seven groups by source and chemical characteristics. A descriptive systematic review was conducted to identify common mechanisms and source-specific differentiations. KEY FINDINGS AND CONCLUSIONS: The enrichment of short-chain fatty acid (SCFA)-producing bacteria and the activation of the SCFA-AMPK/PGC-1&#x3b1; axis were shared core events across all product categories. However, source-dependent mechanistic divergences emerged: polysaccharides acted primarily as fermentable substrates with an optimal dose window; polyphenols and saponins exerted dual modulation on both microbiota and host signaling pathways; compound extracts achieved systemic synergy through functional complementation; marine- and animal-derived products exhibited unique targeting profiles and rapid action. Intestinal barrier maintenance and brain-gut axis regulation further extended the anti-fatigue repertoire. Collectively, natural products possess a solid mechanistic basis for alleviating exercise-induced fatigue via gut microbiota remodeling. The differentiated characteristics of these methods in targeting precision and pathway engagement provide a theoretical foundation for designing precision intervention strategies tailored to specific fatigue contexts.

Humans

Study of prescription-indication of antivirals for herpesviruses in a Colombian population: a cross-sectional study.

BACKGROUND: To describe the utilization patterns and therapeutic indications of antivirals used for herpesvirus infections in Colombian patients. RESEARCH DESIGN/METHODS: A cross-sectional study on the use of antivirals for treating outpatients with herpesviruses between November 2023 and January 2024 in a Colombian population database. The Micromedex&#xae; database was used to identify Food and Drug Administration (FDA)-approved indications, off-label uses, and potentially inappropriate indications. RESULTS: A total of 14,816 individuals were included (median age:53.0 years [IQR:35.0-65.0]; 60.5% women). Acyclovir was the most frequently prescribed antiviral (oral:77.3%; topical:43.4%). Overall, 56.1% received oral therapy only, 25.2% combined oral and topical therapy, and 18.7% topical therapy only. FDA-approved indications accounted for 29.1% of use (herpes zoster), off-label use for 26.9% (mainly prophylaxis in immunocompromised patients), and potentially inappropriate use for 25.3% (primarily topical treatment of herpes zoster). Acyclovir use (OR:5.93; 95%CI:4.60-7.64) and specialist care (OR:2.17; 95%CI:1.73-2.71) were associated with off-label use. CONCLUSIONS: Antiviral prescribing for herpesvirus infections in a group of patients in Colombia is largely driven by acyclovir, with a substantial proportion of off-label and potentially inappropriate use, particularly involving topical therapies for herpes zoster. These findings highlight significant gaps in adherence to evidence-based recommendations and underscore the need for targeted interventions to optimize prescribing practices.

Humans

Ten years on, still out of reach: barriers to PrEP access and retention in France according to frontline actors (QualiPrEP Study).

Pre-exposure prophylaxis (PrEP) for HIV has been available in France since 2014, and reimbursed since 2016, with general practitioners allowed to prescribe it since 2021. Despite these policy advances, uptake remains low among some of the most affected populations. This community-based qualitative study explored barriers to PrEP access and retention ten years into its implementation.Interviews were conducted with 28 PrEP frontline actors (healthcare professionals and community-based workers involved in promoting, prescribing, or supporting PrEP). The sample included one group discussion (n = 5), two triads (n = 6), two dyads (n = 4), and nine individual interviews (n = 13). Thematic analysis was inductive, with barriers classified across four main domains.Participants were mostly cisgender men, median age 48, born in France and abroad, and employed by NGOs in Paris. Thirteen barriers and four major themes emerged: (1) Internal psychosocial barriers: lack of knowledge, negative health-related reactions; HIV stigma; STI risk perception, taboos; (2) Internal pragmatic barriers: perceived limits of protection, usage and follow-up constraints; (3) External psychosocial barriers: limited physician knowledge and reluctance; (4) External pragmatic barriers: communication failures; structural constraints, lack of human and financial resources.Findings call for more targeted messaging, simplified care models and provider training. They highlight the need to address social and symbolic dimensions of PrEP, with insights from those supporting users to ensure more equitable implementation.

Humans

Contribution of the Arg-33-His replacement in the histidine kinase CpxA to carbapenem and cefiderocol resistance in Serratia marcescens.

OBJECTIVE: The Serratia marcescens ROT_R clinical isolate, which was resistant to almost all &#x3b2;-lactams, including cefiderocol (4 mg/L), was recovered from a neonate 2 months after the isolation of the S. marcescens ROT_S strain that was susceptible to extended-spectrum cephalosporins (ESCs). In this study, we attempted to decipher the mechanism of resistance displayed by the ROT_R isolate. METHODS: The genomes of ROT_S and ROT_R were sequenced using the Illumina and the Oxford Nanopore Technologies. Long and short reads were assembled together, giving rise to a circularized hybrid genome. RESULTS: Genomic comparison between ROT_S and ROT_R disclosed only one mutation (G98A) in the cpxA gene of ROT_R, which led to the Arg-33-His substitution in the histidine kinase of the two-component system CpxA/CpxR. The cpxA alleles of ROT_S and ROT_R were amplified and cloned, thus giving rise to the pCpxA_WT and pCpxA_R33H recombinant plasmids, respectively, which were subsequently introduced into the S. marcescens HatR recipient strain, which lacks functional CpxA. The S. marcescens HatR (pCpxA_R33H) recombinant clone, which produced the altered CpxA_R33H variant, differed from the S. marcescens HatR (pCpxA_WT) recombinant clone, which produced the wild-type CpxA, by enhanced MICs of carbapenems and ESCs, including cefiderocol (1 mg/L). CONCLUSIONS: This study demonstrates that CpxA alteration, such as Arg-33-His substitution, can contribute to cefiderocol resistance. Although it increases slightly the MIC of cefiderocol without resulting per se in clinical resistance, it can contribute, in combination with other additional mechanisms, to achieve a high level of resistance to this siderophore cephalosporin.

Cefiderocol

Risk factors for bleeding after endoscopic retrograde cholangiopancreatography: a systematic review and meta-analysis.

BACKGROUND AND AIMS: ERCP is associated with adverse events, including bleeding, which occurs in up to 1.3% of cases. This meta-analysis aims to identify and quantify risk factors associated with post-ERCP bleeding. METHODS: A comprehensive literature search of electronic databases was conducted from inception to January 10, 2025. Studies were eligible if they used multivariate analysis to identify predictors of post-ERCP bleeding. Risk factors reported in at least 2 studies were pooled using a random-effects model to calculate odds ratios (ORs) with 95% CIs. A further subgroup analysis was performed, including risk factors for postsphincterotomy bleeding and postendoscopic papillectomy bleeding. RESULTS: Twenty-seven studies (4 prospective and 23 retrospective studies) comprising 149,870 patients were included, of whom 1865 experienced post-ERCP bleeding. Twenty potential risk factors were analyzed. The meta-analysis identified several factors significantly associated with increased odds of post-ERCP bleeding in the pooled adjusted analysis, including male gender (OR, 1.24; 95% CI, 1.05-1.46), anticoagulation therapy (OR, 2.75; 95% CI, 1.66-4.56), cirrhosis (OR, 2.54; 95% CI, 1.76-3.65), hemodialysis (OR, 5.82; 95% CI, 3.32-10.18), coagulopathy (OR, 11.01; 95% CI, 2.50-48.40), endoscopic sphincterotomy (EST) (OR, 3.19; 95% CI, 1.69-6.01), precut sphincterotomy (OR, 2.24; 95% CI, 1.52-3.30), and intraoperative bleeding (OR, 2.57; 95% CI, 1.80-3.66). Several factors in the pooled adjusted analysis were not found to be significantly associated with higher odds of post-ERCP bleeding, including high body mass index (BMI), nonsteroidal anti-inflammatory drug (NSAID) use, antiplatelet therapy, thrombocytopenia, common bile duct stones, cholangitis, endoscopic papillary balloon dilatation, and covered self-expandable metal stent insertion. CONCLUSIONS: This meta-analysis identified that the anticoagulation therapy, cirrhosis, hemodialysis, coagulation disorder, EST, precut sphincterotomy, and male gender are associated with increased odds of post-ERCP bleeding in the pooled adjusted analysis. Conversely, age, high BMI, cholangitis, choledocholithiasis, pancreatic duct stones, needle-knife sphincterotomy, NSAID use, and antiplatelet therapy were not significantly associated with higher odds of post-ERCP bleeding in the pooled adjusted analysis. Incorporating our results into a prediction model may assist in identifying patients at increased risk, optimizing informed consent, and guiding prevention and management strategies for post-ERCP bleeding.

Humans

The Long Road to Long-Acting: What Oral PrEP and CAB-LA Teach Us About Scaling Lenacapavir.

Despite significant biomedical advances, human immunodeficiency virus (HIV) remains a persistent global health crisis, with over 40 million people affected as of 2023, two-thirds of whom live in the World Health Organization (WHO) African Region. However, from an HIV prevention perspective, the more urgent concern is the continued occurrence of approximately 1.3 million new infections annually, particularly in sub-Saharan Africa and in settings where incidence is stable or increasing. This commentary explores the evolving landscape of HIV prevention, focusing on the trajectory of oral pre-exposure prophylaxis (PrEP), long-acting injectable cabotegravir (CAB-LA), and the newly emerging lenacapavir. While oral PrEP opened new possibilities, adherence challenges have limited its impact. CAB-LA demonstrated superior efficacy but encountered access, cost, and delivery barriers that restricted uptake. Lenacapavir, offering 6-monthly subcutaneous dosing with &#x2265;&#xa0;99.9% efficacy in trials, holds the potential to overcome these hurdles. As of May 2026, lenacapavir had received regulatory approval in 17 countries, including several African nations, while regulatory reviews remained ongoing in multiple additional countries, reflecting the rapid global expansion of access to this long-acting HIV prevention option. However, its success depends on clinical promise, timely licensing, affordability, and integration into health systems. Drawing from real-world lessons of oral PrEP and CAB-LA, this paper argues that a proactive, coordinated rollout of lenacapavir could dramatically expand prevention reach. With global stakeholders aiming for 3 million users by 2028 and strategic licensing in 120 countries, the groundwork is in place. The recent release of WHO guidance recommending lenacapavir as an additional PrEP option further strengthens this momentum. Yet, equitable delivery, user-centred models, and strong policy backing will be critical. Ultimately, long-acting PrEP is not just a clinical breakthrough; it is a test of health systems' ability to deliver innovation at scale.

Humans

Herd-level heterogeneity of antimicrobial resistance in commensal Escherichia coli: A nationwide high-throughput survey of Australian pig herds.

Antimicrobial resistance in commensal Escherichia coli provides a useful indicator for overall antimicrobial resistance burden. We applied this approach to assess antimicrobial resistance within and between commercial pig herds across Australia. A high-throughput robotic workflow was used to isolate 2730 E. coli colonies from rectal contents collected in 2022 from healthy slaughter pigs (n&#x202f;=&#x202f;300) representing 30 herds (&#x223c;70% of national production). Up to 94 isolates per herd underwent antimicrobial susceptibility testing using the Robotic Antimicrobial Susceptibility Platform. Isolate- and herd-level antimicrobial resistance indices were calculated, weighting antimicrobials by their human health importance. Resistance to first-line agents was widespread: ampicillin 77% and tetracycline 79%. By contrast, resistance to critically important antimicrobials was rare (ciprofloxacin 0.11%; extended-spectrum cephalosporins 0.04%), and no clinical resistance to carbapenems or colistin was detected. Overall, 56.9% of isolates were multi-class resistant. Herd-level antimicrobial resistance within indices ranged from 1.51 to 5.76, revealing substantial between-herd heterogeneity. Three herds carried critically important antimicrobials-resistant isolates that would likely have been missed using conventional, lower-density sampling approaches. Whole-genome sequencing identified fluoroquinolone-resistant isolates belonging to ST10 and ST69 (both qnrS1), and ST744 (Quinolone Resistance Determining Region mutations plus blaCTX-M-27). By testing approximately tenfold more isolates than conventional surveys, we uncovered considerable antimicrobial resistance with heterogeneity within and between animals and herds, including farm-specific variability. This expanded sampling also enabled detection of critically important antimicrobial resistance at very low prevalence. In conclusion, high-throughput, high-density testing offers a practical early-warning system and herd-level benchmark to inform surveillance and targeted interventions.

Animals