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PubMed2026

In vitro evaluation of sacituzumab govitecan in non-small cell lung cancer with actionable genomic alterations.

PURPOSE: The TROP2-directed antibody-drug conjugate sacituzumab govitecan (SG) has shown substantial therapeutic benefit in several malignancies; however, preclinical evidence supporting its activity in non-small cell lung cancer (NSCLC) is rare. MATERIALS AND METHODS: We evaluated 16 NSCLC cell lines harboring actionable genomic alterations for TROP2 expression and treated them with SG or its unconjugated payload, SN-38, for 3 days to determine cytotoxic effects. Apoptosis and DNA damage signaling were assessed using flow cytometry and western blot. SG internalization and lysosomal trafficking were visualized by confocal microscopy. RESULTS: SG had greater cytotoxic potency than SN-38, across all NSCLC cell lines, independent of genomic subtype or TROP2 expression level. Cell lines that were sensitive to SN-38 showed enhanced vulnerability to SG (P < 0.0001). Higher SLFN11 expression, a recognized determinant of SN-38 responsiveness, correlated with lower SG IC50 values. Both SG and SN-38 triggered apoptotic and DNA damage responses within 6-48 h, with SG inducing stronger activation of these pathways than SN-38. SG was efficiently taken up in CUTO17 and SNU-3173 adenocarcinoma cells, with more than 60% of the conjugate internalized within 3 h and subsequently localized to lysosomes. CONCLUSION: Our study provides in vitro evidence supporting the potential activity of SG in NSCLC with actionable genomic alterations. The efficacy of SG closely paralleled intrinsic sensitivity to the SN-38 payload, suggesting that DNA-damage responses, rather than oncogenic drivers, predominantly contribute to SG activity.

Actionable genomic alterations↗

PubMed2026

Adeno-Associated Virus Gene Therapy Translation: Lessons from Early Regulatory Meetings.

The Platform Vector-Gene Therapy (PaVe-GT) program is a National Institutes of Health (NIH) initiative that aims to develop adeno-associated virus (AAV) gene therapies for four monogenic rare diseases, two organic acidemias and two congenital myasthenic syndromes. PaVe-GT's platform-based approach identifies and diminishes redundancies and applies efficiencies in preclinical, clinical, and regulatory activities. The program's hypothesis is that implementing these efficiencies can accelerate clinical trial initiation. Based on its platform-centric experience and public-serving mission, the PaVe-GT program actively shares its scientific and regulatory learnings with the public to benefit the development of similar gene therapy products for rare diseases. PaVe-GT's first investigational AAV gene therapy candidate is AAV serotype 9 human propionyl-CoA carboxylase alpha subunit (AAV9-hPCCA) for propionic acidemia caused by PCCA deficiency, which received initial feedback from the Food and Drug Administration (FDA) in an INitial Targeted Engagement for Regulatory Advice on CBER/Center for Drug Evaluation and Research (CDER) ProducTs (INTERACT) meeting. Upon further product development that took into consideration the FDA's initial advice, the program obtained the Agency's feedback in pre-investigational new drug (IND) (Type B) and Type C meetings. Here, we share our experience from these meetings, including strategy, preparation, pre- and post-meeting feedback from the FDA, and lessons learned during the AAV9-hPCCA regulatory process, which the program plans to apply across the PaVe-GT platform. Topics discussed in the regulatory meetings included animal model and efficacy studies, toxicology study plans, manufacturing of the investigational AAV product, and clinical trial design. The main lessons learned from the pre-IND and Type C meetings for AAV9-hPCCA are: (1) Pharmacology/Toxicology studies in a single rodent species are sufficient for filing an initial IND; (2) FDA feedback guides product quality improvements and early development of a quantitative potency assay; (3) use of biomarkers as potential surrogate endpoints in a future efficacy trial benefits from collection of data in the natural history study and the first-in-human Phase 1/2 study; and (4) evidence from the Phase 1/2 clinical trial could be leveraged to support a license application. Lightly redacted regulatory documents and comprehensive templates developed by the PaVe-GT team are available on the PaVe-GT website.

Dependovirus↗

PubMed2026

Heterogeneity in Teriflunomide Treatment Arms: A Systematic Review and Meta‑Regression of Randomised Multiple Sclerosis Trials.

BACKGROUND: Teriflunomide is widely used as an active comparator in Phase 3 randomised trials for relapsing multiple sclerosis (RMS). Temporal changes in disease activity within teriflunomide-treated cohorts have not been systematically examined. OBJECTIVES: To assess temporal trends in relapse and disability outcomes across teriflunomide arms of Phase 3 multiple sclerosis (MS) trials and identify predictors of between-trial heterogeneity. METHODS: We performed a systematic review and meta-analysis of Phase 3 randomised controlled trials including a teriflunomide arm. PubMed, Scopus, and ClinicalTrials.gov were searched up to October 2025. Annualised relapse rate (ARR) and 12- and 24-week confirmed disability worsening (CDW) were extracted together with baseline characteristics. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses, meta-regression, and sensitivity analyses were performed. RESULTS: Twelve teriflunomide cohorts from eight trials involving 4,900 adults with RMS were included. ARR ranged from 0.11 to 0.37 with substantial heterogeneity (I2 = 94%). Trial start year was inversely associated with ARR and explained a large proportion of between-study variability in exploratory meta-regression analyses. Confirmed disability worsening outcomes also showed substantial heterogeneity with a weaker trend toward lower event rates in more recent trials. CONCLUSION: Teriflunomide-treated trial populations have shifted toward lower relapse activity over time, and trial start year was the principal predictor of between-trial heterogeneity in ARR in exploratory analyses. These findings most plausibly reflect evolving recruitment and diagnostic practices rather than changes in drug efficacy. Accounting for these temporal dynamics is essential when interpreting outcomes from RMS trial using teriflunomide as comparator.

Humans↗

PubMed2026

Effectiveness of peer recovery support services for substance use disorders: A systematic review of healthcare utilization, behavioral health, and engagement outcomes.

BACKGROUND: Peer recovery support services (PRS) delivered by individuals with lived experience of substance use, are increasingly incorporated into substance use disorder (SUD) care systems to improve care engagement, reduce acute care use, and support recovery. However, existing systematic reviews have focused on substance use outcomes, with limited attention to healthcare utilization, psychosocial functioning, and outcomes across settings, and populations. METHODS: This systematic review, registered in PROSPERO (CRD42023469279), synthesized peer-reviewed studies from 2003 to 2026 evaluating PRS for individuals with alcohol or drug-related SUD. Using MEDLINE, Embase, PsycINFO, and CINAHL, the review included 53 studies primarily conducted in high-income countries that reported quantitative outcomes across substance use, healthcare utilization, behavioral health, and treatment engagement. Risk of bias was assessed using Cochrane RoB 2, ROBINS-I, and ROBINS-E tools. RESULTS: Overall, evidence was most favorable for selected treatment-linkage and engagement outcomes, whereas findings for substance use, emergency department use, hospitalization, overdose, and mortality were inconsistent. Uncontrolled longitudinal studies frequently reported improvements in depression and anxiety, but no randomized trials evaluated these outcomes, limiting causal inference. Exploratory cross-study patterns suggested that sustained navigation, practical assistance, and repeated peer contact were more often present in programs reporting favorable outcomes; however, these components were not independently evaluated. Substantial heterogeneity, frequent multicomponent interventions, high risk of bias in many nonrandomized studies, and limited long-term and economic data constrain conclusions. CONCLUSIONS: Findings support the promise of PRS while underscoring the need for more rigorous comparative studies, cost-effectiveness data, and further research in low- and middle-income countries.

Humans↗

PubMed2026

Can host genetics transform the sustainable control of tropical theileriosis? Insights from the Tick-Theileria interface.

Tropical theileriosis, caused by the tick-transmitted apicomplexan parasite Theileria annulata, remains a major constraint on cattle production across North Africa, the Mediterranean basin, the Middle East and South Asia. Current control depends on acaricides, the theilericidal drug buparvaquone and live attenuated schizont vaccines, but acaricide resistance, buparvaquone-resistance mutations and the logistical demands of vaccination are eroding the sustainability of these tools. Host genetics offers a complementary and durable alternative. Indigenous Bos indicus breeds are consistently more resistant to ticks and tolerate T. annulata infection better than exotic Bos taurus cattle, and this advantage has a measurable heritable component. Unlike previous reviews, which treat tick resistance, T. annulata immunobiology and livestock genomic selection as separate subjects, we integrate all three and assess host genetics specifically against the failure modes of current control. We review the tick, parasite and host interface, the evidence for natural resistance, and the genetic and immunological mechanisms involved, including signal-regulatory protein, bovine major histocompatibility complex class II and inflammatory pathway genes. We then assess whether genomic selection, multi-omics, machine learning and gene editing can translate these mechanisms into resistant cattle, and we weigh the biological, economic and infrastructural barriers to implementation. The evidence indicates that host genetics will not replace existing control but could reduce reliance on acaricides and chemotherapy. That contribution remains prospective rather than demonstrated: no resistance marker for T. annulata has yet been validated, prediction accuracies are moderate and transfer poorly between breeds, and no endemic production system has implemented selection for resistance.

Animals↗

PubMed2026

Psychiatric Diagnoses and Psychotropic Medications Among Military-Affiliated Adolescents and Young Adults With Polycystic Ovary Syndrome.

PURPOSE: To study rates of psychiatric diagnoses and psychotropic medication prescription among U.S. military-affiliated adolescents and young adults (AYA) with polycystic ovary syndrome (PCOS). METHODS: This retrospective matched cohort study included U.S. military-affiliated AYA (aged 15-21 years) enrolled in TRICARE Prime for at least 6 months during the surveillance period (January 2016 to October 2023). Military-affiliated AYA were grouped into three categories: individuals diagnosed with PCOS (N = 6,911), age-matched individuals with no diagnosed PCOS symptoms (N = 35,814), and individuals with diagnosed symptoms suggestive of PCOS (N = 2,136). The presence of a psychiatric diagnoses and prescriptions for psychotropic medications were obtained via the International Classification of Diseases, 10th Revision, Clinical Modification codes and National Drug codes, respectively. RESULTS: AYA with diagnosed PCOS had higher odds of having a psychiatric diagnosis and being prescribed a psychotropic medication compared to an age-matched comparison group (psychiatric diagnosis odds ratio [OR] = 2.48 [2.35-2.62], medication OR = 2.14 [2.03-2.25]) and individuals with symptoms suggestive of PCOS (psychiatric diagnosis OR = 1.11 [1.003-1.23], medication OR = 1.16 [1.05-1.28]). DISCUSSION: The odds of psychiatric comorbidities and psychotropic medication prescription were more than twice as high as among U.S. military-affiliated AYA with PCOS. More research is needed to determine whether health-care utilization and military-related factors impact mental health outcomes among AYA with PCOS. Additionally, tailored, multidisciplinary mental health services for AYA with PCOS are needed.

Humans↗

PubMed2026

Non-smoked cannabis consumption formats and Cannabis Use Disorder severity in an illicit setting: Evidence from Chile, 2020-2024.

BACKGROUND: Cannabis Use Disorder (CUD) has become an increasing public health burden, particularly in Chile. Non-smoked cannabis formats and products have been independently associated with CUD but remain understudied in the region. This study compares CUD severity among individuals aged 12 to 65 in Chile who consume cannabis via edibles, vaporization or both versus those who exclusively smoke it. METHODS: We obtained secondary data from three waves of the Chilean National Survey on Drugs in the General Population (ENPG), a three-stage stratified probabilistic sampling design study conducted in 2020, 2022, and 2024. Our pooled cross-sectional sample included individuals (n = 3543) who reported cannabis use in vaped, edible, both vaped and edible or exclusively smoked format in the past 12 months. We used a partial proportional odds model to estimate the association between CUD severity and consumption formats. RESULTS: Cannabis vaping group showed higher odds of presenting at least mild CUD (OR = 6.21 [95% CI: 3.75-10.3]), as did the edible group (OR = 1.73 [95% CI: 1.08-2.78]) and both group (OR = 5.92 [95% CI: 2.72-12.87]), compared to exclusive smokers. However, only the vaped group demonstrated higher odds for all severity levels. CONCLUSION: Compared with exclusive smokers, users of vaporizers and/or edibles showed a stronger association with CUD. This association may be explained by consumption patterns and total THC exposure. Further research is needed to characterize the average THC exposure by consumption format, acknowledging contextual confounders such as the legal framework.

Humans↗

PubMed2026

Determinants of Nonspecific Response to Treatment in Randomized Controlled Trials of Major Depressive Disorder: A Narrative Review.

The design, conduct, and interpretation of double-blind randomized placebo-controlled clinical trials in major depressive disorder (MDD) are complicated by determinants of nonspecific response to treatment (NSRT). This narrative review provides a comprehensive overview of the determinants of NSRT in randomized controlled trials (RCTs) for MDD, including the placebo effect, factors related to measurement of the primary endpoint, the inclusion of misdiagnosed patients, the relapsing-remitting course of MDD, and factors related to functional unblinding. Potential strategies to reduce the impact of the determinants of NSRT and to improve the interpretation of RCT outcomes in MDD are also summarized. These strategies include use of centralized rating and standardized rater training, independent diagnostic confirmation, optimized site selection, minimizing financial incentives, exclusion of subjects participating in multiple clinical trials, exclusion of patients with unstable major depressive episode trajectories, and use of active placebo and alternative trial designs. Uniformity among experts in the definitions of determinants of NSRT and related concepts, as well as in strategies to address them, may facilitate progress in the development of novel treatments for MDD.

Humans↗

PubMed2026

Antibiotic-impregnated bone graft to prevent infection after total hip arthroplasty (ABOGRAFT): protocol for a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Studies have shown promising results using bone graft as a carrier for local administration of antibiotics to reduce the risk of prosthetic joint infection (PJI). The objective of this clinical trial is to determine if tobramycin and vancomycin-impregnated bone graft is safe and effective in reducing the rate of PJI after total hip arthroplasty (THA). METHODS AND ANALYSIS: This study is an international, randomised, double-blinded, placebo-controlled clinical drug trial. Patients scheduled for THA (n=1100) requiring bone grafting (excluding revisions due to an ongoing infection) are randomised in a 1:1 ratio to prophylactic treatment with tobramycin and vancomycin or placebo-impregnated bone graft.The primary outcome is the time to reoperation due to infection or diagnosis of PJI, expressed as a relative risk difference between the two groups. A risk reduction of at least 50% is considered clinically relevant. Secondary outcomes are time to and reason for reoperation and implant revision, type of micro-organism and antibiotic susceptibility pattern within 2 and 5 years after surgery. Safety outcomes are the number of adverse events and revision rate due to aseptic loosening. The primary analysis will be performed using proportional hazard models. ETHICS AND DISSEMINATION: The study has been approved under the Clinical Trial Regulation No 536/2014 (EU CT; 2024-510921-25-00). Results will be published in open-access peer-reviewed journals and disseminated to patient organisations and the media, and de-identified individual participant data will be curated and shared on reasonable request in accordance with the Findability, Accessibility, Interoperability and Reuse principles, subject to the laws and regulations governing data protection in each participating country. TRIAL REGISTRATION NUMBER: NCT05169229.

Humans↗

PubMed2026

Simultaneous determination of imiquimod and terbinafine in skin permeation studies: Validation of a liquid chromatography method with fluorescence detection.

Chromoblastomycosis is a chronic, neglected subcutaneous mycosis posing significant therapeutic challenges. A topical strategy combining terbinafine (TBF), an antifungal, with imiquimod (IMQ), a TLR-7/8 agonist immunomodulator, has emerged a promising alternative. However, no validated analytical method is currently available to simultaneously quantify both drugs in skin, which is crucial for novel formulation development. This study reports the development and validation of a simple HPLC method with fluorescence detection (excitation 236 nm, emission 340 nm) for the simultaneous determination of TBF and IMQ extracted from porcine skin. Separation was achieved on a C8 reversed-phase column (125 × 4.0 mm, 5 μm) using a mobile phase of methanol and water (60,40, v/v), both containing 0.1% formic acid at a flow rate of 0.8 mL/min. The method showed excellent linearity (r > 0.999) over 0.01-1.0 μg/mL for IMQ and 0.1-2.0 μg/mL for TBF. Intra- and inter-day precision demonstrated coefficients of variation below 5%, and recovery rates from skin (79-105%) confirmed accuracy. Limits of detection were 0.001 μg/mL for IMQ and 0.004 μg/mL for TBF, with quantification limits of 0.02 μg/mL and 0.16 μg/mL, respectively. This selective, sensitive, and reproducible method represents a valuable analytical tool for supporting the development and quality control of topical formulations for chromoblastomycosis and other fungal skin diseases.

Animals↗

PubMed2026

Hepatotoxicity of OBS: A review of the emerging PFOS substitute.

As an alternative to perfluorooctanesulfonic acid (PFOS), sodium perfluorononenyl oxobenzene sulfonate (OBS) is widely used due to its cost-effectiveness. Multiple studies have shown that the liver is a classic target organ for OBS. However, there is currently no systematic review on the hepatotoxic effects of OBS. This review systematically summarizes the exposure characteristics of OBS in the environment and human populations, as well as its mechanisms of liver toxicity. In vivo studies consistently demonstrate that OBS induces hepatotoxic effects, such as hepatomegaly, vacuolization, elevated serum transaminases, and lipid dysregulation, though the manifestation of these phenotypes varies across species and exposure routes. In vitro evidence further shows that OBS reduces cell viability and survival, and triggers necrosis accompanied by inflammation. Mechanistically, oxidative stress, inflammatory signaling, and metabolism disorder are implicated. Critically, most existing work addresses subacute or subchronic exposure, leaving a gap in chronic risk assessment for long-term, low-dose OBS exposure. Moreover, mechanistic studies have focused predominantly on downstream transcriptional and signaling changes, with limited exploration of upstream epigenetic controls. Overall, this study aims to provide a comprehensive reference for future toxicological investigations and liver injury risk assessments related to OBS exposure.

Humans↗

PubMed2026

Theta-range SEEG stimulation for intracranial mapping: extending conventional 1-Hz and 50-Hz protocols.

OBJECTIVE: Electrical brain stimulations (EBS) are central to epileptic network identification and functional mapping during stereo-electroencephalography, yet stimulation frequencies remain empirical, and standardized across patients and brain regions, producing false negatives and false positives, and potentially compromising surgical outcome. We prospectively investigated theta-range EBS (7 Hz) in the temporal lobe, a prominent physiological frequency band in this region, and compared it with conventional 1-Hz and 50-Hz protocols. METHODS: We analyzed 1,408 temporal EBS in 25 drug-resistant epileptic patients. Epileptic responses (afterdischarges, seizures) and clinical signs were assessed across the epileptic network and temporal structures (amygdala, hippocampus, neocortex, parahippocampal gyrus, white matter), and confronted to stimulation parameters (frequency, intensity, duration, total charge). RESULTS: At matched intensity and duration, 7-Hz EBS were associated with a higher occurrence of afterdischarges and clinical signs than 1-Hz EBS in several temporal structures. Effects on usual seizure induction were less consistent. Comparisons with 50 Hz showed no systematic significant differences, with responses observed at one or both frequencies depending on structure and outcome. When controlling for total charge, frequency-related differences were attenuated. Some effects were sporadically observed at both intermediate frequency and charge quantity. CONCLUSIONS: EBS responses emerge from the interaction between all electrical parameters and anatomical location and local excitability, and can hardly be disentangled. However, 7-Hz EBS can provide complementary clinical information during temporal-lobe mapping, with a targeted approach. SIGNIFICANCE: These findings support targeted evaluation of broader stimulation parameter spaces, including intermediate frequencies, rather than routine reliance on fixed low- and high-frequency protocols alone.

Humans↗

PubMed2026

Perioperative care for patients with opioid exposure and opioid use disorder: screening and treatment strategies.

PURPOSE OF REVIEW: The prevalence of opioid tolerance, dependence, and use disorder is increasing among patients presenting for surgical care, yet perioperative management strategies for these patients remain inconsistent. This review examines the impact of preoperative opioid exposure on surgical outcomes, the scope of untreated opioid use disorder (OUD) among surgical patients, and advances in clinical and systems-level approaches to perioperative care. RECENT FINDINGS: Preoperative opioid exposure independently predicts worse surgical outcomes, including higher opioid consumption, readmissions, complications, and mortality, in a dose-dependent manner. Perioperative opioid exposure predicts persistent opioid use after surgery, with the duration of exposure a stronger predictor of subsequent OUD than daily dose. Data-driven prescribing guidelines and structured opioid tapering reduce overprescribing without compromising pain control. Among surgical patients with diagnosed OUD, approximately two-thirds do not receive medications for opioid use disorder (MOUD), though treatment engagement and maintenance substantially improve outcomes. Evidence now clearly supports perioperative buprenorphine continuation over interruption. SUMMARY: Effective perioperative management of opioid-complex surgical patients requires systematic screening, evidence-based prescribing, MOUD continuation, and institutional infrastructure. The primary barrier is shifting from evidence generation to implementation.

Humans↗

PubMed2026

Workplace Safety Champions: Strengthening safety culture through nurse engagement.

Workplace violence is a growing concern in health care, disproportionately affecting frontline nurses and nursing assistants. Despite high prevalence, underreporting remains a barrier to effective prevention and response. This article describes the development, implementation, and outcomes of a Workplace Safety Champion program designed to increase reporting of violent incidents and strengthen a culture of safety. A multidisciplinary task force developed an evidence-based Workplace Safety Champion course that emphasizes de-escalation strategies, reporting processes, and staff support. Champions were appointed across inpatient and emergency units and integrated into a hospital-wide Workplace Safety Champion Council. Program evaluation used course completion data and posttraining surveys. The organizational goal of having at least one trained champion in 90% of inpatient and emergency units was exceeded, with 98% of units represented (N = 93 champions). More than 85% of learners reported intent to change their response to workplace violence, and 90% endorsed improved knowledge of resources and de-escalation strategies. The Workplace Safety Champion program successfully improved staff awareness, reporting, and engagement in workplace violence prevention. Embedding champions across units can serve as a sustainable strategy to strengthen safety culture and support frontline health care workers.

Humans↗

PubMed2026

External ventricular drain safety campaign and opportunities for global neuroanesthesiology quality and safety.

PURPOSE OF REVIEW: This review describes the conceptualization and implementation of the External Ventricular Drain (EVD) Safety Campaign, a global patient safety initiative by the Society for Neuroscience in Anesthesiology and Critical Care. It summarizes recent literature on EVD insertion and maintenance, highlights opportunities to advance quality and safety in neuroanesthesiology, and outlines priorities and a framework for future work. RECENT FINDINGS: The Society for Neuroscience in Anesthesiology and Critical Care launched a global initiative to improve EVD management. EVD insertion and maintenance remain key areas of ongoing research and quality improvement, particularly in reducing complications. SUMMARY: The EVD Safety Campaign provides a structured framework to improve care delivery and patient outcomes worldwide. Continued focus on standardization, education, and complication reduction, especially infection prevention, will be essential to advancing the field.

Humans↗

PubMed2026

UNCX/SIN3A-Mediated H4K8 decrotonylation suppresses FOXO3 to drive TNBC progression and docetaxel resistance.

Triple-negative breast cancer (TNBC) remains a clinically challenging subtype characterized by aggressive behavior and limited treatment options. Though docetaxel remains a cornerstone chemotherapy for TNBC, the frequent emergence of resistance highlights the urgent need to identify novel therapeutic targets. In this study, we report that uncoordinated homeobox (UNCX) is upregulated in docetaxel-resistant breast cancer cells, genomically amplified in breast cancer, and associated with poor survival in breast carcinoma patients. Functional studies revealed that UNCX promotes breast cancer cell proliferation, migration and reduces the docetaxel sensitivity. Mechanistically, UNCX functions as a transcriptional repressor by recruiting the SIN3A complex. Genome-wide profiling indicated that the UNCX/SIN3A complex directly binds to the promoters of tumor-suppressor genes including FOXO3, and represses their transcription by removing histone H4K8 crotonylation (H4K8cr). Additionally, the UNCX/SIN3A complex enhances FOXO3 phosphorylation and inhibits its nuclear translocation, further inhibiting its activity. Notably, SIN3A knockdown, FOXO3 overexpression, or crotonylation restoration effectively reverses UNCX-induced malignant phenotypes. These findings collectively establish the UNCX/SIN3A-H4K8cr-FOXO3 axis as a pivotal epigenetic regulator of TNBC progression and chemoresistance, revealing new avenues for targeted therapeutic development against this aggressive breast cancer subtype.

Humans↗

PubMed2026

Complicated urinary tract infections: evolving definitions, clinical burden, and treatment landscape amid antimicrobial resistance.

INTRODUCTION: Complicated urinary tract infection (cUTI) is a common and heterogeneous infection associated with substantial morbidity, high healthcare utilization, and increasing antimicrobial resistance. Evolving definitions, increasing device use, and changing patient populations have altered its epidemiology and management. Marked variability in diagnostic criteria, clinical trial endpoints within and outside registrational settings, and treatment strategies complicates clinical decision-making and interpretation of therapeutic advances. AREAS COVERED: This review examines contemporary cUTI epidemiology, classification frameworks, and drivers of disease burden. It evaluates resistance trends and their therapeutic implications, alongside stewardship-based management strategies, including empiric antibiotic selection, intravenous-to-oral transition, treatment duration, and source control. Challenges in catheter-associated infection, recurrence, and regulatory endpoint design are discussed, together with the emerging role of novel agents targeting resistant Gram-negative pathogens. EXPERT OPINION: Rising multidrug resistance and limited oral options are reshaping cUTI management, necessitating individualized, stewardship-aligned therapy guided by illness severity and local epidemiology. Current regulatory endpoints inadequately reflect patient-centered outcomes, particularly in the context of asymptomatic bacteriuria. Expanding availability of effective oral agents may enable earlier discharge and outpatient care. Integration of rapid diagnostics and risk stratification will be essential to optimize therapy, limit resistance, and improve outcomes.

Humans↗

PubMed2026

Cefiderocol susceptibility rates in carbapenem-resistant Gram-negative bacteria in a comparative, multicenter surveillance study in China.

BACKGROUND: Cefiderocol is a siderophore cephalosporin with potent, broad spectrum of activity against carbapenem-resistant (CR) Gram-negative bacteria. The objective of this surveillance study was to assess cefiderocol susceptibility in molecularly characterized CR Gram-negative pathogens collected from hospitalized patients across China. METHODS: Susceptibility testing was performed by the broth microdilution method according to Clinical and Laboratory Standards Institute guidelines, using pre-prepared frozen 96-well microtiter Thermo Fisher plates. Susceptibilities to cefiderocol and most comparators were determined by Clinical and Laboratory Standards Institute breakpoints, to tigecycline by US Food and Drug Administration breakpoints, and to colistin by European Committee on Antimicrobial Susceptibility Testing criteria. Carbapenemases were identified by whole-genome sequencing and polymerase chain reaction. RESULTS: Of 149 CR Klebsiella pneumoniae, 95.3% were susceptible to cefiderocol (OXA-48-positive 100% [n = 15]; IMP-positive 100% [n = 9]; KPC-positive 95.4% [n = 108]; NDM-positive 88.2% [n = 17]) and against 103 NDM-positive CR Escherichia coli, cefiderocol susceptibility was 45.6%. Among comparator antibiotics, ceftazidime-avibactam was only active against K. pneumoniae carbapenemase-positive and OXA-48-positive K. pneumoniae isolates. Susceptibilities to tigecycline and colistin were between 22.2% and 97.1% and between 88.2% and 100% across CR Enterobacterales with different carbapenemases, respectively. High cefiderocol susceptibility rates were found for CR Pseudomonas aeruginosa (98.4%), CR Acinetobacter baumannii (99.6%), and Stenotrophomonas maltophilia (99.6%). Among comparator antibiotics, only colistin showed high activity against CR P. aeruginosa (99.2%) and CR A. baumannii (99.2%). CONCLUSIONS: Cefiderocol susceptibility rates were ≥88% against a collection of carbapenemase-positive CR Gram-negative isolates, except for lower susceptibility in NDM-positive CR E. coli isolates. Continuous monitoring of cefiderocol susceptibility is warranted.

Cefiderocol↗