Microbial drug resistance最新文献

Background: The usage of antimicrobials is commonly associated with the emergence of resistant phenotypes in microorganisms. Health care facilities are required to measure antimicrobial consumption and monitor consumption trends to promote its rationale use. The aim of this study is to estimate the antimicrobial consumption in the hospital using the defined daily dose (DDD) methodology and to determine the percentage of antibiotics consumed as per the Access, Watch, and Reserve classification.

Methods: This retrospective observational study was conducted at Apollo Proton Cancer Centre, Chennai over a period of 1 year from January 2023 to December 2023. All inpatients admitted to the multidisciplinary critical care unit, surgical intensive care units, and wards were included in the study. Antimicrobial stewardship data collected by the clinical pharmacist were reviewed retrospectively. The calculation of antibiotic consumption was done using the DDD/1,000 patient-days formula, and the average of it was estimated using Microsoft Excel 2022 edition.

Results: A total of 5,029 inpatients were included in the study. The average antimicrobial consumption for the high-end antibiotics, restricted antifungals, and other antibiotics was found to be 637.9, 87.6, and 559.2, respectively. The most commonly consumed antibiotic was meropenem (51.4%) followed by cefoperazone-sulbactam (34.7%), piperacillin-tazobactam (34.2%), and teicoplanin (15.2%).

Conclusion: In this study, the utilization of Watch (73%) group antibiotics was more than that of the Access (18%) group and Reserve (9%) antibiotics. These findings suggest an urgent need for strengthening the existing antimicrobial stewardship program in the health care setting to improve the antibiotic metrics.

Ethambutol (EMB) serves as a critical first-line antimycobacterial agent pivotal in the management of Mycobacterium tuberculosis. The emergence of resistance to EMB, primarily driven by mutations in the embB gene, constitutes a formidable challenge to global tuberculosis (TB) eradication efforts. This meta-analysis followed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines and synthesized data from multiple databases, including PubMed, Embase, MEDLINE, Web of Science, and Elsevier Science, through August 2024. The selection criteria targeted studies reporting the prevalence and patterns of EMB resistance, utilizing both phenotypic and genotypic diagnostic methods. Data were extracted using Microsoft Excel, and statistical analyses were performed with Stata 17.0. Study heterogeneity was evaluated using the I² statistic and Cochran's Q test. A random-effects model using the DerSimonian-Laird method estimated the pooled prevalence of EMB resistance, with subgroup analyses distinguishing new cases from those with a treatment history exceeding 1 month. Fifty-one studies (34,215 isolates; 2,776 EMB-resistant) were included. The pooled prevalence of EMB resistance was 10% (95% confidence interval [CI]: 8-12%; I² = 92.99%), with substantial regional variation (Africa [15.56%] vs. Southeast Asia [6.60%]). Among multidrug-resistant TB patients, EMB resistance was 54% (95% CI: 45-63%) and reached 68% (95% CI: 65-72%) in the Eastern Mediterranean; previously treated patients had higher resistance than new cases (31% vs. 13%). Only 12 studies reported codon-specific embB data eligible for pooling, with embB306 most frequently reported and notable regional gaps for embB406/497 (e.g., Americas ND; Europe lacking 406/497). The study identifies substantial regional variations in EMB resistance and the prevalence of specific embB mutations. However, uneven regional representation (particularly limited data from Africa and the Americas) may affect the precision of global estimates. Enhancing diagnostic accuracy through molecular methods and developing regional surveillance systems are essential for effective management of EMB-resistant TB. Future research should prioritize comprehensive genomic analyses to identify novel resistance mutations and advance diagnostic methodologies. Future studies should adopt whole-genome sequencing and standardized codon-level reporting to enable comprehensive mutation profiling and improve comparability across surveillance systems.

Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) poses a significant therapeutic challenge with high mortality rates. This study evaluated the clinical efficacy of high-dose ampicillin-sulbactam combined with colistin compared to standard colistin-based regimens. This retrospective study was conducted on 83 patients with CRAB-VAP at Hanoi Medical University Hospital, Vietnam, from May 2024 to May 2025. Patients were divided into an intervention group (n = 33) treated with high-dose ampicillin-sulbactam combined with colistin and a control group (n = 50) receiving other antibiotic regimens combined with colistin. Primary outcomes included 28-day mortality and total ventilation duration. The intervention group achieved significantly lower 28-day mortality (6.1% vs. 38.0%; p < 0.001) and higher microbiological clearance rates by day 14 (93.9% vs. 30.0%; p < 0.001). While early acute kidney injury was more frequent in the intervention group (66.7% vs. 24.0%), renal function outcomes were comparable by day 14. Multivariable analysis identified day-14 microbiological clearance as the strongest independent predictor of survival (hazard ratio [HR] = 13.03; p < 0.001). High-dose ampicillin-sulbactam combined with colistin significantly improves microbiological clearance and survival in patients with CRAB-VAP. Despite a higher incidence of transient nephrotoxicity, the regimen provides a substantial survival benefit.

Newer methicillin-resistant antimicrobials are needed to address the rising prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative (MRCONS) infections. We describe two contrasting, recalcitrant staphylococcal infections successfully managed using early transition to the oral benzoquinolizine antibiotic alalevonadifloxacin, highlighting its utility in complex clinical settings. Two high-severity cases of staphylococcal infections are presented. Patient 1, a 58-year-old metastatic lung and orthopedic implant infection on hemodialysis, developed catheter-associated MRSA sepsis with bacteremia, endocarditis, and metastatic lung and orthopedic implant infection. Patient 2, a 41-year-old male with a prior craniotomy, presented with a chronic cranial wound infection due to methicillin-resistant Staphylococcus hominis (MRCONS) originating from an infected ex vivo bone flap. Both patients initially received intravenous therapy and were transitioned to oral alalevonadifloxacin upon availability of susceptibility data. Levonadifloxacin susceptibility testing showed an MIC of 2 µg/mL for MRSA and 0.047 µg/mL for MRCONS-SCV. Patient 1 received 7 weeks of oral therapy aligned with POET recommendation for endocarditis, while Patient 2 completed 8 weeks of oral therapy consistent with OVIVA-based management of osteomyelitis. Despite significant challenges, both patients demonstrated rapid clinical improvement, resolution of infection, and no relapse during follow-up. These cases support oral alalevonadifloxacin as an effective and safe step-down option for complex MRSA and MRCONS infections, including endocarditis, osteomyelitis and meningitis. Alalevonadifloxacin (prodrug of levonadifloxacin) offers a promising oral treatment option when conventional agents are not suitable.

Human infections with non-Helicobacter pylori Helicobacter species (NHPH) are rare. The diagnosis of such infection relies strongly on histological methods, as these bacteria cannot be easily cultured. We describe microbiological analyses that were performed on three cases of infection reported between 2020 and 2023, for which molecular biology was used to identify the species and facilitate the investigation of markers of resistance to macrolides and fluoroquinolones. 16S rRNA sequencing identified two Helicobacter suis strains and one Helicobacter heilmannii sensu strictostrain. Sequencing of 23S rRNA and quinolone resistance determining region of the gyrA gene, classically described as carrying mutations associated with resistance to macrolide and levofloxacin, respectively, did not reveal any mutations. RIDA^®GENE H. pylori, the Allplex™ H. pylori and ClariR Assay and Amplidiag^® H. pylori+ClariR cross-react with these NHPH strains. Any case of NHPH infection diagnosed by histology should be confirmed by molecular biology in specialized laboratories to identify the species and investigate the resistome.

Since their first identification in Türkiye in 2001, OXA-48-like carbapenemases have posed diagnostic challenges due to variant-specific phenotypic and resistance profiles. We investigated the distribution of OXA-48 variants and their association with antimicrobial susceptibility, carbapenem minimum inhibitory concentrations (MICs), phenotypic detection performance, and single- or dual-carbapenemase production. A total of 703 clinical carbapenem-resistant Enterobacterales isolates recovered over 5 years were included. Identification and antimicrobial susceptibility testing were performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and an automated system; carbapenem MICs by broth microdilution; carbapenemase genes by multiplex qPCR; and OXA-48 variants by sequence analysis. CNPt-direct and mCIM were performed for OXA-48 variants. OXA-48-like, NDM, and KPC carbapenemases were detected in 52.3%, 11.7%, and 11.5% of isolates, respectively, with co-production observed in 11.7% of OXA-48-like-positive isolates. The most common OXA-48 variants were OXA-48/245 (39.1%), OXA-232 (36.4%), and OXA-181 (17.6%), while OXA-244, OXA-162, and OXA-1200 were less frequent. This study represents the first report of the OXA-1200 variant from Türkiye. OXA-48/245 was the variant most commonly co-produced with other carbapenemases, whereas OXA-244 predominated among CNPt-direct-negative isolates. Susceptibility to meropenem and imipenem among OXA-48-like producers was 31% and 39.1%, respectively, with higher carbapenem MIC₅₀ values observed for OXA-181, OXA-232, and OXA-48/245 compared to OXA-244. In K. pneumoniae, meropenem resistance rates were higher with OXA-48/245, OXA-232, and OXA-181 than with other variants. MIC₅₀ values of carbapenem were higher in dual carbapenemase producers compared to single carbapenemase producers. Our findings show that OXA-48 variants significantly impact resistance profiles, MIC values, and the sensitivity of phenotypic tests and detection of co-produced carbapenemases. Understanding their regional distribution is crucial for targeted prevention strategies.

This study evaluated a 6-month, on-farm antimicrobial stewardship model integrating veterinary oversight, appropriate antimicrobial use, enhanced biosecurity, and an all-in/all-out system on five Korean pig farms lacking prior oversight. Antimicrobial usage and resistance of Escherichia coli were compared before and after implementation. The number of antimicrobial prescriptions decreased significantly following the implementation of the model (from 15.2 ± 9.2 to 7.2 ± 4.7). After model implementation, prescriptions for suckling piglets decreased from 2.2 ± 1.6 to 0.4 ± 0.9, and for weaned piglets from 4.4 ± 2.4 to 1.8 ± 1.1. Overall antimicrobial resistance decreased following model implementation, with the largest decreases were observed in ciprofloxacin (from 57.3% to 21.9%), nalidixic acid (from 60.0% to 34.2%), and cefazolin (from 92.0% to 64.4%). The multidrug-resistance rates in eight antimicrobial classes decreased significantly across all stages (from 28.0% to 4.1%), with decreases for suckling piglets (from 33.3% to 7.1%), weaned piglets (from 40.0% to 0.0%), growers (from 26.7% to 0.0%), finishers (from 26.7% to 14.3%), and sows (from 13.3% to 0.0%). The model effectively reduced both antimicrobial use and resistance, supporting its value for antimicrobial stewardship in pig production.

Antimicrobial resistance (AMR) represents a critical global health crisis, driving increased mortality, treatment failure, and economic burden. Artificial intelligence (AI) offers transformative potential to counter this threat by enhancing detection, diagnostics, and therapeutic precision. This narrative review synthesizes recent advances in AI-based approaches for AMR prediction, antimicrobial discovery, and clinical decision support, drawing on representative peer-reviewed studies published between January 1, 2015, and April 24, 2026. Models such as Deeparg-LS, XGBoost, and vision transformers achieved remarkable predictive accuracy using genomic, spectroscopic, and clinical data (AUC > 0.90; sensitivity/specificity >95%). AI-driven clinical decision support systems reduced antibiotic mismatches by up to 67%, while generative algorithms accelerated antimicrobial peptide discovery with 76% validation success. Deep learning frameworks improved metagenomic resistance profiling, and microscopy-based diagnostics shortened antimicrobial susceptibility testing by 50-70%. However, major challenges persist, including dataset heterogeneity, computational intensity, limited model transferability, and ethical concerns related to data privacy, bias, and interpretability. Emerging strategies such as explainable AI and federated learning show promise in addressing these issues. Overall, AI stands as a pivotal enabler in the fight against AMR, with future progress hinging on interdisciplinary collaboration, standardized validation, and responsible integration into clinical practice.

Background: Klebsiella pneumoniae is a major etiological agent of pediatric sepsis. The emergence and dissemination of carbapenem-resistant K. pneumoniae (CRKP) and hypervirulent strains (hvKp) represent an escalating global health concern. However, data regarding the coexistence of carbapenem resistance and hypervirulence in pediatric populations, especially in low- and middle-income countries, remain limited.

Objectives: This study aimed to determine the prevalence of carbapenem resistance and hypervirulence-associated genes among pediatric K. pneumoniae bloodstream infections in Egypt and to assess their association.

Methods: A cross-sectional study was conducted involving 100 pediatric patients with culture-confirmed K. pneumoniae sepsis at Mansoura University Children's Hospital between January 2023 and January 2025. Clinical and laboratory data were collected. Antimicrobial susceptibility testing was performed using standard disc diffusion and carbapenemase inhibition assays. Polymerase chain reaction (PCR) was employed to detect carbapenemase genes (including blaNDM for New Delhi metallo-β-lactamase, blaOXA-48 for oxacillinase-48, blaKPC for K. pneumoniae carbapenemase, blaVIM for Verona integron-encoded metallo-β-lactamase, and blaIMP for imipenemase). Hypervirulence genes tested included iucA (aerobactin siderophore synthesis), iroN and iroB (salmochelin siderophore cluster), and peg-344 (putative transporter). Genotypic hvKp was defined as the presence of two or more hypervirulence-associated genes.

Results: Carbapenem resistance was identified in 64% of isolates, with blaNDM (New Delhi metallo-β-lactamase) and blaOXA-48-like (oxacillinase-48) genes being the most prevalent carbapenemase determinants. Hypervirulence-associated genes were detected in 86% of isolates, which were classified as genotypic hvKp, most frequently iucA (aerobactin system) and peg-344 (putative transporter). No significant demographic or inflammatory differences were observed between CRKP and carbapenem-susceptible groups. Hypervirulence was present at similarly high frequencies in CRKP (87%) and carbapenem-susceptible K. pneumoniae (84%) isolates, with no significant association between these traits (p = 0.782). Logistic regression analysis did not identify any clinical predictors of hypervirulent infection.

Conclusion: The detection of multidrug-resistant K. pneumoniae isolates harboring multiple hypervirulence-associated genes highlights the potential convergence of resistance and virulence determinants. However, further phenotypic and functional studies are required to confirm the hypervirulent phenotype and assess its clinical significance.

Background: Nakaseomyces glabratus exhibits intrinsic tolerance to azole antifungals, frequently mediated by gain-of-function (GOF) mutations in the transcription factor CgPDR1. While efflux-mediated resistance is well established, its potential interaction with oxidative stress-dependent cell death pathways in biofilms remains insufficiently characterized.

Materials and methods: Fifteen clinical isolates (susceptible, n = 5; resistant, n = 10) were analyzed under planktonic and biofilm conditions. Antifungal susceptibility to itraconazole (0.03-32 µg/mL) was determined, while apoptosis and intracellular reactive oxygen species (ROS) were quantified using Annexin V/PI staining and fluorescence-based assays, respectively. The role of oxidative stress was evaluated using ascorbic acid co-treatment. CgPDR1 mutations were identified by sequencing.

Results: Resistant isolates exhibited significantly elevated minimum inhibitory concentration (MIC) values (up to 32 µg/mL) and a high prevalence of CgPDR1 mutations (K274N: 100%; D1082G: 30%; S343F: 10%). Itraconazole induced a marked increase in ROS production and apoptosis in susceptible biofilms (Annexin V⁺ ≈ 70%), whereas resistant isolates demonstrated attenuated ROS generation and reduced apoptosis (≈10%, p < 0.01). Although ascorbic acid significantly decreased ROS levels in susceptible isolates, it did not alter MIC values or restore antifungal susceptibility.

Conclusions: CgPDR1 GOF mutations are associated with a coordinated resistance phenotype in N. glabratus biofilms, characterized by enhanced drug tolerance and reduced ROS-mediated apoptosis. These findings support a multifactorial resistance model and identify K274N as a potential population-specific biomarker.