Background Antibiotic therapy remains the mainstay for the management of bacterial infections. However, the rapid emergence of multidrug-resistant (MDR) organisms has become a major clinical concern, leading to limited treatment options and increased healthcare burden. Ceftriaxone-sulbactam-EDTA (CSE) is a cephalosporin-beta-lactamase inhibitor combination containing disodium edetate, an antibiotic resistance breaker that may help restore antibacterial activity against resistant Gram-negative organisms. This study aimed to evaluate CSE as a potential therapeutic option by assessing its susceptibility pattern against MDR-Gram-negative bacilli (GNB) isolated from intensive care unit patients. Material and methods A laboratory-based study was conducted on 92 MDR-GNB isolates from ICU patients at Krishna Charitable & Medical Research Centre, Karad, India. Clinical specimens, including urine, endotracheal tube secretions, sputum, pus/wound swabs, blood, and body fluids, were processed using standard microbiological methods. Bacterial isolates were identified, and antimicrobial susceptibility testing was carried out as per Clinical and Laboratory Standards Institute recommendations. Phenotypic detection of extended-spectrum beta-lactamase (ESBL), metallo-beta-lactamase (MBL), and AmpC beta-lactamase production was performed to characterize resistance mechanisms. Additionally, the susceptibility profile of MDR-GNB isolates to CSE and other commonly used antimicrobial agents was evaluated. Results The study analyzed a total of 92 MDR-GNB isolates. The highest number of isolates were observed in the 31-40 and 41-50 age groups, with male predominance. Urine was the most common specimen source, with 39 (42.39%) isolates, followed by endotracheal tube secretions, with 20 (21.74%), and sputum, with 11 (11.96%) isolates. Pseudomonas aeruginosa was the predominant organism, followed by Klebsiella pneumoniae, Klebsiella oxytoca, Acinetobacter baumannii, Escherichia coli, and Enterobacter cloacae complex. Among the isolates, 51 were ESBL producers, 48 were MBL producers, and 38 were AmpC producers, indicating a significant burden of beta-lactamase-mediated resistance. High resistance was observed against meropenem (94.57%), netilmicin (93.48%), and ciprofloxacin (90.22%). Nitrofurantoin showed good activity among urinary isolates, with 35 (89.74%) susceptible. Co-trimoxazole showed susceptibility in 6 (14.63%) of 41 tested isolates, while tigecycline showed susceptibility in 5 (12.20%) of 41 tested isolates. CSE showed substantial in vitro activity, with 80 (86.96%) isolates susceptible and 12 (13.04%) resistant. Conclusions MDR-GNBs were frequently isolated from ICU patients, mainly from urine and respiratory specimens, with P. aeruginosa and K. pneumoniae being the most common organisms. The presence of ESBL, MBL, and AmpC producers highlights the serious burden of antimicrobial resistance. CSE showed promising in vitro activity against MDR-GNB isolates and may be considered when guided by susceptibility testing. Strict infection control practices, routine resistance screening, and antimicrobial stewardship are essential in ICU settings.

Emerging contaminants (ECs) have raised worldwide concerns due to their potential environmental and ecological risks. ECs in sediments from the Yangtze River, Poyang Lake, and its tributaries were analyzed to investigate river-lake interaction and assess their hazard and risk. A total of 166 chemicals were identified by nontargeted screening, and their ToxPi hazard scores ranged from 0.0527 to 0.6559. The chemical compositions of different sections in Poyang Lake were dominated by seasonal water exchange, limited hydrological connectivity, and tributary inputs. The spatial distributions of nine representative ECs exhibited halo-like patterns according to targeted and interpolation analysis. The distributions of their hot spots were also influenced by inflows from tributaries and backflow from the Yangtze River. These ECs were mainly sourced from domestic wastewater, industrial emissions, and agricultural non-point source pollution. Netilmicin and mesulfenfos exhibited high risks to aquatic organisms by risk quotient assessment. Insight of ECs behaviors will provide fundamental information to propose potential monitoring management strategies in similar river-lake interaction water bodies.

Background Multidrug-resistant (MDR) Gram-negative bacilli (GNB) are a major cause of healthcare-associated infections in intensive care units (ICUs), leading to increased morbidity, mortality, and limited treatment options. This study was conducted to determine the prevalence of MDR-GNB among ICU clinical specimens and to evaluate their antimicrobial susceptibility patterns. Material and methods This cross-sectional observational study was carried out at the Department of Microbiology, Krishna Institute of Medical Sciences, Karad, from August 2024 to March 2025. A total of 370 clinical specimens obtained from ICU patients were processed using standard microbiological methods. The VITEK 2 compact automated system (Marcy-l'Étoile, France: bioMérieux) was used to identify Gram-negative bacilli, and VITEK 2 AST cards were used for antibiotic susceptibility testing. Multidrug-resistant isolates were defined as resistance to three or more antimicrobial classes. Results A total of 370 specimens were processed; growth was observed in 228 specimens. Among these, 109 were Gram-positive, and 119 were Gram-negative. Multidrug-resistant Gram-negative bacteria were identified in 101 isolates. The highest burden of infection was observed in both the 31-40 year and 41-50 year age groups, with each group contributing 26 cases (25.74%). Males were more frequently affected than females, contributing 69 (68.32%) cases compared to 32 (31.68%). Among the pathogens, Pseudomonas aeruginosa was the most commonly isolated organism (31, 30.69%), followed by Klebsiella spp. (25, 24.75%), and Klebsiella pneumoniae (18, 17.82%). Escherichia coli (12, 11.88%) and Acinetobacter spp. (11, 10.89%), were also notable contributors. Urine was the predominant specimen source (43, 42.57%), followed by endotracheal tube samples (22, 21.78%), wound swabs (10, 9.90%), sputum (9, 8.91%), and blood (9, 8.91%). Antimicrobial resistance was high for meropenem (96, 95.05%), netilmicin (94, 93.07%), amikacin (93, 92.08%), and ceftazidime (92, 91.09%). In contrast, nitrofurantoin showed the lowest resistance (5, 11.63%) and the highest susceptibility (38, 88.37%) among urine isolates. The second most effective antimicrobial combination was piperacillin/tazobactam, with susceptibility observed in 34 (33.66%) isolates. These findings indicate a significant prevalence of MDR-GNB infections among middle-aged male intensive care unit (ICU) patients, with limited effective treatment options. Conclusion This study demonstrates a high prevalence of multidrug-resistant Gram-negative bacilli among patients in the intensive care unit with Pseudomonas aeruginosa, Klebsiella spp., Acinetobacter spp., and Escherichia coli as the predominant pathogens. The predominance of urine and respiratory specimens may be associated with the frequent use of urinary catheters and mechanical ventilation in critically ill ICU patients, contributing to hospital-acquired infections. The high level of resistance across multiple antimicrobial classes, including carbapenems, aminoglycosides, cephalosporins, fluoroquinolones, and piperacillin/tazobactam, highlights the challenge of having few options for treatment. These results show the urgent need for early microbiological diagnosis, culture, and susceptibility-guided therapy; strict methods for infection prevention and control; and robust antimicrobial stewardship programs to reduce the burden of MDR infections and improve patient outcomes in the ICU.

Background/Aim: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer and is characterized by high genetic heterogeneity and poor prognosis. TP53 is the most frequently mutated gene in LUAD and plays a critical role in tumor initiation, progression, and therapeutic resistance. The present study aimed to prioritize TP53-associated drug repurposing candidates in LUAD using an integrative in silico approach. Materials and Methods: A total of 1309 TP53-associated compounds were retrieved from the Gene2Drug database. Drug sensitivity profiles of lung adenocarcinoma cell lines were evaluated using PRISM Repurposing Public 22Q2 viability data obtained from the DepMap platform. Candidate compounds were ranked according to Gene2Drug significance scores (p < 1 × 10-3), and compounds with concordant sensitivity patterns in PRISM data were prioritized. Results: LUAD cell lines showed the strongest sensitivity to atropine (p = 6.83 × 10-5). Additionally, LUAD cell lines displayed consistent sensitivity signals for dropropizine (p = 8.47 × 10-3), terazosin (p = 1.11 × 10-3), morantel (p = 9.05 × 10-3), netilmicin (p = 8.37 × 10-3), altretamine (p = 9.82 × 10-3), and perphenazine (p = 9.58 × 10-3). These findings indicate that several non-oncology drugs exhibit distinct and reproducible sensitivity profiles in LUAD cell lines. Conclusions: Based on TP53-associated drug sensitivity profiles, this in silico analysis identifies atropine among the prioritized candidates, showing the strongest TP53-associated sensitivity signal in LUAD cell lines. Although experimental validation is required, the integration of independent computational datasets provides a robust framework for candidate prioritization and our findings provide a rationale for further preclinical investigation of atropine and related compounds in LUAD.

Antimicrobial resistance is one of the most current global health challenges, due to the increasing ineffectiveness of antibiotics and the increasing difficulty in treating infections. Approximately two-thirds of microbial antibiotics are produced by actinomycetes, of which approximately 74% come from the genus Streptomyces. In this study, a novel actinomycete strain, Streptomyces sp. BPA-6, isolated from pollen collected by Algerian bees, was investigated for its antimicrobial potential and chemical composition by GC-MS and HPLC-MS analyses. The strain showed strong antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, and Candida albicans, with minimum inhibitory concentrations (MICs) ranging from 62.5 to 250 µg/mL. Molecular identification using 16S rRNA gene sequencing and scanning electron microscopy confirmed the affiliation of the isolate to the genus Streptomyces. GC-MS analysis of the ethyl acetate extract revealed a complex mixture of volatile organic compounds, including fatty acid methyl esters, long-chain hydrocarbons, and sesquiterpenes, many of which are associated with antimicrobial, antioxidant, or anti-inflammatory properties. Complementary HPLC-MS profiling identified more than 40 nonvolatile bioactive compounds, including macrolides (erythromycin), polyethers (nigericin), aminoglycosides (netilmicin), polyketides (cytosporone C), and various sugar and lipid derivatives. The chemical diversity of the extract highlights the rich biosynthetic capacity of BPA-6 and its potential as a source of novel natural products.

To investigate the cause of the large-scale death of farmed bullfrog (Lithobates catesbeianus) in a certain area of Hubei Province. Bacterial isolates were revealed from the liver, brain, and lung of bullfrogs exhibiting typical symptoms of cataract. Regression infection studies confirmed that a strain Z20240301 was responsible for the white eyes and high mortality rate among bullfrogs. Histopathological analysis revealed that the infection could lead to varying degrees of hemorrhage in the meningeal connective tissue of the bullfrogs. The further 16S rRNA sequence identification and Genome-wide analysis confirmed that the Z20240301 belongs to Acinetobacter johnsonii, which carries 566 virulence factor-related genes, include hlyA, hlyB, and lipopolysaccharide (LPS); and 257 drug resistance-related genes, including those conferring resistance to major antibiotic classes such as macrolides, aminoglycosides, fluoroquinolones, and tetracyclines. The isolate Z20240301 was highly sensitive to cefazolin oxime, cefradine, gentamicin, streptomycin, netilmicin, and tobramycin; moderately sensitive to cefotaxime, azithromycin, erythromycin, enrofloxacin, doxycycline, and neomycin; and resistant to enoxacin, norfloxacin, and kanamycin. This study is the first to confirm A. johnsonii as a causative agent of cataracts in bullfrogs, providing a new theoretical basis for the diagnosis, prevention, and treatment of this disease.

While Yersinia ruckeri is known for causing systemic vascular damage, its potential to invade the central nervous system remains poorly understood. This study investigated the spatiotemporal distribution, pathological progression, antimicrobial resistance (AMR), and biochemical alterations associated with Y. ruckeri across 12 commercial rainbow trout farms in Türkiye. Advanced diagnostics using MALDI-TOF MS enabled rapid and accurate identification of the pathogen. Disease prevalence peaked in farms experiencing thermal stress (18 °C) and high biomass density. Histopathological examination revealed inflammatory alterations suggestive of neural involvement, including perivascular cuffing, neuronal degeneration, and focal neuroinflammation. In addition, Y. ruckeri was isolated from brain tissue in 15 infected fish and confirmed by MALDI-TOF MS, supporting the possibility of central nervous system involvement during systemic infection. Furthermore, the observation of neuroinflammation and perivascular cuffing suggests that the pathogenesis of Y. ruckeri is not limited to systemic vascular damage but also involves the central nervous system, which may explain the distinct behavioral changes and complex clinical progression of the disease. Antimicrobial susceptibility testing showed consistent multidrug resistance to amoxicillin, gentamicin, netilmicin, erythromycin, and sulfisoxazole. Serum biochemical analysis confirmed significantly elevated ALT levels, with ROC analysis identifying ALT as an excellent early biomarker (AUC = 0.956), having an optimal cut-off value of 71.4 U/L with high sensitivity (91.8%) and specificity (92.5%). The identified ALT threshold may provide a practical biomarker for the early detection and monitoring of ERM under field conditions. Collectively, this study provides new insights into ERM pathogenesis and highlights the need for improved antimicrobial stewardship and environmental risk management in aquaculture.

Burkholderia pseudomallei (B. pseudomallei) exhibits inherent resistance to multiple antibiotics and Strong pathogenicity, highlighting the urgent need for effective antibiotics. The type VI secretion system (T6SS) is a key virulence factor in B. pseudomallei, and its core structural protein hemolysin coregulated protein (Hcp) represents a conserved, essential target for potential intervention. In this study, Hcp was utilized as a molecular target to screen antibacterial agents from the FDA Orange Book database. Subsequent functional assays and mechanistic analyses identified netilmicin sulfate, which specifically binds to Hcp and exhibits a potent bacteriostatic effect. In vitro and in vivo studies demonstrated that it effectively eliminates B. pseudomallei and enhances host survival post-infection. Combination with ceftazidime exhibits synergism, strengthening host cell protection and reducing the required dosage. Mechanistically, it disrupts Hcp's tubular structure, compromising T6SS functional architecture and attenuating B. pseudomallei viability. Beyond identifying a promising antibiotic candidate, this approach underscores a potential strategy for future antimicrobial drug discovery targeting T6SS components.

Antimicrobial resistance (AMR) remains a significant threat. To ensure efficient use of antibiotics, the WHO AWaRe Antibiotics classification framework classifies antibiotics into three groups: Access, Watch, and Reserve. Tracking antibiotic resistance across these groups remains a critical task. This retrospective study examined the prevalence of resistance within the AWaRe Antibiotics classification framework in two large hospitals in Abuja Nigeria. A total of 14,423 microbial culture test results were sourced and retrieved from the hospitals between January and December 2023, of which 3,987 (27.64%) showed microbial growth and with antimicrobial susceptibility results. Six different sample types were analyzed, with urine samples (36.22%) yielding the highest number of isolates. Escherichia coli (23.78%) was the most identified microbe. The overall AMR rate across the AWaRe classification was 41.96%. For the Access category, highest resistance was reported for Doxycycline at 100% resistance while the lowest resistance was reported for Amikacin at 24.63%. For the Watch category, the highest resistance was reported for Cefuroxime at 85.71% while the lowest resistance was reported for ticarcillin/clavulanic acid and Netilmicin, both with 0% resistance. For the Reserve category, the highest resistance was reported for Aztreonam at 67.96% while the lowest resistance was reported for Polymixin B at 9.71%. Cumulatively, antimicrobials in the Access category had a resistance prevalence rate of 44.29%; those in the Watch category had a resistance prevalence rate of 46.65%; while those in the Reserve category had a resistance prevalence rate of 34.95%. More than 70% of multi-drug resistance was observed in frequently used antibiotics such as Cefuroxime, Ceftazidime, and Meropenem. Additionally, over 60% resistance was found in antibiotics like Ertapenem, Aztreonam, and Teicoplanin even though they are not readily available in Nigeria. Every microbe reported in this study was resistant to more than one antimicrobial agent. The most resistant microbes were Staphylococcus aureus, Klebsiella spp., Streptococcus spp., and Escherichia coli. Across gender, positive isolates were found more in women than men across almost all the microbes identified. These results, based on real patient data, highlight the urgent need for an institutionalized AWaRe Antibiotics framework across healthcare facilities in addition to broader strategies of antimicrobial stewardship, pharmaceutical supply chain enhancement, and national AMR surveillance.

Background/Objectives: Antibiotic-resistant strains have been reported in aquatic ecosystems, with varying prevalence and resistance patterns by region. In Tamaulipas, Mexico, little information has been generated on this topic, making it difficult to estimate their potential risk to environmental and human health. Therefore, the objective of this study was to evaluate the presence and virulence of antibiotic-resistant strains of Pseudomonas aeruginosa in environmental water from Tamaulipas, Mexico. Methods: One hundred water samples were collected from different water bodies in Tamaulipas to identify P. aeruginosa by PCR and MALDI-TOF, virulence gene detection, antimicrobial susceptibility testing, and detection class 1 integrons. Results: In this study, 109 P. aeruginosa strains were isolated. Eight virulence genes were identified in 47.7% to 80.7% of the strains, with the rhlAB gene being the most frequent. The strains showed resistance or intermedia resistance to 10 of the 16 antibiotics tested, in a range of resistance values 0.9-66.2%. In total, 100% (109/109) were susceptible to ceftazidime (CAZ), gentamicin (GM), amikacin (AN), netilmicin (NET), tobramycin (NN) and norfloxacin (NOR), and 65.7% were resistant to ticarcillin/clavulanic acid and 53.5% to ticarcillin; the resistance to the remaining antibiotics was between 19.4% and 0.9%. The class 1 integron was not identified in any of the strains analyzed. Conclusions:P. aeruginosa in environmental waters of Tamaulipas showed potential to cause infections and low rates of resistance to most of the antibiotics tested. However, 20% were resistant to one of the most common treatments, which could pose a risk to public health.

Antisepsis is a critical aspect of ocular surgery, particularly in intraocular procedures, due to the high risk of postoperative infections. Povidone-iodine is widely recognized for its broad-spectrum antimicrobial properties. This systematic review evaluates the intraoperative use of povidone-iodine applied to the conjunctiva in ocular surgeries. A systematic literature search was conducted using PubMed, Scopus, and Google Scholar for randomized controlled trials (RCTs) published between 2009 and 2023 in English that involved individuals who had undergone an ophthalmological intervention. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and a PRISMA flow diagram was used to illustrate the study selection process. Keywords used included the following: ("Povidone-iodine" OR "Betadine") AND ("Conjunctiva" OR "Ocular surgery"). Studies were selected based on predefined inclusion criteria focusing on the intraoperative antiseptic application of povidone-iodine in human ocular procedures, omitting conference abstracts or unpublished studies. Four RCTs met the inclusion criteria. The evidence base is limited by the small number of included RCTs, which restricts the statistical power and generalizability of the findings. This small sample increases susceptibility to methodological bias, reduces the reliability of pooled estimates, and limits the ability to explore heterogeneity. Furthermore, the potential for publication bias cannot be excluded, particularly given the limited number of studies, which may overestimate treatment effects. These studies compared povidone-iodine 5% to other concentrations or antibiotic agents such as povidone-iodine 1%, chloramphenicol 5%, netilmicin, commercial ozonized antiseptic solution (ozone), moxifloxacin 0.5%, and gatifloxacin. The application of all agents was topically on the conjunctiva just before the ophthalmological procedure started, and only gatifloxacin was applied for three days prior to the procedure. Across all included trials, povidone-iodine demonstrated superior antiseptic efficacy, significantly reducing conjunctival bacterial flora before surgery. The comparative agents showed minimal or less consistent antimicrobial effects. No serious or minor adverse effects related to povidone-iodine use were reported in any of the trials. Povidone-iodine remains a highly effective and safe antiseptic agent for intraoperative use in ocular surgery, while a need exists for additional high-quality independently conducted RCTs to confirm the observed effects and expand the evidence base. Its broad antimicrobial spectrum and favorable safety profile support its continued and widespread application for conjunctival antisepsis, outperforming several commonly used alternatives.

Gold nanoparticles (AuNPs) are increasingly explored as antimicrobial agents for the detection and treatment of multidrug-resistant (MDR) bacterial infections. This research tries to establish an eco-friendly, biological process for synthesizing AuNPs using Proteus mirabilis and studies their antibacterial efficacy against MDR Gram-negative pathogens and their potential to enhance standard antibiotic efficacy. Using the Vitek-2 system, 51 P.mirabilis isolates were analyzed, of which 74.5 % were MDR. Netilmicin was effective against 75 % of these isolates. P.mirabilis extracellularly biosynthesized AuNPs, which were then characterized by XRD, FTIR, TEM, and FE-SEM. Characterization showed AuNPs measuring ∼6-12 nm in size; the presence of amino and amide groups from FTIR spectra; and predominantly spherical or ellipsoidal morphology. Antibacterial activity, through broth microdilution, revealed that biosynthesized AuNPs inhibited Gram-negative bacilli at MICs of 156-1250 μg/mL. Moreover, biosynthesized AuNPs enhanced the effectiveness of antibiotics at low concentrations. Notably, when biosynthesized AuNPs were combined with ceftriaxone (commercial antibiotic), a marked synergistic effect was observed (P < 0.0001), with significantly enhanced prevention of pathogens compared to ceftriaxone used alone. These findings marched the function of biosynthesized AuNPs as adjuvants in drug development against MDR infections.