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Reports indicate that vegetables are becoming a source of multidrug-resistant (MDR) bacteria, including Escherichia coli. Here, we present genome sequences of five MDR E. coli strains to assist future genomic analysis of this bacterium. These E. coli strains were isolated from vegetable samples of different gardening systems in Dhaka, Bangladesh.

Introduction and aim of study: Chronic wounds are increasingly challenging global healthcare. These wounds, which take over 3 months to heal, are complicated by untreated infections and the formation of biofilm, hindering healing and antibiotic effectiveness. To tackle these issues, new treatments like bacteriophage therapy are being explored. Bacteriophages, viruses that target bacteria, offer promise in overcoming antibiotic resistance. However, their use presents challenges that need to be addressed. Material and methods: Our review is based on the analysis of materials collected in Pubmed, Elsevier and other scientific articles using keywords: “chronic wound”, “chronic wounds infection”, “biofilms”, “MDR”, “bacteriophage”, “phage therapy”. Conclusions: The rise of chronic wounds due to resistant infections poses a significant challenge for patients and healthcare systems. Multidrug-resistant bacteria, often forming biofilm, evade current treatments, urging the search for alternatives. Phage therapy, showing efficacy against various stubborn infections, including those from surgery or diabetes, gains attention. Advanced delivery systems enhance targeted treatment, while phage cocktails improve effectiveness, especially against multiple resistant strains. Safety is generally observed, but larger trials are needed. Though not a replacement for antibiotics, phage therapy offers hope, needing robust clinical validation. While challenges exist, its societal, commercial, and economic benefits suggest a promising future beyond clinical use. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of GeneXpert MTB/RIF assay by comparing its results with sputum smear microscopy. Study Design: Comparative Cross-Sectional Study. Setting: Department of Outpatient (OPD), Taluka and District Head Quarter Hospitals of District Ghotki Sindh. Period: October 2022 to 2023. Methods: In this study 350 Participants were included and all sputum specimens were tested for both above mentioned diagnostic tools that are sputum smear microscopy and GeneXpert MTB/RIF assay during the period October 2022 to April 2023. All details regarding the study such as Demographic details, sputum smear microscopy results, and GeneXpert MTB/RIF assay test results of patients were collected. A case of pulmonary tuberculosis (PTB) was considered to be a patient having mycobacterium tuberculosis detected in sputum by GeneXpert MTB/RIF assay. Results: In this study, 61 cases (17.4%) out of 350 participants, were detected in GeneXpert MTB/RIF assay and 35 cases (10%) out of 350 participants were positive in sputum smear microscopy. Male ratio is slightly higher than female among GeneXpert positive cases. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy sputum smear microscopy were 57%, 100%, 100%, 91.7%, and 92.5%, respectively, when GeneXpert test is taken as reference test. Conclusion: Sputum smear microscopy is as specific as GeneXpert but less sensitive test for the diagnosis of pulmonary tuberculosis than GeneXpert MTB/RIF assay. [ABSTRACT FROM AUTHOR]

Escherichia coli is one of the most common human and animal pathogens responsible for a broad spectrum of diseases. It has also been shown to be a significant reservoir of genes coding for antimicrobial drug resistance (AMR) and, therefore, is a useful indicator for resistance in bacterial communities. Azadirachta indica A. Juss (Neem), Zanthoxylum armatum DC (Timur), and Curcuma longa L. (Turmeric) are Nepalese medicinal plants that are known to be used against various illnesses by traditional healers. In this study, we investigated the antimicrobial activity of the ethanolic extracts of selected medicinal plants against multi‐drug resistant (MDR) E. coli isolated from normal individuals. All three plant extracts showed antibacterial properties against isolated multidrug resistant (MDR) E. coli with, 100% efficacy by Curcuma longa, 94.4% by Zanthoxylum armatum, and 68.51% by Azadirachta indica. From the total of 278 stool samples cultured, 241 E. coli were isolated, and 54 were identified as MDR. Among 54 MDR E. coli, 20.37% were extended‐spectrum beta‐lactamases (ESBL) producers, metallo beta‐lactamase (MBL) producers were identified as 0% and 70.37% were AmpC beta‐lactamases producers. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were reported as 40 mg/mL and 80 mg/mL for Curcuma longa, 40 mg/mL and 80 mg/mL for Zanthoxylum armatum, and 20 mg/mL and 40 mg/mL for Azadirachta indica, respectively. Thus, based on our results, these plant extracts can be good options against MDR E. coli‐related diseases and demonstrated that folk medicine can be as effective as modern medicine in combating pathogenic microorganisms. Medicinal plants have great potential for finding new clinically effective antimicrobial compounds. [ABSTRACT FROM AUTHOR]

Background: Resistance to carbapenem, the last line of treatment for gram-negative bacterial infections has been increasing globally and becoming a public health threat. Since integrons may aid in the transmission of resistance genes, the purpose of this study was to detect the frequency of class 1, 2, and 3 integrons as well as carbapenem-resistant genes in clinical isolates of P. aeruginosa that are resistant to carbapenem. Methods: This study was carried out on 97 clinical isolates of P. aeruginosa isolated from wound and urine samples. The antimicrobial susceptibility for all isolates was tested by the disc diffusion method. The presence of integrons and carbapenem-resistant genes among carbapenem-resistant P. aeruginosa isolates was evaluated by conventional PCR. Results: The antimicrobial resistance rate among P. aeruginosa clinical isolates was high, with imipenem resistance in 58.8% of the studied isolates. In this study, 86% of the carbapenem-resistant P. aeruginosa isolates carry carbapenemase genes, with blaVIM being the most common gene followed by the blaOXA−48 gene. Class 1 and class 2 integrons were reported in 37 (64.9%) and 10 (17.5%) of the tested carbapenem-resistant P. aeruginosa isolates, respectively. Conclusion: Our data reported a high prevalence of class 1 integrons in carbapenem-resistant P. aeruginosa clinical isolates, suggesting the important role of integrons in carbapenem-resistant gene transfer among such isolates. [ABSTRACT FROM AUTHOR]

The global public health addiction crisis has been stark, with over 932,400 deaths in the USA and Canada from opioid overdose since 1999–2020, surpassing the mortality rates at the top of the HIV/AIDS epidemic. Both nations exhibit opioid consumption rates significantly above the norm for developed countries. Analgesic type of opioids present both therapeutic benefits and substantial health risks, necessitating balanced drug regulation, careful prescribing, and dedicated opioid stewardship. The role of the cytochrome P450 2D6 (CYP2D6) system (Enzymatic functions) in metabolizing opioids highlights the potential of genotype-guided analgesia. By integrating Pharmacogenomics (PGx), this approach aims to optimize pain management, enhance safety, and reduce addiction risks. This understanding prompted the utilization of multifactor dimensionality reduction (MDR) to explore a range of phenotypes including PGx and gene–gene interactions (GGI) in a healthy cohort, thereby personalizing pain management strategies. The study sampled 100 unrelated healthy Western Iranians and 100 individuals from the 1000 Genome Project. Pre-testing involved searching for PGx annotations (variants associated with drug-gene-diseases) related to pain sensitivity and inflammation using the PharmGKB database, which identified 128 relevant genes. A questionnaire helped select 100 participants who had never used potent opioids but also other psychoactive agents (e.g., nicotine, amphetamines, etc.) and disease-related drugs. Whole-exome sequencing (WES) was then employed to analyze these genes in an Iranian cohort. Further analyses included MDR for identifying synergistic gene annotations and GGI for exploring complex gene interactions through the Visualization of Statistical Epistasis Networks (ViSEN). The study identified a Pain, Anti-Inflammatory, and Immunomodulating agents (PAIma) panel from the 128 genes, resulting in 55,590 annotations across 21 curated pathways. After filtering, 54 significant structural or regulatory variants were identified. This research also highlighted novel gene relationships involving the CYP3A5 gene, hsa-miR-355-5p, Paliperidone, and CYP2D6, which warrant further investigation. This study offers a novel pharmacogenetic framework that could potentially transform opioid prescribing practices to mitigate misuse and enhance personalized pain management. Further validation of these findings from multi countries and ethnic groups could guide clinicians in implementing DNA-based opioid prescribing, aligning treatment more closely with individual genetic profiles. [ABSTRACT FROM AUTHOR]

The rapid progress of antibiotic resistance among bacteria has prompted serious medical concerns regarding how to manage multidrug-resistant (MDR) bacterial infections. One emerging strategy to combat antibiotic resistance is the use of antimicrobial peptides (AMPs), which are amino acid chains that act as broad-spectrum antimicrobial molecules and are essential parts of the innate immune system in mammals, fungi, and plants. AMPs have unique antibacterial mechanisms that offer benefits over conventional antibiotics in combating drug-resistant bacterial infections. Currently, scientists have conducted multiple studies on AMPs for combating drug-resistant bacterial infections and found that AMPs are a promising alternative to conventional antibiotics. On the other hand, bacteria can develop several tactics to resist and bypass the effect of AMPs. Therefore, it is like a battle between the bacterial community and the AMPs, but who will win? This review provides thorough insights into the development of antibiotic resistance as well as detailed information about AMPs in terms of their history and classification. Furthermore, it addresses the unique antibacterial mechanisms of action of AMPs, how bacteria resist these mechanisms, and how to ensure AMPs win this battle. Finally, it provides updated information about FDA-approved AMPs and those that were still in clinical trials. This review provides vital information for researchers for the development and therapeutic application of novel AMPs for drug-resistant bacterial infections. [ABSTRACT FROM AUTHOR]

Background: Dementia causes the loss of functional independence, resulting in a decrease in the quality of life of those who suffer from it. Aims: This study aimed to investigate the interactions influencing susceptibility to the development of dementia through multifactor dimensionality reduction (MDR). Methods: the study population was made up of 221 cases and 534 controls. We performed an MDR analysis as well as a bioinformatic analysis to identify interactions between the genes GSTO1_rs4925, AGER_rs2070600, and ESR1_rs3844508 associated with susceptibility to dementia. Results: We observed associations between the polymorphism of GSTO1 and risk of dementia for the site rs4925 with the recessive model (OR = 1.720, 95% CI = 1.166–2.537 p = 0.006). Similarly, the site AGER rs2070600 showed risk of dementia with an additive model of inheritance (OR = 7.278, 95% CI = 3.140–16.868; p < 0.001). Furthermore, we identified the best risk model with a high precision of 79.6% that, when combined with three environmental risk factors, did not give an OR = 26.662 95%CI (16.164–43.979) with p < 0.001. Conclusions: The MDR and bioinformatics results provide new information on the molecular pathogenesis of dementia, allowing identification of possible diagnostic markers and new therapeutic targets. [ABSTRACT FROM AUTHOR]

Overexpression of permeability-glycoprotein (P-gp) transporter leads to multidrug resistance (MDR) through cellular exclusion of chemotherapeutics. Co-administration of P-gp inhibitors and chemotherapeutics is a promising approach for improving the efficacy of therapy. Nevertheless, problems in pharmacokinetics, toxicity and solubility limit the application of P-gp inhibitors. Herein, we developed a novel all-in-one hybrid nanoparticle system to overcome MDR in doxorubicin (DOX)-resistant breast cancer. First, folic acid-modified DOX-loaded mesoporous silica nanoparticles (MSNs) were prepared and then loaded into PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles along with a P-gp inhibitor, elacridar. This hybrid nanoparticle system had high drug loading capacity, enabled both passive and active targeting of tumour tissues, and exhibited sequential and pH-triggered release of drugs. In vitro and in vivo studies in DOX-resistant breast cancer demonstrated the ability of the hybrid nanoparticles to reverse P-gp-mediated drug resistance. The nanoparticles were efficiently taken up by the breast cancer cells and delivered elacridar, in vitro. Biodistribution studies demonstrated substantial accumulation of the folate receptor-targeted PLGA/MSN hybrid nanoparticles in tumour-bearing mice. Moreover, deceleration of the tumour growth was remarkable in the animals administered with the DOX and elacridar co-loaded hybrid nanoparticles when compared to those treated with the marketed liposomal DOX (Caelyx®) or its combination with elacridar. [ABSTRACT FROM AUTHOR]

Urinary tract infections are one of the main complications in kidney transplant patients, with a significant impact on graft function and survival. In fact, it is estimated that up to 74% of kidney transplant patients experience at least one episode of UTIs in the first year after transplantation, with an increased risk of graft loss and an increased risk of mortality. Several risk factors have been identified, such as female gender, old age, diabetes mellitus, immunosuppression, pre-transplant UTIs, urinary tract abnormalities, and prolonged dialysis. The worsening burden of antimicrobial resistance is also in itself a risk factor and a major complication in evolution and management. The management of prophylaxis, asymptomatic bacteriuria, and UTIs is still an open challenge, with some points to be clarified. Faced with such scenarios, our review aimed to evaluate the current epidemiology, examine the risk factors, and consider all the possibilities and methods of management, giving a current view and evaluation of the topic. [ABSTRACT FROM AUTHOR]

Background: This study aims to assess the effectiveness and safety of cefiderocol in treating severe infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) in critically ill patients, particularly those in intensive care units (ICUs). Methods: A meta-analysis of studies, including randomized clinical trials and observational studies in adult patients, was performed. Studies with at least 50% of critically ill patients were included. Studies with small sample size or without comparison groups were excluded. Sources included PubMed, Scopus, or Google Scholar, up to 14 August 2024. Risk of bias was assessed according to the Cochrane tool. The main outcome examined was 30-day mortality, while secondary outcomes assessed included clinical cure rates and adverse effects. Results were expressed with odds ratios. No funding was received for this study. It was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with reference CRD42024563041. Results: eight studies, with 1339 patients were included in the meta-analysis. Cefiderocol treatment was associated with a lower 30-day mortality rate than other available therapies (pooled OR 0.47; 95% CI: 0.23–0.97, p = 0.04), particularly in cases of carbapenem-resistant A. baumannii infections (pooled OR 0.29; 95% CI: 0.14–0.60, p < 0.001). Although there was a non-significant trend toward higher clinical cure rates in the cefiderocol group (OR 1.59; 95% CI: 0.96–2.62, p = 0.07), the drug demonstrated at least non-inferiority when compared to other treatment options. Study limitations included moderate heterogeneity between studies, and a high risk of bias in non-RCT studies. (Five cohort studies were included). Another limitation is that five of the eight studies compared cefiderocol versus colistine, an antibiotic with known toxicity. Conclusions: The findings suggest that cefiderocol is a promising therapeutic option for managing severe MDR-GNB infections in critically ill patients, offering a potential global benefit on mortality and at least non-inferiority in the cure rate when compared with other therapies. [ABSTRACT FROM AUTHOR]

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Simple Summary: Public health concerns continue about the spread of colistin resistance, especially after the discovery of the mobile colistin resistance (mcr) gene in Eschierichia coli a decade ago, which could potentially transfer resistance to other bacteria, posing risks to humans, animals and the environment. This study investigated the presence of colistin-resistant and ESBL-producing E. coli in both conventional indoor and organic outdoor Wallon meat lambs from birth to slaughter. Assessing n = 109 fecal samples in 2020 and 2021, 15% of E. coli isolates from conventional sheep showed reduced sensitivity to colistin, and 8% of these were multi-resistant. Genetic analysis showed the resistance was due to chromosomal mutations rather than the mcr-1 gene. In contrast, no resistant E. coli was isolated from the n = 32 samples from organic sheep, potentially due to different husbandry practices. The results highlight the importance of careful antimicrobial use and strict hygiene during slaughter to minimize risks to consumers, aligning with the One Health approach. Major efforts have been made to reduce the use of colistin in livestock since the discovery of the plasmid-borne mobile colistin resistance (mcr) gene in E. coli a decade ago, to curb the burden of its potential transmission to other bacterial species, spread between animals, humans and the environment. This study explored the longitudinal prevalence and characteristics of colistin-resistant and extended-spectrum beta-lactamase-producing (ESBL) E. coli via in vivo fecal and ex vivo carcass swabs from two batches of conventional indoor and organic outdoor Wallon meat sheep from birth to slaughter in 2020 and 2021. Antimicrobial susceptibility testing via broth microdilution revealed that n = 16/109 (15%) E. coli isolates from conventional meat lamb fecal samples had a reduced colistin sensitivity (MIC = 0.5 μg/mL) and thereof, n = 9/109 (8%) were multi-drug-resistant E. coli, while no resistant isolates were recovered from their carcasses. Sequencing revealed causative pmrB genes, indicating that the reduced sensitivity to colistin was not plasmid-borne. While the sample size was small (n = 32), no colistin-resistant and ESBL-producing E. coli were isolated from the organic meat sheep and their carcasses, potentially due to the different husbandry conditions. Prudent and judicious antimicrobial use and strict slaughter hygiene remain imperative for effective risk management to protect consumers in a sustainable One Health approach. [ABSTRACT FROM AUTHOR]

Alpha-helical AMPs' specific targeting on both cell wall and cytoplasmic membrane of Gram-positive S. aureus , and their obvious behaviour of inducing membrane microphase-separation in bacterial killing. [Display omitted] Multidrug resistance (MDR) is a rising threat to global health because the number of essential antibiotics used for treating MDR infections is increasingly compromised. In this work we report a group of new amphiphilic peptides (AMPs) derived from the well-studied G 3 (G(IIKK) 3 I-NH 2) to fight infections from Gram-positive bacteria including susceptible Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA), focusing on membrane interactions. Time-dependent killing experiments revealed that substitutions of II by WW (GWK), II by FF (GFK) and KK by RR (GIR) resulted in improved bactericidal efficiencies compared to G 3 (GIK) on both S. aureus and MRSA, with the order of GWK > GIR > GFK > GIK. Electronic microscopy imaging revealed structural disruptions of AMP binding to bacterial cell walls. Fluorescence assays including AMP binding to anionic lipoteichoic acids (LTA) in cell-free and cell systems indicated concentration and time-dependent membrane destabilization associated with bacterial killing. Furthermore, AMP's binding to anionic plasma membrane via similar fluorescence assays revealed a different extent of membrane depolarization and leakage. These observations were supported by the penetration of AMPs into the LTA barrier and the subsequent structural compromise to the cytoplasmic membrane as revealed from SANS (small angle neutron scattering). Both experiments and molecular dynamics (MD) simulations revealed that GWK and GIR could make the membrane more rigid but less effective in diffusive efficiency than GIK and GFK through forming intramembrane peptide nanoaggregates associated with hydrophobic mismatch and formation of fluidic and rigid patches. The reported peptide-aggregate-induced phase-separation emerged as a crucial factor in accelerated membrane disintegration and fast bacterial killing. This work has demonstrated the importance of membrane interactions to the development of more effective AMPs and the relevance of the approaches as reported in assisting this area of research. [ABSTRACT FROM AUTHOR]

Background/Objectives: Gastric cancer (GC) is a globally frequent cancer, in particular leading in mortality caused by digestive tract cancers in China. Vascular endothelial growth factor A (VEGFA) is excessively expressed in cancers including GC; its involvement in GC development, particularly in multidrug resistance (MDR), and the signal route it affects in GC remain unknown. To explore the roles VEGFA plays during progression and MDR formation in GC, we studied its function in a VEGFA-deleted GC cell platform. Methods: We initially assessed the importance of VEGFA in GC and MDR using database analysis. Then, using CCK8, wound healing, transwell, scanning electron microscopy, immunofluorescence, flow cytometry, and other techniques, the alterations in tumor malignancy-connected cell behaviors and microstructures were photographed and evaluated in a VEGFA-gene-deleted GC cell line (VEGFA−/−SGC7901). Finally, the mechanism of VEGFA in GC progression and MDR was examined by Western blot. Results: Database analysis revealed a strong correlation between high VEGFA expression and a poor prognosis for GC. The results showed that VEGFA deletion reduced GC cell proliferation and motility and altered microstructures important for motility, such as the depolymerized cytoskeleton. VEGFA deletion inhibited the growth of pseudopodia/filopodia and suppressed the epithelial–mesenchymal transition (EMT). The occurrence of MDR is induced by overactivation of the MAPK-AKT and TGFβ signaling pathways, while PTEN inhibits these pathways. Conclusions: All findings suggested that VEGFA acts as a cancer enhancer and MDR inducer in GC via the MAPK-AKT/PTEN/TGFβ signal pathway. [ABSTRACT FROM AUTHOR]

After the pandemic COVID-19, global health agencies remind us that tuberculosis is the deadliest infectious disease worldwide. As per WHO reports, approximately ten million people are infected with tuberculosis every year. Only a small portion of global cases receive imperative life-saving medicines. Even in the face of enduring efforts in the discovery of effective management of tuberculosis, the disease remains to affect millions of patients worldwide, with a high rate of morbidity and mortality. Considering the low treatment success, high drug treatment failure, and resistance to existing antituberculosis drugs, there is an urgency for the development of new chemical entities as antituberculosis agents. The development of resistance in tuberculosis (TB) patients to the medications used to treat and prevent the disease presents a significant challenge worldwide. Extensive research confines the molecules to counteract this disease has led to identifying many inhibitory pharmacophores. A wide range of compounds has been screened to find a novel ideal drug candidate for curing tuberculosis. Chalcone and its derivatives are considered precursors of flavonoids and isoflavonoids and display a diverse array of reported pharmacological activities including anti-inflammatory and antituberculosis activities. As this field continues to evolve, these molecules present further opportunities for understanding the mechanism of antituberculosis action and the treatment of MDR. Here, we summarize the impact of chalcone derivatives in tuberculosis treatment. The current statuses of various synthetic chalcone-based approaches for tuberculosis treatment are systematically reviewed here. [ABSTRACT FROM AUTHOR]

The Global increase in colonization by multidrug-resistant (MDR) bacteria poses a significant concern. The precise impact of MDR colonization in solid organ transplant recipients (SOTR) remains not well established. To assess the impact of MDR colonization on SOTR's mortality, infection, or graft loss. Data from PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library, ProQuest Dissertations, Theses Global, and SCOPUS were systematically reviewed, spanning from inception until 20 March 2023. The study protocol was registered with PROSPERO (CRD42022290011) and followed the PRISMA guidelines. Cohorts and case–control studies that reported on adult SOTR colonized by Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum β-lactamase (ESBL) or carbapenem-resistant Enterobacteriaceae. (CRE), or MDR-pseudomonas, and compared to noncolonized, were included. Two reviewers assessed eligibility, conducted a risk of bias evaluation using the Newcastle-Ottawa Scale, and rated certainty of evidence using the GRADE approach. We employed RevMan for a meta-analysis, using random-effects models to compute pooled odds ratios (OR) and 95% confidence intervals (CI). Statistical heterogeneity was determined using the I2 statistic. 15,202 SOTR (33 cohort, six case–control studies) were included, where liver transplant and VRE colonization (25 and 14 studies) were predominant. MDR colonization significantly increased posttransplant 1-year mortality (OR, 2.35; 95% CI, 1.63–3.38) and mixed infections (OR, 10.74; 95% CI, 7.56–12.26) across transplant types (p < 0.001 and I2 = 58%), but no detected impact on graft loss (p 0.41, I2 = 0). Subgroup analysis indicated a higher association between CRE or ESBL colonization with outcomes (CRE: death OR, 3.94; mixed infections OR, 24.8; ESBL: mixed infections OR, 10.3; no mortality data) compared to MRSA (Death: OR, 2.25; mixed infection: OR, 7.75) or VRE colonization (Death: p 0.20, mixed infections: OR, 5.71). MDR colonization in SOTR, particularly CRE, is associated with increased mortality. Despite the low certainty of the evidence, actions to prevent MDR colonization in transplant candidates are warranted. [ABSTRACT FROM AUTHOR]

This study continues surveillance of antimicrobial resistance associated with combat injuries in Ukraine. To compare species composition, antibiotic resistance profiles, and emergence of new resistance genes between 2014–2020 and 2022–2023. This was a retrospective multi-centre microbiological survey in Ukrainian hospitals. Antibiotic susceptibility, whole-genome sequencing and multi-locus sequence typing were conducted on 154 organisms obtained from 125 casualties between 2022 and 2023. The data revealed a predominance of Gram-negative bacteria, particularly Acinetobacter baumannii (35.7%), Pseudomonas aeruginosa (14.9%) and Klebsiella pneumoniae (20.7%). High levels of carbapenem resistance were observed among A. baumannii {meropenem 72.2% [39/54, 95% confidence interval (CI) 58.4–83.5]; imipenem 66.7% (36/54, 95% CI 52.5–78.9)}, K. pneumoniae [meropenem 90.6% (29/32, 95% CI 75.0–98.0); imipenem 81.2% (26/32, 95% CI 63.6–92.8)] and P. aeruginosa [meropenem 47.8% (11/23, 95% CI 26.8–69.4); imipenem 60.8% (14/23, 95% CI 38.5–80.3)] strains. A. baumannii sequence type (ST)-78 and ST-400 were prevalent from 2014 to 2020, while five strains of ST-1077 were newly identified in 2022–2023. P. aeruginosa strains showed diversity across 16 STs, with ST-773 increasing in frequency and new STs emerging, but lacking carbapenemase genes. K. pneumoniae exhibited increased genetic diversity over time, with three STs from 2014 to 2020 and six new STs, including bla NDM-1 , bla OXA-48 and bla KPC2 carriers, in 2022–2023. The prevalence of multi-drug-resistant isolates with STs associated with a high risk of global dissemination is increasing. [ABSTRACT FROM AUTHOR]

The pathogenic strains of Escherichia coli (E. coli) are frequent cause of urinary tract infections including catheter-associated, soft tissue infections and sepsis. The growing antibiotic resistance in E. coli is a major health concern. Bacteriophages are specific for their bacterial host, thus providing a novel and effective alternatives. This study focuses on isolation of bacteriophages from urban sewage treatment plants. Initially 50 different bacteriophages have been isolated against non-resistant reference E. coli strain and fifty multidrug resistant clinical isolates of extraintestinal infections. Out of which only thirty-one lytic phages which gave clear plaques were further analysed for different physico-chemical aspects such as thermal inactivation, pH, effect of organic solvents and detergents. Two bacteriophages, ASEC2201 and ASEC2202, were selected for their ability to withstand temperature fluctuation from −20 to 62 °C and a pH range from 4 to 10. They also showed good survival (40–94%) in the presence of organic solvents like ethanol, acetone, DMSO and chloroform or ability to form plaques even after the treatment with detergents like SDS, CTAB and sarkosyl. Both efficiently killed reference strain and 40–44% of multidrug resistant clinical isolates of E. coli. Later ASEC2201 and ASEC2202 were subjected to morphological characterisation through transmission electron microscopy, which revealed them to be tailed phages. The genomic analysis confirmed them to be Escherichia phages which belonged to family Drexlerviridae of Caudovirales. [ABSTRACT FROM AUTHOR]

The swine production chain can be a reservoir of antimicrobial-resistant Escherichia coli, which transfers resistance genes to other bacteria, serving as an important biomarker in the One Health approach. This study aimed to identify the frequency and antimicrobial resistance profile of E. coli in the swine production chain, assess the presence of extended-spectrum beta-lactamases (ESBL), and compare resistance profiles across different sample types. A total of 622 samples of swine carcasses from various points of the slaughter process (n = 400), swine feces (n = 100), commercial cuts (n = 45), environment (n = 67), and feces from employees (n = 10) of a pig slaughterhouse certified by the Federal Inspection Service, located in São Paulo state, Brazil, were collected. A total of 1260 E. coli isolates were obtained from the samples, with 73.6% of the samples testing positive. The agar disk diffusion test was performed with 10 different classes of antimicrobials. To confirm the production of ESBLs, the isolates were submitted to a double-disk synergism test using cefotaxime, ceftazidime, and amoxicillin with clavulanic acid. Of the total isolates, 80.71% were multidrug resistant. All ESBL-producing isolates were multidrug resistant and resistant to amoxicillin, tetracycline, and chloramphenicol. Isolates from human feces samples had less chance of being multidrug resistant than samples from other sources. The diversity of resistance profiles was verified in the samples, not clustering according to the sources, except for human feces isolates that clustered, evidencing lower antimicrobial resistance variability of these samples. Antimicrobial resistance is significantly present in the pork production chain, necessitating a comprehensive multidisciplinary approach to effectively mitigate risks within the One Health framework. [ABSTRACT FROM AUTHOR]

Simple Summary: The present work primarily focuses on the monitoring of antimicrobial resistance from fecal Escherichia coli from wildlife, an important environmental task due to the spread of resistant bacteria. In total, 128 E. coli isolates recovered from 66 wild animals were analyzed. Their resistance was tested against 17 antibiotics. An approximate percentage of 22.1% of the animals was found to carry multidrug-resistant E. coli, and 0.93% carried strains producing extended-spectrum β-lactamase (ESBL). The highest resistance was observed against ampicillin; all of the isolates were susceptible to amikacin and carbapenems. Therefore, such findings bring concerns about the dissemination of resistant bacteria among wildlife and any further impacts on public health. Antimicrobial resistance (AMR) surveillance in fecal Escherichia coli isolates from wildlife is crucial for monitoring the spread of this microorganism in the environment and for developing effective AMR control strategies. Wildlife can act as carriers of AMR bacteria and spread them to other wildlife, domestic animals, and humans; thus, they have public health implications. A total of 128 Escherichia coli isolates were obtained from 66 of 217 fecal samples obtained from different wild animals using media without antibiotic supplementation. Antibiograms were performed for 17 antibiotics to determine the phenotypic resistance profile in these isolates. Extended-spectrum β-lactamase (ESBL) production was tested using the double-disc synergy test, and 29 E. coli strains were selected for whole genome sequencing. In total, 22.1% of the wild animals tested carried multidrug-resistant E. coli isolates, and 0.93% (2/217) of these wild animals carried E. coli isolates with ESBL-encoding genes (blaCTX-M-65, blaCTX-M-55, and blaEC-1982). The E. coli isolates showed the highest resistance rates to ampicillin and were fully susceptible to amikacin, meropenem, ertapenem, and imipenem. Multiple resistance and virulence genes were detected, as well as different plasmids. The relatively high frequency of multidrug-resistant E. coli isolates in wildlife, with some of them being ESBL producers, raises some concern regarding the potential transmission of antibiotic-resistant bacteria among these animals. Gaining insights into antibiotic resistance patterns in wildlife can be vital in shaping conservation initiatives and developing effective strategies for responsible antibiotic use. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a significant pathogen in healthcare-associated infections, particularly in immunocompromised and cystic fibrosis patients. This study aimed to assess the antibiotic susceptibility of 111 P. aeruginosa isolates from various clinical specimens collected between May 2023 and April 2024 at Integral Institute of Medical Sciences and Research, Lucknow. Isolates were identified using standard microbiological techniques and antimicrobial susceptibility testing was performed using the Kirby-Bauer disc diffusion method according to CLSI guidelines. The study focused on multidrug-resistant (MDR), extensively drug-resistant (XDR) and pan-drug-resistant (PDR) classifications based on resistance patterns. The prevalence of P. aeruginosa was 16.5%, with 54% of isolates from males and 46% from females. The highest isolation rate was from pus samples (49.5%), followed by sputum (18%) and urine (15.3%). The majority of isolates came from the Department of Surgery (19.8%) and inpatient cases (52.3%). Resistance was highest to ceftazidime (57.7%) and imipenem (51.4%), while piperacillin-tazobactam showed the lowest resistance (19%). MDR isolates were most frequently found in pus samples (50%), while urine samples had the highest PDR rate (33.3%). These findings highlight the increasing antibiotic resistance in P. aeruginosa, with significant MDR and PDR rates, particularly in pus and urine samples. This study underscores the need for stringent antibiotic stewardship to mitigate resistance and develop effective treatment strategies. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is a growing global health concern, necessitating the development of innovative treatments. This study explores the potential of nanoparticle-based antibiotics (nano-antibiotics) as a novel solution to enhance drug efficacy and reduce resistance development. The research involved the synthesis and characterization of nanoparticles with an average size of 150 ± 20 nm and a zeta potential of -25 mV, ensuring stability in solution. Transmission Electron Microscopy (TEM) confirmed the spherical shape and uniform distribution of the nanoparticles. The study compared the antibacterial efficacy of nano-Ciprofloxacin with its free form against E. coli and S. aureus. Results showed that nano-Ciprofloxacin had significantly lower minimum inhibitory concentration (MIC) values-0.5 µg/mL for E. coli and 1 µg/mL for S. aureus-compared to 2 µg/mL and 4 µg/mL, respectively, for the free antibiotic. Furthermore, nano-Ciprofloxacin exhibited lower minimum bactericidal concentration (MBC) values, indicating enhanced antibacterial activity. Cytotoxicity assays using HEK-293 cells revealed that nano-Ciprofloxacin was less toxic than the free antibiotic, with 90% cell viability at 10 µg/mL compared to 70% for the free form. Additionally, the study demonstrated that bacteria exposed to nano-antibiotics developed significantly less resistance over 30 days, with only a 2-fold increase in MIC, compared to a 16-fold increase for E. coli and an 8-fold increase for S. aureus with free antibiotics. In summary, nano-antibiotics offer a promising approach to combat antibiotic-resistant infections, showing improved efficacy, reduced cytotoxicity and a lower propensity for resistance development. [ABSTRACT FROM AUTHOR]

The study was to isolate and characterize fructophilic lactic acid bacteria (FLAB) species from the honey bee gut. Based on the results of this study, it was found that the FLAB species obtained from honey were gram-positive and catalase-negative, and this identification was confirmed through 16S rRNA gene sequencing.

Objective: The colistin-resistant Klebsiella pneumoniae causes complicated urinary tract infections (UTIs). Of them, 73% of strains of K. pneumoniae formed moderate to strong biofilm. Multidrug-resistant (MDR)/Pandrug-resistant (PDR) bacteria causing UTIs are very challenging to conventional antibiotic therapy. However, bacteriophages may be a promising alternative as they easily disrupt the biofilm and act on receptors unrelated to antibiotic resistance mechanisms. This preclinical study evaluated the efficacy of a phage cocktail with different routes and dosages (in quantity and frequency) to eradicate the K. pneumoniae-associated UTI in the mice model. Methods: The three lytic phages with the broadest spectrum activity (ΦKpnBHU1, ΦKpnBHU2 and ΦKpnBHU3) were meticulously characterized using SEM and sequencing. The cocktails were administered to mice through urethral, rectal, subcutaneous and oral routes after establishing the UTI with 1 × 108 colony-forming unit/mouse (CFU/mouse) of K. pneumoniae (KpnBHU09) resistant to both the drugs carbapenem and colistin. The efficacy of different routes with varying dosages and frequency of administration was thoroughly optimized. Results: We observed that two doses of a phage cocktail containing 1 × 105 Plaque-Forming Unit (PFU/mouse) and a single dose of 1 × 109 PFU/mouse per urethra could eradicate KpnBHU09. Intriguingly, the non-invasive administration through oral and rectal routes required higher concentration and many dosages of phages to eliminate KpnBHU09 at any stage of acute UTI. The subcutaneous route was found unsatisfactory in curing the infection. Conclusion: Bacteriophage cocktails administered through transurethral, oral and rectal routes may cure UTIs.

Background: The most susceptible group of people to spread methicillin-resistant Staphylococcus aureus (MRSA) among domestic cats is their owners' relatives. Aim: Considering the aforementioned, research at the Surabaya City Animal Hospital is necessary to determine whether the mecA gene may be detected in cat nasal swabs. Methods: Samples were taken using a sterile cotton swab, and the transport medium was buffered peptone water. Standard operating procedures in microbiology were then employed to identify the samples. Using five distinct antibiotic discs, the Kirby-Bauer diffusion method was used to determine the antibiotic resistance profile of S. aureus. All cefoxitin-resistant S. aureus isolates were tested for MRSA and then the mecA gene was detected. Results: Based on morphological culture features, Gram staining, and biochemical assays, 64 samples (64%) of the 100 isolated cat nose swab samples were positive for S. aureus, according to the results of the biochemical tests. The profile of antibiotic resistance developed from the results of the S. aureus resistance test to antibiotics revealed that five (7.81%) of the 64 S. aureus isolates were confirmed to be multidrug resistant. Out of the 6 MRSA isolates analyzed, the mecA gene was detected in 5 isolates. Conclusion: Based on the findings of this study, a thorough assessment of the impact of using antibiotics to prevent the spread of MRSA in veterinary hospitals on the general public's health is required in light of the detection of MRSA isolates bearing the mecA gene in the Surabaya veterinary hospital. [Open Vet J 2024; 14(11.000): 3026-3036]

Abstract Background Resistance to carbapenem, the last line of treatment for gram-negative bacterial infections has been increasing globally and becoming a public health threat. Since integrons may aid in the transmission of resistance genes, the purpose of this study was to detect the frequency of class 1, 2, and 3 integrons as well as carbapenem-resistant genes in clinical isolates of P. aeruginosa that are resistant to carbapenem. Methods This study was carried out on 97 clinical isolates of P. aeruginosa isolated from wound and urine samples. The antimicrobial susceptibility for all isolates was tested by the disc diffusion method. The presence of integrons and carbapenem-resistant genes among carbapenem-resistant P. aeruginosa isolates was evaluated by conventional PCR. Results The antimicrobial resistance rate among P. aeruginosa clinical isolates was high, with imipenem resistance in 58.8% of the studied isolates. In this study, 86% of the carbapenem-resistant P. aeruginosa isolates carry carbapenemase genes, with bla VIM being the most common gene followed by the bla OXA−48 gene. Class 1 and class 2 integrons were reported in 37 (64.9%) and 10 (17.5%) of the tested carbapenem-resistant P. aeruginosa isolates, respectively. Conclusion Our data reported a high prevalence of class 1 integrons in carbapenem-resistant P. aeruginosa clinical isolates, suggesting the important role of integrons in carbapenem-resistant gene transfer among such isolates.

Abstract Background To assess the prevalence and epidemic pattern of multidrug-resistant tuberculosis in Hangzhou City, Zhejiang Province, China during 2012–2022. Methods All the tuberculosis cases undergoing drug susceptibility testing during 2012–2022 were included in this study. De-identified information was extracted from the electronic database Tuberculosis Information Management System for analysis of drug resistance prevalence in Hangzhou and ecdemic multidrug-resistant tuberculosis which originated from other regions. Chi-square tests were used to compare drug resistance rates between different groups, while Chi-square tests for trend were used to evaluate the change of drug resistance rates over the years of 2012–2022. The sources and destinations of ecdemic multidrug-resistant tuberculosis were illustrated using a Sankey diagram. Results Of 21,127 cases included in this study, 1119 (5.3%) were multidrug-resistant tuberculosis. A significant decline in multidrug-resistant tuberculosis rates was observed during 2012–2022. There was a significant difference in multidrug-resistant tuberculosis rates among immigrant population and local residents in Hangzhou City. Of 1119 multidrug-resistant tuberculosis cases, 515(46%) were ecdemic multidrug-resistant tuberculosis cases, of which 277(53.8%) were from other parts of Zhejiang Province and 238(46.2%) were from other provinces in China. Anhui, Jiangxi and Sichuan were among top three provinces which were the source of ecdemic multidrug-resistant tuberculosis cases. Three districts including Xiaoshan, Shangcheng and Linping districts had the most cases in Hangzhou. The proportion of ecdemic multidrug-resistant tuberculosis cases in Binjiang, Xiaoshan, Qiantang and Linping districtalso exceeded 30% of total cases. Conclusions Multidrug-resistant tuberculosis prevalence has been declining in Hangzhou. Migrant population contributed to a significant potion of cases in Hangzhou. Interventions should be tailed to local and migrant residents.

This study announces the sequence of a multidrug-resistant Escherichia coli MAHK_SCM_BAU_30A strain isolated from bovine subclinical mastitis milk in 2022 in Bangladesh. Our assembled genome had a length of 4,884,948 bp, three plasmids, two CRISPR arrays, five prophages, 51 predicted antibiotic resistance, and 72 predicted virulence factor genes.

Azurin, a secondary metabolite from Pseudomonas aeruginosa, has attracted much attention owing to its valuable therapeutic and biological applications. This work aimed to study and chartly maximize the azurin production process using different doses of gamma irradiation (5–400 Gy) in P. aeruginosa isolates. Seventy-six P. aeruginosa isolates were sourced from 135 environmental samples and 35 clinical bacterial isolates with the following descending order: 35 isolates (46%) from clinical samples, 26 isolates (34%) from water samples, and 15 isolates (20%) from soil samples. The disc diffusion technique was used for antimicrobial susceptibility testing, revealing that the multidrug-resistant (MDR) rate among all collected isolates according to the criteria determined by Clinical and Laboratory Standards Institute (CLSI) was 54 (71%). The genomic experimental results revealed that only 37 MDR isolates tested positive for the azurin gene, as detected by the PCR product at 446 bp. These findings were further supported by FTIR analysis, which revealed peaks around 1636.96 cm− 1, indicating a prominent α-helix secondary structure of azurin in these isolates. Related to their pathogenicity and antibiotic resistance, isolates from clinical origin exhibited the higher azurin gene expression level. Besides, this study confirmed the potency of gamma radiation exposure at 50 and 100 Gy significantly increased the azurin expression levels in three tested clinical isolates (P ≤ 0.05), with a maximum fold expression level of 63.55 compared to the non-irradiated samples. In conclusion, low doses of gamma irradiation effectively enhanced expression level of a secondary metabolite azurin, providing a considerable benefit for subsequent purification processes in both biological and medical applications. [ABSTRACT FROM AUTHOR]

Nguyen Van An,1 Hai Thi Nguyen,2 Van Nguyen Le,1 Ha Thi Thu Van,1 Nguyen Minh Hai,1 Vu Huy Luong,3,4 Vinh Thi Ha Nguyen,4,5 Hoa Quynh Pham,6 Hung Van Le,4,6 Dinh Viet Hung,7 Hoang Trung Kien,8 Minh Nhat Le,9,10 Nguyen Hoang Viet,11 Luong Cong Thuc,12 Ta Ba Thang,13 Tran Viet Tien,14 Le Huy Hoang,15 Nguyen Thuy Tram,15 Tuan Dinh Le,16 Nguyen Tien Son,16 Hai Ha Long Le17,18 1Department of Microbiology, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 2Department of Central Laboratory, Bac Ninh Provincial General Hospital, Bac Ninh, Vietnam; 3Department of Laser and Skincare, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 4Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; 5Department of General Planning, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 6Department of Microbiology, Mycology and Parasitology, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 7Department of Psychiatry, Military Medical 103, Vietnam Military Medical University, Hanoi, Vietnam; 8Department of Immunology, Vietnam Military Medical University, Hanoi, Vietnam; 9Tay Nguyen Institute of Science Research, Vietnam Academy of Science and Technology, VAST, Hanoi, Vietnam; 10Antimicrobial Resistance Research Center, National Institute of Infectious Disease, Tokyo, Japan; 11Molecular Pathology Department, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 12Cardiovascular Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 13Respiratory Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 14Department of Infectious Diseases, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 15Department of Bacteriology, National of Hygiene and Epidemiology, Hanoi, Vietnam; 16Department of Rheumatology and Endocrinology, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 17Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 18Department of Biochemistry, Hematology and Immunology, National Hospital of Dermatology and Venereology, Hanoi, VietnamCorrespondence: Hai Ha Long Le, Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, 100000, Vietnam, Tel +84978520055, Email lehalonghai@gmail.comPurpose: Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA) strain, can become resistant to all classes of clinically available antibiotics and causes skin infections and severe infections in the lungs, heart, and bloodstream. The study aimed to evaluate antimicrobial susceptibility patterns and MRSA exhibiting multidrug resistance obtained through a microbiological culture of clinical specimens at Bac Ninh Provincial General Hospital in Bac Ninh Province, Vietnam.Methods: We employed a cross-sectional analysis at Bac Ninh Provincial General Hospital in Vietnam. 15,232 clinical samples from inpatients were examined. S. aureus isolates were identified using established protocols and tested for MRSA and antibiotic susceptibility. Data was analyzed using R software, with statistical calculations to assess associations between variables.Results: Staphylococcus aureus was isolated from 417 samples (2.7%), with 77.2% being MRSA and 22.8% methicillin-susceptible Staphylococcus aureus (MSSA). Significant sources of MRSA were wounds (64.6%) and the surgical unit (50%) according to sample types and hospital wards, respectively. S. aureus showed high resistance rates, the highest being azithromycin (83.2%), and was fully susceptible to vancomycin. Among 294 multidrug-resistant (MDR) strains, the prevalence was 82.0% in MRSA and 18.0% in MSSA.Conclusion: The study highlights widespread antimicrobial resistance among MRSA isolates from a provincial hospital in Vietnam, emphasizing the urgent need for antibiotic surveillance, formulation of antibiotic policies, and preventive measures to tackle the increasing prevalence of multidrug-resistant MRSA.Keywords: Staphylococcus aureus, antibiotic resistance, MRSA, MDR, Vietnam

Bovine mastitis is the principal leading cause of monetary losses to dairy farmers. This disease impacts the udder health as well as the quantitative and qualitative parameters of milk. The disease is multi-etiological, but Staphylococcus aureus (S. aureus) contributing to intramammary infections is the principal cause. Our work intended to go through the sensitivity pattern of S. aureus obtained from milk samples of bovines. The samples used in the study were received at College Central Laboratory, LUVAS, Hisar. The bovine milk samples were inoculated on blood agar to obtain bacterial isolates, followed by morphological and biochemical characterization. S. aureus was confirmed by phenotypic as well as molecular assays. Ninety-five staphylococci were preliminarily isolated from 381 quarter milk samples based on morphological features of a bacterial colony, Gram stain, catalase reaction, oxidase test, and HiStaph latexTM kit from bovines. Out of these, 86 S. aureus isolates were confirmed based on phenotypic (mannitol salt agar) as well as a molecular test (23S rRNA PCR). All these isolates were used for sensitivity profiling by Kirby Bauer disc diffusion method. Maximum sensitivity was observed for chloramphenicol and doxycycline, least against cloxacillin and methicillin. From 86 isolates, 62.79% were found to be multidrug-resistant (MDR). From MDR isolates, 11.11% were extensively drug-resistant (XDR) and none were pan-drug-resistant (PDR). The presence of a high percentage of MDR phenotypes among S. aureus isolates in this study draws our attention that treatment of animals must be carried out after the identification of pathogens, followed by patterns of sensitivity to antimicrobials.

Background:Diabetic foot ulcers (DFUs) are severe complications of diabetes, leading to osteomyelitis, gangrene, and limb amputation. These outcomes increase mortality risk and bacterial resistance in surviving patients. The selection of the most effective antibiotics for DFUs remains a growing challenge. Objectives:The study aimed to identify risk factors, bacterial pathogens, and drug resistance in DFU patients, and explore the correlation between interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) levels, and DFUs. Materials and Methods:Sixty isolates of bacteria were isolated aerobically from 100 samples of DFU (30 isolates from Pseudomonas aeruginosa and 30 isolates from Staphylococcus aureus). All isolates were identified by biochemical tests, then confirmation diagnosis was done by using VITEK-2. Determination multiple drug resistance isolates by susceptibility tests, then estimation of the activity of silver nanoparticles (AgNPs) as antibacterial with different concentrations were done. VEGF and IL-6 levels were determined by using Enzyme-linked immunosorbent assay (ELISA) technique. Results:The study revealed that many bacteria-resistant antibiotics, but AgNPs significantly inhibit multi-drug resistant bacteria, suggesting their potential as an alternative treatment. VEGF and IL-6 levels were significantly higher (P-value < 0.001) in DFU patients, with IL-6 negatively correlating with VEGF. Conclusion:Diabetic foot infections, caused by various bacteria, require understanding of antibiotic sensitivity for effective treatment. AgNPs showed strong antimicrobial effects against common bacteria, suggesting potential as an alternative treatment. The study also found elevated VEGF and IL-6 levels in DFU patients, with IL-6 potentially inhibiting VEGF, thus impairing healing.

The ATP-binding cassette (ABC) transporter superfamily comprises membrane proteins that efflux various substrates across extra- and intracellular membranes. Among them, ABCB1, ABCG2, and ABCC1 are directly linked to tumor multidrug resistance (MDR). This review provides an overview of the current understanding on the novel mechanisms and functions of ABCB1, ABCG2, and ABCC1 transporters in tumor MDR, discusses the latest strategies to target these transporters, and explores further opportunities to overcome MDR.

Abstract Background Enterobacter cloacae complex (ECC) including different species are isolated from different human clinical samples. ECC is armed by many different virulence genes (VGs) and they were also classified among ESKAPE group by WHO recently. The present study was designed to find probable association between VGs and antibiotic susceptibility in different ECC species. Methods Forty-five Enterobacter isolates that were harvested from different clinical samples were classified in four different species. Seven VGs were screened by PCR technique and antibiotic susceptibility assessment was performed by disk-diffusion assay. Result Four Enterobacter species; Enterobacter cloacae (33.3%), Enterobacter hormaechei (55.6%), Enterobacter kobei (6.7%) and Enterobacter roggenkampii (4.4%) were detected. Minimum antibiotic resistance was against carbapenem agents and amikacin even in MDR isolates. 33.3% and 13.3% of isolates were MDR and XDR respectively. The rpoS (97.8%) and csgD (11.1%) showed maximum and minimum frequency respectively. Blood sample isolated were highly virulent but less resistant in comparison to the other sample isolates. The csgA, csgD and iutA genes were associated with cefepime sensitivity. Conclusion The fepA showed a predictory role for differentiating of E. hormaechei from other species. More evolved iron acquisition system in E. hormaechei was hypothesized. The fepA gene introduced as a suitable target for designing novel anti-virulence/antibiotic agents against E. hormaechei. Complementary studies on other VGs and ARGs and with bigger study population is recommended.

Background: ESKAPE “(Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter sp.)” pathogens are commonly found in infections affecting the skin and underlying tissues. ESKAPE pathogens often exhibit widespread multidrug resistance in hospitals, contributing significantly to Hospital-acquired infections. ESKAPE pathogen prevalence can combat the vast challenge of Antibiotic Resistance (ABR). Materials and Methods: “The microbiological statistics of ESKAPE infections and sensitivity between January 2020 and October 2022 were extracted from the laboratory records and analysed for the bacterial profile and antibiotic sensitivity pattern”. Results: Out of the 2037 pathogens isolated from Skin and soft tissue infection, 1308 were ESKAPE pathogens accounting for a prevalence of 64.2%. Staphylococcus aureus (n=340/1308; 25.99%) was the predominant pathogen followed by Pseudomonas aeruginosa (n=332/1308; 25.38%). Among Gram-negative isolates, 29.43% exhibited multidrug resistance (MDR). Carbapenemase was found to be a frequent mechanism of resistance, highest among Acinetobacter species (n=99; 64.7%), followed by Klebsiella pneumoniae (n=109; 37.07%). Amp C production was seen most commonly in Enterobacter species (n=93; 61.2%), followed by Klebsiella pneumoniae (n=172; 58.5%) whereas ESBL production was seen in Enterobacter species (n=46; 30.03%). Conclusion: ESKAPE pathogens are critical etiologic agents of Skin and soft infections. Regular studies are vital for evaluating bacterial susceptibility and highlighting the importance of policies to reduce hospital infections and enhance antibiotic prescription oversight. Understanding virulence and resistance markers is critical for tailoring treatment strategies based on local antibiograms and managing related infections.

BACKGROUND: The emergence of the global problem of multi-drug resistant bacteria (MDR) is closely related to the improper use of antibiotics, which gives birth to an urgent need for antimicrobial innovation in the medical and health field. Silver nanoparticles (AgNPs) show significant antibacterial potential because of their unique physical and chemical properties. By accurately regulating the morphology, size and surface properties of AgNPs, the antibacterial properties of AgNPs can be effectively enhanced and become a next generation antibacterial material with great development potential. OBJECTIVE: The detection of the inhibitory effect of AgNPs on MDR provides more possibilities for the research and development of new antimicrobial agents. METHODS: Promote the formation of AgNPs by redox reaction; determine the minimum inhibitory concentration (MIC) of AgNPs to bacteria by broth microdilution method; evaluate the killing efficacy of AgNPs against multi-drug-resistant bacteria by plate counting; evaluate the inhibitory effect of AgNPs on biofilm construction by crystal violet staining; study the drug resistance of bacteria by gradually increasing the concentration of AgNPs; and detect the toxicity of AgNPs to cells by CCK-8 method. RESULTS: AgNPs has a significant bactericidal effect on a variety of drug-resistant bacteria. After exposure to AgNPs solution for 12 hours, the number of E. coli decreased sharply, and S. aureus was basically eliminated after 16 hours. In particular, AgNPs showed stronger inhibition against Gram-negative bacteria. In addition, AgNPs can effectively hinder the formation of bacterial biofilm, and its inhibitory effect increases with the increase of AgNPs solution concentration. When AgNPs is used for a long time, the development of bacterial resistance to it is slow. From the point of view of safety, AgNPs has no harmful effects on organisms and has biosafety. CONCLUSION: AgNPs can inhibit MDR, and the bacteriostatic ability of Gram-negative bacteria is higher than that of Gram-positive bacteria. It can also inhibit the formation of bacterial biofilm, avoid drug resistance and reduce cytotoxicity. [ABSTRACT FROM AUTHOR]

The urgency of multidrug-resistant (MDR) bacterial infections in wounds is a significant concern due to the high prevalence of MDR in healthcare settings. Black pigmented marine bacteria, strain PS1C, were isolated from marine sediment on Awur Beach Jepara, Central Java, Indonesia, and cultured in the laboratory. The aim of this research includes molecular identification of strain PS1C, extracting black pigment from strain PS1C, isolation of MDR bacteria from wounds, and evaluating the antibacterial activity of black pigment from strain PS1C against MDR bacteria isolates of wound infections. We examined the 16S rRNA gene sequences strain PS1C to identify the species. Then, the black pigment from PS1C was extracted using methanol: acetone (7:3) solvent. Antibacterial activity was evaluated against MDR bacteria from wounds with the microdilution method. A black-pigmented bacterium was isolated and identified as Pseudomonas aeruginosa PS1C. We found that the black pigment from P. aeruginosa PS1C can be developed as an antibacterial agent against the MDR bacterial isolate of wounds with MIC and MBC values of 6.25-12.5 mg/ml and 6.25-25 mg/ml, respectively. In conclusion, the study's findings highlight the potential of the extract of black pigment from P. aeruginosa PS1C as an antibacterial agent against wound-causing MDR bacteria and reinforce previous research into P. aeruginosa can be isolated from marine sources. Additional in vivo investigations and the identification of the antibacterial activity's mode of action are required. [ABSTRACT FROM AUTHOR]

Background: This study aims to facilitate the identification of similar devices for both, the European Medical Device Regulation (MDR) and the US 510(k) equivalence pathway by leveraging existing data. Both are related to the regulatory pathway of read across for chemicals, where toxicological data from a known substance is transferred to one under investigation, as they aim to streamline the accreditation process for new devices and chemicals. Research design and methods: This study employs latent semantic analysis to generate similarity values, harnessing the US Food and Drug Administration 510k-database, utilizing their 'Device Descriptions' and 'Intended Use' statements. Results: For the representative inhaler cluster, similarity values up to 0.999 were generated for devices within a 510(k)-predicate tree, whereas values up to 0.124 were gathered for devices outside this group. Conclusion: Traditionally, MDR equivalence involves manual review of many devices, which is laborious. However, our results suggest that the automated calculation of similarity coefficients streamlines this process, thus reducing regulatory effort, which can be beneficial for patients needing medical devices. Although this study is focused on the European perspective, it can find application within 510(k) equivalence regulation. The conceptual approach is reminiscent of chemical fingerprint similarity analysis employed in read-across. Plain Language Summary: This study addresses improvement of the registration process for medical devices by using automated methods to determine how similar they are to existing devices. Such a process is already used in chemistry for analysis of related substances. In the context of Medical Device Regulation (MDR), which sets standards for these devices, this process might be applicable in device equivalence evaluation. Traditionally, proving equivalence involves manually finding devices that are similar, but this is time-consuming, repetitive and labor-intensive. This study proposes a new approach, using advanced computer methods and a database from the US Food and Drug Administration (FDA) to automatically identify similar devices. This could make the process much quicker and more accurate and furthermore reduce bias. The study suggests that by applying these automated methods, the impact of recent regulatory changes could be reduced. This means that proving equivalence, a critical step to facilitate device accreditation, could be done more efficiently. The study shows potential for a significant transformation in compliance processes within the medical device industry, making them more streamlined and automated. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) poses a significant worldwide health challenge associated with prolonged illnesses, increased healthcare costs, and high mortality rates. The present study examined the patterns and predictors of AMR among human Staphylococcus isolates obtained from diagnostic laboratories in South Africa between 2012 and 2017. This study examined data from 404 217 isolates, assessing resistance rates across different characteristics such as age, sample origin, Staphylococcus species, and study period. The highest resistance was observed against cloxacillin (70.3%), while the lowest resistance was against Colistin (0.1%). A significant (p < 0.05) decreasing trend in AMR was observed over the study period, while a significant increasing temporal trend (p < 0.05) was observed for multidrug resistance (MDR) over the same period. A significant (p < 0.05) association was observed between specimen type, species of organism, and year of isolation with AMR outcome. Significant (p < 0.05) associations were observed between specimen type and season with MDR. The observed high levels of AMR and a growing trend in MDR are concerning for public health. Clinicians should take these findings into account when deciding on therapeutic options. Continued monitoring of AMR among Staphylococcus spp. and judicious use of antimicrobials in human medicine should be promoted. [ABSTRACT FROM AUTHOR]

With approximately half a billion events per year, lower respiratory tract infections (LRTIs) represent a major challenge for the global public health. Among LRTI cases, those caused by Gram-negative bacteria (GNB) are associated with a poorer prognostic. Standard-of-care etiologic diagnostics is lengthy and difficult to establish, with more than half of cases remaining microbiologically undocumented. Recently, syndromic molecular diagnostic panels became available, enabling simultaneous detection of tens of pathogen-related and antimicrobial-resistance genetic markers within a few hours. In this narrative review, we summarize the available data on the performance of molecular diagnostics in GNB pneumonia, highlighting the main strengths and limitations of these assays, as well as the main factors influencing their clinical utility. We searched MEDLINE and Web of Science databases for relevant English-language articles. Molecular assays have higher analytical sensitivity than cultural methods, and show good agreement with standard-of-care diagnostics regarding detection of respiratory pathogens, including GNB, and identification of frequent patterns of resistance to antibiotics. Clinical trials reported encouraging results on the usefulness of molecular assays in antibiotic stewardship. By providing early information on the presence of pathogens and their probable resistance phenotypes, these assays assist in the choice of targeted therapy, in shortening the time from sample collection to appropriate antimicrobial treatment, and in reducing unnecessary antibiotic use. [ABSTRACT FROM AUTHOR]

Purpose: Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA) strain, can become resistant to all classes of clinically available antibiotics and causes skin infections and severe infections in the lungs, heart, and bloodstream. The study aimed to evaluate antimicrobial susceptibility patterns and MRSA exhibiting multidrug resistance obtained through a microbiological culture of clinical specimens at Bac Ninh Provincial General Hospital in Bac Ninh Province, Vietnam. Methods: We employed a cross-sectional analysis at Bac Ninh Provincial General Hospital in Vietnam. 15,232 clinical samples from inpatients were examined. S. aureus isolates were identified using established protocols and tested for MRSA and antibiotic susceptibility. Data was analyzed using R software, with statistical calculations to assess associations between variables. Results: Staphylococcus aureus was isolated from 417 samples (2.7%), with 77.2% being MRSA and 22.8% methicillin-susceptible Staphylococcus aureus (MSSA). Significant sources of MRSA were wounds (64.6%) and the surgical unit (50%) according to sample types and hospital wards, respectively. S. aureus showed high resistance rates, the highest being azithromycin (83.2%), and was fully susceptible to vancomycin. Among 294 multidrug-resistant (MDR) strains, the prevalence was 82.0% in MRSA and 18.0% in MSSA. Conclusion: The study highlights widespread antimicrobial resistance among MRSA isolates from a provincial hospital in Vietnam, emphasizing the urgent need for antibiotic surveillance, formulation of antibiotic policies, and preventive measures to tackle the increasing prevalence of multidrug-resistant MRSA. [ABSTRACT FROM AUTHOR]

Background: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a rapidly expanding life-support technique worldwide. The most common indications are severe hypoxemia and/or hypercapnia, unresponsive to conventional treatments, primarily in cases of acute respiratory distress syndrome. Concerning potential contraindications, there is no mention of microbiological history, especially related to multi-drug resistant (MDR) bacteria isolated before V-V ECMO placement. Our study aims to investigate: (i) the prevalence and incidence of MDR Gram-negative (GN) bacteria in a cohort of V-V ECMOs; (ii) the risk of 1-year mortality, especially in the case of predetected MDR GN bacteria; and (iii) the impact of annual hospital V-V ECMO volume on the probability of acquiring MDR GN bacteria. Methods: All consecutive adults admitted to the Intensive Care Units of 5 Italian university-affiliated hospitals and requiring V-V ECMO were screened. Exclusion criteria were age < 18 years, pregnancy, veno-arterial or mixed ECMO-configuration, incomplete records, survival < 24 h after V-V ECMO. A standard protocol of microbiological surveillance was applied and MDR profiles were identified using in vitro susceptibility tests. Cox-proportional hazards models were applied for investigating mortality. Results: Two hundred and seventy-nine V-V ECMO patients (72% male) were enrolled. The overall MDR GN bacteria percentage was 50%: 21% (n.59) detected before and 29% (n.80) after V-V ECMO placement. The overall 1-year mortality was 42%, with a higher risk observed in predetected patients (aHR 2.14 [1.33–3.47], p value 0.002), while not in 'V-V ECMO-acquired MDR GN bacteria' group (aHR 1.51 [0.94–2.42], p value 0.090), as compared to 'non-MDR GN bacteria' group (reference). Same findings were found considering only infections. A larger annual hospital V-V ECMO volume was associated with a lower probability of acquiring MDR GN bacteria during V-V ECMO course (aOR 0.91 [0.86–0.97], p value 0.002). Conclusions: 21% of MDR GN bacteria were detected before; while 29% after V-V ECMO connection. A history of MDR GN bacteria, isolated before V-V ECMO, was an independent risk factor for mortality. The annual hospital V-V ECMO volume affected the probability of acquiring MDR GN bacteria. Trial Registration ClinicalTrial.gov Registration Number NCTNCT06199141, date 12.26.2023. [ABSTRACT FROM AUTHOR]

Background In 2018 the World Health Organization recommended a switch to an all oral bedaquiline-based second-line regimen for treatment of drug-resistant tuberculosis (DR-TB). How these new second-line regimens fare in comparison to first-line regimens for treatment of drug-sensitive tuberculosis (DS-TB) is not well known. Methods In this study, we contemporaneously enrolled subjects with DS-TB (n = 31) or DR-TB (n = 23) and assessed their response to therapy with first-line (rifampin, isoniazid, ethambutol, pyrazinamide) or second-line (bedaquiline, pyrazinamide, levofloxacin, linezolid, clofazimine) regimens, respectively. Results We found that the early bactericidal activity of first- and second-line regimens was similar during the first 2 weeks of therapy as determined by BACTEC MGIT, colony-forming units, and a liquid limiting dilution assay capable of detecting differentially detectable/culturable Mycobacterium tuberculosis. Furthermore, an identical percentage (77.8%) of subjects from the DS-TB and DR-TB cohorts converted to culture negative after 2 months of therapy. Conclusions Despite presenting with more advanced disease at time of treatment, subjects with DR-TB receiving an all oral bedaquiline-based second-line treatment regimen displayed a similar microbiological response to therapy as subjects with DS-TB receiving a first-line treatment regimen. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is one of the most alarming global public health challenges of the 21st century. Over 3 million antimicrobial-resistant infections occur in the United States annually, with nearly 50,000 cases being fatal. Innovations in drug discovery methods and platforms are crucial to identify novel antibiotics to combat AMR. We present the isolation and characterization of potentially novel antibiotic lead compounds produced by the cross-feeding of two rhizosphere bacteria, Acinetobacter sp. RIT 592 and Exiguobacterium sp. RIT 594. We used solid-phase extraction (SPE) followed by liquid chromatography (LC) to enrich antibiotic extracts and subsequently mass spectrometry (MS) analysis of collected fractions for compound structure identification and characterization. The MS data were processed through the Global Natural Product Social Molecular Networking (GNPS) database. The supernatant from RIT 592 induced RIT 594 to produce a cocktail of antimicrobial compounds active against Gram-positive and negative bacteria. The GNPS analysis indicated compounds with known antimicrobial activity in the bioactive samples, including oligopeptides and their derivatives. This work emphasizes the utility of microbial community-based platforms to discover novel clinically relevant secondary metabolites. Future work includes further structural characterization and antibiotic activity evaluation of the individual compounds against pathogenic multidrug-resistant (MDR) bacteria. [ABSTRACT FROM AUTHOR]

AbstractOne can recognize multidrug resistance (MDR) and residue as a biggest difficulty in cancer specialist. Chemotherapy-resistant cancer may be successfully treated by combining MDR-reversing phytochemicals with anticancer drugs. Though, clinical application of phytochemicals either alone or in conjunction with chemotherapy is still in its early stages or requires more research to determine their safety and efficacy. In this review we highlighted topics related to MDR in cancer, including an introduction to subject, mechanism of action of efflux pump, specific proteins involved in drug resistance, altered drug targets, increased drug metabolism, and potential role of phytochemicals in overcoming drug resistance. [ABSTRACT FROM AUTHOR]

Background: The study focuses on the clinical profiles, antibiotic susceptibility, and genetic characteristics of 25 A. baumannii isolates from patients with urinary tract infections (UTIs). Patient Cohort: Ages range from 18 to 70 years, with a male to female ratio of 1.375. Notable Finding: Some multidrug-resistant (MDR) isolates had commonalities with extensively drug-resistant (XDR) variations, showing the evolution of drug resistance. Methods: Antibiotic Efficacy Analysis: Evaluation of antibiotic efficacy when the variable moved from lower (Bin 1) to higher (Bin 2) levels. Correlation Matrix: An analysis of antibiotic correlations to better identify potential cross-resistance and shared characteristics. Genetic Diversity Analysis: An examination of variants in the OmpR gene, including mutations and polymorphisms. Sequence analysis is used to identify point mutations in OmpR, with an emphasis on transitions such as adenine (A) to guanine (G). Results: Significant improvement in antibiotic efficacy from Bin 1 to Bin 2. Correlation Findings: Antibiotics have complex interactions, which may indicate cross-resistance. Genetic diversity: Variations in the OmpR gene have implications for virulence and adaptability. Sequence Analysis: The majority of point mutations in OmpR were transitions, with A typically changing to G. Conclusion: In Iraq, researchers have discovered the first evidence that clinical resistance in A. baumannii may be caused by structural alterations in the OmpR gene. A. baumannii isolates' genetic diversity at certain locations suggests possible implications on virulence and adaptation. [ABSTRACT FROM AUTHOR]

The current investigation explores the antibacterial properties of Quercetin, a flavonoid found in plants, and lemon peel extract, renowned for its rich bioactive content, against multiple drug resistant bacteria. The study method involved the identification of multidrug-resistant bacteria through antimicrobial susceptibility testing (AST). Nine standard bacterial strains exhibited resistance to different antibiotics, with a MAR index exceeding 0.10, including Ampicillin, Vancomycin, Polymyxin B, Nitrofurantoin, Trimethoprim, and Penicillin. In the present study bioactive compounds from lemon peel were extracted using two solvents, methanol and water, and their efficacy was assessed against drug-resistant bacteria. Minimum Inhibitory Concentration (MIC) values, determined by using the well plate method, revealed higher MIC values for the water extract (LPWE) compared to the methanol extract (LPME) and quercetin. For instance, the MIC for LPWE against E. hermanniensis ATCC 700323 was 140 mg/ml, whereas it was 50 mg/ml for quercetin & 1 mg/ml for LPME. From the results, it can be interpreted that Methanol extract was most effective against drug-resistant bacteria when compared to water extract and quercetin. Furthermore, GC-MS analysis was performed to analyze the chemical entities present in each extract. Given the activity of LPME, LPWE, and Quercetin against both Gram-negative bacteria and Gram-positive bacteria, these extracts hold promise as broadspectrum antibacterial agents applicable in various fields such as medicine, food, and cosmetics. [ABSTRACT FROM AUTHOR]

Globally, antibiotic resistance is a challenging issue in healthcare sector. The emergence of multiple drug-resistant bacteria has forced us to modify existing medicines and or formulate newer medicines that are effective and inexpensive. In this perspective, this study involves the formation of zinc oxide nanoparticles (ZnO NPs) by utilizing the Lawsonia inermis (Li) leaf extract. The prepared L. inermis leaf extract mediated ZnO NPs (Li-ZnO NPs) were bio-physically characterized. The antibacterial and radical scavenging effects of Li-ZnO NPs were evaluated. In addition, ZnO NPs were conjugated with standard antibiotic (ciprofloxacin) and its drug loading efficiency, drug release and antibacterial efficacy were tested and compared with non-drug loaded ZnO NPs. An absorbance peak at 340 nm was noted for Li-ZnO NPs. After conjugation with the drug, two absorbance peaks- one at 242 nm characteristic of ciprofloxacin and the other at 350 nm characteristics of ZnO NPs were observed. The crystallite size was 18.7 nm as determined by XRD. The antibacterial effect was higher on Gram-positive (S. aureus and S. pyogenes) than the Gram-negative pathogens (E. coli and K. pneumoniae). Inhibition of S. aureus and S. pyogenes biofilm at 100 μg mL−1were, respectively, 97.5 and 92.6%. H2O2 free radicals was inhibited to 90% compared to the standard ascorbic acid at 100 μg mL−1. After drug loading, the FTIR spectrum confirmed the existence of ciprofloxacin peaks at 965 cm−1 and Zn–O bond at 492 cm−1. The drug loading capacity of 15 nm sized ZnO NPs was higher (58, 75, 90 and 95% at 1, 2.5, 5 and 10% drug concentrations, respectively) compared to 20 nm. Similarly, the percentage of drug (ciprofloxacin) released from 15 nm ZnO NPs were increased to 90% at 10% drug-loaded samples, respectively. Also, the antibiotic loaded ZnO NPs had significant antibacterial effects against tested bacteria compared to Li-ZnO NPs and ciprofloxacin alone. This revealed that the antibiotic loaded ZnO NPs offer a sustainable route to treat multi-drug-resistant bacterial infections. [ABSTRACT FROM AUTHOR]