Search Results (3,053)

Pharmacotherapy in the geriatric population is one of the greatest challenges in modern medicine. Elderly patients, characterized by multimorbidity and the resulting polypharmacy, are significantly more exposed to adverse drug reactions (ADRs), which often lead to hospitalization and a decline in quality of life. Understanding the reasons for this difference requires an analysis of the physiological changes that occur during the aging process at the molecular level. This article presents a perspective on the molecular aspects of geriatric pharmacotherapy, focusing on the fundamental mechanisms that are modified with age. The analysis covers changes in pharmacokinetics, including the role and regulation of cytochrome P450 (CYP) enzymes, whose activity, especially in phase I reactions, is significantly reduced. The age-dependent dysfunction of drug transporters from the ABC (ATP-binding cassette) and SLC (solute carrier) families in key organs such as the intestines, liver and kidneys is discussed, which affects the absorption, distribution and elimination of xenobiotic compounds, including drugs. The article also provides a comprehensive analysis of the blood–brain barrier (BBB), describing changes in neurovascular integrity, including the dysfunction of tight junctions and a decrease in the activity of P-glycoprotein, sometimes referred to as multidrug resistance protein (MDR). This increases the susceptibility of the central nervous system to the penetration and action of drugs. In the realm of pharmacodynamics, changes in the density and sensitivity of key receptors (serotonergic, dopaminergic, adrenergic) are described based on neuroimaging data, explaining the molecular basis for increased sensitivity to certain drug classes, such as anticholinergics. The paper also explores new research perspectives, such as the role of the gut microbiome in modulating pharmacokinetics by influencing gene expression and the importance of pharmacoepigenetics, which dynamically regulates drug response throughout life via changes in DNA methylation and histone modifications. The clinical implications of these molecular changes are also discussed, emphasizing the potential of personalized medicine, including pharmacogenomics, in optimizing therapy and minimizing the risk of adverse reactions. Such an integrated approach, incorporating data from multiple fields (genomics, epigenomics, microbiomics) combined with a comprehensive geriatric assessment, appears to be the future of safe and effective pharmacotherapy in the aging population. Full article

Foodborne pathogenic bacteria, like Salmonella spp. and Listeria monocytogenes, can be detected in the primary food production environment. On the other hand, and in the current context of One Health, antimicrobial resistance (AMR) is gaining increased attention worldwide, as it poses significant threat to public health. The purpose of this study was to confirm the presence of Salmonella spp. and L. monocytogenes in pet food and feed samples, by means of biochemical and/or serological testing of the microbial isolates, and then to screen for AMR against a panel of selected antibiotics. Serotyping of the isolates with multiplex polymerase chain reaction revealed the presence of three of the most common clinical Salmonella serovars (S. Enteritidis, S. Typhimurium, S. Thompson) and the major epidemiologically important L. monocytogenes serotypes (1/2a, 1/2b, 1/2c, 4b) in 15 and 9 confirmed isolates of the pathogens, respectively. Strains of Salmonella spp. showed resistance to tetracycline (n = 3) and combined AMR to tetracycline with either ampicillin (n = 2) or trimethoprim-sulfamethoxazole (n = 3), without any multidrug resistance (MDR) being recorded whatsoever. AMR in L. monocytogenes was documented in 55.5% of the bacterial strains (n = 5) tested against ciprofloxacin, meropenem, penicillin, trimethoprim-sulfamethoxazole, and tetracycline. Alarmingly, one strain of L. monocytogenes was MDR to the latter five antibiotics and deemed resistant in three antibiotic groups (carbapenems, penicillins, tetracyclines), after exhibiting minimum inhibitory concentrations (MICs) to meropenem (MIC = 4 μg/mL), penicillin (MIC = 4 μg/mL), and tetracycline (MIC = 48 μg/mL). To the best of our knowledge, finding an MDR L. monocytogenes in pet food is something reported for the first time herein. The results presented in this study highlight the presence of important foodborne bacterial pathogens, such as Salmonella spp. and L. monocytogenes, with increased AMR to antibiotics and possible MDR at the primary production and at the farm level, due to the misuse of pharmacological substances used to treat zoonotic diseases, probably resulting in detection of resistant strains of these pathogenic bacteria in animal-originated food products (e.g., meat, milk, eggs). Full article

Background: The aims of this paper are to examine the impact of the COVID-19 pandemic on the non-rational use of antibiotics and potential alterations in the antibiotic resistance profiles of multi-drug resistant (MDR) isolates of Klebsiella pneumoniae (KPN), Pseudomonas aeruginosa (PAE), and Acinetobacter baumannii (ABA). Material and Methods: This study was conducted at the tertiary University Hospital “Dr Dragisa Misovic-Dedinje” (Belgrade, Serbia) and was divided into three periods: pre-pandemic (1.4.2019–31.3.2020, period I), COVID-19 pandemic (1.4.2020–31.3.2021, period II), and COVID-19 pandemic-second phase (1.4.2021–31.3.2022, period III). Cultures were taken from each patient with clinically suspected infection (symptoms, biochemical markers of infection). All departments of the hospital were included in this study. Based on the source, all microbiological specimens were divided into 1° blood, 2° respiratory tract (tracheal aspirate, bronchoalveolar lavage fluid, throat, sputum), 3° central-line catheter, 4° urine, 5° urinary catheter, 6° skin and soft tissue, and 6° other (peritoneal fluid, drainage sample, bioptate, bile, incisions, fistulas, and abscesses). After the isolation of bacterial strains from the samples, an antibiotic sensitivity test was performed for each individual isolate with the automated Vitek^® 2 COMPACT. Antibiotic consumption testing was performed by the WHO guideline equations (ATC/DDD). Results: A total of 2196 strains of KPN, PAE, and ABA from 41,144 hospitalized patients were isolated (23.6% of the number of total isolates). The number of ABA isolates statistically increased (p = 0.021), while the number of PAE isolates statistically decreased (p = 0.003) during the pandemic. An increase in the percentage of MDR strains was observed for KPN (p = 0.028) and PAE (p = 0.027). There has been an increase in the antibiotic resistance of KPN for piperacillin–tazobactam, the third and fourth generations of cephalosporins (ceftriaxone, ceftazidime, and cefepime), all carbapanems (imipenem, meropenem, and ertapenem), and levofloxacin; of PAE for imipenem; and of ABA for amikacin. Total antibiotic consumption increased (from 755 DBD to 1300 DBD, +72%), especially in the watch and reserve group of antibiotics. The highest increases were noted for vancomycin, levofloxacin, azithromycin, and meropenem. MV positively correlated with the increased occurrence of MDR KPN (r = 0.35, p = 0.009) and MDR PAE (r = 0.43, p = 0.009) but not for MDR ABA (r = 0.09, p = 0.614). There has been a statistically significant increase in the Candida sp. isolates, but the prevalence of Clostridium difficile infection remained unchanged. Conclusions: The COVID-19 pandemic has influenced the increase in total and MDR strains of KPN, ABA, and PAE and worsened their antibiotic resistance profiles. An increase in the consumption of both total and specific antibiotics was observed, mostly of fluoroquinolones and carbapenems. A positive correlation between the number of patients on MV and an increase in MDR KPN and MDR PAE strains was noted. It is necessary to adopt and demand the implementation of appropriate antimicrobial stewardship interventions to decrease the resistance of intrahospital pathogens to antibiotics. Full article

Klebsiella pneumoniae, a member of the Enterobacterales Order, often colonises the gut and causes diverse infections, including bloodstream, urinary, and respiratory infections. The rise in carbapenem-resistant sFtrains, especially those producing enzymes like K. pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Oxacillinase 48 (OXA48), or combinations (NDM+OXA48-like), poses a significant threat across Europe, notably in Romania. These strains spread rapidly via mobile genetic elements, complicating treatment. Methods: A retrospective study of multidrug-resistant (MDR) K. pneumoniae strains isolated from clinical samples collected at an infectious diseases hospital in Romania. Results: We analysed the evolution of carbapenemases and their combinations from 2010 to 2024, with the rising antibiotic consumption, particularly during the COVID-19 pandemic. The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) rose from 4.9% in 2010 to 41.6% in 2024. There was an overall antibiotic use increase, especially colistin (186%) between 2019–2024. Additionally, we examined the dynamics of antibiotic susceptibility that decreased in 2023–2024 and found that susceptibility of NDM+OXA48-like isolates to colistin was 16.5% and to cefiderocol 58.5%. Conclusions: The rising prevalence of K. pneumoniae strains with complex resistance mechanisms, coupled with a significant reduction in available treatment options, demands a fundamental paradigm shift in the management of these infections. Full article

Background: Tuberculosis (TB) remains a primary global health concern, despite the widespread availability of effective chemotherapeutic interventions. The emergence and dissemination of drug-resistant strains of Mycobacterium tuberculosis, particularly those exhibiting resistance to rifampicin, present significant obstacles to the success of TB control programs. Consequently, there is an urgent need for rapid, sensitive, and specific molecular diagnostic tools to inform timely clinical decision-making and reduce the transmission of disease. Loop-mediated isothermal amplification (LAMP) has gained attention as a promising alternative to conventional polymerase chain reaction (PCR) techniques. This method, which facilitates DNA amplification under constant temperature conditions, offers advantages including high specificity, rapid turnaround time, and operational simplicity—features that render it especially suitable for implementation in resource-limited settings. Methods: In this study, a LAMP assay targeting the rpoB gene was developed, with particular focus on detecting the codon 531 C→T mutation associated with rifampicin resistance. A set of four to six primers was designed to recognize six distinct regions of the target sequence. Allele-specific amplification was achieved by incorporating a deliberate single nucleotide mismatch at the 3′ terminus of the B2 primer to enable precise discrimination between wild-type and mutant alleles. The assay was conducted at an optimized temperature of 61 °C for 60 min, followed by visual detection using a lateral flow dipstick (LFD) within five minutes. Results: The LAMP-LFD assay demonstrated 100% concordance with drug susceptibility testing (DST) and DNA sequencing. No cross-reactivity with wild-type strains was observed, underscoring the assay’s high specificity. Conclusions: This platform offers a robust, field-deployable solution for detecting the codon 531 C→T mutation associated with rifampicin resistance in low-resource settings. Full article

Chronic myeloid leukemia (CML) is a blood disorder caused by a genetic alteration that creates the BCR-ABL fusion gene, leading to continuous activation of cell growth signals and uncontrolled proliferation of the blood cells. Imatinib (IMA) resistance remains a major obstacle in CML treatment. Integrins, particularly integrin α2 (ITGA2), have been associated with cancer progression and drug resistance. In the current study, we investigated the role of ITGA2 in IMA resistance using IMA-sensitive K562 (K562S) and IMA-resistant K562 (K562R) cells. Our findings showed that ITGA2 is overexpressed in K562R cells and ITGA2 inhibitor E7820 (2.5 µM) treatment significantly decreased cell viability and induced apoptosis in both sensitive and resistant cells. Combination treatment with E7820 and imatinib enhanced pro-apoptotic gene expression (BAX, BIM) and decreased anti-apoptotic BCL2 levels in imatinib-resistant K562R cells. Flow cytometry confirmed ITGA2 inhibition at the protein level, and rhodamine assays revealed reduced MDR1 activity in treated cells. These results demonstrate that targeting ITGA2 may overcome imatinib resistance and offer a novel therapeutic strategy for CML. Full article

Multidrug resistance (MDR) is an emerging global health concern worldwide, driving the need for innovative solutions. Herbal approaches are gaining attention and acceptance due to safer profiles and very few side effects. In this study, silver nanoparticles (VN-AgNPs) were synthesized using Vitex negundo, a medicinally valuable plant. A methanolic extract was prepared from Vitex negundo and the phytochemical evaluation confirmed the presence of flavonoids, alkaloids, and terpenoids, with quantitative analysis revealing high total phenolic content (TPC: 23.59 mg GAE/g) and total flavonoid content (TFC: 45.23 mg rutin/g), both maximized under microwave-assisted extraction (MAE). The antioxidant activity was also highest (18.77 mg AA/g). Characterization of the optimized extract by GC–MS identified various bioactive compounds. VN-AgNPs were synthesized using the aqueous leaf extract under specified conditions and were structurally characterized using many techniques and evaluated for antibacterial activity against four bacterial strains. VN-AgNPs exhibited significant antibacterial efficacy with inhibition zones measuring 16 ± 0.87 mm against Bacillus (Gram-positive), 15 ± 0.46 mm against E. coli (Gram-negative), 12 ± 0.64 mm against Pseudomonas (Gram-negative), and 11 ± 0.50 mm against Pectobacterium (Gram-negative plant pathogen). These findings highlight the efficacy of green-synthesized VN-AgNPs as a promising alternative to combat MDR pathogens, paving the way for sustainable and effective antimicrobial strategies. Full article

Increasing antimicrobial resistance (AMR) levels in Enterobacterales from pigs in Ghana prompted us to investigate farm feed, pig slurry, and farm water for Enterobacterales isolates, their antimicrobial resistance patterns, and antimicrobial residues. Between August and November 2024, we collected one sample each of feed, slurry, and water from 14 pig farms for microbiological analysis. Out of 42 samples, Enterobacterales (E. coli and Enterobacter spp.) were isolated from 30 (71.4%) samples, with the highest prevalence found in feed (85.7%), followed by slurry (78.6%) and water (50.0%). The prevalence of AMR to tetracyclines, trimethoprim-sulfamethoxazole, and ampicillin was high, with over 50% of isolates from slurry and water and 40% from feed exhibiting tetracycline resistance. Multi-drug resistance (MDR) was identified in nine (27.3%) isolates of Enterobacterales, with the highest prevalence found in feed (38.5%), then slurry (23.1%), and water (14.3%). Among 42 farm samples screened for colistin-resistant Enterobacterales, 10 (23.8%) exhibited phenotypic colistin resistance. No antimicrobial residues were detected. Risk factors associated with MDR included large farms with high pig turnover (p < 0.05) and the channelling of slurry into both covered and uncovered pits on the farm (p < 0.05). These high resistance levels underscore the urgent need for improved hygiene in feed, water, and slurry management, stricter antibiotic stewardship with veterinary oversight, and better enforcement of existing antibiotic use regulations on pig farms. Full article

Antimicrobial resistance continues to escalate worldwide, threatening effective medical care, patient safety, and global health security. Traditional antibiotics are increasingly unreliable against multidrug-resistant pathogens, resulting in delayed appropriate therapy, prolonged illness, higher healthcare costs, and increased mortality. In this context, antimicrobial stewardship must evolve beyond the preservation of older drugs to include the judicious, evidence-based use of newer antibiotics. When used empirically in high-risk scenarios, novel agents can improve clinical outcomes by ensuring timely, effective coverage against MDR organisms while reducing the need for broad-spectrum combinations that drive collateral resistance and adverse effects. A major challenge, however, is the underutilization of these agents, which not only limits patient benefit but also undermines incentives for continued pharmaceutical innovation. To address this gap, stewardship programs must incorporate strategies for appropriate empiric deployment of new antibiotics, guided by local epidemiology, risk stratification, rapid diagnostics, and multidisciplinary decision-making. A coordinated global effort, linking stewardship, innovation, and policy reform, will be critical to optimize the role of novel antimicrobials in clinical practice moving forward. Full article

The emergence and dissemination of extended-spectrum beta-lactamase (ESBL)-producing bacteria pose a major public health threat, necessitating a One Health approach to addressing this threat. Thus, the diversity, ESBL production, and potential public health implications of Gram-negative bacteria recovered from man-made lakes and surrounding lettuce in Yamoussoukro, Côte d’Ivoire were assessed in this study. Also, the lakes’ physicochemical parameters were assessed and correlated with bacteria community using Pearson correlation. A total of 68 Gram-negative bacterial isolates were recovered from the samples and identified via 16S rDNA gene sequencing. Phylogenetic analysis suggested multiple genus-/species-level variations within the isolates. Escherichia coli was the most prevalent in lake water (39.5%), while Acinetobacter was the dominant genus in lettuce (30%). E. coli isolates showed high resistance to ampicillin (90.9%), cefepime (72.7%), cefotaxime (68.2%), and aztreonam (63.6%). Moreover, ESBL production was confirmed in E. coli isolates (22.05%), predominantly mediated by the bla_CTX-M gene. Multidrug-resistant phenotypes were widespread, yielding similar multiple antibiotic resistance index (MARI) values in water (0.27–0.63) and lettuce (0.27–0.81). These data indicate high environmental contamination, which unfortunately is not being taken into account by lettuce producers according to an interview. Statistical analyses showed a significant relationship between bacterial diversity and lakes’ physicochemical parameters, including dissolved oxygen, pH, and turbidity. The basic education level of farmers, the prevalence of ESBL-producing E. coli, and the high prevalence of MDR Gram-negative bacteria in both environmental and crop sources in Yamoussoukro underscore the need for both integrated surveillance and management strategies to mitigate potential microbial public health risks within a One Health framework. Full article

Antimicrobial resistance (AMR) in environmental reservoirs is an emerging global health concern, particularly in urban settings with inadequate wastewater management. This study aimed to investigate the prevalence and resistance profiles of Salmonella spp. in canal water in Bangkok and assess the distribution of key antibiotic resistance genes (ARGs). Between 2016 and 2019, a total of 1381 water samples were collected from 29 canals. Salmonella spp. were isolated using standard microbiological methods and tested for susceptibility to 13 antibiotics. Polymerase chain reaction (PCR) was used to detect extended-spectrum β-lactamase (ESBL) genes and class 1 integron. Salmonella was found in 89.7% of samples. Among these, 62.1% showed resistance to at least one antimicrobial, and 54.8% were multidrug-resistant (MDR). The highest resistance was observed against streptomycin (41.4%). ESBL genes, predominantly blaCTX-M, were detected in 72.2% of tested isolates, while class 1 integrons were found in 67.8%, indicating a strong potential for gene dissemination. The results highlight urban canals as critical environment reservoirs of AMR Salmonella serovars, posing significant public health risks, particularly where canal water is used for agriculture, household, or recreational purposes. Strengthened environmental surveillance and effective wastewater regulation are urgently needed to mitigate AMR bacteria transmission at the human–environment–animal interface. Full article

The primary goal of this study was to assess the suitability of the proposed method for modifying the surface of cobalt alloys in dental prosthetics, taking into account the specific characteristics of the stomatognathic system during long-term use and their impact on physicochemical properties and the adhesion of cariogenic bacteria such as Streptococcus mutans. Technological factors influencing the quality of the product and its final dimensional characteristics were considered, confirming or ruling out the possibility of iatrogenic errors (related to poorly shaped prostheses) occurring during laboratory fabrication. This study demonstrates that atomic layer deposition of ZrO₂ on CoCr dental alloys results in a chemically stable, uniform, and protective surface layer, reducing ion release and improving surface quality. These improvements address key safety and performance requirements outlined in MDR 2017/745, supporting the use of ALD as a state-of-the-art technique for functionalizing dental prosthetic devices. Such coating development may influence the final quality of the denture and also verify its suitability for use in the oral environment (reducing the likelihood of denture stomatitis). Full article

Klebsiella pneumoniae, due to its capacity to produce numerous virulence factors and form biofilms, is one of the most significant etiological agents of nosocomial infections. The extensive and often unwarranted use of antibiotic therapy has driven the emergence of various mutations, adaptive mechanisms, and horizontal gene transfer among K. pneumoniae strains, resulting in resistance to most beta-lactam antibiotics, carbapenems, and the last-resort drug—colistin. A promising alternative or adjunctive treatment is the application of rotating magnetic fields (RMFs). The present study aimed to evaluate changes in colistin susceptibility among 20 extended-spectrum beta-lactamases (ESBLs) and 20 K. pneumoniae carbapenemase (KPC)-positive K. pneumoniae strains isolated from hospital infections following exposure to RMF at frequencies of 5 and 50 Hz. Exposure to RMF at 5 Hz resulted in decreased colistin minimum inhibitory concentration (MIC) values in over half of the tested (ESBLs) and (KPC)-positive strains. Additionally, RMF at 50 Hz reduced colistin MIC values in 30% of (ESBL)-positive and 40% of (KPC)-positive strains. Therefore, in the future, RMF may be developed as a supportive therapeutic strategy to improve the efficacy of antibiotics in the treatment of infections caused by multidrug-resistant (MDR) pathogens, including colistin-resistant K. pneumoniae. Full article

Background/Objectives: The presence of multi-drug-resistant (MDR) bacteria in healthy individuals poses a significant public health concern, as these strains may contribute to or even facilitate the dissemination of antibiotic resistance genes (ARGs) and virulence factors. In this study, we investigated the genomic features of antimicrobial-producing Escherichia coli strains from the gut microbiota of healthy individuals in Singapore. Methods: Using a large-scale screening approach, we analyzed 3107 E. coli isolates from 109 fecal samples for inhibitory activity against E. coli DH5α and performed whole-genome sequencing on 37 representative isolates. Results: Our findings reveal genetically diverse strains, with isolates belonging to five phylogroups (A, B1, B2, D, and F) and 23 unique sequence types (STs). Bacteriocin gene clusters were widespread (92% of isolates carried one or more bacteriocin gene clusters), with colicins and microcins dominating the profiles. Notably, we identified an hcp-et3-4 gene cluster encoding an effector linked to a Type VI secretion system. Approximately 40% of the sequenced isolates were MDR, with resistance for up to eight antibiotic classes in one strain (strain D96). Plasmids were the primary vehicles for ARG dissemination, but chromosomal resistance determinants were also detected. Additionally, over 55% of isolates were classified as potential extraintestinal pathogenic E. coli (ExPEC), raising concerns about their potential pathogenicity outside the intestinal tract. Conclusions: Our study highlights the co-occurrence of bacteriocin genes, ARGs, and virulence genes in gut-residing E. coli, underscoring their potential role in shaping microbial dynamics and antibiotic resistance. While bacteriocin-producing strains show potential as probiotic alternatives, careful assessment of their safety and genetic stability is necessary for therapeutic applications. Full article

Micro-organisms are abundant in nature and can also be found in hospital settings, causing high rates of infections. This study aimed to identify bacteria isolated from a veterinary hospital, as well as to perform antimicrobial susceptibility testing using the disk diffusion method (Kirby–Bauer), biofilm production tests using 96-well polystyrene microtiter plates and crystal violet dye, and genetic analysis of the ica operon of Staphylococcus isolates. Three collections were made from eleven surfaces and objects in the hospital’s non-critical areas (general areas) and critical areas (surgical center), totaling thirty-three samples. A total of 66 different bacterial isolates were obtained, with 77% (51/66) Gram-positive and 23% (29/66) Gram-negative. Resistance profiles were found for multidrug-resistance (MDR), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), and other unidentified species of methicillin-resistant coagulase-negative (MRCNS) and extended-spectrum beta-lactamase (ESBL), as well as biofilm production rates of 57% (38/66) of the isolates. Analysis of the operon genes for Staphylococcus sp. showed divergence in some samples when compared to the phenotypic test performed. In summary, there is a high presence of micro-organisms with resistance and virulence factors spread throughout the various areas of the veterinary hospital. Full article