Search Results (809)

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

Background: Antimicrobial resistance (AMR) is a growing global health threat, with children in low- and middle-income countries bearing a disproportionate burden. Data on resistance patterns and diagnostic practices in pediatric populations remain limited. This study evaluated diagnostic utilization and AMR among children hospitalized with bacterial infections at a national referral hospital in Kenya. Methods: We conducted a retrospective cohort study of pediatric inpatients (0–12 years) admitted with bacterial infections between 2017 and 2021. Patient records were identified using ICD-10 codes and reviewed for diagnostic testing and antimicrobial susceptibility. Descriptive statistics were conducted to show infection counts, diagnostic testing, and resistance outcomes. Results: Among 1608 patients, 1009/1608 (63%) were infants under one year. Culture was conducted in 640/1608 (40%) and antimicrobial sensitivity testing in 111/640 (17%) patients. Gastroenteritis (46%) was the most common infection and blood the most frequently collected specimen (31%). Of 1039 cultured specimens, 896/1039 (86%) showed no growth. The most commonly isolated organisms were Klebsiella pneumoniae 19/128 (15%), Staphylococcus epidermidis (13%, 17/128), and Enterococcus faecium (13%, 16/128). Notably, K. pneumoniae showed 100% resistance to third-generation cephalosporins, suggestive of ESBL production. Among the tested samples, 92/128 (72%) had MDROs, and 26/92 (28%) were extensively drug-resistant (XDR). Among the patients tested, 84/111 (76%) had MDROs, of which 25/84 (30%) were XDR. Children under 5 years had higher odds (OR = 5.84, 95% CI: 1.17-38.21) of having MDRO infections, as well as those with multiple admissions (OR = 3.77, 95% CI: 1.06–20.34). Further, increasing age was inversely associated with MDRO presence. The odds of MDRO infection decreased by 24% for every year increase in age (aOR = 0.76; 95% CI: 0.60–0.93; p = 0.006). Conclusions: The findings highlight the limited diagnostic use and a high burden of MDROs and XDR infections in hospitalized children. Strengthening diagnostic capacity and pediatric antimicrobial stewardship is urgently needed in such settings. 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

Background: The emergence of multidrug-resistant Gram-negative bacteria, particularly extended-spectrum β-lactamase (ESBL) and AmpC-producing Enterobacterales, has brought renewed interest in temocillin, a narrow-spectrum β-lactam antibiotic first introduced in the 1980s. Objectives: We aimed to provide a comprehensive overview of the microbiological, pharmacological, and clinical profile of temocillin. Methods: We conducted a narrative review of the literature using the PubMed database to identify relevant studies concerning the microbiology, pharmacokinetics, pharmacodynamics, clinical applications, and safety of temocillin. Results: Temocillin shows strong in vitro activity against ESBL- and AmpC-producing organisms, and partial efficacy against certain Klebsiella pneumoniae carbapenemase (KPC)-producing strains. Its pharmacokinetic and pharmacodynamic characteristics, including β-lactamase stability and low ecological impact, support its use in urinary tract infections, bloodstream infections, intra-abdominal infections, pneumonia, and central nervous system infections. Additionally, evidence supports its utility in outpatient parenteral antimicrobial therapy (OPAT), including subcutaneous administration, and in vulnerable populations such as pediatric, elderly, and immunocompromised patients. Temocillin demonstrates a favorable safety profile, minimal disruption of gut microbiota, and cost-effectiveness. It also exhibits synergistic activity with agents like fosfomycin, further enhancing its clinical value. Most of the current evidence is derived from retrospective and observational studies. Conclusions: Temocillin emerges as a promising carbapenem-sparing option for the treatment of challenging infections caused by multidrug-resistant Gram-negative bacteria. 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

Current diagnostic methods for bacterial infections in critically ill patients, including ventilator-associated pneumonia (VAP), are time-consuming, while empirical antibiotic therapy contributes to rising resistance. Bacteria-derived volatile organic compounds (VOCs) are being explored as specific biomarkers for pathogen identification and treatment monitoring. This study expands knowledge of Escherichia coli metabolism by identifying VOCs produced by both multidrug-resistant and susceptible strains, characterizing their temporal profiles during growth, and assessing VOC profile changes after imipenem exposure. Reference strains and 21 clinical isolates (derived from BAL samples of VAP patients) were cultured under controlled conditions. Headspace VOCs were preconcentrated using multibed sorption tubes and analyzed by gas chromatography–mass spectrometry (GC-MS), with compound identities confirmed using external standards. Sampling at seven time points over 24 h cultures revealed three VOC emission patterns: continuous release, temporary maximum, and compound uptake. In total, 57 VOCs were identified from the susceptible strain and 41 from the resistant one, with dimethyl disulfide, 2-butenal, ethyl acetate, and furan elevated in the resistant strain. Imipenem addition altered VOC production in the susceptible strain, with levels of six compounds elevated and seven reduced, while resistant profiles remained stable. Clinical isolates produced 71 VOCs, showing greater metabolic diversity and highlighting the relevance of isolate-derived VOCs in future studies. Full article

Background: Hansen’s disease or leprosy is one of the 21 neglected tropical diseases (NTDs). In Ecuador, leprosy is considered eliminated as a public health problem; however, new cases are reported annually. Additionally, Mycobacterium leprae infection was detected in nine-banded armadillos across the country, suggesting a potential zoonotic reservoir. This literature review aims to provide an updated overview of the epidemiological situation of leprosy in Ecuador, identify knowledge gaps, and outline research priorities to support the development of a comprehensive national strategy for achieving zero autochthonous cases. Methods: This article analyses the current situation of leprosy in Ecuador based on international and national publications. A retrospective literature search using five international, regional, and national publications on leprosy published between 1954 and 2024 (70 years) with no restriction on language or publication date, was performed. Findings: Our review identified 28 publications with the earliest article dating back to 1954. Of these, 14 were published in international journals, 15 (53.6%) were in Spanish. Four nationwide studies documented leprosy cases across Ecuador’s three continental regions (Coast, Andes, and Amazon) with a predominance in the tropical coast. No cases have been reported from the Galápagos Islands. From 1983, Ecuador started multi-drug therapy. Data from the Ministry of Public Health (MoH) system identified 1539 incident cases, showing a significant decline in new cases from 2000 to 2024, with no cases in children. New cases detection rate by 100,000 inhabitants was 0.51 in 2019 according to the World Health Organization (WHO). No study has genotyped the Mycobacterium spp. in human cases, other animal species, or environment. According to the MoH, multibacillary leprosy accounts for 78.95% of diagnosed cases, with confirmation based on Ziehl–Neelsen staining and histopathology. No survey has assessed disabilities, knowledge, attitudes, and practices (KAP) or stigma related to leprosy. Research is needed on transmission routes, Mycobacterium genotyping, genetic susceptibility, and antibiotic resistance. BCG vaccination coverage fell to 75.3% in 2021. Cases are currently diagnosed and treated on an outpatient basis in large hospitals. Conclusions: This comprehensive review highlights persistent gaps in leprosy research and critical information, despite seven decades of documented cases in Ecuador. The disease is still endemic across the country, particularly at subnational level in the subtropics and tropics of the Pacific coast and the Amazon. There is a need for nationwide epidemiological research on reservoirs and the environment applying the One Health concept. Increased laboratory facilities and readily available official data are required to improve our understanding of leprosy in Ecuador. Strengthening community-level efforts is essential for Ecuador to meet the targets of the “WHO’s Towards Zero Leprosy: Strategy 2021–2030.” Full article

The growing threat of antimicrobial resistance has necessitated the development of alternative, non-antibiotic therapies for effective microbial control. Antimicrobial photodynamic therapy, which uses photosensitizers activated by light to generate reactive oxygen species, offers a promising solution. Among natural photosensitizers, curcumin, a polyphenolic compound from Curcuma longa, has demonstrated broad-spectrum antimicrobial activity through reactive oxygen species-mediated membrane disruption and intracellular damage. However, curcumin’s poor water solubility, low stability, and limited bioavailability hinder its clinical utility. Nanotechnology has emerged as a transformative strategy to overcome these limitations. This review comprehensively explores advances in nanocurcumin- and curcumin-loaded nanoparticles, highlighting their physicochemical enhancements, photodynamic mechanisms, and antimicrobial efficacy against multidrug-resistant and biofilm-associated pathogens. A range of nanocarriers, including chitosan, liposomes, nanobubbles, hybrid metal composites, metal–organic frameworks, and covalent organic frameworks, demonstrate improved microbial targeting, light activation efficiency, and therapeutic outcomes. Applications span wound healing, dental disinfection, food preservation, water treatment, and medical device sterilization. Conclusions and future directions are given, emphasizing the integration of smart nanocarriers and combinatorial therapies to enhance curcumin’s clinical translation. Full article

Hospital infection prevention is critical to patient safety, yet data on the prevalence and contributing factors of healthcare-associated infections (HAIs) in Aljouf, Saudi Arabia, are scarce. This retrospective cross-sectional study aimed to investigate the prevalence, microbiological profile, and associated risk factors of HAIs among intensive care unit (ICU) patients in a referral hospital between January 2020 and December 2023. Medical records of 260 ICU patients were reviewed for demographic details, comorbidities, infection types, pathogens, and invasive device use. Forty patients (15.38%) developed HAIs with the highest prevalence in 2020 (50.0%). Infections were more common in males (56.5%) and those aged ≥56 years (54.6%). The predominant infections were catheter-associated urinary tract infections (47.5%), ventilator-associated pneumonia (35.0%), and central line-associated bloodstream infections (17.5%). Klebsiella pneumoniae (35.0%) and Acinetobacter baumannii (27.5%), pathogens commonly associated with multidrug resistance, were the most frequently isolated organisms. All HAI cases involved invasive device use with the use of three or more devices significantly increasing infection risk (p < 0.05). Additionally, 85% of infected patients had chronic conditions, primarily hypertension or diabetes. These findings emphasize the urgent need for strengthened infection control practices and targeted antimicrobial strategies to reduce HAIs and improve ICU patient outcomes in underreported regions. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Acinetobacter (CRA) cause significant mortality and morbidity among the elderly population. We conducted a territory-wide point prevalence survey in Hong Kong to estimate the prevalence of MRSA and resistant Acinetobacter among residents of residential care homes of the elderly (RCHEs). A total of 26 RCHEs with 1529 residents were recruited, including 20 private homes and 6 non-private homes. The size of the homes ranged from 13 to 135 residents, with a median of 57 residents. Overall, the prevalence rates of MRSA, CRA, and multidrug-resistant Acinetobacter were 33.9% (95% CI: 31.5–36.3%), 8.1% (95% CI: 6.8–9.6%), and 0.8% (95% CI: 0.4–1.4%), respectively. Private homes had a greater prevalence of MDROs than non-private homes did, whereas RCHEs in the Hong Kong region had a greater prevalence of most resistant organisms, followed by those in the Kowloon region and then those in the New Territories. We detected a high prevalence of MRSA during the COVID-19 pandemic, with additional information on CRA that was not previously known. Continuous surveillance and stringent infection control measures are needed to combat these resistant pathogens among this vulnerable population. Full article

The use of untreated livestock manure in urban agriculture sustains soil fertility but risks disseminating antimicrobial resistance (AMR) in resource-limited settings. This study characterized antibiotic-resistant bacteria (ARB) prevalence across manure–soil–vegetable pathways in Blantyre, Malawi. Using a cross-sectional design, we collected 35 samples (poultry/pig manure, farm/home soils, Brassica rapa subsp. chinensis, Brassica rapa, and Amaranthus spp.) from five livestock farms. Microbiological analysis with API 20E identification and disk diffusion testing revealed clear differences in contamination: Escherichia coli dominated pig manure (52%) and farm soil (35%), with detection in vegetables suggesting possible transfer (e.g., 20% in Brassica rapa subsp. chinensis), while Klebsiella pneumoniae contaminated all sample types (peak: 60% vegetables and 67% home soils). All manure isolates exhibited sulfamethoxazole–trimethoprim resistance, with 50% of pig manure E. coli showing cefotaxime resistance. Soil isolates mirrored these patterns (100% ampicillin resistance in K. pneumoniae and 77% cefotaxime resistance in farm soil E. coli). Vegetables displayed severe multidrug resistance (100% E. coli and 80% K. pneumoniae resistant to ≥3 classes), including critical gentamicin resistance (100% E. coli). Composting for ≤6 weeks, as practiced on the studied farms, did not eliminate ARBs, suggesting that longer durations may be needed. Notably, this study provides the first phenotypic evidence of presumptive Pasteurella-like organisms on edible leafy vegetables, specifically 45% in Amaranthus spp. and 6.1% in Brassica rapa, suggesting a potential zoonotic transmission route from livestock farms that requires molecular confirmation. These findings demonstrate manure-amended farms as AMR reservoirs, necessitating extended composting and antibiotic stewardship to mitigate One Health risks. Full article

Background: Klebsiella pneumoniae represents a major cause of healthcare-associated infections in intensive care units, with resistance profiles ranging from multidrug-resistant to extensively drug-resistant and pandrug-resistant. Critically ill patients, who often require invasive devices and prolonged antibiotic therapy, are especially vulnerable to colonization and infection by these strains. Surveillance data on resistance trends and specimen-specific patterns in Romanian intensive care units (ICUs) remain limited. Methods: We conducted a four-year surveillance study (2021–2024) in a tertiary Romanian ICU, analyzing K. pneumoniae isolates collected from diverse clinical specimens. Resistance phenotypes were classified as MDR, XDR, PDR, or susceptible based on standard definitions. Trends over time were assessed using Cramér’s V and correspondence analysis, while stratification by specimen type evaluated associations between anatomical site and resistance profiles. Results: A total of 254 K. pneumoniae isolates were analyzed. MDR strains predominated in 2021 and 2022 but sharply declined by 2024 (from 80% to 8.3%). In parallel, XDR and PDR phenotypes increased substantially, indicating a shift toward more complex resistance profiles. A significant temporal association was found (Cramér’s V = 0.43), with 2024 marked by a sharp decline in MDR isolates and a predominance of XDR and PDR phenotypes, reflecting an advanced resistance profile. Specimen-type analysis showed tracheal aspirates as the main reservoir for resistant strains, followed by urine and blood cultures, with a weaker but meaningful association (Cramér’s V = 0.24). Conclusions: These findings reveal a change in resistance patterns in ICU-acquired K. pneumoniae infections, with MDR strains being displaced by XDR and PDR phenotypes. These findings highlight the urgent need for time- and specimen-informed resistance monitoring and adaptive antimicrobial stewardship. Without targeted interventions, gains made in controlling MDR strains risk being rapidly eclipsed by the spread of highly resistant organisms. Full article

Background/Objectives: Despite overlapping inflammatory responses and frequent culture-negative results in severe burn patients, early and accurate sepsis diagnosis remains challenging. We aimed to evaluate the diagnostic performance of seven candidate biomarkers and their clinical utility, particularly in culture-negative cases. Methods: We conducted a prospective diagnostic accuracy study (January 2021–December 2022; N = 221) in the burn intensive care unit, applying a two-step feature selection to 41 candidate variables. Seven top biomarkers—presepsin, procalcitonin (PCT), albumin, C-reactive protein (CRP), prothrombin time (PT), hematocrit (Hct), and D-dimer—were measured at the moment of clinical sepsis suspicion, concurrently with blood cultures and prior to empirical antibiotic administration, within ±2 h of Sequential Organ Failure Assessment (SOFA). Diagnostic performance was evaluated using a Receiver Operating Characteristic (ROC) curve analysis to determine the area under the curve (AUC), Youden index-derived cut-offs, decision curve analysis, and Net Reclassification Improvement (NRI). Results: Presepsin achieved the highest overall AUC (0.810; 95% CI, 0.742–0.878) and outperformed other markers in culture-negative cases (AUC, 0.846 vs. 0.604; p = 0.015). In the decision curve analysis, presepsin and PCT maintained the largest net benefits at high thresholds, although PT, D-dimer, and Hct also retained smaller positive benefits. Patients were stratified into high- vs. low-risk groups for survival analysis using Youden index cut-offs; Cox regression confirmed PCT (Hazard Ratio 3.78; p < 0.001) and PT (HR 2.12; p = 0.018) as a significant mortality predictor, with presepsin showing borderline significance (HR 3.14; p = 0.055). Conclusions: The high rate of culture-negative sepsis reflects early antibiotic use suppressing culture yield rather than resistance patterns alone. Presepsin’s rapid rise and preserved accuracy under pre-sampling antibiotics suggest its value for early sepsis detection and antimicrobial stewardship. Future work will incorporate polymicrobial and multidrug-resistant bloodstream infection profiles to refine biomarker utility. Full article

Background: Urinary tract infections (UTIs) remain a leading cause of community- and hospital-onset bacterial infections worldwide. Although many countries have implemented antimicrobial resistance (AMR) surveillance systems, longitudinal multicenter data on key uropathogens in Korea remain limited. Methods: We retrospectively evaluated Escherichia coli and Klebsiella pneumoniae isolates from patients with clinically diagnosed UTIs at three tertiary-care Korean hospitals (2012–2021). Using a harmonized Observational Medical Outcomes Partnership Common Data Model (OMOP CDM), we analyzed antibiotic susceptibility based on Clinical and Laboratory Standards Institute breakpoints. Trends in resistance to key antibiotics (including fluoroquinolones, cephalosporins, and carbapenems) were assessed using the Cochran–Armitage test. Results: From 2012 to 2021, ESBL-producing E. coli and K. pneumoniae increased from 24.1% to 38.2% and 39.2% to 46.4%, respectively. The rates for K. pneumoniae remained stable over the last 6 years, and for E. coli, they remained stable over the last 3 years. Resistance rates for E. coli increased from 44.5% to 60.0% (ciprofloxacin) and from 26.3% to 40.2% (cefotaxime), while carbapenem resistance (ertapenem) remained low, at 0.3% to 1.2%. In contrast, K. pneumoniae exhibited high resistance levels to fluoroquinolones, cephalosporins, and other broad-spectrum antibiotics, with notable increases in resistance to ertapenem, from 3.0% to 18.1%, and imipenem, from 0.4% to 16.8%. This escalation mainly stemmed from the rise in ertapenem (6.6% to 17.0%) and imipenem (0.8% to 14.6%) resistance rates among Klebsiella-ESBL producers. Conclusions: We conclude that in Korea, the proportion of ESBL-producing E. coli and K. pneumoniae increased significantly from 2012 to 2018 and has since remained stable for the last 3 years (E. coli) and 6 years (K. pneumoniae). Although carbapenem resistance in E. coli remains low, K. pneumoniae has experienced a significant rise, primarily attributable to its ESBL-producing strains. These findings underscore the importance of vigilant antimicrobial stewardship and continuous surveillance to guide empirical UTI therapies in Korean clinical practice. Full article

Background: Urinary tract infections (UTIs) represent a significant public health concern, particularly in children with structural abnormalities such as vesicoureteric reflux. Prolonged antibiotic exposure in these patients often contributes to the emergence of multidrug-resistant organisms and restricts therapeutic options. Probiotics have emerged as a potential adjuvant strategy to reduce infection recurrence. Case Presentation: A female infant born at term (38.6 weeks), with a prenatal diagnosis of bilateral hydronephrosis, experienced recurrent UTIs from the neonatal period despite both prophylactic and therapeutic antibiotic regimens. Serial urine cultures revealed infections caused by extended-spectrum beta-lactamase (ESBL)-producing E. coli and K. pneumoniae. Methods: The isolated strains were evaluated in vitro against Lactiplantibacillus sp. LH01, a probiotic strain derived from human milk. Following confirmation of its antimicrobial activity, an individualised intervention was initiated: daily oral administration of 1 mL of the probiotic (10⁹ CFU/mL) for one month, under medical supervision and without concurrent antibiotic therapy. Results: The probiotic demonstrated 89% inhibition efficiency against multidrug-resistant strains, accompanied by a notable reduction in UTIs frequency. Follow-up cultures showed reduced pathogen growth and a loss of the ESBL phenotype, facilitating clinical management and allowing previously contraindicated surgical interventions. Conclusions: Lactiplantibacillus sp. LH01 proved a safe and effective adjuvant in managing recurrent, resistant UTIs in a paediatric patient, highlighting the promise of probiotic therapies. Full article