Next-generation gene therapy for infectious disease: Advances, challenges, and future directions.

Antimicrobial resistance (AMR) poses a critical global public health threat, exacerbated by the presence of multidrug-resistant (MDR) bacteria in environmental matrices, particularly in Low- and Middle-Income Countries (LMICs). This study investigated the potential of Lawsonia inermis (Henna) extracts to inhibit MDR bacteria in surface water, sewage, and abattoir leachate. Using cold maceration extraction method, and methanol and aqueous as solvent, the antibacterial activity of Henna leaf and seed extracts was assessed against eight MDR isolates obtained from surface water, sewage, and abattoir leachate. The results showed exceptional antimicrobial activity, especially with seed methanol extracts demonstrating 100% inhibition against MDR bacteria, followed by the seed aqueous and leaf methanol (93.7%). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values confirmed the efficacy of Henna extracts. All the extracts displayed profound activity (AI) against S. enterica AGS2 strain. Citrobacter freundii ADAI was the most susceptible isolate. Our findings suggest that Henna extracts could serve as a viable, eco-friendly, and cost-effective solution to reducing MDR bacteria in environmental matrices, particularly in LMICs. This study highlights the potential of plant-based antimicrobials in combating AMR in environmental settings and promoting global public health.

IntroductionPrevious studies have described some risk factors for multidrug-resistant (MDR) bacteria in urinary tract infection (UTI). However, the clinical impact of MDR bacteria on older hospitalized patients with community-acquired UTI has not been broadly analyzed. We conducted a study in older adults with community-acquired UTI in order to identify risk factors for MDR bacteria and to know their clinical impact.MethodsCohort prospective observational study of patients of 65 years or older, consecutively admitted to a university hospital, diagnosed with community-acquired UTI. We compared epidemiological and clinical variables and outcomes, from UTI due to MDR and non-MDR bacteria. Independent risk factors for MDR bacteria were analyzed using logistic regression.Results348 patients were included, 41.4% of them with UTI due to MDR bacteria. Median age was 81 years. Hospital mortality was 8.6%, with no difference between the MDR and non-MDR bacteria groups. Median length of stay was 5 [4–8] days, with a longer stay in the MDR group (6 [4–8] vs. 5 [4–7] days, p = 0.029). Inadequate empirical antimicrobial therapy (IEAT) was 23.3%, with statistically significant differences between groups (33.3% vs. 16.2%, p < 0.001). Healthcare-associated UTI variables, in particular previous antimicrobial therapy and residence in a nursing home, were found to be independent risk factors for MDR bacteria.ConclusionsThe clinical impact of MDR bacteria was moderate. MDR bacteria cases had higher IEAT and longer hospital stay, although mortality was not higher. Previous antimicrobial therapy and residence in a nursing home were independent risk factors for MDR bacteria.

The growing problem of multidrug-resistant (MDR) bacteria in poultry farming is a significant concern for public health, particularly in developing countries where poultry farming plays a vital role in the food system. The emergence and spread of these resistant bacteria are exacerbated by poor sanitation, limited access to clean water, and the overuse of antibiotics in poultry farming. Vulnerable populations, such as those who are poor, malnourished, or living in areas with limited healthcare access, are at heightened risk of severe infections caused by these resistant pathogens. The result is not only an increase in healthcare costs but also significant losses in productivity, further deepening the economic burden on these communities. This study examines the root causes of antimicrobial resistance (AMR) in poultry farming and proposes practical solutions to mitigate its spread. Education plays a crucial role, with programs aimed at teaching poultry farmers better hygiene practices, biosecurity measures, and the importance of using antibiotics responsibly. Shifting towards antibiotic-free feed and ensuring that antibiotics are only used, when necessary, can significantly reduce the risk of resistance. The study also emphasizes the need for better governance and regulations, particularly in low- and middle-income countries, to manage the use of antibiotics in farming. Public awareness campaigns targeting consumers and workers can help foster a culture of responsible antibiotic use. By addressing these issues collaboratively, we can safeguard both public health and economic stability, thereby ensuring a healthier future for both animals and humans.

Wound infections became a great challenge, especially after the emergence of bacterial resistance to commonly used antibiotics. Medicinal plants can be the source of alternative antibacterial agents effective against multi drug resistant (MDR) bacteria. This research aimed to evaluate the effectiveness of different Silybum marianum seed extracts in fighting MDR bacteria that infect wounds. First, thirty purified bacterial cultures obtained from superficial, infected wounds were subjected to antibiotic sensitivity tests. The selected MDR isolates were then used to test the antimicrobial effects of different S. marianum seed extracts. The most potent extract was evaluated for its impact on the ultrastructure of the cells of sensitive bacterial isolates using transmission electron microscopy (TEM). The bioactive ingredients of this extract were analyzed by means of gas chromatography-mass spectroscopy (GC-MS). Then, in-silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were predicted for the main components. The results indicated that four out of 30 bacterial isolates were considered MDR bacteria. Primary morphological features of colonies, secondary (automatic) identification using the Biomerieux Vitek 2 System, and 16S rRNA sequencing of the four isolates confirmed that they represent Staphylococcus aureus, Stenotrophomonas maltophilia, Klebsiella pneumoniae, and Escherichia coli. Among different extracts of S. marianum seeds, ethanol extract showed the strongest inhibitory effect on both Gram-positive and Gram-negative bacteria, with minimum inhibitory concentration (MIC) values between 9.375 and 1.172 mg/mL. However, at concentrations four times higher, this extract was unable to kill bacterial cells, indicating that it had a bacteriostatic effect on the tested MDR strains. TEM revealed denaturation and distorted cell ultrastructure in S. aureus and S. maltophilia after exposure to ethanol extract. In addition, GC-MS analysis of the ethanol extract identified nine compounds known to have important biological activities, and ADMET analysis showed good drug-likeness for two of these compounds. Consequently, S. marianum seeds could be a good source of alternative bacteriostatic agents effective against MDR bacterial strains that cause wound infections.

Antimicrobial resistance (AMR) threatens to claim 10million lives annually by 2050, yet vaccines-proven tools to prevent infections and reduce antibiotic use-remain underutilized in AMR strategies. Despite evidence that pediatric vaccination could prevent 181,500 AMR-associated deaths annually in low- and middle-income countries (LMICs) and that pneumococcal conjugate vaccines reduce nonsusceptible infections by 56.9%, vaccines are rarely integrated into National AMR Action Plans with explicit targets, financing mechanisms, or surveillance linkages. AMR and immunization programs operate as separate vertical structures with different champions, financing streams, and data systems. This siloed approach prevents operationalization of vaccine-AMR evidence into policy and limits coordinated action. National AMR Action Plans prioritize stewardship, surveillance, and drug discovery while overlooking vaccines' role in reducing infection burden, limiting resistant pathogen circulation, and decreasing antibiotic consumption. This commentary argues that vaccines must be treated as core AMR infrastructure in LMICs, requiring five governance shifts: (1) institutionalized collaboration between immunization and AMR stakeholders; (2) vaccine coverage targets embedded in AMR action plans; (3) coordinated surveillance linking immunization registries with AMR data systems; (4) financing mechanisms recognizing vaccines as AMR infrastructure investments; and (5) research prioritizing next-generation vaccines against resistant pathogens. Drawing on efforts in the Philippines to convene physician societies, government agencies leading AMR and immunization efforts, and academic institutions, we demonstrate how these shifts can be piloted through a formal AMR-Vaccine Network, offering a testable model for operationalizing vaccine-AMR integration in LMICs. The challenge extends beyond establishing the evidence base to operationalizing that evidence through governance reform.

Background – Antimicrobial resistance (AMR) is a major health threat worldwide as it brings about poorer outcomes and places economic burdens to society. This study aims to estimate the economic burdens from nosocomial infections (NI) caused by multi-drug resistant (MDR) bacteria in Thailand. Research design and methods – A retrospective cohort study was conducted at a tertiary hospital over 2011–2012. A multivariate log-linear regression model was used to estimate the excess treatment costs of AMR to those non-AMR patients. Results – Switching from a non-AMR case to an AMR infection case, resulted in 42% increase in expected average treatment costs per patient. The annual treatment from hospital perspective and antibiotic costs associated with the management of AMR infections were estimated to be US$ 2.3 billion and US$ 262 million, respectively. The estimated annual benefit from eradicating AMR NI were US$ 4.2 billion from a societal perspective with the annual gains in quality-adjusted life years (QALYs) of 0.6 million due to the absence of 111,295 AMR cases each year. Conclusions – Large amount of money was spent on treatment and antibiotic costs to manage AMR infections. Benefit of eliminating these infections was estimated and it would be highly cost-effective.

Antibacterial drug resistance is considered one of the biggest threats tohuman health worldwide, and the overuse of antibiotics accelerates this problem. Multidrug-resistant (MDR) bacteria are becoming harder to treatas the antibiotics used to treat them become less effective. Therefore, it is necessary to evaluate novel methods to control MDR bacteria. In this study, 40 bacterial isolates were collected from diabetic patients. The sensitivity of 40 bacterial isolates to seven antibiotics was evaluated. Four bacterial isolates were resistant to all antibiotic groups. The MDR pathogenic bacteria were selected and identified morphologically and biochemicallyand confirmed by VITEK® 2 system as follows: Staphylococcus aureus W35, Pseudomonas aeruginosa D31, Klebsiella pneumoniae DF30, and K. pneumoniae B40. Identification of the most resistant P. aeruginosa D31 was confirmed by the sequencing of a 16S ribosomal RNA gene with an accession number (MW241596). The inhibitory activity of eight types of native grown plant extracts against MDR bacteria was studied. Clove alcoholic extract (CAE) showed the highest inhibitory activity against MDR bacteria. Gas chromatography-mass spectrometry analysis of partially purified CAE at 0.9 Rf detected by thin-layer chromatography showed an active compound named hexadecenoic acid methyl ester with the highest antimicrobial effect against clinical pathogenic bacteria. The formation of silver nanoparticles (AgNPs) by CAE was studied. Evaluation of AgNPs was investigated by X-ray diffraction, UV-Vis, and transmission electron microscopy. The antibacterial effect of AgNPs after 2, 4, and 6 days in light and dark conditions was evaluated. Finally, the AgNPs synthesized using CAE possessgood inhibition activity against the tested pathogenic bacteria. As a result, the bactericidal components listed above were promising in reducing MDR bacteria and can be used for treatments of bacterial infection and in the development of safe products with a natural base.

Background: Antimicrobial resistance (AMR) and multidrug resistance (MDR) are escalating global health threats, particularly in low- and middle-income countries (LMICs). Understanding gender-specific resistance patterns is essential for inclusive antimicrobial stewardship and gender-targeted interventions.Objective: This study aimed to investigate gender-specific trends in AMR and MDR among clinical bacterial isolates collected from Mbarara Regional Referral Hospital, Uganda, within a 10-year period (2014-2024).Methods: A total of 4,170 non-duplicate clinical isolates subjected to antimicrobial susceptibility testing (AST) were retrospectively analyzed. Gender-specific resistance patterns were calculated and compared using the Wilcoxon signed-rank test, Chi-square, and Fisher’s exact test. All analyses were performed in Python (Google Colab).Results: Among all isolates, 92.7% were resistant to at least one antibiotic, while 71.6% were multidrug resistant. While resistance appeared higher in female-submitted isolates in unadjusted analysis, adjusted models showed that urinary AMR was significantly higher among reproductive-age women (OR = 1.38, 95% CI: 1.22-1.57), while non-urine AMR was elevated in male-submitted specimens from children (OR = 1.45, 95% CI: 1.20-1.76) and adults aged ≥50 (OR = 1.36, 95% CI: 1.13-1.63). MDR showed distinct organism-gender associations: it was more common in male-associated urinary Enterobacterales (OR = 1.41, 95% CI: 1.10-1.82), in female-linked non-urine Staphylococcus aureus (OR = 1.62, 95% CI: 1.16-2.27), and in male-linked Pseudomonas aeruginosa (OR = 1.56, 95% CI: 1.12-2.18).Conclusion: This study reveals distinct gender disparities in AMR and MDR patterns, structured by age, specimen type, and organism. These findings support the integration of gender-sensitive variables such as pregnancy status, contraceptive use, and care-seeking behavior to better explain resistance pathways and support gender-responsive AMR control in LMICs.

Introduction: Sepsis is a serious and expensive healthcare problem, when caused by a multidrug-resistant (MDR) bacteria mortality and costs increase. A reduction in the time until the start of treatment improves clinical results. The objective is to perform a systematic review of economic evaluations to analyze the cost-effectiveness of diagnostic methods in sepsis and to draw lessons on the methods used to incorporate antimicrobial resistance (AMR) in these studies. Material and Methods: the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the Consolidated Health Economic Evaluation Reporting standards (CHEERS) checklist was used to extract the information from the texts. Results: A total of 16 articles were found. A decision model was performed in 14. We found two ways to handle resistance while modelling: the test could identify infections caused by a resistant pathogen or resistance-related inputs, or outcomes were included (the incidence of AMR in sepsis patients, antibiotic use, and infection caused by resistant bacterial pathogens). Conclusion: Using a diagnostic technique to detect sepsis early on is more cost-effective than standard care. Setting a direct relationship between the implementation of a testing strategy and the reduction of AMR cases, we made several assumptions about the efficacy of antibiotics and the length-of-stay of patients.

Typhoid in Africa and vaccine deployment

Introduction: Bronchiectasis exacerbations are often treated with broad spectrum antibiotics and patients are thus at risk of acquiring multidrug resistant (MDR) bacteria. The aim was to identify risk factors associated with isolation of MDR pathogens in bronchiectasis exacerbations. Methods: Retrospective observational study of bronchiectasis exacerbations in hospitalized patients. Data was compared between two groups according to isolation of MDR bacteria. Results: The sample included 84 patients with a mean age of 75,6. MDR bacteria were isolated in 28,6% of the patients being MDR Pseudomonas aeruginosa (PA) the most frequent isolation, n=18. The most common empiric antibiotherapy was Levofloxacin. Patients with MDR pathogen isolation were older, had longer hospitalizations and were more resistance to empiric treatment, p Conclusion: Various factors, such as recent hospitalization, number of exacerbations, PA colonization, recent antibiotherapy and systemic corticosteroids, may contribute for MDR bacteria infection in hospitalized patients with acute exacerbations of bronchiectasis. Awareness is required to consider empiric broad spectrum antibiotics in certain high risk patients.

Multidrug-resistant (MDR) Gram-negative bacterial infection is widespread all over the world, and recently it led to the reintroduction of colistin for treatment of MDR Pseudomonas aeruginosa and Acinetobacter spp. infection [1]. According to the 2007 European antimicrobial resistance surveillance system (EARSS) consisting of 33 European countries, six countries reported carbapenem resistance rates higher than 25 % among P. aeruginosa isolates [2]. The rate of imipenem-resistant Acinetobacter reached up to 51 % in Korea according to the report of the Korean Nationwide Surveillance of Antimicrobial Resistance (KONSAR) [3]. Polymyxin E (colistin) that was developed in the 1940s is still the principal therapeutic agent for MDR Gram-negative pathogens. Because of the nephrotoxicity and neurotoxicity of colistin, it was not used for a long time [4]. Colistin has lately been considered for MDR treatment due to the emergence of MDR bacteria. However, the efficacy test results of colistin have been quite controversial. Most studies have been retrospective, and the clinical data analysis has been done without control groups [5, 6]. In this study, we evaluated the clinical efficacy of colistin in MDR bacterial infection. We conducted a retrospective hospital-based cohort study at an 850-bed hospital by reviewing the medical records of patients who received intravenous colistin for MDR bacterial infection from May 2007 to December 2010. Demographics, clinical presentation, causative organism, and outcomes were recorded. Patients were excluded if they received colistin treatment for \72 h and were under the age of 18. Types of infection were evaluated, following the United States Centers for Disease Control and Prevention (CDC) criteria. Recent invasive procedure was defined as preceding an invasive procedure within 48 h, including arterial, central venous catheter, urinary catheter, or applying mechanical ventilation before the culture results of MDR infection. MDR bacteria were defined to be resistant to all antibiotic agents such as penicillins, aminoglycosides, ampicillin/sulbactam, cephalosporins, aztreonam, carbapenems, fluoroquinolones, and tetracyclines, except colistin. Interpretation of susceptibility results was carried out according to the current Clinical and Laboratory Standards Institute guidelines. A total of 107 patients were enrolled in this study, and their demographic and clinical data are summarized in Table 1. Sixty-six patients (61.7 %) were over 64 years, and 36 patients (33.6 %) had a hospital stay of more than 125 days before MDR bacteria culture. Common underlying diseases were hypertension (63.5 %), diabetes (34.6 %), chronic obstructive pulmonary disease (24.3 %), cancer (19.6 %), chronic renal failure (CRF), and end-stage renal disease (ESRD; 12.1 % for both CRF and ESRD). More than 95 % of colistin therapy took place in ICUs. Cerebrovascular event (27.1 %) including cerebral infarction or hemorrhage was the most common cause of admission. We evaluated the clinical and microbiological responses both to colistin and to previously exposed antibiotics combined with colistin. Efficacy was evaluated as both clinical and bacteriological responses. After 3 days of colistin therapy, clinical improvement was graded as a good or poor clinical response. A good responder was defined as a patient whose symptoms were improved with bacteriologically clear pathogen within 1 week. Baseline characteristics and various risk factors were compared Y. H. Jun S. J. Jeun S. H. Kang H. J. Choi (&) Division of Infectious Disease, Department of Internal Medicine, Ewha Womans University, Mokdong Hospital, 911-1 MokDong, Yangcheon-Ku, Seoul, Korea e-mail: heechoi@ewha.ac.kr

The global rise of antimicrobial resistance (AMR), particularly among diarrheal pathogens, poses a severe public health threat, especially in developing regions where diarrheal diseases remain a leading cause of child mortality. Conventional antibiotics are increasingly losing efficacy against multi-drug resistant (MDR) strains of Escherichia coli, Vibrio cholerae, and Salmonella spp. This calls for alternative therapeutic interventions. Medicinal plants, long employed in traditional medicine, offer a promising, sustainable solution due to their diverse phytochemical profiles and antimicrobial potential. This paper explores the role of selected medicinal plants in enhancing the treatment of diarrheal diseases and inhibiting resistant microbial strains. Focusing on plants such as Acacia nilotica, Julbernardia paniculata, and Maerua angolensis, the study highlights their inhibitory effects on key diarrheagenic bacteria, supported by in vitro findings. Mechanistic insights into plant-based bioactives such as phenolics, terpenes, and flavonoids suggest these compounds interfere with microbial resistance pathways and membrane integrity. The paper concludes that integrating medicinal plant research into mainstream therapeutic frameworks could play a vital role in addressing AMR and improving diarrheal disease outcomes globally. Keywords: Medicinal plants, Antimicrobial resistance (AMR), Diarrheal pathogens, Traditional medicine, Phytochemicals, Multi-drug resistant bacteria, Escherichia coli, Vibrio cholera.

Antimicrobial resistance (AMR) is a rising global health concern, as bacteria continue to develop resistance to antibiotics through time. A very common resistance process in multidrug-resistant (MDR) bacteria is the efflux pump system that pumps antibiotics and other toxic substances out of the bacterial cell. Both gram-positive and gram-negative bacteria have efflux pumps, with gram-negative organisms having all types of efflux pumps. The chemical efflux pump inhibitors (EPIs) exist, but toxicity at higher doses restricts their utilization, emphasizing the search for plant-based alternatives. The objective of the study was to determine the presence of efflux pumps in MDR strains of Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterobacter cloacae using the Ethidium Bromide (EtBr)-agar cartwheel assay and investigate the role of certain Indian plants in inhibiting the efflux pump activity. The extracts obtained from the plants such as Tagetes erecta (Marigold), Mangifera indica (Mango) and Allium sativum (Garlic) were screened for their potential as a source of natural EPIs. Antibacterial action of these extracts was evaluated using agar cup and broth dilution assays to determine the Minimum inhibitory (MIC) and bactericidal (MBC) concentrations of the potential extracts. The study illustrated that Garlic and Marigold plant extracts have the potential to be employed as MDR bacterial efflux pump inhibitors.

Antibacterial and photocatalytic activities of 5-nitroindole capped bimetal nanoparticles against multidrug resistant bacteria