Search Results (3,015)

The emergence and spread of antimicrobial resistance among pathogens are significantly reducing available therapeutic options, highlighting the urgent need for novel and complementary treatment strategies. Antimicrobial photodynamic therapy (aPDT) is a promising alternative approach that can overcome antimicrobial resistance through a multitarget mechanism of action, exerting direct bactericidal and fungicidal effects with minimal risk of resistance development. Although aPDT has shown efficacy against a variety of pathogens, data on its activity against large collections of clinical multidrug-resistant strains are still limited. In this study, we assessed the antimicrobial activity of the photosensitizer RLP068/Cl combined with a red light-emitting LED source at 630 nm (Molteni Farmaceutici, Italy) against a large panel of Gram-negative and Gram-positive bacterial strains harboring relevant resistance traits and Candida species. Our results demonstrated the significant microbicidal activity of RLP068/Cl against all of the tested strains regardless of their resistance phenotype, with particularly prominent activity against Gram-positive bacteria (range of bactericidal concentrations 0.05–0.1 µM), which required significantly lower exposure to photosensitizer compared to Candida and Gram-negative species (range 5–20 µM). Overall, these findings support the potential use of RLP068/Cl-mediated aPDT as an effective therapeutic strategy for the management of localized infections caused by MDR organisms, particularly when conventional therapeutic options are limited. Full article

The aim of this work is to evaluate the effectiveness of antimicrobial photodynamic therapy (aPDT) against oral MDR (multi-drug-resistant) Candida spp. infections related to orthodontic treatment with palatal expanders through in vitro study. Methods: PDT protocol: Curcumin + H₂O₂ was used as a photosensitizer activated by a 460 nm diode LED lamp, with an 8 mm blunt tip for 2 min in each spot of interest. In vitro simulation: A palatal expander sterile device was inserted into a custom-designed orthodontic bioreactor, realized with 10 mL of Sabouraud dextrose broth plus 10% human saliva and infected with an MDR C. albicans clinical isolate CA95 strain to reproduce an oral palatal expander infection. After 48 h of incubation at 37 °C, the device was treated with the PDT protocol. Two samples before and 5 min after the PDT process were taken and used to contaminate a Petri dish with a Sabouraud field to evaluate Candida spp. CFUs (colony-forming units). Results: A nearly 99% reduction in C. albicans colonies in the palatal expander biofilm was found after PDT. Conclusion: The data showed the effectiveness of using aPDT to treat palatal infection; however, specific patient oral micro-environment reproduction (Ph values, salivary flow, mucosal adhesion of photosensitizer) must be further analyzed. Full article

Background: Various predisposing factors contribute to the emergence and dissemination of the multidrug-resistant (MDR) phenotype in Escherichia coli and Klebsiella pneumoniae. Understanding these factors is crucial for guiding appropriate antimicrobial therapy and infection control strategies. This study investigated the predisposing factors contributing to the MDR characteristics of E. coli and K. pneumoniae isolated in a community hospital in northeastern Thailand. Methods: This case–control study utilized retrospective data from bacterial culture, as well as demographic, clinical, and antibiotic susceptibility records collected during 5 years (January 2016–December 2020). E. coli and K. pneumoniae isolates were analyzed from various clinical samples, including blood, urine, pus, sputum, and other body fluids. Data were analyzed using descriptive statistics and univariate logistic regression. Results: In total, 660 clinical isolates were analyzed (421 E. coli and 239 K. pneumoniae). Blood was the most common source of the detection of E. coli (63.0%) and sputum was the most common source of K. pneumoniae (51.0%). The median ages of patients were 67 and 63 years for E. coli and K. pneumoniae, respectively. E. coli cases were significantly associated with prior antibiotic use (OR = 1.79, 95% CI: 1.17–2.74 p = 0.008). MDR was observed in 50.1% of E. coli and 29.7% of K. pneumoniae (p < 0.001). E. coli compared to K. pneumoniae had lower resistance to third-gen cephalosporins (64.9% versus 95.8%) and carbapenems (8.0% versus 6.9%). ICU admission was the only factor significantly associated with MDR E. coli (OR = 2.40, 95% CI: 1.11–5.20 p = 0.026). No significant differences were observed in gender, age, or comorbidities between MDR cases. Antibiotic usage patterns also differed, with E. coli more likely to receive third-gen cephalosporins compared to carbapenems (OR = 3.02, 95% CI:1.18–7.74 p = 0.021). Conclusions: The use of third-generation cephalosporin may drive MDR E. coli more than K. pneumoniae. Prior antibiotic exposure was linked to E. coli bloodstream infections, while MDR E. coli showed greater clinical severity. These findings highlighted the need for improved antibiotic stewardship in rural hospitals. Full article

Nosocomial infections caused by ESKAPE pathogens represent a significant burden to global health. These pathogens may exhibit multidrug resistance (MDR) mechanisms, of which mechanisms such as efflux pumps and biofilm formation are gaining significant importance. Multidrug resistance mechanisms in ESKAPE pathogens have led to an increase in the effective costs in health care and a higher risk of mortality in hospitalized patients. These pathogens utilize antimicrobial efflux pump mechanisms and bacterial biofilm-forming capabilities to escape the bactericidal action of antimicrobials. ESKAPE bacteria forming colonies demonstrate increased expression of efflux pump-encoding genes. Efflux pumps not only expel antimicrobial agents but also contribute to biofilm formation by bacteria through (1) transport of molecules and transcription factors involved in biofilm quorum sensing, (2) bacterial fimbriae structure transport for biofilm adhesion to surfaces, and (3) regulation of a transmembrane gradient to survive the difficult conditions of biofilm microenvironments. The synergistic role of these mechanisms complicates treatment outcomes. Given the mechanistic link between biofilms and efflux pumps, therapeutic strategies should focus on targeting anti-biofilm mechanisms alongside efflux pump inactivation with efflux pump inhibitors. This review explores the molecular interplay between efflux pumps and biofilm formation, emphasizing potential therapeutic strategies such as efflux pump inhibitors (EPIs) and biofilm-targeting agents. Full article

Background/Objectives: Staphylococcus aureus is a major pathogen of concern in raw milk due to its potential to cause foodborne illness and its increasing antimicrobial resistance (AMR). In Romania, data on the occurrence and resistance patterns of S. aureus in raw sheep milk from traditional farming systems remain limited. This study investigated the presence and antimicrobial resistance of S. aureus in 106 raw sheep milk samples collected from traditional farms in the Banat region of western Romania. Methods: Coagulase-positive staphylococci (CPS) were enumerated using ISO 6888-1:2021 protocols. Isolates were identified at the species level using the Vitek 2 system and molecularly confirmed via PCR targeting the 16S rDNA and nuc genes. Methicillin resistance was assessed by detecting the mecA gene. Antimicrobial susceptibility was determined using the Vitek 2 AST-GP79 card. Results: CPS were detected in 69 samples, with S. aureus confirmed in 34.9%. The mecA gene was identified in 13.5% of S. aureus isolates, indicating the presence of methicillin-resistant S. aureus (MRSA). Resistance to at least two antimicrobials was observed in 97.3% of isolates, and 33 strains (89.2%) met the criteria for multidrug resistance (MDR). The most frequent MDR phenotype involved resistance to lincomycin, macrolides, β-lactams, tetracyclines, and aminoglycosides. Conclusions: The high prevalence of S. aureus, including MRSA and MDR strains, in raw sheep milk from traditional farms represents a potential public health risk, particularly in regions where unpasteurized dairy consumption persists. These findings underscore the need for enhanced hygiene practices, prudent antimicrobial use, and AMR monitoring in small-scale dairy systems. Full article

Resistance to cytarabine (Ara-C) remains a major obstacle to the successful treatment of acute myeloid leukemia (AML). Therefore, modulating Ara-C resistance is indispensable for improving clinical outcomes. We previously demonstrated that sodium caseinate (SC), a salt derived from casein, the principal milk protein, inhibits proliferation and modulates the expression of Ara-C resistance-related genes in chemoresistant cells. However, it remains unclear whether the combination of SC with antineoplastic agents enhances apoptosis, modulates chemoresistance-related genes, and prolongs the survival of tumor-bearing mice implanted with chemoresistant cells. Here, we investigated the effects of SC in combination with Ara-C or daunorubicin (DNR) on cell proliferation, apoptosis, the expression of chemoresistance-associated genes, and the survival of tumor-bearing mice. Crystal violet assays, quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunofluorescence, flow cytometry, and Kaplan–Meier survival curves were used to evaluate the effects of combinations in chemoresistant cells. We demonstrate that the IC₂₅ concentration of SC, when combined with antileukemic agents, increases the sensitivity of chemoresistant WEHI-CR50 cells to Ara-C by downregulating SIRT1 and MDR1, upregulating the expression of ENT1 and dCK, enhancing apoptosis, and prolonging the survival of WEHI-CR50 tumor-bearing mice. Our data suggest that SC in combination with antileukemic agents could be an effective adjuvant for Ara-C-resistant AML. Full article

Proteus mirabilis is a zoonotic pathogen that poses a growing threat to both animal and human health due to rising antimicrobial resistance (AMR). It is widely found in animals, including China’s nationally protected captive giant and red pandas. This study isolated Proteus mirabilis from panda feces to assess AMR and virulence traits, and used whole-genome sequencing (WGS) to evaluate the spread of resistance genes (ARGs) and virulence genes (VAGs). In this study, 37 isolates were obtained, 20 from red pandas and 17 from giant pandas. Multidrug-resistant (MDR) strains were present in both hosts. Giant panda isolates showed the highest resistance to ampicillin and cefazolin (58.8%), while red panda isolates were most resistant to trimethoprim/sulfamethoxazole (65%) and imipenem (55%). Giant panda-derived strains also exhibited stronger biofilm formation and swarming motility. WGS identified 31 ARGs and 73 VAGs, many linked to mobile genetic elements (MGEs) such as plasmids, integrons, and ICEs. In addition, we found frequent co-localization of drug resistance genes/VAGs with MGEs, indicating a high possibility of horizontal gene transfer (HGT). This study provides crucial insights into AMR and virulence risks in P. mirabilis from captive pandas, supporting targeted surveillance and control strategies. Full article

This review addresses the urgent need for alternative strategies to combat drug-resistant mycobacterial infections, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, as well as non-tuberculous mycobacterial (NTM) diseases. Traditional antibiotics are increasingly limited by resistance, toxicity, and poor efficacy, particularly in immunocompromised patients. A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar, covering publications primarily from 2000 to 2025. Only articles published in English were included to ensure consistency in data interpretation. Search terms included “mycobacteriophages,” “phage therapy,” “drug-resistant mycobacteria, “diagnostic phages,” and “phage engineering.” The review examines the therapeutic and diagnostic potential of mycobacteriophages—viruses that specifically infect mycobacteria—focusing on their molecular biology, engineering advances, delivery systems, and clinical applications. Evidence suggests that mycobacteriophages offer high specificity, potent bactericidal activity, and adaptability, positioning them as promising candidates for targeted therapy. Although significant obstacles remain—including immune interactions, limited host range, and regulatory challenges—rapid progress in synthetic biology and delivery platforms continues to expand their clinical potential. As research advances and clinical frameworks evolve, mycobacteriophages are poised to become a valuable asset in the fight against drug-resistant mycobacterial diseases, offering new precision-based solutions where conventional therapies fail. Full article

Feline urinary tract infections (UTIs) present a common challenge in veterinary practice, underscoring the importance of understanding local bacterial pathogens and antimicrobial resistance (AMR). This study determined bacterial prevalence and antimicrobial susceptibility in cats at Kasetsart University’s Veterinary Teaching Hospital in Bangkok, Thailand. Of the 543 cystocentesis urine samples collected from 428 cats, 115 (21.2%) tested positive for bacterial cultures, leading to a diagnosis of UTIs in 95 cats (22.2%). The most prevalent isolates included Escherichia coli (24.8%), Staphylococcus species (19.2%), Proteus mirabilis (13.6%), Pseudomonas aeruginosa (12.0%), and Enterococcus species (12.0%). Staphylococcus felis (8.8%) and Staphylococcus pseudintermedius (5.6%) were the predominant Staphylococcus species. Rare pathogens such as Corynebacterium urealyticum and Lactococcus garvieae were also identified. Antimicrobial testing revealed alarming resistance, with 69.2% of isolates exhibiting multidrug resistance (MDR). Escherichia coli and Proteus mirabilis showed high resistance to amoxicillin/clavulanic acid (AMC) (45.2–70.6%) and sulfamethoxazole/trimethoprim (SXT) (51.6–52.9%). Enterococcus faecium exhibited 85.7% resistance to AMC. Methicillin resistance was identified in 41.7% of Staphylococcus isolates, particularly high in Staphylococcus epidermidis (75.0%) and Staphylococcus pseudintermedius (71.4%). High fluoroquinolone resistance among MDR isolates further exacerbates AMR concerns. These results indicate that MDR Gram-negative, Staphylococcus, and Enterococcus species complicate the empirical treatment of feline UTIs, highlighting significant implications for AMR in veterinary practice. Full article

This study describes the first complete genomic sequence of an NDM-19 and QnrS11-producing multidrug-resistant (MDR) Escherichia coli isolate collected from a fecal swab from a poultry farm in 2019 in Egypt. The bla_NDM-19 was identified by PCR screening and DNA sequencing. The isolate was then subjected to antimicrobial susceptibility testing, conjugation and transformation experiments, and complete genome sequencing. The chromosome of strain M2-13-1 measures 4,738,278 bp and encodes 4557 predicted genes, with an average G + C content of 50.8%. M2-13-1 is classified under ST167, serotype O101:H5, phylogroup A, and shows an MDR phenotype, having minimum inhibitory concentrations (MICs) of 64 mg/L for both meropenem and doripenem. The genes bla_NDM-19 and qnrS11 are present on 49,816 bp IncX3 and 113,285 bp IncFII: IncFIB plasmids, respectively. M2-13-1 harbors genes that impart resistance to sulfonamides (sul1), trimethoprim (dfrA14), β-lactams (bla_TEM-1B), aminoglycosides (aph(6)-Id, aph(3′)-Ia, aph(3″)-Ib, aac(3)-IV, and aph(4)-Ia), tetracycline (tet(A)), and chloramphenicol (floR). It was susceptible to aztreonam, colistin, fosfomycin, and tigecycline. The genetic context surrounding bla_NDM-19 includes ISAba125-IS5-bla_NDM-19-ble_MBL-trpF-hp1-hp2-IS26. Hierarchical clustering of the core genome MLST (HierCC) indicated M2-13-1 clusters with global ST167 E. coli lineages, showing HC levels of 100 (HC100) core genome allelic differences. Plasmids of the IncX3 group and the insertion sequence (ISAba125) are critical vehicles for the dissemination of bla_NDM and its related variants. To our knowledge, this is the first genomic report of a bla_NDM-19/IncX3-carrying E. coli isolate of animal origin globally. Full article

Background: The spread of ESBL-producing Enterobacteriaceae (ESBL-PE) strains in food poses a potential risk to human health. The aim of the study was to determine the occurrence of ESBL-PE and to investigate their distribution on foods. Methods: A total of 1000 food samples, including both raw and ready-to-eat products, was analyzed for the presence of ESBL-producing Enterobacteriaceae using chromogenic selective agar. Antibiotic resistance in the isolated strains was assessed using conventional methods, while whole-genome sequencing was employed to predict antimicrobial resistance and virulence genes. Results: The overall occurrence of ESBL-PE strains was 2.8%, with the highest contamination in raw meat samples (10%). A total of 31 multidrug-resistant (MDR) strains was isolated, mainly Escherichia coli, followed by Klebsiella pneumoniae, Salmonella enterica, and Enterobacter hormaechei. All strains exhibited high levels of resistance to at least four different β-lactam antibiotics, as well as to other antimicrobial classes including sulfonamides, tetracyclines, aminoglycosides, and quinolones. Whole-genome sequencing identified 63 antimicrobial resistance genes, with bla_CTX-M being the most prevalent ESBL gene. Twenty-eight (90%) isolates carried Inc plasmids, known vectors of multiple antimicrobial resistance genes, including those associated with ESBLs. Furthermore, several virulence genes were identified. Conclusions: The contamination of food with ESBL-PE represents a potential public health risk, underscoring the importance of the implementation of genomic surveillance to monitor and control the spread of antimicrobial resistance. Full article

Background/objectives: The increasing prevalence of multidrug-resistant (MDR) bacteria, particularly Klebsiella pneumoniae, calls for the development of new antimicrobial agents. This study investigates a series of fluorinated azolium salts and their rhodium(I) complexes for antibacterial activity against clinical and reference strains of K. pneumoniae. Methods: Eleven fluorinated azolium salts and their corresponding Rh(I) complexes (22 compounds total) were synthesized and tested against several K. pneumoniae strains, including three MDR clinical isolates (U–13685, H–9871, U–13815) and ATCC reference strains. Minimum inhibitory concentrations (MICs) were determined. In silico ADMET analyses were conducted to evaluate intestinal absorption, oral bioavailability, Caco-2 permeability, carcinogenicity, solubility, and synthetic accessibility. Results: Among the Rh(I) complexes, Rh–1, Rh–3, and Rh–11 showed activity against the three MDR isolates (MIC = 62.5–250 µg/mL), while Rh–1, Rh–4, Rh–6, and Rh–11 were active against all ATCC strains (MIC = 3.9–250 µg/mL). The corresponding azolium salts displayed weak or no activity, highlighting the critical role of the metal center. ADMET predictions indicated that most Rh complexes had good intestinal absorption, and all except Rh–3, Rh–4, and Rh–9 were predicted to be orally bioavailable. Compounds Rh–1 to Rh–7 showed Caco-2 permeability, and all were classified as non-carcinogenic. Rh–8 to Rh–11 exhibited lower solubility and synthetic accessibility. Conclusions: The results underscore the potential of fluorinated Rh(I) complexes as antibacterial agents against MDR K. pneumoniae, with Rh–1 and Rh–11 emerging as promising leads based on activity and favorable predicted pharmacokinetics. Full article

Background and Objectives: Cancer patients are particularly susceptible to infections caused by multidrug-resistant Gram-negative bacteria (MDR GNB) due to chemotherapy- or radiation therapy-induced immunosuppression. Colistin is often prescribed as a last-resort agent for MDR GNB infection, but its clinical benefit in oncology patients remains unclear. This study aims to evaluate the mortality risk associated with colistin versus non-colistin regimens in cancer patient with MDR GNB infections, stratified by resistance profiles, infection sites, and concomitant medication use. Materials and Methods: A retrospective cohort study was conducted in adult cancer patients with MDR GNB infections that are resistant to at least three antibiotic classes and identified from at least two anatomical sites at a tertiary care hospital in Korea. Propensity score-matched in a 1:3 ratio either to the colistin group or non-colistin group and multivariate Cox hazard regression analyses were used to evaluate mortality in cancer patients with MDR GNB infections, primarily Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Results: A total of 85 patients (29 patients in the colistin and 56 patients in the non-colistin group) were included in the analysis. Overall, colistin use did not show a statistically significant mortality benefit compared to non-colistin regimens (hazard ratio (HR) 0.93, 95% CI 0.47–1.87). However, the subgroup analysis revealed that colistin had a potential association with significantly lower mortality in pneumonia patients with aminoglycoside-resistant infections (HR 0.04, 95% CI 0.002–0.69). Concomitant use of antipsychotics and benzodiazepines in selected resistance profiles also correlated with improved outcomes. In contrast, a potential association was found between concomitant macrolide use and increased mortality in patients with fluoroquinolone- or penicillin-resistant profiles. Conclusions: Colistin may offer survival benefits in selected high-risk cancer patients with MDR GNB pneumonia. Treatment outcomes are influenced by resistance profiles, infection sites, and concomitant medications, indicating the significant importance of individualized antimicrobial therapy and antimicrobial stewardship in oncology patients. Full article

Objective: This study aimed to evaluate the in vitro efficacy of silver nanoparticles (AgNPs) synthesized by bioreduction using lemongrass (Cymbopogon citratus) essential oil against multidrug-resistant (MDR) bacteria isolated from an Intensive Care Unit (ICU). Methods: The essential oil was extracted and characterized by gas chromatography–mass spectrometry (GC-MS). Antioxidant activity was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, the 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, and total phenolic content. AgNPs (3 mM and 6 mM silver nitrate) were characterized by UV-Vis spectroscopy, dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), and Fourier-transform infrared (FTIR) spectroscopy. Bacterial isolates were obtained from ICU surfaces and personal protective equipment (PPE). Results: The essential oil presented citral A, citral B, and β-myrcene as major components (97.5% of identified compounds). AgNPs at 3 mM showed smaller size (87 nm), lower Polydispersity Index (0.14), and higher colloidal stability (−23 mV). The 6 mM formulation (147 nm; PDI 0.91; −10 mV) was more effective against a strain of Enterococcus spp. resistant to all antibiotics tested. FTIR analysis indicated the presence of O–H, C=O, and C–O groups involved in nanoparticle stabilization. Discussion: The higher antimicrobial efficacy of the 6 mM formulation was attributed to the greater availability of active AgNPs. Conclusions: The green synthesis of AgNPs using C. citratus essential oil proved effective against MDR bacteria and represents a sustainable and promising alternative for microbiological control in healthcare environments. Full article

Background: This study aimed to (a) assess the prevalence of multidrug-resistant (MDR) Enterobacteriaceae in the waters of two rivers and wastewater treatment plants (WWTPs) in a region of Catalonia, Spain; (b) genetically characterize the MDR strains; and (c) compare extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolates from environmental and human sources. Methods: A total of 62 samples were collected from the influent and effluent of 31 WWTPs and 29 river water samples from 11 sites. Simultaneously, 382 hospitalized patients were screened for MDR Enterobacteriaceae using rectal swabs. All isolates underwent antibiotic susceptibility testing and whole-genome sequencing. Results: MDR Enterobacteriaceae were detected in 48.4% of WWTP samples, with 18.5% ESBL-producing E. coli and 1.5% (one sample) OXA-48-producing K. pneumoniae in influents, and 12.8% ESBL-producing E. coli in effluents. In river waters, 5.6% of samples contained ESBL-producing E. coli and 1.4% (1 sample) contained VIM-producing Enterobacter cloacae complex strains. Among patients, 10.2% (39/382) carried MDR Gram-negative bacilli, of which 66.7% were ESBL-producing E. coli. In aquatic ecosystems E. coli ST131 (13.3%) and ST162 (13.3%) were the most common strains, while in humans the common were E. coli ST131 (33.3%), ST69 (11.1%) and ST410 (7.4%) in humans. The most frequent environmental antibiotic resistance genes (ARG) were bla_CTX-M-15 (24%) and bla_TEM-1B (20%), while the most common ARGs were bla_TEM-1B (20.4%), bla_CTX-M15 (18.4%) and bla_CTX-M-27 (14.3%). IncF plasmids were predominant in environmental and human strains. Conclusions: ESBL-producing E. coli and carbapenemase-producing Enterobacteriaceae are present in aquatic environments in the region. Phylogenetic similarities between environmental and clinical strains suggest a possible similar origin. Further studies are necessary to clarify transmission routes and environmental impact. Full article