Search Results (74)

Avian pathogenic Escherichia coli (APEC) infections cause substantial economic losses in the poultry industry, primarily due to high mortality rates, reduced productivity, and increased treatment costs. With the emergence of antibiotic-resistant APEC strains, including multidrug-resistant (MDR) variants, alternative therapeutic strategies have gained increasing attention. This study reports the isolation and characterization of an Escherichia phage, vB_EcoG_APECPW12 (phage vAPECPW12), which specifically targets MDR APEC. Both antibacterial and antibiofilm activities of the phage were evaluated. Phage vAPECPW12 produced small plaques with halos and exhibited strong lytic activity against MDR APEC. Whole-genome sequencing revealed a genome size of 77,812 base pairs with 123 open reading frames. No tRNA, antibiotic-resistant, or lysogenic genes were identified. Phylogenetic analysis and genome comparison suggest that phage vAPECPW12 is a novel member of the genus Kuravirus within the Gordonclarkvirinae family. It also demonstrated good stability across a range of temperatures and pH levels and remained viable after exposure to UV radiation. Phage vAPECPW12 showed a high adsorption rate, a short latent period of 10 min, and a burst size of 258 plaque-forming units per cell. A depolymerase domain was identified in the genome, prompting investigation of its antibiofilm efficacy. Results showed that vAPECPW12 significantly inhibited biofilm formation and removed preformed biofilms, indicating its potential as an alternative antimicrobial agent for controlling MDR APEC and their biofilms in poultry farming. Full article

Crystalline TiO₂ films were synthesized on hydrophilic glass substrates by Peroxo sol–gel and sedimentation (S1–S4) and compared with conventional sol–gel protocols (S5–S10). The films were deposited on soda-lime glass and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and UV–Vis absorption. Photocatalytic activity was evaluated through the inactivation of multidrug-resistant Escherichia coli and Salmonella Typhimurium, and the removal of chemical oxygen demand (COD) from greywater under UV irradiation. The obtained films exhibited anatase crystallinity, crystallite sizes of ~60 nm, and grain sizes between 1.5 and 3.0 µm. S1 films showed a bandgap of 3.26 eV (380 nm). Under UV exposure, S1 reduced E. coli and S. Typhimurium by 4.78 and 3.00 Log₁₀ units, respectively, at pH 5.0 after 30 min, while COD decreased to 380 mg L⁻¹ compared to 433 mg L⁻¹ with UV photolysis alone. Increasing TiO₂ loading and extending irradiation to 120 min further enhanced bacterial inactivation (93 and 78% for E. coli and S. Typhimurium), COD (33%), NH₄⁺ (90%), and H₂S (89%) oxidation, outperforming UV-light controls. These results indicate that S1 films exhibited superior crystallinity, photocatalytic performance, and bacterial inactivation compared to other protocols, although complete mineralization was not achieved. Full article

Background and Clinical Significance: Atrophic rhinitis (AR) is a rare, chronic inflammatory condition characterized by progressive atrophy of the nasal mucosa and underlying bone. The present report describes a case of severe secondary AR as a sequela of COVID-19-associated necrotizing rhinitis, highlighting the diagnostic and management challenges posed by multi-drug resistant pathogens and extensive anatomical destruction. Case Presentation: A 75-year-old female developed progressive necrotizing rhinosinusitis with osteomyelitis following a COVID-19 infection. Computed tomography (CT) confirmed an osteolytic process and subsequent profound anatomical destruction, while histopathology ruled out invasive fungal disease. The resulting cavity was colonized by multi-drug resistant Pseudomonas aeruginosa and Staphylococcus aureus. Management and Outcome: Management focused on preventing crust formation through a structured “nasal rest” protocol, supplemented by cleansing nasal douching with a surfactant (baby soap) and mechanical crust removal. This treatment led to significant clinical improvement, with reduced crusting and complete resolution of ozena symptoms. Conclusions: This case illustrates the potential for SARS-CoV-2 infection to precipitate severe necrotizing sinonasal complications leading to secondary AR. It demonstrates the efficacy of a management strategy focused on mechanical cleansing and nasal rest, particularly when conventional antibiotic therapy is limited by extensive drug resistance. Full article

This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange and waste removal. Exopolysaccharides, proteins, lipids, and extracellular DNA create a protective matrix. Persister cells within the biofilm contribute to antibiotic resistance and survival. The heterogeneous architecture of the E. faecalis biofilm contains both dense clusters and loosely packed regions that vary in thickness, ranging from 10 to 100 µm, depending on the environmental conditions. The pathogenicity of the E. faecalis biofilm is mediated through complex interactions between genes and virulence factors such as DNA release, cytolysin, pili, secreted antigen A, and microbial surface components that recognize adhesive matrix molecules, often involving a key protein called enterococcal surface protein (Esp). Clinically, it is implicated in a range of nosocomial infections, including urinary tract infections, endocarditis, and surgical wound infections. The biofilm serves as a nidus for bacterial dissemination and as a reservoir for antimicrobial resistance. The effectiveness of first-line antibiotics (ampicillin, vancomycin, and aminoglycosides) is diminished due to reduced penetration, altered metabolism, increased tolerance, and intrinsic and acquired resistance. Alternative strategies for biofilm disruption, such as combination therapy (ampicillin with aminoglycosides), as well as newer approaches, including antimicrobial peptides, quorum-sensing inhibitors, and biofilm-disrupting agents (DNase or dispersin B), are also being explored to improve treatment outcomes. Environmentally, E. faecalis biofilms contribute to contamination in water systems, food production facilities, and healthcare environments. They persist in harsh conditions, facilitating the spread of multidrug-resistant strains and increasing the risk of transmission to humans and animals. Therefore, understanding the biofilm architecture and drug resistance is essential for developing effective strategies to mitigate their clinical and environmental impact. Full article

Multidrug-resistant (MDR) Mycoplasma genitalium (M. genitalium) presents a significant risk of treatment failure in many sexually transmitted infections (STIs) and can result in persistent and recurrent urethritis or cervicitis. This case report describes a recurrent M. genitalium urethritis resistant to sulfamethoxazole-trimethoprim (TMP-SMX), doxycycline, and moxifloxacin. The infection was ultimately cured after both the removal of a nidus of infection and through the use of Lefamulin. Lefamulin is a novel agent approved for use in community-acquired bacterial pneumonia and bacterial skin infections that may be useful in difficult sexually transmitted infections. Background/Objectives: Deciding whether or not to treat M. genitalium can be challenging as it can be a colonizer, or present with a symptomatic pathogen, and even if it is causing symptoms, it can be drug-resistant. Our objective here is to highlight important considerations on whether or not to treat and, if so, what options exist. Conclusions: In a world of increasing drug-resistant STIs, this case highlights the challenges of managing MDR M. genitalium and how foreign bodies can allow reoccurrence. Also highlighted in this case, Lefamulin appears to be a viable alternative line of treatment of MDR M. genitalium that defies other first-line antibiotics. Full article

Urethroplasty is a highly effective surgical treatment for urethral stricture disease. While overall complication rates are low, surgical site infections and urinary tract infections (UTIs) represent the most common complications. Due to the prolonged need for catheterization following reconstruction, many urologists place patients on extended antibiotic prophylaxis postoperatively. However, antibiotic stewardship is important given the risks of antibiotic overuse including opportunistic infections and the emergence of multidrug-resistant organisms. There are currently no established guidelines for the management of antibiotics for patients undergoing urethroplasty, specifically with regard to postoperative prophylaxis through the time of foley catheter removal. In this review, we examine the current literature regarding antibiotic prophylaxis and urethroplasty. Research has shown no clear benefit for extended antibiotic prophylaxis in preventing symptomatic urinary tract infections or stricture recurrence. This is congruent with evidence from other urologic procedures requiring indwelling catheters and/or stents including radical prostatectomy, hypospadias repair, and pyeloplasty. Prospective, randomized trials are needed to further understand the impact of antibiotic prophylaxis on both urethroplasty outcomes and its broader impact on recurrent UTIs and microbial resistance. Full article

Congenital anomalies of the kidney and urinary tract (CAKUT) are common developmental malformations and a leading cause of pediatric renal dysfunction. Severe hydronephrosis, especially when accompanied by ureteral duplication, ureterocele, or neurogenic bladder, poses significant diagnostic and therapeutic challenges. This case report presents a 7-year-old male with prenatally diagnosed bilateral grade IV/V hydronephrosis (according to the radiology hydronephrosis grading system), complicated by the right pyeloureteral duplication, the left ureterocele, and the neurogenic bladder. The patient’s clinical course was marked by recurrent urinary tract infections (UTIs), progressive renal dysfunction, and multiple surgical interventions. Initial decompression via bilateral ureterostomy and stenting led to significant improvements in renal function. However, the patient experienced recurrent febrile UTIs caused by multidrug-resistant pathogens, necessitating repeated hospitalizations and intravenous antibiotic therapy. Serial imaging studies documented persistent hydronephrosis, a neurogenic bladder, and vesicoureteral reflux. Subsequent surgical interventions included bilateral ureteral reimplantation, excision of the left ureterocele, and removal of a fibroepithelial polyp from the bladder wall. Despite these interventions, residual left hydronephrosis and right kidney hypoplasia persisted, underscoring the need for long-term surveillance. This case highlights the diagnostic and therapeutic challenges of managing CAKUT and emphasizes the importance of a multidisciplinary approach integrating imaging, functional assessment, and surgical planning. Early diagnosis and timely intervention can stabilize renal function, but ongoing monitoring and individualized treatment remain crucial for optimizing long-term outcomes in children with complex CAKUT. Full article

Vancomycin-resistant enterococci (VRE) are a major cause of healthcare-associated infections (HAIs). However, the clinical significance of VRE colonization and the subsequent risk of VRE infection in hospitalized patients are not fully established. Prolonged hospital stays have been observed in neonates colonized by VRE. The mortality rate in pediatric patients with VRE infections ranges from 0% to 42% in both endemic and outbreak settings, often occurring in VRE-colonized neonates. Host and bacterial factors associated with a worse outcome are not fully understood yet. We describe an outbreak of VRE colonization in 21 newborns admitted to our neonatal intensive care unit in January 2024. Microbiological analyses on rectal swabs were performed using molecular testing and culture. Results: In January, VRE was first detected in the urine culture of a 3-week-old patient, followed by a subsequent positive rectal swab result. In accordance with our infection control policy, all the NICU patients were tested, leading to the identification of another 12 colonized patients. The implementation of molecular testing led to rapid VRE identification and the subsequent isolation of colonized neonates, which promptly contained the outbreak. The median time from NICU admission to colonization was 34 (6–37) days. Only one patient developed a CVC-related bloodstream infection, which was successfully treated with linezolid and CVC removal. No VRE-related deaths occurred, even among three patients who underwent abdominal surgery (one gastroschisis, one incarcerated abdominal hernia, and one umbilical hernia) and one patient with necrotizing enterocolitis. Our data show a low infection rate (4%) among VRE-colonized patients (4%) during a NICU outbreak. The rapid identification of multidrug-resistant genes by molecular testing may be implemented in specific settings to enable timely patient identification, adopt infection control measures, and administer appropriate antimicrobial therapy. Full article

Farms are a major source of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB), and previous research mainly focuses on polluted soils and breeding environments. However, slaughtering is an important link in the transmission of ARGs and ARB from farmland to dining table. In this study, we aim to reveal the pollution of ARGs and ARB in the slaughter process of broilers. First, by qualitative and quantitative analysis of ARGs in samples collected from the broiler slaughtering and processing production chain, the contamination level of ARGs was reflected; secondly, potential hosts for ARGs and microbial community were analyzed to reflect the possible transmission rules; thirdly, through the antibiotic susceptibility spectrum analysis of four typical food-borne pathogens, the distribution of ARB was revealed. The results showed that 24 types of ARGs were detected positive on the broiler slaughter production line, and tetracycline-resistance genes (20.45%) were the most frequently detected. The types of ARGs vary with sampling process, and all sampling links contain high levels of sul2 and intI1. The most abundant ARGs were detected in chicken surface in the scalding stage and entrails surface in the evisceration stage. There was a significant correlation between intI1 and tetM, suggesting that tetM might be able to enter the human food chain through class-1 integrons. The host range of the oqxB gene is the most extensive, including Sphingobacterium, Bacteroidia unclassified, Rothia, Microbacterium, Algoriella, etc. In the relevant links of the slaughter production line, the microbial community structure is similar. Removing viscera may cause diffusion of ARGs carried by intestinal microorganisms and contaminate chicken and following processing production. The four food-borne pathogens we tested are widely present in all aspects of the slaughter process, and most of them have multi-drug resistance and even have a high degree of resistance to some veterinary drugs banned by the Ministry of Agriculture. Our study preliminarily revealed the pollution of ARGs and ARB in the slaughter process of broilers, and these results are helpful to carry out food safety risk assessment and formulate corresponding control measures. Full article

Background/Objectives: Streptococcus pneumoniae (S. pneumoniae) is a major pathogen causing severe infectious diseases, with an escalating issue of antimicrobial resistance that threatens the efficacy of existing antibiotics. Given the challenges in developing traditional antibiotics, drug repurposing strategies offer a novel approach to address the resistance crisis. This study aims to evaluate the antibacterial and anti-biofilm activities of the approved non-antibiotic anticancer drug carmofur against multidrug-resistant S. pneumoniae, and investigate the mechanism of action, and assess therapeutic potential in vivo. Methods/Results: Antimicrobial tests revealed that carmofur exhibited strong antibacterial activity against multidrug-resistant S. pneumoniae strains, with minimum inhibitory concentrations (MICs) ranging from 0.25 to 1 µg/mL. In the biofilm detection experiments, carmofur not only inhibited the formation of biofilms, but also effectively removed biofilms under high concentration conditions. Mechanistic studies showed that carmofur disrupted bacterial membrane permeability and decreased intracellular ATP levels. Molecular docking and dynamics simulation assays indicated that carmofur could stably bind to thymidylate synthase through hydrogen bonding and hydrophobic interactions, thereby exerting antibacterial effects. Meanwhile, carmofur was able to repress the expression of the thyA gene at the mRNA level. In a mouse infection model, the carmofur treatment group showed a reduction of approximately two log levels in bacterial load in lung tissue and blood, a significant decrease in the levels of inflammatory cytokines TNF-α and IL-6, and an improvement in survival rate to 60%. Conclusions: In summary, carmofur demonstrated significant antibacterial and anti-biofilm activities against multidrug-resistant S. pneumoniae and showed good anti-infective effects in vivo, suggesting its potential clinical application as a therapeutic agent against drug-resistant bacteria. Full article

Background/Objectives: The significant outbreak of multidrug-resistant Klebsiella pneumoniae has emerged as a primary global concern associated with high morbidity and mortality rates. Certain strains of K. pneumoniae are highly resistant to most antibiotics available in clinical practice, exacerbating the challenge of bacterial infections. Methods: Phage vB_KpnP_PW7 (vKPPW7) was isolated and characterized. Its morphology, stability, adsorption rate, one-step growth curve, lytic activity, whole-genome sequence analysis, and antibacterial and antibiofilm activities were evaluated. Results: The virulent phage has a 73,658 bp linear dsDNA genome and was classified as a new species of the genus Kaypoctavirus, subfamily Enquatrovirinae, and family Schitoviridae. Phage vKPPW7 has a high adsorption rate, a short latent period, and a large burst size. The phage showed activity against 18 K. pneumoniae isolates with the K24 capsular type but was unable to lyse K. pneumoniae isolates whose capsular type was not classified as K24. Additionally, phage vKPPW7 demonstrated strong stability across various temperatures and pH values. The phage exhibited antibacterial activity, and scanning electron microscopy (SEM) confirmed its ability to lyse MDR K. pneumoniae with the K24 capsular type. Furthermore, phage vKPPW7 effectively removed preformed biofilm and prevented biofilm formation, resulting in reduced biofilm biomass and biofilm viability compared to controls. The architecture of phage-treated biofilms was confirmed under SEM. Conclusions: These findings suggest that phage vKPPW7 holds promise for development as a therapeutic or biocontrol agent. Full article

Multidrug (MDR) and extensive drug (XDR) resistance in Gram-negative bacteria (GNB) emerges worldwide. Although bone and joint infections are mostly caused by Gram-positive bacteria, mainly Staphylococci, MDR GNB substantially increase also as a complication of hospitalization and previous antibiotic administration. This narrative review analyzes the epidemiological trend, current experimental data, and clinical experience with available therapeutic options for the difficult to treat (DTR) GNB implicated in bone and joint infections with or without orthopedic implants. The radical debridement and removal of the implant is adequate therapy for most cases, along with prompt and prolonged combined antimicrobial treatment by older and novel antibiotics. Current research and clinical data suggest that fluoroquinolones well penetrate bone tissue and are associated with improved outcomes in DTR GNB; if not available, carbapenems can be used in cases of MDR GNB. For XDR GNB, colistin, fosfomycin, tigecycline, and novel β-lactam/β-lactamase inhibitors can be initiated as combination schemas in intravenous administration, along with local elution from impregnated spacers. However, current data are scarce and large multicenter studies are mandatory in the field. Full article

Background: ATP-binding cassette (ABC) transporters are expressed in the vascular walls of brain capillaries and remove toxic chemicals from the brain. The expression of ABC transporters in peripheral organs is transcriptionally regulated by clock genes and exhibits 24 h periodic fluctuations. In addition, clock gene outputs diminish with aging. In this study, we evaluated whether the expression of ABC transporters in the blood–brain barrier (BBB) of young mice had a 24 h cycle, and whether the expression of ABC transporters in the BBB decreased with age. Methods: Brain microvascular (BMV) fractions from the cerebral cortex of male C57BL/6J mice were prepared using dextran. BMV fractions from young mice (12 weeks old) were prepared every four hours to evaluate 24 h rhythmicity. BMV fractions from both young and aged mice (85 weeks old) were prepared when protein expression peaked (Zeitgeber Time 5). Protein and mRNA expression of ABC transporters in BMV fractions were measured. Results: In young mice, protein expression of P-glycoprotein, breast cancer resistance protein, and multidrug resistance protein 4 showed time-dependent variations with a peak in the light phase (Zeitgeber Time 5); mRNA expression showed no time-dependent variation. The protein expression of these transporters was lower in the BBB of aged mice than in that of young mice, although mRNA expression did not differ between young and aged mice. Conclusions: ABC transporter protein expression levels in BMV endothelial cells decreased with aging; however, mRNA levels did not change, which suggests changes in protein expression did not result from diminished clock gene output. Further studies are needed to elucidate the mechanisms by which ABC transporter expression in the BBB decreases with aging. Full article

The increasing prevalence of heavy metals and antibiotic-resistant bacteria in wastewater (WW) raises serious environmental and public health concerns. This study investigates the efficiency of the microalgal strain Chlorella vulgaris EV-465 in treating wastewater and evaluates the antibiotic resistance profile of bacterial strains obtained from WW samples. Chlorella vulgaris EV-465 was used to treat four types of wastewater—domestic, municipal, hospital, and industrial wastewater—through 21 days of incubation. The findings demonstrated pH stabilization and significant decreases in nutrients (total nitrogen—TN, total phosphorus—TP), biological oxygen demand (BOD), chemical oxygen demand (COD), heavy metal (HM) concentrations, and bacterial count. Copper (Cu) showed the highest reduction, decreasing by 80% in industrial wastewater within 14 days, while lead (Pb) proved more resistant to removal, with only a 50% decrease by day 21. Additionally, the algae decreased bacterial counts, lowering colony-forming units (Log CFU/mL) from 9.04 to 4.65 in municipal wastewater over the 21-day period. Antibiotic susceptibility tests for isolated bacterial strains revealed high levels of resistance, with seven out of nine bacterial strains exhibiting multidrug resistance. Notably, Enterococcus faecium (PBI08), Acinetobacter baumannii (YBH19), and Pseudomonas aeruginosa (NBH16) displayed resistance to all nine antibiotics tested. Among the tested antibiotics, Ciprofloxacin showed the highest efficacy, with 66% susceptibility of tested bacterial strains. Cluster and phylogenetic analyses showed that the majority of the isolated bacterial strains belonged to the genera Pseudomonas and Escherichia, highlighting their genetic diversity and varied resistance mechanisms. Full article

Endolysin, a bacteriophage-derived lytic enzyme, has emerged as a promising alternative antimicrobial agent against rising multidrug-resistant bacterial infections. Two novel endolysins LysPEF1-1 and LysPEF1-2 derived from Enterococcus phage PEF1 were cloned and overexpressed in Escherichia coli to test their antimicrobial efficacy against multidrug-resistant E. faecalis strains and their biofilms. LysPEF1-1 comprises an enzymatically active domain and a cell-wall-binding domain originating from the NLPC-P60 and SH3 superfamilies, while LysPEF1-2 contains a putative peptidoglycan recognition domain that belongs to the PGRP superfamily. LysPEF1-1 was active against 89.86% (62/69) of Enterococcus spp. tested, displaying a wider antibacterial spectrum than phage PEF1. Moreover, two endolysins demonstrated lytic activity against additional gram-positive and gram-negative species pretreated with chloroform. LysPEF1-1 showed higher activity against multidrug-resistant E. faecalis strain E5 than LysPEF1-2. The combination of two endolysins effectively reduced planktonic cells of E5 in broth and was more efficient at inhibiting biofilm formation and removing biofilm cells of E. faecalis JCM 7783^T than used individually. Especially at 4 °C, they reduced viable biofilm cells by 4.5 log after 2 h of treatment on glass slide surfaces. The results suggest that two novel endolysins could be alternative antimicrobial agents for controlling E. faecalis infections. Full article