Search Results (329)

Background and Clinical Significance: Mycotic aortic aneurysm is a rare but life-threatening vascular condition characterized by infection-induced dilation or pseudoaneurysm formation in the aorta. The condition carries a high risk of rupture and mortality, especially in individuals with underlying cardiovascular disease, who have undergone recent vascular procedures, or with immunocompromising comorbidities such as diabetes. Its diagnosis is challenging due to its non-specific symptoms and often requires a high index of suspicion, especially in patients presenting with persistent fever and negative initial imaging. Early recognition and intervention are critical, as delayed treatment significantly worsens outcomes. Case Presentation: A 68-year-old male with a history of coronary artery disease, recent stent placement, and hypertension presented with two days of fever, chills, rigors, and a mild nonproductive cough. The laboratory findings were only significant for leukocytosis. The initial chest X-ray and non-contrast CT scans were unremarkable. He was admitted for presumed pneumonia and started on intravenous antibiotics. Persistent fever prompted further investigation with contrast-enhanced CT, which revealed a distal-aortic-arch pseudoaneurysm and mild mediastinal stranding. Blood cultures grew methicillin-sensitive Staphylococcus aureus (MSSA). Transthoracic echocardiogram was negative for endocarditis. The patient was transferred to a tertiary center, where repeat imaging confirmed a 1.5 cm pseudoaneurysm and a 4 mm penetrating atherosclerotic ulcer. After multidisciplinary assessment, he underwent thoracic endovascular aortic repair (TEVAR) and completed four weeks of intravenous cefazolin. Follow-up imaging showed successful aneurysm repair with no complications. Conclusions: Thoracic mycotic aneurysm is a rapidly fatal entity despite intervention. High clinical suspicion is necessary given its non-specific presentation. It is diagnosed most practically using CTA. In addition to antibiotics, TEVAR is gaining traction as a feasible and a safe alternative to open surgical repair (OSR). Full article

Staphylococcus aureus, a Gram-positive coccus commonly found in the environment, is indeed a common cause of both superficial and deep infections. The aim of the study was to determine the virulence factors of S. aureus characteristic of chronic infections, including chronic furunculosis and chronic osteomyelitis. Phenotypic characteristics of the bacteria (ability to produce hemolysis, clumping factor, and coagulase; antibiotic susceptibility) and genotypic characteristics (presence of genes responsible for the production of enzymes and toxins; ability to form biofilm) were examined. The real-time PCR method was used to determine the presence of virulence genes. Biofilm production was confirmed using the crystal violet method. Antibiotic and chemotherapeutic susceptibility tests were performed using the disk diffusion method. In 90% of cases, S. aureus strains possessed the following virulence genes: clfA, clfB, spa, cna, eap, hlgA, hlgB, hlg, hld, bap, bbp, ebpS, fib, fnbA, fnbB, and pvl. A total of 82% of S. aureus strains showed susceptibility to methicillin (MSSA), whereas 12% of strains were susceptible to methicillin and simultaneously resistant to macrolides, lincosamides, and streptogramin B, including 10.5% with inducible resistance and 1.5% with constitutive resistance (MSSA/MLSB). In addition, 1.5% were methicillin-resistant S. aureus (MRSA) and susceptible to the remaining antimicrobial agents. The predominance of MSSA in the etiology of chronic furunculosis and chronic osteomyelitis was observed. It has been demonstrated that MSSA possesses a similar set of virulence genes to MRSA and that MSSA is responsible for most cases of chronic osteomyelitis and furunculosis. The findings indicate that S. aureus possesses numerous virulence factors that play a key role in the processes of adhesion to and proliferation within host cells. Full article

Background: Staphylococcus aureus is one of the most prevalent bacteria in skin and soft tissue infections (SSTIs). Multidrug-resistant strain emergence, particularly methicillin-resistant S. aureus (MRSA), highlights the need for alternative treatments. Objectives: This study investigates the antimicrobial properties of olive leaf extract (OLE) and describes an epidemiological profiling of patients with SSTI who may benefit from it. Methods: OLE was tested in two reference strains, methicillin-susceptible S. aureus (MSSA) ATCC 29213 and MRSA ATCC 700699, and in 126 clinical isolates from patients with SSTIs according to Clinical Laboratory Standards Institute guidelines. Results: The minimum bactericidal concentration (MBC) ranged from 3.12% to 6.25% w/v for MSSA and 1.56% to 3.12% for MRSA. The lethal curve showed a reduction of 6 log₁₀CFU/mL after two hours of incubation. Most of the 126 clinical samples (103 MSSA and 23 MRSA) came from skin lesions, surgical wounds, and ulcers. Over 90% of MSSA strains were resistant to less than five antibiotics, while 82% of MRSA strains were resistant to more than six. Penicillins demonstrated the lowest susceptibility rate (19.8%), whereas linezolid, daptomycin, pristinamycin, trimethoprim–sulfamethoxazole, teicoplanin, vancomycin, and OLE exhibited 100% susceptibility. No growth was observed for all clinical strains with OLE at ≥6.25% w/v. Conclusions: The findings suggest that OLE could become a promising alternative treatment for skin infections, particularly in the context of increasing antibiotic resistance. Full article

Pelvic organ prolapse (POP) cases have been rising, affecting women’s quality of life. Severe cases often require surgical mesh implants, which can cause complications like tissue erosion and infection, leading the FDA to ban transvaginal meshes for POP. To address this, polycaprolactone (PCL) mesh implants, produced via melt electrowriting (MEW), were evaluated mechanically and coated with azithromycin, an antibiotic for genitourinary infections. Uniaxial tensile and cyclic tests assessed the long-term behavior of the meshes over 100 cycles. The results show that while all PCL meshes had similar behavior, those with 1 mm pores sustained higher stress, whereas 1.5 mm pore size meshes had mechanical properties closer to vaginal tissue but remained stiffer. Cyclic tests revealed initial damage and hardening during plastic deformation, with tensile tests confirming increased stiffness, as Young’s modulus rose between 19.2% and 29.3%. Zone inhibition and biofilm assays evaluated azithromycin’s effectiveness against bacterial infection. Even though FTIR analysis could not confirm antibiotic incorporation, the drug coated meshes show inhibitory activity against E. coli biofilm formation and MSSA in its planktonic state. Scanning Electron Microscopy supported these findings. These results suggest that MEW-fabricated PCL meshes coated with azithromycin hold promise as improved implants for POP treatment. Full article

Persistent bacteria (PB) are a subpopulation of dormant cells that tolerate high antibiotic concentrations and cause chronic, hard-to-treat infections, posing a serious global health threat. In this study, the antibacterial efficacy of six cationic polymers, poly(hexamethylene guanidine) (PHMG), polyethyleneimines of different molecular weights, α-polylysine, ε-polylysine, and polyacrylamide, against persistent bacteria was systematically evaluated. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of these cationic polymers against susceptible and persistent methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and Escherichia coli (E. coli) were determined using a microbroth dilution method, while cytotoxicity to mouse fibroblast (L929) cells was assessed via MTT assay. PHMG demonstrated superior antibacterial activity, with MBC values as low as 2 μg/mL against persistent MSSA, markedly outperforming the other polymers tested. The key novelties of this work are (i) the first establishment of a cationic polymer library with diverse structural parameters for persistent bacteria clearance, offering a potential strategy for treating recalcitrant infections; and (ii) the elucidation of quantitative correlations between polymer charge density and hydrophobic chain segments with antimicrobial efficacy through structure–activity relationship analysis, providing a theoretical basis for the rational design of anti-persistent materials. Full article

Hydrogel materials have become an efficient, bioactive, and multifunctional alternative with great potential for biomedical applications. In this work, photoactive films were successfully designed for optical processing, and their photoactivity was tested in photodynamic therapy (PDT), such as antimicrobial patches. The stimulus-response hydrogel films are made of a hydrophilic polymer based on vinyl monomers, specifically 2-hydroxyethyl methacrylate (HEMA) and acrylamide (AAm), in a 1:1 molar ratio, along with the photochromic agent, 3,3-dimethylindolin-6′-nitrobenzoespiropirano (BSP), and a crosslinking agent, N,N’-methylenebisacrylamide (MBA). These hydrogel films were successfully created using the photoinitiator 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone (IRGACURE 2959), MBA, and BSP in different concentrations (0.1, 0.3, and 0.5 mol%), which were later tested in photodynamic therapy (PDT) with the photosensitizer Ru(bpy)₂²⁺ against Staphylococcus aureus. The results showed that, while free Ru(bpy)₂²⁺ needed concentrations of 4–8 µg/mL to eliminate methicillin-sensitive (MSSA) strains, only partial inactivation was achieved for methicillin-resistant (MRSA) strains. The addition of the hydrogel films with BSP improved their effectiveness, lowering the minimum inhibitory concentration (MIC) to 2 µg/mL to fully inactivate MSSA and MRSA strains. These findings demonstrate that the combined use of hydrogel films containing BSP and Ru(bpy)₂²⁺ within a hydrogel matrix not only boosts antimicrobial activity but also highlights the potential of these photoactive films as innovative photosensitive antimicrobial coatings. This synergistic effect of BSP and Ru(bpy)₂²⁺ indicates that these materials are promising candidates for next-generation antimicrobial coatings and creative photosensitive materials. Full article

Infections following spinal surgery can result in potentially devastating complications. An accurate microbiological diagnosis is crucial for proper treatment. Sonication is a diagnostic method that can be beneficial in patients with acute or low-grade infections. This study aimed to assess the sensitivity and effectiveness of sonication as a method for diagnosing spinal implant infections in cases of both suspected and unsuspected infections during spinal surgical revision. We conducted a retrospective observational study that included all patients who underwent revision spinal surgery between March 2011 and October 2022. We collected the implants and surrounding tissues from these patients for microbiological analysis. The implant sonication was performed according to a previously published protocol. Patients were categorised into those undergoing surgical revision for suspected spinal implant infection (SSII) and those for non-suspected spinal implant infection (NSSII). We collected comprehensive patient data, including demographics, risk factors, Charlson Comorbidity Index (CCI), surgical details, microbiological findings, antibiotic regimens, and clinical outcomes. Sensitivity and specificity analyses were conducted on both sonicated and non-sonicated samples. A total of 158 patients met the inclusion criteria; 51 of them were diagnosed with infection during surgery revision. Patients with SSII had higher CCIs than those with NSSII. The sensitivity was significantly higher in sonicated samples (68.6%; 95% CI: 55.9–81.4%) than in non-sonicated samples (42%; 95% CI: 28.3–55.7%). The specificities were similar, with sonicated samples at 93.5% (95% CI: 88.8–98.1%) and non-sonicated samples at 99.05% (95% CI: 97.2–100.9%). Combining both methods resulted in sensitivity and specificity rates of 76% (95% CI: 64.2–87.8%) and 93.3% (95% CI: 88.2–98.1%), respectively. Methicillin-susceptible Staphylococcus aureus (MSSA) was common in SSII, whereas Cutibacterium acnes and coagulase-negative Staphylococcus (CNS) were predominant in NSSII. This study supports the routine use of implant sonication as a valuable supplementary method for peri-implant tissue cultures, especially for identifying low-grade spinal implant infections. Full article

This study explores the potential of biodegradable Bioglass 45S5 formulations as a dual-function approach for preventing and treating Staphylococcus aureus infections in orthopaedic surgery while addressing the growing concern of antimicrobial resistance (AMR). The research focuses on the development and characterisation of antibiotic-loaded BG45S5 formulations, assessing parameters such as drug loading efficiency, release kinetics, antimicrobial efficacy, and dissolution behaviour. Key findings indicate that the F2l-BG45S5-T-T-1.5 and F2l-BG45S5-T-V-1.5 formulations demonstrated controlled antibiotic release for up to seven days, with size distributions of D(10): 7.11 ± 0.806 µm, 4.96 ± 0.007 µm; D(50): 25.34 ± 1.730 µm, 25.20.7 ± 0.425 µm; and D(90): 53.7 ± 7.95 µm, 56.10 ± 0.579 µm, respectively. These formulations facilitated hydroxyapatite formation on their surfaces, indicative of osteogenic potential. The antimicrobial assessments revealed zones of inhibition against methicillin-susceptible Staphylococcus aureus (MSSA, ATCC-6538) measuring 20.3 ± 1.44 mm and 24.6 ± 1.32 mm, while for methicillin-resistant Staphylococcus aureus (MRSA, ATCC-43300), the inhibition zones were 21.6 ± 1.89 mm and 22 ± 0.28 mm, respectively. Time-kill assay results showed complete bacterial eradication within eight hours. Additionally, biocompatibility testing via MTT assay confirmed cell viability of >75%. In conclusion, these findings highlight the promise of antibiotic-loaded BG45S5 as a multifunctional biomaterial capable of both combating bone infections and supporting bone regeneration. These promising results suggest that in vivo studies should be undertaken to expedite these materials into clinical applications. Full article

Antimicrobial resistance (AMR) poses a critical global health threat by rendering existing antibiotics ineffective against infections, leading to increased mortality, prolonged illnesses, and higher healthcare costs. Developing new antibiotics is essential to combat resistant pathogens, safeguard modern medical procedures, and prevent a return to a pre-antibiotic era where common infections become untreatable. We report a series of chiral tricarbonyl rhenium(I) complexes incorporating enantiopure pinene-substituted bipyridine ligands (L#) of the general formula fac-[Re(CO)₃L#X] and fac-[Re(CO)₃L#Py]⁺ (where X = Cl or Br and Py = pyridine). These complexes were isolated as mixtures of two diastereomers, characterized by standard techniques, and evaluated for cytotoxic activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus (MRSA and MSSA). The results revealed notable antibacterial efficacy (MIC = 1.6 μM), reflected in high therapeutic indices (Ti > 10). In contrast, analogous complexes bearing non-chiral 2,2′-bipyridine ligands exhibited no activity, underscoring the critical role of chirality in modulating biological interactions at the molecular level. These findings highlight the potential of chiral Re(I) complexes as promising scaffolds for the development of more potent and selective antibacterial agents. Full article

Water buffalo (Bubalus bubalis) are a primary source of milk in Pakistan, where bovine mastitis is a significant health issue among cattle, leading to substantial economic losses. Staphylococcus aureus is a predominant pathogen associated with mastitis; however, a detailed molecular characterization of the strains in the country remains limited. We previously characterized mastitis strains from the Hazara division of Khyber Pakhtunkhwa, Pakistan. In this study, we investigated mastitis cases in the Peshawar division, including samples from both animals and human farm workers for comparison. Higher rates of mastitis (67.27% of animals) and sub-clinical mastitis (91.03% of positive animals) were identified in Peshawar than for those (34.55% and 75.31%, respectively) previously observed in Hazara. Methicillin-susceptible S. aureus (MSSA) belonging to clonal complex 9 (ST2454) were predominant. Methicillin-resistant S. aureus (MRSA) belonging to ST22 and ST8 were also detected in the Nowshera district. While no S. aureus colonization was observed among animal handlers, evidence of hand contamination suggests a potential route for pathogen spread. Low levels of antibiotic resistance were noted amongst isolates, but higher rates were seen in MRSA. This study presents only the second comprehensive molecular investigation of S. aureus isolated from buffalo mastitis in Pakistan and indicates a concerning rise in mastitis within the province. Full article

Phage therapy shows promise as an adjunct to antibiotics for treating Staphylococcus aureus infections. We previously reported a combined flucloxacillin/two-phage cocktail treatment selected for resistance to podovirus phage 66 in a rodent model of methicillin-susceptible S. aureus (MSSA) endocarditis. Here we show that resistant clones harbor mutations in tarS, which encodes a glycosyltransferase essential for β-GlcNAcylation of wall teichoic acid (WTA). This WTA modification has been described in vitro as critical for podoviruses adsorption. Transcriptomics confirmed continued tarS expression in resistant clones, supporting a loss-of-function mechanism. Accordingly, phage 66 binding and killing were restored by WT tarS complementation. In addition, we investigated the counterintuitive innate susceptibility to phage 66 of the tarM + Laus102 strain used in the endocarditis model. We show that it likely results from a significant lower tarM expression, in contrast to the innate resistant strain RN4220. Our findings demonstrate that tarS-mediated WTA β-GlcNAcylation is critical for podovirus infection also in vivo and identify tarM transcriptional defect as a new mechanism of podoviruses susceptibility in S. aureus. Moreover, and since tarS disruption has been previously shown to enhance β-lactam susceptibility, our results support the development of combined podovirus/antibiotic strategies for the management of MRSA infections. Full article

Background: Staphylococcus aureus is a significant pathogen causing both local and systemic infections in children, with deep tissue involvement leading to severe complications. This study aimed to assess clinical manifestations and identify risk factors for deep tissue involvement in pediatric S. aureus infections. Methods: All children between 1 month and 18 years who had S. aureus growth in blood, pus, or joint fluid culture were included. Results: A total of 61 patients (median age 55 months) were included, with 22.9% having deep tissue infections. Osteoarticular infections, pyomyositis, and pulmonary involvement were common. Deep-seated infections were significantly associated with community-acquired infections and positive hemocultures after 72 h (p < 0.01). Laboratory results showed significantly higher levels of C-reactive protein, sedimentation rate, D-dimer, and fibrinogen in the group with deep-seated infections (p = 0.02, p = 0.018, p = 0.01, and p = 0.015, respectively). The decision tree model showed that the first indicator of deep-seated infection was a D-dimer level above 1.15 mg/L, followed by a fibrinogen level above 334 mg/dL. Conclusions: Deep-seated S. aureus infections are more frequently associated with community-acquired cases, persistent hemoculture positivity, and methicillin-susceptible Staphylococcus aureus (MSSA) strains. Additionally, elevated D-dimer and fibrinogen levels may serve as valuable markers for identifying deep-seated infections in pediatric patients. Full article

Antibiotic resistance and biofilm formation complicate Staphylococcus aureus infections, raising concerns for global health. Understanding antimicrobial resistance and biofilm formation in these pathogens is essential for effective infection management. The current research aimed to assess antibiotic resistance patterns, biofilm formation, and the occurrence of integron classes 1, 2, and 3 in clinical S. aureus isolates. The disc diffusion method tested antibiotic susceptibility. MRSA strains were identified by cefoxitin disc diffusion, and the mecA gene by PCR. The D-test also assessed macrolide–lincosamide–streptogramin B. A microtiter plate assay assessed biofilm formation. By PCR, integron classes were examined. Of the 63 S. aureus isolates, 25 were MSSA and 38 were MRSA. Pus (39.5%) was the most prevalent clinical source of MRSA isolates, while blood (24%) was the predominant source of MSSA isolates. MRSA isolates were more resistant to clindamycin, ciprofloxacin, ofloxacin, levofloxacin, tetracycline, and doxycycline than MSSA isolates. In total, 76.2% of the isolates produced biofilm. Biofilm-producing isolates were more resistant to cefoxitin and clindamycin. The isolates had 33.3% cMLSB resistance. The intI1 gene was found in 21 S. aureus isolates (33.3%), whereas the intI2 or intI3 genes were not detected. Our findings demonstrate the need for strict infection control to prevent the spread of resistant bacteria. Full article

In recent years, pelvic organ prolapse (POP) cases have been rising, affecting women’s quality of life. Synthetic surgical transvaginal meshes used for POP treatment were withdrawn from the United States market in 2019 due to high risks, including infection, vaginal mesh erosion, and POP reoccurrence. Biodegradable mesh implants with three-dimensional printing technology have emerged as an innovative alternative. In this study, polycaprolactone (PCL) meshes for POP repair were fabricated using melt electrospinning writing (MEW) and mechanically evaluated through uniaxial tensile tests. Following this, they were coated with antibiotics—azithromycin, gentamicin sulfate, and ciprofloxacin—commonly used for genitourinary tract infections. Zone inhibition and biofilm assays evaluated antibiotic effectiveness in preventing mesh infections by Escherichia coli, and methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus. The meshes presented a mechanical behavior closer to vaginal tissue than commercially available meshes. Fourier transform infrared analysis confirmed antibiotic incorporation. Ciprofloxacin demonstrated antibacterial activity against MRSA, with a 92% reduction in metabolic activity and a 99% biomass reduction. Gentamicin and ciprofloxacin displayed inhibitory activity against MSSA and E. coli. Scanning electron microscopy images support these conclusions. This methodology may offer a more effective, patient-friendly solution for POP repair, improving healing and the quality of life for affected women. Full article

The repurposing potential of Efavirenz (EFV), a clinically established non-nucleoside reverse transcriptase inhibitor, was comprehensively evaluated for its in vitro antibacterial effect either alone or in combination with other antibacterial agents on several Gram-positive clinical strains showing different antibiotic resistance profiles. The binding potential assessed by an in silico study included Penicillin-binding proteins (PBPs) and WalK membrane kinase. Despite the relatively high minimum inhibitory concentration (MIC) limiting the use of EFV as a single antibacterial agent, it exhibits significant synergistic activity at sub-MIC levels when paired with various antibiotics against Enterococcus species and Staphylococcus aureus. EFV showed restored sensitivity of β-lactams against Methicillin-resistant S. aureus (MRSA). It increased the effectiveness of antibiotics tested against Methicillin-sensitive S. aureus (MSSA). It also helped to overcome the intrinsic resistance barrier for several antibiotics in Enterococcus spp. In silico binding studies aligned remarkably with experimental antimicrobial testing results and highlighted the potential of EFV to direct the engagement of PBPs with moderate to strong binding affinities (pK_a 5.2–6.1). The dual-site PBP2 binding mechanism emerged as a novel inhibition strategy, potentially circumventing resistance mutations. Special attention should be paid to WalK binding predictions (pK_a = 4.94), referring to the potential of EFV to interfere with essential regulatory pathways controlling cell wall metabolism and virulence factor expression. These findings, in general, suggest the possibility of EFV as a promising lead for the development of new antibacterial agents. Full article