RESUMO

This study delves into the potential of amorphous titanium oxide (aTiO2) nano-coating to enhance various critical aspects of non-Ti-based metallic orthopedic implants. These implants, such as medical-grade stainless steel (SS), are widely used for orthopedic devices that demand high strength and durability. The aTiO2nano-coating, deposited via magnetron sputtering, is a unique attempt to improve the osteogenesis, the inflammatory response, and to reduce bacterial colonization on SS substrates. The study characterized the nanocoated surfaces (SS-a TiO2) in topography, roughness, wettability, and chemical composition. Comparative samples included uncoated SS and sandblasted/acid-etched Ti substrates (Ti). The biological effects were assessed using human mesenchymal stem cells (MSCs) and primary murine macrophages. Bacterial tests were carried out with two aerobic pathogens (S. aureusandS. epidermidis) and an anaerobic bacterial consortium representing an oral dental biofilm. Results from this study provide strong evidence of the positive effects of the aTiO2nano-coating on SS surfaces. The coating enhanced MSC osteoblastic differentiation and exhibited a response similar to that observed on Ti surfaces. Macrophages cultured on aTiO2nano-coating and Ti surfaces showed comparable anti-inflammatory phenotypes. Most significantly, a reduction in bacterial colonization across tested species was observed compared to uncoated SS substrates, further supporting the potential of aTiO2nano-coating in biomedical applications. The findings underscore the potential of magnetron-sputtering deposition of aTiO2nano-coating on non-Ti metallic surfaces such as medical-grade SS as a viable strategy to enhance osteoinductive factors and decrease pathogenic bacterial adhesion. This could significantly improve the performance of metallic-based biomedical devices beyond titanium.

Assuntos

Materiais Revestidos Biocompatíveis , Macrófagos , Teste de Materiais , Células-Tronco Mesenquimais , Osteogênese , Aço Inoxidável , Propriedades de Superfície , Titânio , Titânio/química , Aço Inoxidável/química , Animais , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Macrófagos/metabolismo , Osteogênese/efeitos dos fármacos , Diferenciação Celular , Próteses e Implantes , Osteoblastos/citologia , Staphylococcus aureus/efeitos dos fármacos , Biofilmes , Staphylococcus epidermidis/efeitos dos fármacos , Aderência Bacteriana , Molhabilidade

RESUMO

BACKGROUND: Resistant infectious diseases caused by gram-negative bacteria are among the most serious worldwide health problems. Antimicrobial peptides (AMPs) have been explored as promising antibacterial, antibiofilm, and anti-infective candidates to address these health challenges. MAJOR CONCLUSIONS: Here we report the potent antibacterial effect of the peptide PaDBS1R6 on clinical bacterial isolates and identify an immunomodulatory peptide fragment incorporated within it. PaDBS1R6 was evaluated against Acinetobacter baumannii and Escherichia coli clinical isolates and had minimal inhibitory concentration (MIC) values from 8 to 32 µmol L-1. It had a rapid bactericidal effect, with eradication showing within 3 min of incubation, depending on the bacterial strain tested. In addition, PaDBS1R6 inhibited biofilm formation for A. baumannii and E. coli and was non-toxic toward healthy mammalian cells. These findings are explained by the preference of PaDBS1R6 for anionic membranes over neutral membranes, as assessed by surface plasmon resonance assays and molecular dynamics simulations. Considering its potent antibacterial activity, PaDBS1R6 was used as a template for sliding-window fr agmentation studies (window size = 10 residues). Among the sliding-window fragments, PaDBS1R6F8, PaDBS1R6F9, and PaDBS1R6F10 were ineffective against any of the bacterial strains tested. Additional biological assays were conducted, including nitric oxide (NO) modulation and wound scratch assays, and the R6F8 peptide fragment was found to be active in modulating NO levels, as well as having strong wound healing properties. GENERAL SIGNIFICANCE: This study proposes a new concept whereby peptides with different biological properties can be derived by the screening of fragments from within potent AMPs.

RESUMO

With the increasing rate of infections caused by multidrug-resistant organisms (MDRO), selecting appropriate empiric antibiotics has become challenging. We aimed to develop and externally validate a model for predicting the risk of MDRO infections in patients with cirrhosis. METHODS: We included patients with cirrhosis and bacterial infections from two prospective studies: a transcontinental study was used for model development and internal validation (n = 1302), and a study from Argentina and Uruguay was used for external validation (n = 472). All predictors were measured at the time of infection. Both culture-positive and culture-negative infections were included. The model was developed using logistic regression with backward stepwise predictor selection. We externally validated the optimism-adjusted model using calibration and discrimination statistics and evaluated its clinical utility. RESULTS: The prevalence of MDRO infections was 19% and 22% in the development and external validation datasets, respectively. The model's predictors were sex, prior antibiotic use, type and site of infection, MELD-Na, use of vasopressors, acute-on-chronic liver failure, and interaction terms. Upon external validation, the calibration slope was 77 (95% CI .48-1.05), and the area under the ROC curve was .68 (95% CI .61-.73). The application of the model significantly changed the post-test probability of having an MDRO infection, identifying patients with nosocomial infection at very low risk (8%) and patients with community-acquired infections at significant risk (36%). CONCLUSION: This model achieved adequate performance and could be used to improve the selection of empiric antibiotics, aligning with other antibiotic stewardship program strategies.

RESUMO

AIM: Natural bioactive products have been tested as alternative antimicrobial agents. This study evaluated the effect of Punica granatum extract (PGE) on oral multispecies biofilms. METHODOLOGY: Lyophilized extracts from pomegranate peel were prepared, and the punicalagin content was assessed by ultra-performance liquid chromatography (UPLC). Oral multispecies biofilms from 2 donors were grown on four collagen-coated hydroxyapatite discs. After incubation for 7 days or 3 weeks, the biofilms were exposed to water (control), 2% CHX, 10% PGE, 20% PGE or 30% PGE for 3 min. The proportions of dead bacteria were assessed by the live/dead staining and confocal microscopy. After the analysis, the best PGE concentration (30%) was combined with CHX. The experimental phases were repeated using water, 2% CHX, 30% PGE and 30% PGE + 2% CHX. Five random areas of the biofilm on each disc were scanned, resulting in 20 scanned areas for each group. RESULTS: Regarding the biofilm volume, no differences were found amongst solutions (p = .111). The PGE solution killed bacteria effectively in 1-week, 2-week and 3-week-old-plaque biofilms, ranging from 37 to 55.3%, depending on the PGE concentration. The 30% PGE (a) (p = .0009) had greater antibiofilm effectiveness than 2% CHX (b), which killed bacteria in the 25.2 to 48.7% range. The 10% and 20% PGE had intermediate values (ab), without significant differences from 30% PGE (p = 1.002). Water (c) had the lowest proportion of dead bacteria (p < .00001) in a range of 5 to 6.7% and lower effectiveness in killing bacteria (p < .05). The PGE alone or mixed with 2% CHX had greater anti-biofilm effectiveness than CHX (p < .05). The old plaque biofilms were more resistant than the 7-day-old plaque (p < .05). CONCLUSIONS: The 30% PGE (alone or combined with CHX) exhibited a greater antibiofilm effect on oral multispecies biofilms grown on hydroxyapatite discs than 2% CHX.

RESUMO

Melipona beecheii pot-pollen is a natural product that has barely been studied, unlike other hive products such as honey and propolis. Its application has been reported since ancient times in traditional Mayan medicine, and it is also a functional food with high nutritional value. In the present study, samples of ethanolic pot-pollen extracts from five locations in the Yucatán Peninsula were analyzed to determine their antibacterial and antioxidant properties. All the extracts showed activity against five medically important bacteria; Pseudomonas aeruginosa and Listeria monocytogenes were the most susceptible bacteria in all samples. The evaluated antioxidant activity was higher than that reported by other studies. Palmitic, linoleic, and linolenic fatty acids and their respective ethyl ethers were detected by Gas Chromatography-Mass Spectrometry (GC-MS) in all samples in different concentrations. Based on these results, pot-pollen extract from Mama, Yucatán exhibited the best biological activities (Minimum Inhibitory Concentrations (MICs) between 6 and 40 mg/mL, EC50 DPPH 28 µg/mL, EC50 RP 30 µg/mL), which could be related to a higher content of unsaturated fatty acids and their ethyl esters. The present study demonstrates that M. beecheii pot-pollen has therapeutic potential in addition to its benefits as a nutritional supplement.

RESUMO

OBJECTIVE: Analyze the effects of the functionalization of pre-functionalized GIC particles with chlorhexidine on the physicochemical properties and antimicrobial activity. MATERIALS AND METHODS: Four groups were prepared: (1) GIC (Bioglass R - Biodinamica) - control group; (2) GIC-CHX 1%: Group containing 1% pre-reacted CHX particles; (3) GIC-CHX 2.5%: Group containing 2.5% pre-reacted CHX particles; (4) GIC-CHX 5%: Group containing 5% pre-reacted CHX particles. Hourglass-shaped specimens (10 mm × 2 mm x 1 mm) were fabricated for mechanical tests including cohesive strength (n = 12), modulus of elasticity (n = 12) and microhardness (n = 10). Discs (10 mm × 2 mm) were prepared for the analysis of Ca+2, PO4- and F- ions release (n = 3), and roughness (n = 12). To evaluate the setting time, a Gilmore needle was used according to ISO 9917-1:2016. Disk-shaped specimens (5 × 1mm) were manufactured and subjected to bacterial activity (n = 9) (Streptococcus mutans ATCC 159). RESULTS: Modulus, roughness, setting time and ions release (Ca+2, PO4-, and F-) there were no statistically significant differences among the groups (p > 0.05). The setting time did not change with the incorporation of CHX. The GIC-CHX 2.5% and GIC-CHX 5% groups exhibited superior antibacterial activity compared to the control group and GIC-CHX 1% (p < 0.001). The GIC-CHX 5% group showed the highest microhardness values (p < 0.041), cohesive strength (p < 0.009) when compared to the control group. CONCLUSION: The pre-reacted CHX in GICs was able to confer antimicrobial activity, improve cohesive strength, microhardness, and did not impair ion release, setting time, and roughness.

Assuntos

Clorexidina , Cimentos de Ionômeros de Vidro , Teste de Materiais , Clorexidina/química , Clorexidina/farmacologia , Cimentos de Ionômeros de Vidro/química , Cimentos de Ionômeros de Vidro/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Streptococcus mutans/efeitos dos fármacos , Dureza , Fenômenos Mecânicos , Propriedades de Superfície , Fenômenos Químicos , Antibacterianos/farmacologia , Antibacterianos/química

RESUMO

OBJECTIVE: To assess whether beta-lactam extended or continuous beta-lactam infusions (EI/CI) improve clinical outcomes in children with proven or suspected bacterial infections. STUDY DESIGN: We included observational and interventional studies that compared beta-lactam EI or CI with standard infusions in children less than 18 years old, and reported on mortality, hospital or intensive care unit length of stay, microbiological cure, and/or clinical cure. Data sources included PubMed, Medline, EBM Reviews, EMBASE, and CINAHL and were searched from January 1, 1980, to November 3, 2023. Thirteen studies (2945 patients) were included: 5 randomized control trials and 8 observational studies. Indications for antimicrobial therapies and clinical severity varied, ranging from cystic fibrosis exacerbation to critically ill children with bacteriemia. RESULTS: EI and CI were not associated with a reduction in mortality in randomized control trials (n = 1464; RR 0.93, 95% CI 0.71, 1.21), but were in observational studies (n = 833; RR 0.43, 95% CI 0.19, 0.96). We found no difference in hospital length of stay. Results for clinical and microbiological cures were heterogeneous and reported as narrative review. The included studies were highly heterogeneous, limiting the strength of our findings. The lack of shared definitions for clinical and microbiological cure outcomes precluded analysis. CONCLUSIONS: EI and CI were not consistently associated with reduced mortality or length of stay in children. Results were conflicting regarding clinical and microbiological cures. More well-designed studies targeting high-risk populations are necessary to determine the efficacy of these alternative dosing strategies.

RESUMO

Persistent bacterial infections are the leading risk factor that complicates the healing of chronic wounds. In this work, we formulate mixtures of polyvinyl alcohol (P), chitosan (CH), collagen (C), and honey (H) to produce nanofibrous membranes with healing properties. The honey effect at concentrations of 0 % (PCH and PCHC), 5 % (PCHC-5H), 10 % (PCHC-10H), and 15 % (PCHC-15H) on the physicochemical, antibacterial, and biological properties of the developed nanofibers was investigated. Morphological analysis by SEM demonstrated that PCH and PCHC nanofibers had a uniform and homogeneous distribution on their surfaces. However, the increase in honey content increased the fiber diameter (118.11-420.10) and drastically reduced the porosity of the membranes (15.79-92.62 nm). The addition of honey reduces the water vapor transmission rate (WVTR) and the adsorption properties of the membranes. Mechanical tests revealed that nanofibers were more flexible and elastic when honey was added, specifically the PCHC-15H nanofibers with the lowest modulus of elasticity (15 MPa) and the highest elongation at break (220 %). Also, honey significantly improved the antibacterial efficiency of the nanofibers, mainly PCHC-15H nanofibers, which presented the best bacterial reduction rates against Staphylococcus aureus (59.84 %), Pseudomonas aeruginosa (47.27 %), Escherichia coli (65.07 %), and Listeria monocytogenes (49.58 %). In vitro tests with cell cultures suggest that nanofibers were not cytotoxic and exhibited excellent biocompatibility with human fibroblasts (HFb) and keratinocytes (HaCaT), since all treatments showed higher or similar cell viability as opposed to the cell control. Based on the findings, PVA-chitosan-collagen-honey nanofibrous membranes have promise as an antibacterial dressing substitute.

Assuntos

Antibacterianos , Bandagens , Quitosana , Colágeno , Mel , Membranas Artificiais , Nanofibras , Cicatrização , Quitosana/química , Quitosana/farmacologia , Nanofibras/química , Bandagens/microbiologia , Colágeno/química , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Cicatrização/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Porosidade , Álcool de Polivinil/química , Fibroblastos/efeitos dos fármacos

RESUMO

Campylobacter jejuni is a major cause of global foodborne illnesses. To develop alternative antimicrobial strategies against C. jejuni, this study designed and optimized the green synthesis of metallic nanoparticles (NPs) with intracellular components of the medicinal fungus Ganoderma sessile to provide the needed reducing and stabilizing agents. NPs were characterized by transmission electron microscopy and dynamic light scattering, and the quasi-spherical NPs had sizes of 2.9 ± 0.9 nm for the copper oxide NPs and 14.7 ± 0.6 nm for the silver NPs. Surface charge assessment revealed zeta potentials of -21.0 ± 6.5 mV and -24.4 ± 7.9 mV for the copper oxide and silver NPs, respectively. The growth inhibition of C. jejuni by the NPs occurred through attachment to the outer cell membrane and subsequent intracellular internalization and resulted in minimum inhibitory concentrations of the silver NPs at 6 µg/mL and copper oxide NPs at 10 µg/mL. On the other hand, a differential ROS production caused by silver and copper NPs was observed. In summary, this research presents the first demonstration of using green synthesis with the medicinal fungus G. sessile to produce metallic NPs that effectively inhibit C. jejuni growth, providing a sustainable and effective approach to the traditional use of antimicrobials.

RESUMO

In this research, several analyses were carried out on concentrated fractions of Mexican oregano essential oil (Poliomintha longiflora Gray) in order to determine its ability to inhibit the growth and the motility of Escherichia coli (swimming), Pseudomonas aeruginosa (swimming), and Proteus vulgaris (swarming); these Gram-negative bacteria associated with urinary tract infections are motile due to the presence of flagella, which is considered an important virulence factor that favors their motility when trying to reach the target organ and cause an infection. Also, the resistance pattern to antibiotics of each strain was determined. The results showed resistance pattern (8 out of 12 antibiotics tested) for P. aureginosa, while E. coli and P. vulgaris were resistant to 4 antibiotics out of the 12 tested. On the other hand, fractionated oregano caused an inhibition of growth and a reduction in motility, varying between fractions and among bacteria. Fraction 4 showed major growth reduction, with MBC values ranging from 0.002 to 23.7 mg/mL. Treatment with fractionated oregano (F1, F2, F3, F4) reduced the motility by 92-81% for P. vulgaris, 90-83% for E. coli, and 100-8.9% for P. aeruginosa. These results demonstrated a higher performance with a lower application dose due to its high content of Carvacrol and Thymol; unlike other concentrated fractions, this synergy of oxygenated monoterpenes may cause greater antimicrobial activity.