RESUMEN
PURPOSE: To evaluate the antimicrobial effect of a new active oxygen fluid (Blue®m) as a root canal irrigant against Enterococcus faecalis compared to sodium hypochlorite (NaOCl). MATERIAL AND METHODS: Forty-five extracted single-canaled human teeth were selected, received root canal preparation, autoclaved, and contaminated with Enterococcus faecalis. The specimens were randomly allocated into three groups: Group (A) served as the negative control, receiving irrigation with saline (n = 15); Group (B) was irrigated with 5.25% NaOCl (n = 15); and Group (C) was irrigated with 10 mL of Blue®m (n = 15). Microbial sampling from the root canals was performed before and after irrigation. The difference between the pre-irrigation and post-irrigation colony-forming units (CFU/mL) was calculated. The data was analysed using a one-way ANOVA followed by post-hoc Tukey tests. The significance level was set at 5%. RESULTS: Blue®m statistically significantly reduced the bacterial load compared to saline (p = 0.009), but NaOCl was most effective, outperforming both (p 0.0001). CONCLUSION: Irrigation with Blue®m demonstrated antibacterial efficacy against Enterococcus faecalis, but it was not as effective as NaOCl.
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Cavidad Pulpar , Enterococcus faecalis , Irrigantes del Conducto Radicular , Hipoclorito de Sodio , Enterococcus faecalis/efectos de los fármacos , Humanos , Irrigantes del Conducto Radicular/farmacología , Hipoclorito de Sodio/farmacología , Cavidad Pulpar/microbiología , Carga Bacteriana/efectos de los fármacos , Preparación del Conducto Radicular/métodos , Ensayo de Materiales , Recuento de Colonia MicrobianaRESUMEN
Despite the high mortality rate, sepsis lacks specific and effective treatment options. Conventional antibiotics, such as TIENAM (TIE; imipenem and cilastatin sodium for injection), face challenges owing to the emergence of bacterial resistance, which reduces their effectiveness and causes adverse effects. Addressing resistance and judicious drug use is crucial. Our research revealed that aloin (Alo) significantly boosts survival rates and reduces inflammation and bacterial load in mice with sepsis, demonstrating strong antimicrobial activity. Using a synergistic Alo + TIE regimen in a cecal ligation and puncture (CLP)-induced sepsis model, we observed a remarkable increase in survival rates from 10 % to 75 % within 72 h compared with the CLP group alone. This combination therapy also modulated inflammatory markers interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α, mitigated tissue damage, regulated immune cells by lowering NK, activated CD8+ and CD4+ T cells while increasing peritoneal macrophages, and decreased the bacterial load in the peritoneal cavity. We noted a significant shift in the abdominal cavity microbiota composition post-treatment, with a decrease in harmful bacteria, such as Lachnospiraceae_NK4A136_group, Klebsiella, Bacillus, and Escherichia, and an increase in beneficial bacteria, such as Lactobacillus and Mucispirillum. Our study emphasizes the efficacy of combining Alo with TIE to combat sepsis, and paves the way for further investigations and potential clinical applications aiming to overcome the limitations of TIE and enhance the therapeutic prospects of Alo.
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Ciego , Emodina , Ratones Endogámicos C57BL , Sepsis , Animales , Sepsis/tratamiento farmacológico , Sepsis/inmunología , Sepsis/microbiología , Emodina/farmacología , Emodina/uso terapéutico , Emodina/análogos & derivados , Ciego/cirugía , Ciego/microbiología , Ratones , Masculino , Ligadura , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Punciones , Modelos Animales de Enfermedad , Imipenem/uso terapéutico , Imipenem/farmacología , Citocinas/metabolismo , Quimioterapia Combinada , Microbioma Gastrointestinal/efectos de los fármacos , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Microbiota/efectos de los fármacos , Carga Bacteriana/efectos de los fármacosRESUMEN
OBJECTIVES: The aim of this study was to quantitatively and comprehensively investigate the combined effects of arginine and fluoride on the suppression of pathogenicity using an in situ biofilm model and next-generation sequencing (NGS). METHODS: Using the in situ model, dental biofilms were formed and the viable bacterial counts and arginine activity in the arginine- and fluoride-containing dentifrice and control groups were measured. We also compared their effects on the bacterial microbiota and predictive functional factors in the control, arginine (arg), and arginine + fluoride (argF) groups using NGS analysis. RESULTS: Compared to the control treatment, the use of 8 % arginine and 1450 ppm fluoride toothpaste resulted in significantly high oral NH4+ concentrations without affecting the number of viable bacteria (P < 0.05). NGS analysis revealed that the oral microbiota of the control, arg, and argF groups were significantly different. Heat map analysis of the predicted functional factors revealed that the arg group had different properties from the other groups and activated specific substrate metabolic pathways; contrastingly, argF treatment inhibited the activity of these pathways and prevented an increase in the abundance of bacterial genera that utilize substrates such as sucrose, suggesting the synergistic effect of arginine and fluoride. CONCLUSIONS: This study indicates that the combination of arginine and fluoride has a synergistic effect on the bacterial microbiota and pathogenicity of dental biofilms compared with arginine alone. CLINICAL SIGNIFICANCE: Our findings suggest that the combination of arginine and fluoride could be used as an effective prebiotic and may inhibit the growth of bacteria associated with dental diseases.
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Arginina , Biopelículas , Cariostáticos , Fluoruros , Pastas de Dientes , Arginina/farmacología , Biopelículas/efectos de los fármacos , Humanos , Fluoruros/farmacología , Pastas de Dientes/farmacología , Cariostáticos/farmacología , Sinergismo Farmacológico , Dentífricos/farmacología , Carga Bacteriana/efectos de los fármacos , Bacterias/efectos de los fármacos , Bacterias/clasificación , Microbiota/efectos de los fármacos , Placa Dental/microbiología , Adulto , Masculino , Adulto Joven , Secuenciación de Nucleótidos de Alto Rendimiento , Saliva/microbiologíaRESUMEN
Staphylococcus aureus is a gram-positive bacteria, and its virulence factors can cause many kinds of infections, such as pneumonia, sepsis, enteritis and osteomyelitis. Traditional antibiotics can not only kill bacteria, but also easily lead to bacterial resistance. Jingfang Mixture (JFM) has the effects of inducing sweating and relieving the exterior, dispelling wind and eliminating dampness, and is commonly used in clinic to prevent and treat epidemic diseases and infectious diseases. The main purpose of this study is to explore the inhibitory effect of JFM on alpha-hemolysin (Hla) of S. aureus and to alleviate the damage caused by Hla. We found that JFM could inhibit the hemolytic activity, transcription level and neutralizing activity of Hla in a dose-dependent manner at the concentrations of 125, 250 and 500 µg/mL, without affecting the growth of bacteria. In addition, JFM reduced the damage of Hla to A549 cells and the release of lactate dehydrogenase (LDH). We also observed that in the S. aureus - induced pneumonia mouse model, JFM could significantly prolong the life of mice, reduce the bacterial load in the lungs, significantly improve the pathological state of the lungs and alleviate the damage caused by inflammatory factors, and the pathogenicity of gene deletion strain DU 1090 of S. aureus to pneumonia mice was also significantly reduced. In conclusion, this study proved that JFM is a potential drug against S. aureus infection, and this study provided a preliminary study for better guidance of clinical drug use.
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Antibacterianos , Proteínas Hemolisinas , Infecciones Estafilocócicas , Staphylococcus aureus , Animales , Femenino , Humanos , Ratones , Células A549 , Antibacterianos/farmacología , Carga Bacteriana/efectos de los fármacos , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Proteínas Hemolisinas/metabolismo , Hemólisis/efectos de los fármacos , Pulmón/microbiología , Pulmón/efectos de los fármacos , Ratones Endogámicos BALB C , Neumonía Estafilocócica/tratamiento farmacológico , Neumonía Estafilocócica/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/efectos de los fármacos , Factores de Virulencia/genéticaRESUMEN
BACKGROUND: There is insufficient clinical and microbiological evidence to support the use of diode laser and air-polishing with erythritol as supplements to scaling and root planning(SRP). The aim of the current study is to evaluate the clinical and microbiologic efficacy of erythritol subgingival air polishing and diode laser in treatment of periodontitis. METHODS: The study encompassed twenty-four individuals seeking periodontal therapy and diagnosed with stage I and stage II periodontitis. Eight patients simply underwent SRP. Eight more patients had SRP followed by erythritol subgingival air polishing, and eight patients had SRP followed by diode laser application. At baseline and six weeks, clinical periodontal parameters were measured, including Plaque Index (PI), Gingival Index (GI), periodontal Probing Depth (PPD), and Clinical Attachment Level (CAL). The bacterial count of Aggregatibacter actinomycetemcomitans(A.A), Porphyromonas gingivalis (P.G) was evaluated at different points of time. RESULTS: The microbiological assessment revealed significant differences in the count of A.A. between the laser and erythritol groups immediately after treatment, indicating a potential impact on microbial levels. However, the microbial levels showed fluctuations over the subsequent weeks, without statistically significant differences. Plaque indices significantly decreased post-treatment in all groups, with no significant inter-group differences. Gingival indices decreased, and the laser group showed lower values than erythritol and control groups. PPD and CAL decreased significantly across all groups, with the laser group exhibiting the lowest values. CONCLUSION: The supplementary use of diode laser and erythritol air polishing, alongside SRP, represents an expedited periodontal treatment modality. This approach leads to a reduction in bacteria and improvement in periodontal health. TRIAL REGISTRATION: This clinical trial was registered on Clinical Trials.gov (Registration ID: NCT06209554) and released on 08/01/2024.
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Aggregatibacter actinomycetemcomitans , Carga Bacteriana , Índice de Placa Dental , Raspado Dental , Eritritol , Láseres de Semiconductores , Índice Periodontal , Porphyromonas gingivalis , Aplanamiento de la Raíz , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aggregatibacter actinomycetemcomitans/aislamiento & purificación , Aggregatibacter actinomycetemcomitans/efectos de los fármacos , Abrasión Dental por Aire/métodos , Carga Bacteriana/efectos de los fármacos , Raspado Dental/métodos , Eritritol/uso terapéutico , Estudios de Seguimiento , Láseres de Semiconductores/uso terapéutico , Pérdida de la Inserción Periodontal/terapia , Pérdida de la Inserción Periodontal/microbiología , Bolsa Periodontal/terapia , Bolsa Periodontal/microbiología , Periodontitis/microbiología , Periodontitis/terapia , Periodontitis/tratamiento farmacológico , Porphyromonas gingivalis/aislamiento & purificación , Porphyromonas gingivalis/efectos de los fármacos , Aplanamiento de la Raíz/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Metformin (MET), by boosting immunity, has been suggested as a host-adjunctive therapy to anti-tuberculosis treatment (ATT). METHODS: We evaluated whether adding MET to the standard ATT can alter the host chemokine response. We investigated the influence of metformin on the plasma levels of a wide panel of chemokines in a group of active tuberculosis patients before treatment, at 2nd month of ATT and at 6-months of ATT as part of our clinical study to examine the effect of metformin on ATT. RESULTS: Our results demonstrated that addition of metformin resulted in diminished CC (CCL1 and CCL3) and CXC (CXCL-2 and CXCL-10) chemokines in MET arm as compared to non-MET arm at the 2nd month and 6th month of ATT. In addition to this, MET arm showed significantly diminished chemokines in individuals with high bacterial burden and cavitary disease. CONCLUSION: Our current data suggest that metformin alters chemokines responses that could potentially curb excessive inflammation during ATT.
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Antituberculosos , Quimiocina CXCL10 , Metformina , Metformina/uso terapéutico , Metformina/farmacología , Humanos , Antituberculosos/uso terapéutico , Femenino , Masculino , Adulto , Quimiocina CXCL10/sangre , Quimiocinas/sangre , Resultado del Tratamiento , Adulto Joven , Factores de Tiempo , Mycobacterium tuberculosis/efectos de los fármacos , Quimiocina CCL1/sangre , Quimiocina CCL3/sangre , Persona de Mediana Edad , Quimioterapia Combinada , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/inmunología , Carga Bacteriana/efectos de los fármacos , Tuberculosis/tratamiento farmacológico , Tuberculosis/sangre , Tuberculosis/inmunologíaRESUMEN
BACKGROUND: Ensuring the safety of dental unit waterlines (DUWLs) has become a pivotal issue in dental care practices, focusing on the health implications for both patients and healthcare providers. The inherent structure and usage conditions of DUWLs contribute to the risk of biofilm formation and bacterial growth, highlighting the need for effective disinfection solutions.The quest for a disinfection method that is both safe for clinical use and effective against pathogens such as Staphylococcus aureus and Escherichia coli in DUWLs underscores the urgency of this research. MATERIALS: Chlorine dioxide disinfectants at concentrations of 5, 20, and 80 mg/L were used to treat biofilms of S. aureus and E. coli cultured in DUWLs. The disinfection effectiveness was assessed through bacterial counts and culturing. Simultaneously, human skin fibroblast cells were treated with the disinfectant to observe changes in cell morphology and cytotoxicity. Additionally, the study included corrosion tests on various metals (carbon steel, brass, stainless steel, aluminum, etc.). RESULTS: Experimental results showed that chlorine dioxide disinfectants at concentrations of 20 mg/L and 80 mg/L significantly reduced the bacterial count of S. aureus and E. coli, indicating effective disinfection. In terms of cytotoxicity, higher concentrations were more harmful to cellular safety, but even at 80 mg/L, the cytotoxicity of chlorine dioxide remained within controllable limits. Corrosion tests revealed that chlorine dioxide disinfectants had a certain corrosive effect on carbon steel and brass, and the degree of corrosion increased with the concentration of the disinfectant. CONCLUSION: After thorough research, we recommend using chlorine dioxide disinfectant at a concentration of 20 mg/L for significantly reducing bacterial biofilms in dental unit waterlines (DUWLs). This concentration also ensures satisfactory cell safety and metal corrosion resistance.
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Biopelículas , Compuestos de Cloro , Equipo Dental , Desinfección , Escherichia coli , Óxidos , Staphylococcus aureus , Compuestos de Cloro/farmacología , Óxidos/farmacología , Biopelículas/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Humanos , Staphylococcus aureus/efectos de los fármacos , Desinfección/métodos , Equipo Dental/microbiología , Desinfectantes/farmacología , Desinfectantes Dentales/farmacología , Fibroblastos/efectos de los fármacos , Carga Bacteriana/efectos de los fármacos , Técnicas In VitroRESUMEN
BACKGROUND: Continuous infusion of meropenem has been proposed to increase target attainment in critically ill patients, although stability might limit its practical use. This study investigated the impact of meropenem degradation and infusion bag changes on the concentration-time profiles and bacterial growth and killing of P. aeruginosa given different continuous-infusion solutions. METHODS: A semi-mechanistic pharmacokinetic-pharmacodynamic (PK-PD) model quantifying meropenem concentrations (CMEM) and bacterial counts of a resistant P. aeruginosa strain (ARU552, MIC = 16 mg/L) over 24 h was used to translate in vitro antibiotic effects to patients with severe infections. Concentration-dependent drug degradation of saline infusion solutions was considered using an additional compartment in the population PK model. CMEM, fT>MIC (time that concentrations exceed the MIC) and total bacterial load (BTOT) after 24 h were simulated for different scenarios (n = 144), considering low- and high-dose regimens (3000/6000 mg/day±loading dose), clinically relevant infusion solutions (20/40/50 mg/mL), different intervals of infusion bag changes (every 8/24 h, q8/24 h), and varied renal function (creatinine clearance 40/80/120 mL/min) and MIC values (8/16 mg/L). RESULTS: Highest deviations between changing infusion bags q8h and q24h were observed for 50 mg/mL solutions and scenarios with CMEM_24h close to the MIC, with differences (Δ) in CMEM_24h up to 4.9 mg/L, ΔfT>MIC≤65.7%, and ΔBTOT_24h≤1.1 log10 CFU/mL, thus affecting conclusions on whether bacteriostasis was reached. CONCLUSIONS: In summary, this study indicated that for continuous infusion of meropenem, eight-hourly infusion bag changes improved PK/PD target attainment and might be beneficial particularly for high meropenem concentrations of saline infusion solutions and for plasma concentrations in close proximity to the MIC.
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Antibacterianos , Meropenem , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa , Meropenem/farmacocinética , Meropenem/farmacología , Meropenem/administración & dosificación , Pseudomonas aeruginosa/efectos de los fármacos , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Humanos , Infusiones Intravenosas , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Carga Bacteriana/efectos de los fármacos , Viabilidad Microbiana/efectos de los fármacos , Estabilidad de MedicamentosRESUMEN
The widespread dissemination of bacterial resistance has led to great attention being paid to finding substitutes for traditionally used antibiotics. Plants are rich in various phytochemicals that could be used as antibacterial therapies. Here, we elucidate the phytochemical profile of Euphorbia canariensis ethanol extract (EMEE) and then elucidate the antibacterial potential of ECEE against Pseudomonas aeruginosa clinical isolates. ECEE showed minimum inhibitory concentrations ranging from 128 to 512 µg/mL. The impact of ECEE on the biofilm-forming ability of the tested isolates was elucidated using crystal violet assay and qRT-PCR to study its effect on the gene expression level. ECEE exhibited antibiofilm potential, which resulted in a downregulation of the expression of the biofilm genes (algD, pelF, and pslD) in 39.13% of the tested isolates. The antibacterial potential of ECEE was studied in vivo using a lung infection model in mice. A remarkable improvement was observed in the ECEE-treated group, as revealed by the histological and immunohistochemical studies. Also, ELISA showed a noticeable decrease in the oxidative stress markers (nitric oxide and malondialdehyde). The gene expression of the proinflammatory marker (interleukin-6) was downregulated, while the anti-inflammatory biomarker was upregulated (interleukin-10). Thus, clinical trials should be performed soon to explore the potential antibacterial activity of ECEE, which could help in our battle against resistant pathogenic bacteria.
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Antibacterianos , Euphorbia , Extractos Vegetales , Pseudomonas aeruginosa , Infecciones del Sistema Respiratorio , Pseudomonas aeruginosa/efectos de los fármacos , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Euphorbia/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Animales , Ratones , Estrés Oxidativo/efectos de los fármacos , Carga Bacteriana/efectos de los fármacos , Regulación Bacteriana de la Expresión Génica/efectos de los fármacosRESUMEN
Aims: Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. Methods: A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 105 colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. Results: The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log10 (95%) and 1.5-log10 (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 103 vs 7.0 × 104; p = 0.022; 3.6 × 103 vs 1.0 × 105; p = 0.007, respectively) at POD 21. There was a significant 1.6-log10 (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 100 vs 4.7 × 101, respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. Conclusion: In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections.
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Antibacterianos , Sulfato de Calcio , Modelos Animales de Enfermedad , Infecciones Relacionadas con Prótesis , Infecciones Estafilocócicas , Vancomicina , Animales , Infecciones Relacionadas con Prótesis/prevención & control , Infecciones Relacionadas con Prótesis/microbiología , Ratones , Vancomicina/administración & dosificación , Antibacterianos/administración & dosificación , Infecciones Estafilocócicas/prevención & control , Carga Bacteriana/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Distribución Aleatoria , Prótesis de la Rodilla/efectos adversos , FemeninoRESUMEN
BACKGROUND: Translational microbiome research using next-generation DNA sequencing is challenging due to the semi-qualitative nature of relative abundance data. A novel method for quantitative analysis was applied in this 12-week clinical trial to understand the mechanical vs. chemotherapeutic actions of brushing, flossing, and mouthrinsing against the supragingival dental plaque microbiome. Enumeration of viable bacteria using vPCR was also applied on supragingival plaque for validation and on subgingival plaque to evaluate interventional effects below the gingival margin. METHODS: Subjects with gingivitis were enrolled in a single center, examiner-blind, virtually supervised, parallel group controlled clinical trial. Subjects with gingivitis were randomized into brushing only (B); brushing and flossing (BF); brushing and rinsing with Listerine® Cool Mint® Antiseptic (BA); brushing and rinsing with Listerine® Cool Mint® Zero (BZ); or brushing, flossing, and rinsing with Listerine® Cool Mint® Zero (BFZ). All subjects brushed twice daily for 1 min with a sodium monofluorophosphate toothpaste and a soft-bristled toothbrush. Subjects who flossed used unflavored waxed dental floss once daily. Subjects assigned to mouthrinses rinsed twice daily. Plaque specimens were collected at the baseline visit and after 4 and 12 weeks of intervention. Bacterial cell number quantification was achieved by adding reference amounts of DNA controls to plaque samples prior to DNA extraction, followed by shallow shotgun metagenome sequencing. RESULTS: 286 subjects completed the trial. The metagenomic data for supragingival plaque showed significant reductions in Shannon-Weaver diversity, species richness, and total and categorical bacterial abundances (commensal, gingivitis, and malodor) after 4 and 12 weeks for the BA, BZ, and BFZ groups compared to the B group, while no significant differences were observed between the B and BF groups. Supragingival plaque vPCR further validated these results, and subgingival plaque vPCR demonstrated significant efficacy for the BFZ intervention only. CONCLUSIONS: This publication reports on a successful application of a quantitative method of microbiome analysis in a clinical trial demonstrating the sustained and superior efficacy of essential oil mouthrinses at controlling dental plaque compared to mechanical methods. The quantitative microbiological data in this trial also reinforce the safety and mechanism of action of EO mouthrinses against plaque microbial ecology and highlights the importance of elevating EO mouthrinsing as an integral part of an oral hygiene regimen. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov on 31/10/2022. The registration number is NCT05600231.
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Dispositivos para el Autocuidado Bucal , Placa Dental , Gingivitis , Microbiota , Antisépticos Bucales , Cepillado Dental , Humanos , Placa Dental/microbiología , Gingivitis/microbiología , Antisépticos Bucales/uso terapéutico , Femenino , Microbiota/efectos de los fármacos , Adulto , Cepillado Dental/métodos , Masculino , Método Simple Ciego , Persona de Mediana Edad , Salicilatos/uso terapéutico , Combinación de Medicamentos , Terpenos/uso terapéutico , Terpenos/farmacología , Carga Bacteriana/efectos de los fármacos , Antiinfecciosos Locales/uso terapéutico , Adulto JovenRESUMEN
AIM: To study the clinical, radiographic and microbiological outcomes after surgical treatment of peri-implantitis, with or without adjunctive systemic antibiotics. MATERIALS AND METHODS: Eighty-four patients (113 implants) with peri-implantitis were randomized into three groups (A, amoxicillin and metronidazole; B, phenoxymethylpenicillin and metronidazole; or C, placebo). Treatment included resective surgery and implant surface decontamination with adjunctive antibiotics or placebo. Primary outcomes were probing pocket depth (PPD) reduction and marginal bone level (MBL) stability. Secondary outcomes were treatment success (defined as PPD ≤ 5 mm, bleeding on probing [BOP] ≤ 1site, absence of suppuration on probing [SOP] and absence of progressive bone loss of >0.5 mm), changes in BOP/SOP, mucosal recession (REC), clinical attachment level (CAL), bacterial levels and adverse events. Outcomes were evaluated for up to 12 months. The impact of potential prognostic indicators on treatment success was evaluated using multilevel logistic regression analysis. RESULTS: A total of 76 patients (104 implants) completed the study. All groups showed clinical and radiological improvements over time. Statistically significant differences were observed between groups for MBL stability (A = 97%, B = 89%, C = 76%), treatment success (A = 68%, B = 66%, C = 28%) and bacterial levels of Aggregatibacter actinomycetemcomitans and Tannerella forsythia, favouring antibiotics compared to placebo. Multiple regression identified antibiotic use as potential prognostic indicator for treatment success. Gastrointestinal disorders were the most reported adverse events in the antibiotic groups. CONCLUSIONS: Adjunctive systemic antibiotics resulted in additional improvements in MBL stability. However, the potential clinical benefits of antibiotics need to be carefully balanced against the risk of adverse events and possible antibiotic resistance.
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Amoxicilina , Antibacterianos , Metronidazol , Periimplantitis , Humanos , Periimplantitis/tratamiento farmacológico , Periimplantitis/microbiología , Periimplantitis/cirugía , Femenino , Masculino , Metronidazol/uso terapéutico , Metronidazol/administración & dosificación , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Persona de Mediana Edad , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Resultado del Tratamiento , Anciano , Pérdida de Hueso Alveolar/cirugía , Pérdida de Hueso Alveolar/tratamiento farmacológico , Bolsa Periodontal/cirugía , Bolsa Periodontal/tratamiento farmacológico , Bolsa Periodontal/microbiología , Placebos , Estudios de Seguimiento , Pérdida de la Inserción Periodontal/cirugía , Pérdida de la Inserción Periodontal/tratamiento farmacológico , Recesión Gingival/cirugía , Recesión Gingival/tratamiento farmacológico , Adulto , Método Doble Ciego , Carga Bacteriana/efectos de los fármacosRESUMEN
PURPOSE: To investigate the microbiological outcomes obtained with either subgingival debridement (SD) in conjunction with a gel containing sodium hypochlorite and amino acids followed by subsequent application of a cross-linked hyaluronic acid gel (xHyA) gel, or with SD alone. MATERIALS AND METHODS: Forty-eight patients diagnosed with stages II-III (grades A/B) generalised periodontitis were randomly treated with either SD (control) or SD plus adjunctive sodium hypochlorite/amino acids and xHyA gel (test). Subgingival plaque samples were collected from the deepest site per quadrant in each patient at baseline and after 3 and 6 months. Pooled sample analysis was performed using a multiplex polymerase chain reaction (PCR)-based method for the identification of detection frequencies and changes in numbers of the following bacteria: Aggregatibacter actinomycetemcomitans (A.a), Porphyromonas gingivalis (P.g), Tannerella forsythia (T.f), Treponema denticola (T.d), and Prevotella intermedia (P.i). RESULTS: In terms of detection frequency, in the test group, statistically significant reductions were found for P.g, T.f, T.d and P.i (p < 0.05) after 6 months. In the control group, the detection frequencies of all investigated bacterial species at 6 months were comparable to the baseline values (p > 0.05). The comparison of the test and control groups revealed statistically significant differences in detection frequency for P.g (p = 0.034), T.d (p < 0.01) and P.i (p = 0.02) after 6 months, favouring the test group. Regarding reduction in detection frequency scores, at 6 months, statistically significant differences in favour of the test group were observed for all investigated bacterial species: A.a (p = 0.028), P.g (p = 0.028), T.f (p = 0.004), T.d (p <0.001), and P.i (p = 0.003). CONCLUSIONS: The present microbiological results, which are related to short-term outcomes up to 6 months post-treatment, support the adjunctive subgingival application of sodium hypochlorite/amino acids and xHyA to subgingival debridement in the treatment of periodontitis.
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Aggregatibacter actinomycetemcomitans , Aminoácidos , Placa Dental , Ácido Hialurónico , Porphyromonas gingivalis , Prevotella intermedia , Hipoclorito de Sodio , Tannerella forsythia , Treponema denticola , Humanos , Ácido Hialurónico/uso terapéutico , Hipoclorito de Sodio/uso terapéutico , Aggregatibacter actinomycetemcomitans/efectos de los fármacos , Aggregatibacter actinomycetemcomitans/aislamiento & purificación , Porphyromonas gingivalis/efectos de los fármacos , Femenino , Persona de Mediana Edad , Masculino , Prevotella intermedia/efectos de los fármacos , Tannerella forsythia/efectos de los fármacos , Treponema denticola/efectos de los fármacos , Adulto , Placa Dental/microbiología , Aminoácidos/uso terapéutico , Desbridamiento Periodontal/métodos , Carga Bacteriana/efectos de los fármacos , Geles , Terapia Combinada , Estudios de Seguimiento , Reactivos de Enlaces Cruzados/uso terapéutico , Bolsa Periodontal/microbiología , Bolsa Periodontal/terapia , Periodontitis/microbiología , Periodontitis/terapia , Periodontitis/tratamiento farmacológicoRESUMEN
The increasing prevalence of multidrug-resistant Pseudomonas aeruginosa (PA) is a significant concern for chronic respiratory disease exacerbations. Host-directed drugs, such as flagellin, an agonist of toll-like receptor 5 (TLR5), have emerged as a promising solution. In this study, we evaluated the prophylactic intranasal administration of flagellin against a multidrug-resistant strain of PA (PAMDR) in mice and assessed the possible synergy with the antibiotic gentamicin (GNT). The results indicated that flagellin treatment before infection decreased bacterial load in the lungs, likely due to an increase in neutrophil recruitment, and reduced signs of inflammation, including proinflammatory cytokines. The combination of flagellin and GNT showed a synergistic effect, decreasing even more the bacterial load and increasing mice survival rates, in comparison to mice pre-treated only with flagellin. These findings suggest that preventive nasal administration of flagellin could restore the effect of GNT against MDR strains of PA, paving the way for the use of flagellin in vulnerable patients with chronic respiratory diseases.
Asunto(s)
Administración Intranasal , Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Flagelina , Gentamicinas , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Pseudomonas aeruginosa/efectos de los fármacos , Gentamicinas/farmacología , Animales , Flagelina/farmacología , Ratones , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Antibacterianos/farmacología , Femenino , Pulmón/microbiología , Pulmón/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Receptor Toll-Like 5/agonistas , Carga Bacteriana/efectos de los fármacos , Sinergismo FarmacológicoRESUMEN
The gut microbiome has major roles in modulating host physiology. One such function is colonization resistance, or the ability of the microbial collective to protect the host against enteric pathogens1-3, including enterohaemorrhagic Escherichia coli (EHEC) serotype O157:H7, an attaching and effacing (AE) food-borne pathogen that causes severe gastroenteritis, enterocolitis, bloody diarrhea and acute renal failure4,5 (haemolytic uremic syndrome). Although gut microorganisms can provide colonization resistance by outcompeting some pathogens or modulating host defence provided by the gut barrier and intestinal immune cells6,7, this phenomenon remains poorly understood. Here, we show that activation of the neurotransmitter receptor dopamine receptor D2 (DRD2) in the intestinal epithelium by gut microbial metabolites produced upon dietary supplementation with the essential amino acid L-tryptophan protects the host against Citrobacter rodentium, a mouse AE pathogen that is widely used as a model for EHEC infection8,9. We further find that DRD2 activation by these tryptophan-derived metabolites decreases expression of a host actin regulatory protein involved in C. rodentium and EHEC attachment to the gut epithelium via formation of actin pedestals. Our results reveal a noncanonical colonization resistance pathway against AE pathogens that features an unconventional role for DRD2 outside the nervous system in controlling actin cytoskeletal organization in the gut epithelium. Our findings may inspire prophylactic and therapeutic approaches targeting DRD2 with dietary or pharmacological interventions to improve gut health and treat gastrointestinal infections, which afflict millions globally.
Asunto(s)
Citrobacter rodentium , Mucosa Intestinal , Receptores de Dopamina D2 , Triptófano , Animales , Femenino , Humanos , Masculino , Ratones , Citoesqueleto de Actina/efectos de los fármacos , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Carga Bacteriana/efectos de los fármacos , Citrobacter rodentium/crecimiento & desarrollo , Citrobacter rodentium/metabolismo , Citrobacter rodentium/patogenicidad , Suplementos Dietéticos , Modelos Animales de Enfermedad , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/prevención & control , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/prevención & control , Escherichia coli O157/patogenicidad , Escherichia coli O157/fisiología , Mucosa Intestinal/citología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Receptores de Dopamina D2/metabolismo , Triptófano/administración & dosificación , Triptófano/metabolismo , Triptófano/farmacologíaRESUMEN
Burn wound healing can be significantly delayed by infection leading to increased morbidity and hypertrophic scarring. An optimal antimicrobial agent would have the ability to kill bacteria without negatively affecting the host skin cells that are required for healing. Currently available products provide antimicrobial coverage, but may also cause reductions in cell proliferation and migration. Cold atmospheric plasma is a partially ionized gas that can be produced under atmospheric pressure at room temperature. In this study a novel handheld Aceso Plasma Generator was used to produce and test Aceso Cold Plasma (ACP) in vitro and in vivo. ACP showed a potent ability to eliminate bacterial load in vitro for a number of different species. Deep partial-thickness and full-thickness wounds that were treated with ACP after burning, after excision, after autografting, and at days 5, 7, and 9 did not show any negative effects on their wound healing trajectories. On par with in vitro analysis, bioburden was decreased in treated wounds vs. control. In addition, metrics of hypertrophic scar such as dyschromia, elasticity, trans-epidermal water loss (TEWL), and epidermal and dermal thickness were the same between the two treatment groups.It is likely that ACP can be used to mitigate the risk of bacterial infection during the phase of acute burn injury while patients await surgery for definitive closure. It may also be useful in treating wounds with delayed re-epithelialization that are at risk for infection and hypertrophic scarring. A handheld cold plasma device will be useful in treating all manner of wounds and surgical sites in order to decrease bacterial burden in an efficient and highly effective manner without compromising wound healing.
Asunto(s)
Quemaduras , Gases em Plasma , Cicatrización de Heridas , Gases em Plasma/uso terapéutico , Gases em Plasma/farmacología , Quemaduras/microbiología , Quemaduras/terapia , Cicatrización de Heridas/efectos de los fármacos , Animales , Infección de Heridas/microbiología , Carga Bacteriana/efectos de los fármacos , Masculino , Cicatriz Hipertrófica/etiología , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Humanos , Trasplante de Piel/métodos , Piel/microbiología , Piel/lesionesRESUMEN
The high prevalence of multidrug-resistant Acinetobacter baumannii has emerged as a serious problem in the treatment of nosocomial infections in the past three decades. Recently, we developed a new small-molecule inhibitor belonging to a class of 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones, Fluorothiazinon (FT, previously called CL-55). FT effectively suppressed the T3SS of Chlamydia spp., Pseudomonas aeruginosa, and Salmonella sp. without affecting bacterial growth in vitro. In this study, we describe that prophylactic use of FT for 4 days prior to challenge with resistant clinical isolates of A. baumannii (ABT-897-17 and 52TS19) suppressed septic infection in mice, resulting in improved survival, limited bacteraemia and decreased bacterial load in the organs of the mice. We show that FT had an inhibitory effect on A. baumannii biofilm formation in vitro and, to a greater extent, on biofilm maturation. In addition, FT inhibited Acinetobacter isolate-induced death of HeLa cells, which morphologically manifested as apoptosis. The mechanism of FT action on A. baumannii is currently being studied. FT may be a promising candidate for the development of a broad-spectrum anti-virulence drug to use in the prevention of nosocomial infections.
Asunto(s)
Infecciones por Acinetobacter/tratamiento farmacológico , Acinetobacter baumannii/efectos de los fármacos , Anilidas/farmacología , Antibacterianos/farmacología , Sepsis/tratamiento farmacológico , Tiadiazinas/farmacología , Animales , Carga Bacteriana/efectos de los fármacos , Biopelículas/efectos de los fármacos , Línea Celular Tumoral , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Femenino , Células HeLa , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos DBA , Pruebas de Sensibilidad Microbiana/métodos , Sepsis/metabolismo , Sepsis/microbiología , Virulencia/efectos de los fármacosRESUMEN
Obesity impairs host defense against Klebsiella pneumoniae, but responsible mechanisms are incompletely understood. To determine the impact of diet-induced obesity on pulmonary host defense against K. pneumoniae, we fed 6-wk-old male C57BL/6j mice a normal diet (ND) or high-fat diet (HFD) (13% vs. 60% fat, respectively) for 16 wk. Mice were intratracheally infected with Klebsiella, assayed at 24 or 48 h for bacterial colony-forming units, lung cytokines, and leukocytes from alveolar spaces, lung parenchyma, and gonadal adipose tissue were assessed using flow cytometry. Neutrophils from uninfected mice were cultured with and without 2-deoxy-d-glucose (2-DG) and assessed for phagocytosis, killing, reactive oxygen intermediates (ROI), transport of 2-DG, and glucose transporter (GLUT1-4) transcripts, and protein expression of GLUT1 and GLUT3. HFD mice had higher lung and splenic bacterial burdens. In HFD mice, baseline lung homogenate concentrations of IL-1ß, IL-6, IL-17, IFN-γ, CXCL2, and TNF-α were reduced relative to ND mice, but following infection were greater for IL-6, CCL2, CXCL2, and IL-1ß (24 h only). Despite equivalent lung homogenate leukocytes, HFD mice had fewer intraalveolar neutrophils. HFD neutrophils exhibited decreased Klebsiella phagocytosis and killing and reduced ROI to heat-killed Klebsiella in vitro. 2-DG transport was lower in HFD neutrophils, with reduced GLUT1 and GLUT3 transcripts and protein (GLUT3 only). Blocking glycolysis with 2-DG impaired bacterial killing and ROI production in neutrophils from mice fed ND but not HFD. Diet-induced obesity impairs pulmonary Klebsiella clearance and augments blood dissemination by reducing neutrophil killing and ROI due to impaired glucose transport.
Asunto(s)
Dieta , Glucosa/metabolismo , Interacciones Huésped-Patógeno , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/fisiología , Neutrófilos/metabolismo , Obesidad/microbiología , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Adiposidad/efectos de los fármacos , Animales , Carga Bacteriana/efectos de los fármacos , Transporte Biológico/efectos de los fármacos , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Médula Ósea/patología , Líquido del Lavado Bronquioalveolar/citología , Citocinas/metabolismo , Desoxiglucosa/farmacología , Dieta Alta en Grasa , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 3/genética , Transportador de Glucosa de Tipo 3/metabolismo , Glucólisis/efectos de los fármacos , Interacciones Huésped-Patógeno/efectos de los fármacos , Infecciones por Klebsiella/sangre , Infecciones por Klebsiella/complicaciones , Klebsiella pneumoniae/efectos de los fármacos , Recuento de Leucocitos , Pulmón/microbiología , Pulmón/patología , Masculino , Ratones Endogámicos C57BL , Neutrófilos/efectos de los fármacos , Obesidad/sangre , Obesidad/complicaciones , Fagocitosis/efectos de los fármacos , Neumonía/microbiología , Neumonía/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Bazo/microbiologíaRESUMEN
To investigate the antimicrobial activity of a preservative-free 0.6% povidone-iodine eye drop as an antiseptic procedure in decreasing the conjunctival bacterial load in eyes scheduled for intravitreal treatment and to compare its efficacy to the untreated fellow eye used as the control group. Prospective cohort analysis in which 208 patients received preservative-free 0.6% povidone-iodine eye drops three times a day for three days before intravitreal injection. Before and after the prophylactic treatment, a conjunctival swab was collected from both the study eye and the untreated contralateral eye, used as control. The swab was inoculated on different culture media and the colony-forming units were counted. Bacteria and fungi were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Treatment with 0.6% povidone-iodine eye drops significantly reduced the conjunctival bacterial load from baseline (p < 0.001 for blood agar and p < 0.001 for chocolate agar) with an eradication rate of 80%. The most commonly isolated pathogen at each time-point and in both groups was coagulase-negative Staphylococci, isolated in 84% of the positive cultures. The study provides evidence about the effectiveness of 0.6% povidone-iodine eye drops treatment in reducing the conjunctival bacterial load in eyes scheduled for intravitreal treatment.
Asunto(s)
Antiinfecciosos , Profilaxis Antibiótica/métodos , Carga Bacteriana/efectos de los fármacos , Conjuntiva/microbiología , Soluciones Oftálmicas/administración & dosificación , Soluciones Oftálmicas/farmacología , Povidona Yodada/administración & dosificación , Povidona Yodada/farmacología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Peritoneal catheter-associated biofilm infection is reported to be the main cause of refractory peritonitis in peritoneal dialysis patients. The application of antimicrobial lock therapy, based on results on central venous catheters, may be a promising option for treatment of biofilm-harboring peritoneal catheters. This study investigated the effects of two lock solutions, EDTA and taurolidine, on an in vitro model of Pseudomonas aeruginosa biofilm-related peritoneal catheter infection. Silicone peritoneal catheters were incubated for 24 h with a bioluminescent strain of P. aeruginosa. Then, serial dilutions of taurolidine and/or EDTA were applied (for 24 h) once or twice onto the contaminated catheters, and P. aeruginosa viability/persistence were evaluated in real time up to 120 h using a Fluoroskan reader. On selected supernatants, high-performance liquid chromatography mass spectrometry (HPLC-MS) analysis was performed to measure the production of autoinducers (AI), phenazines, and pyocyianines. Taurolidine alone or in combination with EDTA caused a significant decrease of bacterial load and biofilm persistence on the contaminated catheters. The treatment did not lead to the sterilization of the devices, yet it resulted in a substantial destructuration of the catheter-associated P. aeruginosa biofilm. HPLC-MS analysis showed that the treatment of biofilm-harboring catheters with taurolidine and EDTA also affected the secretory activity of the pathogen. EDTA and taurolidine affect P. aeruginosa biofilm produced on peritoneal catheters and profoundly compromise the microbial secretory profile. Future studies are needed to establish whether such lock solutions can be used to render peritoneal catheter-related infections more susceptible to antibiotic treatment. IMPORTANCE An in vitro model allows studies on the mechanisms by which the lock solutions exert their antimicrobial effects on catheter-associated biofilm, thus providing a better understanding of the management of devise-associated infections.