The Effects of Antimicrobial Mouthwashes on Systemic Disease: What Is the Evidence?

The potential association between antimicrobial mouthwash use and systemic health has gained attention in recent years with reports highlighting how some common systemic conditions are influenced by the use of different types of mouthwashes. In this context, links between mouthwash use and cardiovascular disease, diabetes mellitus, oral cancer, Alzheimer's disease, and preeclampsia have been proposed, albeit with limited levels of evidence. Chlorhexidine mouthwash in particular has been the most widely studied agent while available data on other types of over-the-counter mouthwashes are generally scarce. Furthermore, there is currently no evidence-based recommendations on the appropriate use of mouthwashes during pregnancy. This article will present the current evidence on the association between mouthwash use and the aforementioned conditions with emphasis on the mechanisms that may underlie such an association.

Microorganismos aislados de hemocultivos en niños con leucemia y linforma: Seis años de seguimiento / Microorganisms isolated from blood cultures in children with leukemia and lymphoma: six years of follow-up

Las Leucemias y linfomas constituyen las enfermedades oncológicas más frecuentes en pediatría y las bacteriemias representan infecciones graves en estos pacientes. Objetivos: describir los microorganismos aislados de sangre en pacientes con leucemia aguda o linfoma pediátrico; comparar la incidencia de aislamientos según enfermedad de base; detallar las variaciones en la incidencia de dichos aislamientos y la evolución de su resistencia antimicrobiana. Estudio retrospectivo, observacional. Se incluyeron 823 episodios de bacteriemia en 467 pacientes pediátricos, entre julio-2016 y junio-2022, dividido en tres períodos (período-1: años 2016- 2018, período-2: años 2018-2020, período-3: años 2020-2022). Se aislaron 880 microorganismos: 55,3% gram negativos (GN), 40% gram positivos (GP) y 4,7% levaduras. En GN predominaron: enterobacterias (72%) y en GP: estreptococos del grupo viridans (SGV) (34,1%). Se encontró asociación entre LLA-enterobacterias (p=0,009) y LMA-SGV (p<0,001). Hubo aumento de GN entre los períodos 1 y 3 (p=0,02) y 2 y 3 (p=0,002) y disminución de GP entre 2 y 3 (p=0,01). Se registraron los siguientes mecanismos de resistencia: BLEE (16,4%), carbapenemasas: KPC (2,5%); MBL (2,7%) y OXA (0,2%); meticilinorresistencia en Staphylococcus aureus (20%) y estafilococos coagulasa negativos (95%), vancomicina resistencia en Enterococcus spp. (39%), SGV no sensibles a penicilina (44%) y a cefotaxima (13%). Hubo aumento de MBL entre los períodos 1 y 2 (p=0,02) y una tendencia en disminución de sensibilidad a penicilina en SGV entre el 1 y 3 (p=0,058). El conocimiento dinámico y análisis de estos datos es esencial para generar estadísticas a nivel local, fundamentales para el diseño de guías de tratamientos empíricos (AU)

Leukemias and lymphomas are the most common cancers in children and bacteremia is a severe infection in these patients. Objectives: to describe the microorganisms isolated from blood in pediatric patients with acute leukemia or lymphoma; to compare the incidence of isolates according to the underlying disease; and to detail the variations in the incidence of these isolates and the evolution of their antimicrobial resistance. Retrospective, observational study. We included 823 episodes of bacteremia in 467 pediatric patients seen between July-2016 and June-2022, divided into three periods (period-1: 2016- 2018, period-2: 2018-2020, period-3: 2020-2022). A total of 880 microorganisms were isolated: 55.3% were gram-negative (GN), 40% gram-positive (GP) and 4.7% yeasts. In GN there was a predominance of: enterobacteria (72%) and in GP viridans group streptococci (VGS) (34.1%). An association was found between ALL-enterobacteria (p=0.009) and AML-VGS (p<0.001). There was an increase in GN between periods 1 and 3 (p=0.02) and 2 and 3 (p=0.002) and a decrease in GP between 2 and 3 (p=0.01). The following resistance mechanisms were recorded: BLEE (16.4%), carbapenemases: KPC (2.5%), MBL (2.7%), and OXA (0.2%); methicillin resistance in Staphylococcus aureus (20%) and coagulase negative staphylococci (95%), vancomycin resistance in Enterococcus spp. (39%), VGS resistant to penicillin (44%) and to cefotaxime (13%). There was an increase in MBL between periods 1 and 2 (p=0.02) and a decreasing trend in penicillin sensitivity in VGS between periods 1 and 3 (p=0.058). Dynamic knowledge and analysis of these data is essential to generate statistics at the local level, which is fundamental for the design of empirical treatment guidelines (AU)

Safety and feasibility of outpatient parenteral antimicrobial therapy for patients with spinal infection.

Outpatient parenteral antimicrobial therapy (OPAT) is a cost-effective method of administering intravenous antimicrobial therapy. Although OPAT is well established in the UK and US healthcare systems, few centres in Europe perform it. Here we analysed OPAT for the treatment of patients with spinal infections at our institution. In this retrospective study, patients with spinal infection who required intravenous (i.v.) antimicrobial treatment between 2018 and 2021 were analysed. The duration of short-term antimicrobial treatment for skin and soft tissue infections and complex infections requiring long-term antimicrobial treatment, such as spinal bone or joint infections, were analysed. All patients were discharged with a peripherally inserted central catheter (PICC) line. Prior to discharge, all patients received training in the safe administration of their medications via the PICC line. The duration of OPAT and the rate of readmission after OPAT were analysed. For this study a total of 52 patients who were treated via OPAT due to spinal infections were analyzed. In 35 cases (69.2%) complex spinal infection was reason for i.v. antimicrobial therapy. Surgery was required in 23 of these 35 patients (65.7%). The average hospital stay for these patients was 12 ± 6 days. The remaining 17 patients were treated for an infection of the soft tissue or the skin and hospital stay for these patients was on average 8 ± 4 days. Gram-positive organisms were isolated in 64.4%. Staphylococcus aureus followed by other Staphylococcus species, was the most common detected organism. After discharging i.v. antimicrobial treatment was given for an average of 20 ± 14 days. The duration of antimicrobial treatment for soft tissue was 10.8 ± 8 days, and for complex infections 25.1 ± 18 days. The mean follow-up was 21 ± 14 months. There was one case of readmission due to treatment failure. There were no difficulties encountered in implementing OPAT. OPAT is a feasible and effective option for delivering intravenous antimicrobial therapy to patients with spinal infections who can be managed without hospitalisation. OPAT offers patient-centred treatment at home while avoiding the risks associated with hospitalisation, with high levels of patient satisfaction.

Safety and Tolerability of Antimicrobial Agents in the Older Patient.

Older patients are at high risk of infections, which often present atypically and are associated with high morbidity and mortality. Antimicrobial treatment in older individuals with infectious diseases represents a clinical challenge, causing an increasing burden on worldwide healthcare systems; immunosenescence and the coexistence of multiple comorbidities determine complex polypharmacy regimens with an increase in drug-drug interactions and spread of multidrug-resistance infections. Aging-induced pharmacokinetic and pharmacodynamic changes can additionally increase the risk of inappropriate drug dosing, with underexposure that is associated with antimicrobial resistance and overexposure that may lead to adverse effects and poor adherence because of low tolerability. These issues need to be considered when starting antimicrobial prescriptions. National and international efforts have been made towards the implementation of antimicrobial stewardship (AMS) interventions to help clinicians improve the appropriateness and safety of antimicrobial prescriptions in both acute and long-term care settings. AMS programs were shown to decrease consumption of antimicrobials and to improve safety in hospitalized patients and older nursing home residents. With the abundance of antimicrobial prescriptions and the recent emergence of multidrug resistant pathogens, an in-depth review of antimicrobial prescriptions in geriatric clinical practice is needed. This review will discuss the special considerations for older individuals needing antimicrobials, including risk factors that shape risk profiles in geriatric populations as well as an evidence-based description of antimicrobial-induced adverse events in this patient population. It will highlight agents of concern for this age group and discuss interventions to mitigate the effects of inappropriate antimicrobial prescribing.

Exposure of anti-infective drugs and the dynamic changes of the gut microbiota during gastrointestinal mucositis in autologous stem cell transplant patients: a pilot study.

Gastrointestinal mucositis could potentially compromise drug absorption due to functional loss of mucosa and other pathophysiological changes in the gastrointestinal microenvironment. Little is known about this effect on commonly used anti-infectives. This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota. A prospective, observational pilot study was performed in HSCT patients aged ≥ 18 years receiving anti-infectives orally. Left-over blood samples and fecal swabs were collected from routine clinical care until 14 days after HSCT to analyze drug and citrulline concentrations and to determine the composition of the gut microbiota. 21 patients with a median age of 58 (interquartile range 54-64) years were included with 252 citrulline, 155 ciprofloxacin, 139 fluconazole, and 76 acyclovir concentrations and 48 fecal swabs obtained. Severe gastrointestinal mucositis was observed in all patients. Due to limited data correlation analysis was not done for valacyclovir and fluconazole, however we did observe a weak correlation between ciprofloxacin and citrulline concentrations. This could suggest that underexposure of ciprofloxacin can occur during severe mucositis. A follow-up study using frequent sampling rather than the use of left-over would be required to investigate the relationship between gastrointestinal mucositis, drug exposure, and gut microbiome.

Curcumin Mediated Gold Nanoparticles and Analysis of its Antioxidant, Anti-inflammatory, Antimicrobial Activity Against Oral Pathogens

ABSTRACT Objective: To green synthesise gold nanoparticles using curcumin and to analyse its antioxidant, anti-inflammatory, and antimicrobial activity among oral pathogens. Material and Methods: Biosynthesised Curcumin Gold nanoparticles (CuAuNP) were evaluated by UV-visible spectrophotometer (UV-Vis), Transmission Electron Microscopy (TEM), and evaluation of antioxidant, anti-inflammatory and antibacterial activity against oral pathogens. Results: Synthesized CuAuNP were characterized using UV-visible spectrophotometry and showed peak absorption at 530nm. CuAuNp showed a 90.3% maximum scavenging ability of DPPH at a concentration of 50 μg/mL. CuAuNP exhibited 79.6 % of the highest anti-inflammatory activity at 50μg/mL than the standard drug diclofenac. TEM image clearly showed uniformly dispersed spherical-shaped gold nanoparticles with a size of about 20 nm. The biosynthesized nanoparticle was tested for its antimicrobial effect, and it showed a potent effect against S. aureus, E. faecalis, and C. albicans at 100µg/ mL. Enterococcus faecalis has a maximum zone of inhibition of 14 mm at 100µg/ mL of CuAuNp. Among gram-positive bacteria, a maximum zone of inhibition of 12 mm at 100µg/ mL was seen in S. aureus compared to S mutans. Candida albicans showed a maximum zone of inhibition of 18 mm at 25 μg/mL of CuAuNp. Conclusion: Curcumin-mediated gold nanoparticles with 20 nm size were effective and had strong antioxidant and anti-inflammatory activity at 50µg/ mL, antimicrobial action inhibiting microbes at 100µg/mL concentration that can be used in treating various Oral mucosal lesions.

Antimicrobial safety considerations in critically ill patients: part II: focused on anti-microbial toxicities.

INTRODUCTION: Antibiotic prescription is a challenging issue in critical care settings. Different pharmacokinetic and pharmacodynamic properties, polypharmacy, drug interactions, and high incidence of multidrug-resistant microorganisms in this population can influence the selection, safety, and efficacy of prescribed antibiotics. AREAS COVERED: In the current article we searched PubMed, Scopus and Google Scholar for neurotoxicities, hematologic toxicity and fluid stewardship in intensive care units. EXPERT OPINION: Critically ill patients who receive antimicrobial agents should be monitored for neurological, hematologic toxicities especially seizure, thrombocytopenia, and clostridioides infections. Other toxicities including QTc prolongation, electrolyte disturbances, liver enzyme elevation, and infusion-related reactions were being considered. Other changes, including fluid overload, hypoalbuminemia, augmented renal clearance, increased cardiac outputs in septic shock, and acute kidney injury, may influence treatment efficiency and patient outcome.

Preparations from Campomanesia reitziana reduce the gastrointestinal motility and castor oil-induced diarrhea in a non-opioid and non-dopaminergic pathway in mice and display antimicrobial activity in vitro.

BACKGROUND: This study investigated the antidiarrheal potential of the aqueous extract (AECR) and hydroalcoholic extract of Campomanesia reitziana leaves (HECR), its ethyl acetate (EAF) and dichloromethane fractions (DCMF), and myricitrin isolated from EAF. METHODS: The total phenols and flavonoids were measured, followed by chromatography and myricitrin isolation. The 2,2-diphenyl-1-picryl-hydrazyl scavenger activity, the cytotoxicity, and the effects on LPS-induced nitrite production in intestinal epithelial cells (IEC-6) were quantified. The effect of HECR, EAF, DCMF, and AECR on intestinal motility (IT), gastric emptying (GE), and castor oil-induced diarrhea in mice was determined, as well as its antimicrobial activity. KEY RESULTS: The administration of AECR 10% (10 ml/kg, p.o), but not HECR (300 mg/kg), reduced the GE and IT by 52 and 51%. The EAF and DCMF at 300 mg/kg also reduced IT but did not change GE. Moreover, AECR and EAF, but not DCMF, inhibited the castor oil-induced diarrhea and naloxone or metoclopramide pretreatment did not change these effects. Myricitrin did not change IT and the evacuation index of mice. Finally, the dry residue of AECR inhibited bacterial growth and EAF showed bacteriostatic activity against S. aureus, E. coli, and S. typhimurium and antifungal for C. albicans. However, none of the preparations alter the viability of Giardia spp. trophozoites. CONCLUSIONS: The AECR and EAF can be effective to treat diarrhea acting through opioid- or dopaminergic type 2 receptor-independent mechanisms and by its antimicrobial actions.

Hepatotoxicity of metronidazole in Cockayne syndrome: A clinical report.

Cockayne syndrome (CS) is a rare autosomal recessive genetic disorder characterized by growth failure and progressive multisystem dysfunction caused by deficient nucleotide excision repair. Whereas metronidazole (MTZ) hepatotoxicity is quite rare in the general population, cases of severe hepatic reaction to MTZ have been reported in CS patients. We report here the case of a 21-year-old CS patient who presented with jaundice following one week of treatment with MTZ combined with spiramycin for dental care. This case is the first one documented with a liver biopsy. Histopathological analysis revealed portal and lobular inflammation with predominance of neutrophils, ballooning degeneration and severe cholestasis without bile duct damage. The outcome was marked by regression of jaundice over 6 weeks. Analysis of this case highlights the probable responsibility of MTZ and adds support to the recommendation to strictly avoid the prescription of this drug in CS patients.

Óleo essencial de Pataqueira (Conobea scoparioides Cham. & Schltdl.) como conservante natural em Cosméticos / Pataqueira essential oil (Conobea scoparioides Cham. & Schltdl.) as a natural preservative in cosmetics

Um dos principais grupos de conservantes utilizados na maioria dos cosméticos são os parabenos que em muitos estudos demonstraram que podem provocar reações alérgicas como dermatite de contato, entre outras sensibilizações cutâneas. A fim de minimizar esses problemas, a indústria está produzindo cosméticos livres de conservantes ou de origem natural e em associações aos sintéticos. Dentre os conservantes naturais utilizados, podemos citar os óleos essenciais como uma alternativa viável. Diante deste contexto o presente trabalho visa avaliar experimentalmente o potencial antimicrobiano do óleo essencial de Conobea scoparioides Cham. & Schltdl., conhecida popularmente como pataqueira, o efeito de sua associação com parabenos e de sua eficácia como conservante em bases cosméticas. A composição do óleo essencial foi avaliada, indicando que este é composto em sua maior parte por terpenos, tendo éter metílico do timol (39,2%), timol (33,8 %) e α-felandreno (15,9%) como compostos majoritários. A atividade antimicrobiana do óleo essencial e do timol foi acessada através da concentração inibitória mínima (CIM), cujos resultados em µg/mL para o óleo essencial e o timol foram respectivamente: Staphylococcus aureus 650,70 e 284,90, Escherichia coli 721,53 e 271,20, Pseudomonas aeruginosa 1748,00 e > 2.000, Burkholderia cepacia 833,03 e 1.077,70, Candida albicans 521,43 e 172,61 e Aspergillus brasiliensis 300 e 400. O efeito sinérgico da associação do óleo essencial com os parabenos foi realizado através de um delineamento experimental centroide simplex para uma mistura de metilparabeno, propilparabeno e óleo essencial frente aos mesmos micro-organismos utilizados na determinação da atividade antimicrobiana. As concentrações ideais obtidas pela análise estatística para cada componente em µg/mL foram: 1120 para o metilparabeno, 350 para o propilparabeno e 675 para o óleo essencial. O teste de eficácia do sistema conservante em formulação cosmética foi efetuado empregando as concentrações ideais e mais duas concentrações superiores e uma abaixo do ideal. Para todas as cepas microbianas desafiadas o resultado do teste foi de redução total da carga microbiana inoculada nos sete dias de ensaio e nenhum aumento até o vigésimo oitavo dia o que demonstra a eficácia da associação do óleo essencial com os conservantes sintéticos. O óleo essencial de C. scoparioides apresentou um potencial antimicrobiano importante tanto sozinho como em associação com conservantes sintéticos. Estes resultados sugerem que esse óleo pode ser usado para compor um sistema conservante para formulações cosméticas contendo uma menor quantidade de sintéticos

One of the main groups of preservatives used in most cosmetics are parabens, that many studies have shown that they can cause allergic reactions such as contact dermatitis, among other skin sensitizations. To minimize these problems, the industry is producing cosmetics preservative free or using natural products instead and their combination with the synthetics. Among the natural preservatives used, we can mention essential oils as a viable alternative. In this context, the present work aims to experimentally evaluate the antimicrobial potential of the Conobea scoparioides Cham. & Schltdl. essential oil, popularly known as pataqueira, the effect of its association with parabens and its effectiveness as a preservative in cosmetic bases. The essential oil composition was analyzed, indicating that it is composed mostly of terpenes, with thymol methyl ether (39.2%), thymol (33.8%) and -phelandrene (15.9%) as major compounds. The antimicrobial activity of essential oil and thymol was accessed through the minimum inhibitory concentration (MIC), whose results in µg/mL for essential oil and thymol were respectively: Staphylococcus aureus 650.70 and 284.90, Escherichia coli 721, 53 and 271.20, Pseudomonas aeruginosa 1748.00 and > 2,000, Burkholderia cepacia 833.03 and 1,077.70, Candida albicans 521.43 and 172.61 and Aspergillus brasiliensis 300 and 400. The synergistic effect of the association of essential oil with parabens was performed through a centroid simplex experimental design for a mixture of methylparaben, propylparaben and essential oil against the same microorganisms used in the antimicrobial activity evaluation The ideal concentrations obtained by statistical analysis for each component in µg/mL were: 1120 for methylparaben, 350 for propylparaben and 675 for essential oil. The effectiveness test of the preservative system in cosmetic formulation was carried out using the ideal concentrations plus two higher concentrations and one below the ideal. For all challenged microbial strains, the test result was a total reduction of the inoculated microbial load in the seven days of testing and no increase until the twenty-eighth day, which demonstrates the effectiveness of the association of essential oil with synthetic preservatives. C. scoparioides essential oil showed an important antimicrobial potential both alone and in association with parabens. These results demonstrated that it can be used to compose a preservative system for cosmetic formulations containing lower amounts of synthetics

Adverse reactions caused by antimicrobials in hospitalized pediatric patients: causality and avoidability analysis

Abstract In pediatrics, drug therapy is commonly performed through adaptations of the dosage forms to adult use, increasing the risk of adverse drug reactions. In this context, studies assessing the severity and avoidability of the adverse reactions in children, especially those caused by antimicrobials, are still scarce. This work aimed to investigate suspected antimicrobial adverse reactions (ATM-ADRs) in pediatric patients admitted to a public hospital in northeastern Brazil, focusing on causality and avoidability analysis. A cohort study was carried out over a period of six months in a 64-bed pediatric unit. The incidence of suspected adverse reactions caused by antimicrobials was 14.65%. Most reactions were rated as probable (89.13%), with moderate severity (84.78%) and possibly avoidable (45.65%). The analysis indicated that the use of a larger number of medications (p<0.0001) and longer hospital stay (p=0.004) were related to the occurrence of ATM-ADR. Our findings demonstrated that almost half of the suspected reactions could be prevented and that the antimicrobial's clinical management is relevant in this context. Besides, increasingly accurate adverse reaction classification instruments are essential. These results can support the development of therapeutic guidelines addressed to a safe and effective pharmacotherapy in the pediatric area

Acute Graft-Versus-Host Disease, Infections, Vascular Events and Drug Toxicities Affecting the Central Nervous System.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy for patients with hematological malignancies. Acute Graft versus host diseases (GVHD) is a major immune mediated side effect of allo-HCT that can affect the central nervous system (CNS) in addition to post-allo-HCT vascular events, drug toxicity or infections. Here we summarize and discuss recent preclinical data on the CNS as a target of acute GVHD and the known mechanisms contributing to neurotoxicity with a focus on microglia and T cells. We also discuss open questions in the field and place the findings made in mouse models in a clinical context. While in mice the neurological deficits can be assessed in a controlled fashion, in patients the etiology of the CNS damage is difficult to attribute to acute GVHD versus infections, vascular events, and drug-induced toxicity. Ultimately, we discuss novel therapies for GVHD of the CNS. Our understanding of the biological mechanisms that lead to neurotoxicity after allo-HCT increased over the last decade. This review provides insights into CNS manifestations of GVHD versus other etiologies of CNS damage in mice and patients.

The effect of additional antimicrobial therapy on the outcomes of patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

BACKGROUND: The effect of additional antimicrobial agents on the clinical outcomes of patients with idiopathic pulmonary fibrosis (IPF) is unclear. METHODS: We performed comprehensive searches of randomized control trials (RCTs) that compared the clinical efficacy of additional antimicrobial agents to those of placebo or usual care in the treatment of IPF patients. The primary outcome was all-cause mortality, and the secondary outcomes were changes in forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and the risk of adverse events (AEs). RESULTS: Four RCTs including a total of 1055 patients (528 receiving additional antibiotics and 527 receiving placebo or usual care) were included in this meta-analysis. Among the study group, 402 and 126 patients received co-trimoxazole and doxycycline, respectively. The all-cause mortality rates were 15.0% (79/528) and 14.0% (74/527) in the patients who did and did not receive additional antibiotics, respectively (odds ratio [OR] 1.07; 95% confidence interval [CI] 0.76 to 1.51; p = 0.71). No significant difference was observed in the changes in FVC (mean difference [MD], 0.01; 95% CI - 0.03 to 0.05; p = 0.56) and DLCO (MD, 0.05; 95% CI - 0.17 to 0.28; p = 0.65). Additional use of antimicrobial agents was also associated with an increased risk of AEs (OR 1.65; 95% CI 1.19 to 2.27; p = 0.002), especially gastrointestinal disorders (OR 1.54; 95% CI 1.10 to 2.15; p = 0.001). CONCLUSIONS: In patients with IPF, adding antimicrobial therapy to usual care did not improve mortality or lung function decline but increased gastrointestinal toxicity.

Preparation, characterization, and application of polysaccharide-based emulsions incorporated with lavender essential oil for skin-friendly cellulosic support.

This study aimed to develop polysaccharide-based emulsions incorporated with lavender essential oil and their application on cellulosic support for patches obtaining. The lavender essential oil has been added to emulsions as an active compound mainly due to its antimicrobial properties. In this study, emulsions were used to deliver active ingredients (lavender essential oil). The chemical composition of essential oil was analyzed using gas chromatography-mass spectrometry (GC/MS). A total of seven emulsions (RiACL) were evaluated by determining rheological parameters and microbiological analysis. One of the emulsions (R7ACL) was applied to cellulosic support to obtain non-irritating textiles with controlled release of the active compound and moisturizing effects. Obtained cellulosic support was analyzed in terms of active compound controlled release, toxicity and antimicrobial testing, and skin analysis in healthy volunteers. It was found that the cellulosic supports treated with O/W emulsions are non-irritating, have softness and moisturizing effects, and can be used safely in topical applications for patches obtaining.

Pharmacovigilance study of anti-infective-related acute kidney injury using the Japanese adverse drug event report database.

BACKGROUND: Acute kidney injury (AKI) is associated with significant increases in short- and long-term morbidity and mortality. Drug-induced AKI is a major concern in the present healthcare system. Our spontaneous reporting system (SRS) analysis assessed links between AKI, along with patients' age, as healthcare-associated risks and administered anti-infectives. We also generated anti-infective-related AKI-onset profiles. METHOD: We calculated reporting odds ratios (RORs) for reports of anti-infective-related AKI (per Medical Dictionary for Regulatory Activities) in the Japanese Adverse Drug Event Report database and evaluated the effect of anti-infective combination therapy. The background factors of cases with anti-infective monotherapy and combination therapy (≥ 2 anti-infectives) were matched using propensity score. We evaluated time-to-onset data and hazard types using the Weibull parameter. RESULTS: Among 534,688 reports (submission period: April 2004-June 2018), there were 21,727 AKI events. The reported number of AKI associated with glycopeptide antibacterials, fluoroquinolones, third-generation cephalosporins, triazole derivatives, and carbapenems were 596, 494, 341, 315, and 313, respectively. Crude RORs of anti-infective-related AKI increased among older patients and were higher in anti-infective combination therapies [anti-infectives, ≥ 2; ROR, 1.94 (1.80-2.09)] than in monotherapies [ROR, 1.29 (1.22-1.36)]. After propensity score matching, the adjusted RORs of anti-infective monotherapy and combination therapy (≥ 2 anti-infectives) were 0.67 (0.58-0.77) and 1.49 (1.29-1.71), respectively. Moreover, 48.1% of AKI occurred within 5 days (median, 5.0 days) of anti-infective therapy initiation. CONCLUSION: RORs derived from our new SRS analysis indicate potential AKI risks and number of administered anti-infectives.

Cinamaldeído e terpineol como inibidores de biofilmes de Candida albicans e Enterococcus faecalis / Cinamaldehído y terpineol como inhibidores de biopelículas de Candida albicans y Enterococcus faecalis / Cinnamaldehyde and terpineol as inhibitors of Candida albicans and Enterococcus faecalis biofilms

Introdução: Os fitoconstituintes são moléculas naturais que apresentam atividade antimicrobiana satisfatória e devem ser estudados quanto ao seu uso como novas substâncias para irrigação dos canais radiculares. Objetivo: Avaliar o efeito inibitório dos fitoconstituintes cinamaldeído e α-terpineol frente a biofilmes monoespécie e duoespécie de microrganismos envolvidos na infecção endodôntica. Métodos: Trata-se de um estudo experimental na área de microbiologia aplicada, in vitro, cego quanto às análises e randomizado. Foram selecionados os fitoconstituintes cinamaldeído e α-terpineol. A atividade antimicrobiana frente Candida albicans e Enterococcus faecalis foi avaliada por meio da análise da capacidade metabólica com o uso da resazurina e análise da viabilidade celular pelo plaqueamento. O meio de cultura e a clorexidina 1 porcento serviram de controle negativo e positivo, respectivamente. Resultados: Observou-se ausência de crescimento para exposição dos biofilmes nas concentrações de 10 e 5 mg/mL de ambos os fitoconstituintes. Na concentração de 2,5 mg/mL de terpineol, constatou-se crescimento somente nos biofilmes monoespécie de C. albicans e duoespécie. Já na concentração de 1mg/mL de terpineol e cinamaldeído, verificou-se crescimento para todos os biofilmes. Conclusão: O cinamaldeído e α-terpineol apresentaram atividade inibitória frente biofilmes monoespécie e duoespécie de Candida albicans e Enterococcus faecalis, nas concentrações de 10 e 5 mg/mL(AU)

Introducción: Los fitoconstituyentes son moléculas naturales que presentan actividad antimicrobiana satisfactoria y deben ser estudiados en cuanto a su uso como nuevas sustancias para irrigación de los canales radiculares. Objetivo: Evaluar el efecto inhibitorio de fitoconstituyentes cinamaldehído y α-terpineol frente a biopelículas monoespecies y duoespecies de microorganismos involucrados en la infección endodóntica. Métodos: Estudio experimental en el campo de la microbiología aplicada, in vitro, ciego al análisis y aleatorizado. Se seleccionaron los fitoconstituyentes cinamaldehído y α-terpineol. La actividad antimicrobiana frente Candida albicans y Enterococcus faecalis fue evaluada por medio del análisis de la capacidad metabólica con el uso de la resazurina y análisis de la viabilidad celular por el plaqueamiento. El medio de cultivo y la clorexidina 1 por ciento sirvieron de control negativo y positivo, respectivamente. Resultados: Se observó ausencia de crecimiento para exposición de las biopelículas en las concentraciones de 10 y 5 mg/mL de ambos fitoconstituyentes. En la concentración de 2,5 mg/mL de terpineol se constató crecimiento solo en los biofilmios monoespecies de C. albicans y duoespecies. En la concentración de 1 mg/mL de terpineol y cinamaldehído se verificó crecimiento para todas las biopelículas. Conclusiones: Cinamaldehído y α-terpineol presentaron actividad inhibitoria frente a biofilmes monoespecies y duoespecies de Candida albicans y Enterococcus faecalis, en las concentraciones de 10 y 5 mg/mL(AU)

Introduction: Phytoconstituents are natural molecules displaying satisfactory antimicrobial activity. Studies should be conducted about their use as new root canal irrigants. Objective: Evaluate the inhibitory effect of the phytoconstituents cinnamaldehyde and α-terpineol against mono- and duo-species biofilms of microorganisms involved in endodontic infection. Methods: An experimental applied microbiology blind randomized in vitro study was conducted. The phytoconstituents selected were cinnamaldehyde and α-terpineol. Antimicrobial activity against Candida albicans and Enterococcus faecalis was evaluated by metabolic capacity analysis with resazurin and cell viability analysis by the plaque. The culture medium and 1 percent chlorhexidine served as negative and positive controls, respectively. Results: An absence of growth was observed for exposure of the biofilms at concentrations of 10 and 5 mg/ml of both phytoconstituents. At a concentration of 2.5 mg/ml terpineol displayed growth only in the mono-species biofilms of C. albicans and duo-species biofilms. At a concentration of 1 mg/ml terpineol and cinnamaldehyde displayed growth in all biofilms. Conclusions: Cinnamaldehyde and α-terpineol displayed inhibitory activity against mono- and duo-species biofilms of Candida albicans and Enterococcus faecalis at concentrations of 10 and 5 mg/ml(AU)

Zinc oxide nanoparticles using plant Lawsonia inermis and their mosquitocidal, antimicrobial, anticancer applications showing moderate side effects.

Microbes or parasites spread vector-borne diseases by mosquitoes without being affected themselves. Insecticides used in vector control produce a substantial problem for human health. This study synthesized zinc oxide nanoparticles (ZnO NPs) using Lawsonia inermis L. and were characterized by UV-vis, FT-IR, SEM with EDX, and XRD analysis. Green synthesized ZnO NPs were highly toxic against Anopheles stephensi, whose lethal concentrations values ranged from 5.494 ppm (I instar), 6.801 ppm (II instar), 9.336 ppm (III instar), 10.736 ppm (IV instar), and 12.710 ppm (pupae) in contrast to L. inermis treatment. The predation efficiency of the teleost fish Gambusia affinis and the copepod Mesocyclops aspericornis against A. stephensi was not affected by exposure at sublethal doses of ZnO NPs. The predatory potency for G. affinis was 45 (I) and 25.83% (IV), copepod M. aspericornis was 40.66 (I) and 10.8% (IV) while in an ZnO NPs contaminated environment, the predation by the fish G. affinis was boosted to 71.33 and 34.25%, and predation of the copepod M. aspericornis was 60.35 and 16.75%, respectively. ZnO NPs inhibited the growth of several microbial pathogens including the bacteria (Escherichia coli and Bacillus subtilis) and the fungi (Alternaria alternate and Aspergillus flavus), respectively. ZnO NPs decreased the cell viability of Hep-G2 with IC50 value of 21.63 µg/mL (R2 = 0.942; P < 0.001) while the concentration increased from 1.88 to 30 µg/mL. These outcomes support the use of L. inermis mediated ZnO NPs for mosquito control and drug development.

Control of scabies in a tribal community using mass screening and treatment with oral ivermectin -A cluster randomized controlled trial in Gadchiroli, India.

BACKGROUND: Scabies is often endemic in tribal communities and difficult to control. We assessed the efficacy of a community-based intervention using mass screening and treatment with oral ivermectin in controlling scabies. METHODS/ FINDINGS: In this cluster randomised controlled trial, 12 villages were randomly selected from a cluster of 42 tribal villages in Gadchiroli district. In these villages, trained community health workers (CHWs) conducted mass screening for scabies. The diagnosis was confirmed by a physician. Six villages each were randomly allocated to the intervention and usual care arm (control arm). In the intervention arm (population 1184) CHWs provided directly observed oral ivermectin to scabies cases and their household contacts. In the usual care arm (population 1567) scabies cases were referred to the nearest clinic for topical treatment as per the standard practice. The primary outcome was prevalence of scabies two months after the treatment. Secondary outcomes were prevalence of scabies after twelve months of treatment and prevalence of impetigo after two and twelve months of treatment. Outcomes were measured by the team in a similar way as the baseline. The trial was registered with the clinical trial registry of India, number CTRI/2017/01/007704. In the baseline, 2 months and 12 months assessments 92.4%, 96% and 94% of the eligible individuals were screened in intervention villages and 91.4%, 91.3% and 95% in the usual care villages. The prevalence of scabies in the intervention and usual care arm was 8.4% vs 8.1% at the baseline, 2.8% vs 8.8% at two months [adjusted relative risk (ARR) 0.21, 95% CI 0.11-0.38] and 7.3% vs 14.1% (ARR 0.49, 95% CI 0.25-0.98) at twelve months The prevalence of impetigo in the intervention and usual care arm was 1.7% vs 0.6% at baseline, 0.6% vs 1% at two months (ARR 0.55, 95% CI 0.22-1.37) and 0.3% vs 0.7% at 12 months (ARR 0.42, 95% CI 0.06-2.74). Adverse effects due to ivermectin occurred in 12.1% of patients and were mild. CONCLUSIONS: Mass screening and treatment in the community with oral ivermectin delivered by the CHWs is superior to mass screening followed by usual care involving referral to clinic for topical treatment in controlling scabies in this tribal community in Gadchiroli.

Relative Risk Analysis of Liver-related Adverse Drug Reactions in Children Based on China's National Spontaneous Reporting System.

OBJECTIVE: To compare the risk of liver-related adverse drug reactions (ADRs) in children and adults. STUDY DESIGN: A case/non-case analysis on spontaneous reports based on the China National Adverse Drug Reactions Monitoring System database were conducted, focusing on events of liver-related ADRs in children younger than 14 years of age. Both the relative risk of liver-related ADRs in children vs entire population and the risk stratification in children were expressed as a measure of disproportionality using the reporting odds ratio (ROR). RESULTS: There were 1206 cases of pediatric liver-related ADRs identified from 2012 to 2016, accounting for 2.82% of the entire population. The greatest ROR values in children from 0 to 14 years vs the entire population were observed for analgesics (3.97, 95% CI 3.27-4.81), respiratory (2.60, 95% CI 1.04-6.43), antineoplastic (2.29, 95% CI 2.02-2.58), immunomodulatory (1.91, 95% CI 1.44-2.53), and antimicrobial agents (1.47, 95% CI 1.33-1.63). Notably, infants aged 0-1 years showed significantly greater risk (3.14, 95% CI 2.85-3.48) of liver-related ADRs than the other age groups of children. For infants, analgesics (3.21, 95% CI 2.20-4.66) and antimicrobials (3.15, 95% CI 2.50-3.97) agents were found to have the greatest adjusted RORs than other drug categories. The highest RORs were found for meropenem, amoxicillin, fluconazole, vancomycin, cefaclor, and ceftazidime in the antimicrobial agents for infants. CONCLUSIONS: Children are sensitive to liver-related ADRs caused by several specific drug categories, and infants are the most sensitive.