Capacidade terapêutica da fitoterapia na odontologia: uma análise abrangente das proteínas antimicrobianas, anti-inflamatórias e reparadoras / Therapeutic capacity of phytotherapy in dentistry: a comprehensive analysis of antimicrobial, anti-inflammatory, and reparative properties

Introdução: A fitoterapia se baseia na utilização de plantas medicinais, através de diferentes formulações farmacêuticas com fins terapêuticos. Na Odontologia, os fitoterápicos têm sido alvo de estudos, devido suas propriedades benéficas, além de apresentarem biocompatibilidade, baixo custo e fácil acesso. Objetivo: Realizar um levantamento na literatura científica sobre a utilização da fitoterapia na Odontologia, com vistas aos efeitos antimicrobiano, anti-inflamatório e reparador. Material e Métodos: A busca ocorreu entre fevereiro a julho/2023, nas bases PubMed e LILACS, além de livre busca, cruzando-se os descritores "Phytotherapy", "Dentistry", "Anti-inflamatory Agents", "Anti-Infective Agents", "Wound Healing", "Fitoterapia", "Odontologia", "Anti-inflamatório", "Antimicrobiano" e "Cicatrização". Após leitura inicial, seguida da análise crítica com aplicação dos critérios estabelecidos, foram selecionadas 50 referências. Desenvolvimento: Diversas plantas são empregadas sob a forma de fitoterapia, como Aloe vera (babosa), Matricaria recutita (camomila), Copaifera (copaíba), Punica granatum (romã), Uncaria tomentosa (unha-de-gato), Malva sylvestris (malva), Althaea officinalis (malvaísco), Myracrodruon urundeuva (Aroeira), Lippia sidoides (Alecrim pimenta) e Glycyrrhiza glabra (Alcaçuz). Na Odontologia, pesquisas evidenciaram resultados satisfatórios para o tratamento de afecções da cavidade oral, especialmente com caráter inflamatório e infeccioso, além de aclerar a cicatrização. Esses achados apontam que a fitoterapia é um tratamento eficaz, acessível e com mínimos efeitos colaterais. Considerações finais: Com base na literatura revisada, a fitoterapia parece ser uma alternativa promissora no tratamento de afecções orais, devido aos seus notáveis efeitos cicatrizantes, antimicrobianos e anti-inflamatórios. Contudo, mais pesquisas com metodologias adequadas são necessárias para que se estabeleçam protocolos clínicos seguros e eficazes.

Introduction: Phytotherapy is based on the use of medicinal plants through different pharmaceutical formulations for therapeutic purposes. In Dentistry, phytotherapeutics have been the subject of studies due to their beneficial properties, as well as their biocompatibility, low cost, and easy accessibility. Objective: To conduct a literature review on the use of phytotherapy in Dentistry, focusing on antimicrobial, anti-inflammatory, and reparative effects. Materials and Methods: The search took place between February and July 2023, using PubMed and LILACS databases, in addition to a free search, crossing the descriptors "Phytotherapy," "Dentistry," "Anti-inflammatory Agents," "Anti-Infective Agents," "Wound Healing," "Fitoterapia," "Odontologia," "Anti-inflammatory," "Antimicrobial," and "Cicatrização." After an initial reading, followed by critical analysis with the application of established criteria, 50 references were selected. Development: Various plants are employed in phytotherapy, such as Aloe vera (aloe), Matricaria recutita (chamomile), Copaifera (copaiba), Punica granatum (pomegranate), Uncaria tomentosa (cat's claw), Malva sylvestris (mallow), Althaea officinalis (marshmallow), Myracrodruon urundeuva (Brazilian copaiba), Lippia sidoides (rosemary pepper), and Glycyrrhiza glabra (licorice). In Dentistry, research has shown satisfactory results for the treatment of oral cavity conditions, especially those with inflammatory and infectious characteristics, as well as accelerating healing. These findings suggest that phytotherapy is an effective, accessible treatment with minimal side effects. Final considerations: Based on the reviewed literature, phytotherapy appears to be a promising alternative in the treatment of oral conditions due to its notable healing, antimicrobial, and anti-inflammatory effects. However, more research with appropriate methodologies is necessary to establish safe and effective clinical protocols.

Wedge Resection and Nail Groove Reconstruction With Hanging Thread Knot in the Treatment of Onychocryptosis.

BACKGROUND: Onychocryptosis is characterized by the nail plate penetrating the lateral nail fold, resulting in varying degrees of infection and deformity. Standardized treatment protocols for onychocryptosis, particularly in Stages IIb, III, and IV, have not been universally established, highlighting the urgent need for the development of effective interventions. OBJECTIVE: To evaluate the effectiveness and safety of wedge resection and nail groove reconstruction using the hanging thread knot for the treatment of onychocryptosis. METHODS: At our hospital, a total of 155 patients with onychocryptosis in Stages IIb, III, and IV underwent treatment. Wedge resection and nail groove reconstruction with the hanging thread knot were applied based on the severity of deformity and infection for treating onychocryptosis. All patients received perioperative systematic and topical anti-infective treatments. Follow-ups conducted over a period of 2-6 months assessed postoperative rehabilitation and complications. RESULTS: The cure rate reached 95%, with a low recurrence rate of 5%. Recurrence, observed in eight patients, was attributed to various causes: three due to improper trimming, three related to trauma, one associated with obesity, and one due to incomplete matrix resection. All eight patients achieved complete recovery through health guidance and secondary surgery. Satisfaction results were reported during the 2-6 months follow-up period. Although 10 patients experienced secondary local infections, all achieved complete recovery following active treatment. CONCLUSION: Wedge resection and nail groove reconstruction with the hanging thread knot prove to be an effective and safe method for treating onychocryptosis.

[What is confirmed in the treatment of sepsis? : An update]. / Was ist gesichert in der Therapie der Sepsis? : Ein Update.

BACKGROUND: Sepsis is defined as "being evoked as a life-threatening organ dysfunction caused by an inadequate host response to infection". The most recent German S3 guidelines were published in 2018 and the Surviving Sepsis Campaign (SSC) last published the current recommendations for the treatment of sepsis and septic shock in 2021. OBJECTIVE: This article explores and discusses which evidence in the treatment of sepsis and septic shock has been confirmed. MATERIAL AND METHODS: Discussion of the 2018 German S3 guidelines, supplementation of the content of the 2021 international guidelines and recent research results since 2021. RESULTS: The primary objective for managing sepsis and septic shock still includes rapid identification, early initiation of anti-infective treatment, and focus cleansing when feasible. In addition, the focus is on hemodynamic stabilization, including the early use of vasopressors for prevention of hypervolemia and, if necessary, the use of organ support procedures. Supportive treatment, such as the administration of corticosteroids and the use of apheresis, can be advantageous in specific scenarios. The focus is increasingly shifting towards post-intensive care unit (ICU) follow-up care, improving the quality of life after surviving sepsis and the close involvement of relatives of the patient. CONCLUSION: Despite the fact that considerable progress has been made in understanding the pathophysiology and treatment of sepsis, the early administration of anti-infective agents, focus control, nuanced volume therapy and the use of catecholamines continue to be fundamental to sepsis management. New recommendations emphasize the early use of vasopressors (primarily norepinephrine) and the administration of corticosteroids, especially in cases of septic shock and pneumonia.

Analysis of the Probiotic Potential of Lactiplantibacillus plantarum LB1_P46 Isolated from the Mexican Fermented Pulque Beverage: A Functional and Genomic Analysis.

The traditional Mexican fermented beverage pulque has been considered a healthy product for treating gastrointestinal disorders. Lactic acid bacteria (LAB) have been identified as one of the most abundant microbial groups during pulque fermentation. As traditional pulque is consumed directly from the fermentation vessel, the naturally associated LABs are ingested, reaching the consumer's small intestine alive, suggesting their potential probiotic capability. In this contribution, we assayed the probiotic potential of the strain of Lactiplantibacillus plantarum LB1_P46 isolated from pulque produced in Huitzilac, Morelos State, Mexico. The characterization included resistance to acid pH (3.5) and exposure to bile salts at 37 °C; the assay of the hemolytic activity and antibiotic resistance profiling; the functional traits of cholesterol reduction and ß-galactosidase activity; and several cell surface properties, indicating that this LAB possesses probiotic properties comparable to other LAB. Additionally, this L. plantarum showed significance in in vitro antimicrobial activity against several Gram-negative and Gram-positive bacteria and in vivo preventive anti-infective capability against Salmonella in a BALB/c mouse model. Several functional traits and probiotic activities assayed were correlated with the corresponding enzymes encoded in the complete genome of the strain. The genome mining for bacteriocins led to the identification of several bacteriocins and a ribosomally synthesized and post-translationally modified peptide encoding for the plantaricin EF. Results indicated that L. plantarum LB1_P46 is a promising probiotic LAB for preparing functional non-dairy and dairy beverages.

Neisseria meningitidis: The Unforeseen Agent of Acute Neonatal Conjunctivitis.

Acute conjunctivitis is a common disease in the neonatal period. Although often underestimated, Neisseria meningitidis is an uncommon but potentially severe cause of acute neonatal conjunctivitis. We describe a case of a 14-day-old healthy female newborn who presented with fever, runny nose, cough, and bilateral purulent ocular discharge. A nasopharyngeal swab tested positive for SARS-CoV-2, and the infant was discharged after becoming afebrile 24 hours later. Four days later, ocular exudate culture revealed the presence of N. meningitidis and Staphylococcus aureus. Blood and cerebrospinal fluid tests were unremarkable. The infant was treated with intravenous cefotaxime and topical azithromycin, with no signs of invasive disease or reported complications. This case highlights noninvasive neonatal acute conjunctivitis caused by a coinfection of N. meningitidis and S. aureus, with a favorable outcome. The ocular exudate culture was crucial in identifying the causative bacteria, which might otherwise have gone undetected and improperly treated. Clinicians should consider N. meningitidis as a potential agent in neonatal acute conjunctivitis.

The antibiotic resistance profiles of Pseudomonas aeruginosa in the Asia Cornea Society Infectious Keratitis Study.

PURPOSE: To describe the prevalence and antibiotic resistance profiles of Pseudomonas aeruginosa isolated from the Asia Cornea Society Infectious Keratitis Study (ACSIKS). METHODS: All bacterial isolates from ACSIKS underwent repeat microbiological identification in a central repository in Singapore. Minimum inhibitory concentration (MIC) determination was conducted for isolates of P. aeruginosa against thirteen antibiotics from 6 different classes, and categorized based on Clinical Laboratory Standard Institutes' reference ranges. The percentage rates of resistance (non-susceptibility) to each antibiotic included isolates of both intermediate and complete resistance. Multi-drug resistance (MDR) was defined as non-susceptibility to at least one agent in three or more antimicrobial classes. RESULTS: Of the 1493 unique bacterial specimens obtained from ACSIKS, 319 isolates were of P. aeruginosa. The majority of isolates were from centers in India (n = 118, 37%), Singapore (n = 90, 28.2%), Hong Kong (n = 31, 9.7%) and Thailand (n = 30, 9.4%). The cumulative antibiotic resistance rate was the greatest for polymyxin B (100%), ciprofloxacin (17.6%) and moxifloxacin (16.9%), and lowest for cefepime (11.6%) and amikacin (13.5%). Isolates from India demonstrated the highest antibiotic resistance rates of all the centers, and included moxifloxacin (47.5%) and ciprofloxacin (39.8%). Forty-eight of the 59 MDR isolates also originated from India. Antibiotic resistance rates were significantly lower in the other ACSIKS centers, and were typically less than 10%. CONCLUSIONS: The antibiotic resistance profiles of P. aeruginosa varied between different countries. While it was low for most countries, substantial antibiotic resistance and a significant number of multi-drug resistant isolates were noted in the centers from India.

Advancing research and development of anti-infectives for children with a focus on antiretroviral therapy: A clinical development perspective.

The HIV treatment landscape for adults has progressed dramatically in recent decades; however, paediatric populations continue to experience delayed and limited access to effective and safe antiretroviral therapy options. Despite current incentive programmes, formulation research and development and approved drug dosing for children have been limited, particularly for neonates (aged <4 wk). Regulatory approval of drug formulations and dosing in children may lag behind adult approvals by years. Formulation and trial design adjustments complicate paediatric drug development, all of which are vital to accommodate for physiological differences, organ maturation, and rapid weight gain, which are most significant in the youngest children. To facilitate more rapid anti-infective drug development for paediatric populations, regulatory agencies provide guidelines that include extrapolating efficacy and safety data from relevant populations; using pharmacokinetic (PK) bridging and modelling to reduce sample sizes and limit the number of PK studies needed before efficacy analyses; and enrolling age- or weight-based cohorts in parallel rather than sequentially for clinical trials. Ensuring access to approved drugs poses an additional challenge, as uncertainty in demand leads to manufacturing and supply complexity with potentially higher costs that can be a barrier to uptake. Here we summarise challenges in drug development for children living with HIV, which are not unique to antiretrovirals. We aim to propose strategies for how model-based approaches and global partnerships can overcome some of these barriers to accelerate paediatric drug development, with particular reference to HIV, and how lessons learnt from HIV could be extended to other anti-infectives.

Endolysosomal channel TMEM175 mediates antitoxin activity of DABMA.

DABMA is a chemical molecule optimized from the parent compound ABMA and exhibits broad-spectrum antipathogenic activity by modulating the host's endolysosomal and autophagic pathways. Both DABMA and ABMA inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a cellular assay, which further expands their anti-pathogen spectrum in vitro. However, their precise mechanism of action has not yet been resolved. TMEM175 is a newly characterized endolysosomal channel which plays an essential role in the homeostasis of endosomes and lysosomes as well as organelle fusion. Here, we show that DABMA increases the endosomal TMEM175 current through organelle patch clamping with an EC50 of 17.9 µm. Depletion of TMEM175 protein significantly decreases the antitoxin activity of DABMA and affects its action on acidic- and Rab7-positive endosomes as well as on endolysosomal trafficking. Thus, TMEM175 is necessary for DABMA's activity and may represent a druggable target for the development of anti-infective drugs. Moreover, DABMA, as an activator of the TMEM175 channel, may be useful for the in-depth characterization of the physiological and pathological roles of this endolysosomal channel.

Synthesis and In vitro evaluation of bichalcones as novel anti-toxoplasma agents.

Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii, an apicomplexan parasite that infects approximately a third of the world's human population. This disease can cause serious complications during pregnancy and can be fatal in immunocompromised hosts. The current treatment options for toxoplasmosis face several limitations. Thus, to address the urgent medical need for the discovery of novel anti-toxoplasma potential drug candidates, our research focused on exploring a series of monomeric and dimeric chalcones, polyphenolic molecules belonging to the class of flavonoids. Chalcones 1aa-1bg and axially chiral A-A'-connected bichalcones 2aa-2bg were evaluated in vitro against the proliferation of the parasite in a cell-based assay. A comparison of the efficacy demonstrated that, in several cases, bichalcones exhibited increased bioactivity compared to their corresponding monomeric counterparts. Among these compounds, a bichalcone with a phenyl substituent and a methyl moiety 2ab showed the most potent and selective inhibitory activity in the nanomolar range. Both enantiomers of this bichalcone were synthesized using an axially chiral biphenol building block. The biaryl bond was forged using Suzuki cross-coupling in water under micellar catalysis conditions. Separation of the atropisomers of this biphenol building block was conducted by chiral HPLC on a preparative scale. The biological evaluation of the enantiomers revealed that the (R a)-enantiomer (R a)-2ab is the eutomer. These studies suggest that bichalcones may be important drug candidates for further in vivo evaluations for the discovery of anti-toxoplasma drugs.

1-Deoxy-d-xylulose 5-phosphate reductoisomerase as target for anti Toxoplasma gondii agents: crystal structure, biochemical characterization and biological evaluation of inhibitors.

Toxoplasma gondii is a widely distributed apicomplexan parasite causing toxoplasmosis, a critical health issue for immunocompromised individuals and for congenitally infected foetuses. Current treatment options are limited in number and associated with severe side effects. Thus, novel anti-toxoplasma agents need to be identified and developed. 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) is considered the rate-limiting enzyme in the non-mevalonate pathway for the biosynthesis of the isoprenoid precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate in the parasite, and has been previously investigated for its key role as a novel drug target in some species, encompassing Plasmodia, Mycobacteria and Escherichia coli. In this study, we present the first crystal structure of T. gondii DXR (TgDXR) in a tertiary complex with the inhibitor fosmidomycin and the cofactor NADPH in dimeric conformation at 2.5 Šresolution revealing the inhibitor binding mode. In addition, we biologically characterize reverse α-phenyl-ß-thia and ß-oxa fosmidomycin analogues and show that some derivatives are strong inhibitors of TgDXR which also, in contrast with fosmidomycin, inhibit the growth of T. gondii in vitro. Here, ((3,4-dichlorophenyl)((2-(hydroxy(methyl)amino)-2-oxoethyl)thio)methyl)phosphonic acid was identified as the most potent anti T. gondii compound. These findings will enable the future design and development of more potent anti-toxoplasma DXR inhibitors.

[Nosocomial pneumonia]. / Nosokomiale Pneumonie.

Nosocomial pneumonia is defined as pneumonia occurring ≥ 48 h after hospital admission in a patient without severe immunosuppression. It can occur in spontaneously breathing patients or with noninvasive ventilation (NIV) and mechanically ventilated patients. In patients with suspected ventilator-associated pneumonia (VAP) (semi)quantitative cultures of tracheobronchial aspirates or bronchoalveolar lavage fluid should be perfomed. The initial empirical antimicrobial treatment is determined by the risk for multidrug-resistant pathogens (MDRP). The advantage of combination treatment increases with the prevalence of MDRPs. The antibiotic treatment should be adapted when the microbiological results are available. After 72 h a standardized re-evaluation including the response to treatment and also checking of the suspected diagnosis of pneumonia in a structured form is mandatory. Treatment failure can occur as a primary or secondary failure and in the case of primary progression necessitates another comprehensive diagnostic work-up before any further antibiotic treatment.

Recurrent urinary tract infections and prophylactic antibiotic use in women: a cross-sectional study in primary care.

BACKGROUND: Despite the considerable morbidity caused by recurrent urinary tract infections (rUTIs), and the wider personal and public health implications from frequent antibiotic use, few studies adequately describe the prevalence and characteristics of women with rUTIs or those who use prophylactic antibiotics. AIM: To describe the prevalence, characteristics, and urine profiles of women with rUTIs with and without prophylactic antibiotic use in Welsh primary care. DESIGN AND SETTING: This was a retrospective cross-sectional study in Welsh general practice using the Secure Anonymised Information Linkage (SAIL) Databank. METHOD: The characteristics of women aged ≥18 years with rUTIs or using prophylactic antibiotics from 2010 to 2020, and associated urine culture results from 2015 to 2020, are described. RESULTS: In total, 6.0% (n = 92 213/N = 1 547 919) had rUTIs, and 1.7% (n = 26 862/N = 1 547 919) were prescribed prophylactic antibiotics with the rates increasing after 57 years of age. Only 49.0% (n =13 149/N = 26 862) of users of prophylactic antibiotics met the definition of rUTIs before initiation. The study found that 80.8% (n = 44 947/N = 55 652) of women with rUTIs had a urine culture result in the preceding 12 months with high rates of resistance to trimethoprim and amoxicillin. Of women taking prophylactic antibiotics, 64.2% (n = 9926/N = 15 455) had a urine culture result before initiation and 18.5% (n = 320/N = 1730) of women prescribed trimethoprim had resistance to it on the antecedent sample. CONCLUSION: A substantial proportion of women had rUTIs or incident prophylactic antibiotic use. However, 64.2% (n = 9926/N = 15 455) of women had urine cultured before starting prophylaxis. There was a high proportion of cultured bacteria resistant to two antibiotics used for rUTI prevention and evidence of resistance to the prescribed antibiotic. More frequent urine cultures for rUTI diagnosis and before prophylactic antibiotic initiation could better inform antibiotic choices.

A carboxymethyl-resistant starch/polyacrylic acid semi-IPN hydrogel with excellent adhesive and antibacterial properties for peri-implantitis prevention.

Hydrogels possess inherent characteristics that render them promising for the prevention of peri-implantitis. Nonetheless, hydrogels with singular network structures are incapable of concurrently achieving the desired adhesion and mechanical properties. In this work, a carboxymethyl resistant starch/polyacrylic acid semi-interpenetrating (CMRS/PAA semi-IPN) hydrogel was successfully prepared in one step. Its morphology, structure, mechanical properties, and adhesion properties were systematically assessed, which revealed a homogeneously porous structure with a commendable mechanical strength of 67.317 kPa and an adhesion strength of 63 kPa. Ciprofloxacin (Cip) was loaded in the CMRS/PAA hydrogel via in situ compounding. The in vitro kinetic study of drug release shows that the slow drug release efficiency exceeds 90 % in the weakly acidic microenvironment at the infection site after 72 h, indicating enhanced antimicrobial properties. The Cip-loaded hydrogel also exhibits a remarkable bacterial inhibition rate exceeding 99 % against the pathogenic bacterium P. gingivalis and good cytocompatibility and hemocompatibility in vitro. In summary, the current work explored a novel solution and direction for the development of anti-infective medical materials applicable to dental implants.

Introducing the NUATEI Consortium: A Mexican Research Program for the Identification of Natural and Synthetic Antimicrobial Compounds for Prevalent Infectious Diseases.

The need for new drugs to treat human infections is a global health concern. Diseases like tuberculosis, trypanosomiasis, amoebiasis, and AIDS remain significant problems, especially in developing countries like Mexico. Despite existing treatments, issues such as resistance and adverse effects drive the search for new alternatives. Herein, we introduce the NUATEI research consortium, made up of experts from the Institute of Biomedical Research at UNAM, who identify and obtain natural and synthetic compounds and test their effects against human pathogens using in vitro and in vivo models. The consortium has evaluated hundreds of natural extracts and compounds against the pathogens causing tuberculosis, trypanosomiasis, amoebiasis, and AIDS, rendering promising results, including a patent with potential for preclinical studies. This paper presents the rationale behind the formation of this consortium, as well as its objectives and strategies, emphasizing the importance of natural and synthetic products as sources of antimicrobial compounds and the relevance of the diseases studied. Finally, we briefly describe the methods of the evaluation of the compounds in each biological model and the main achievements. The potential of the consortium to screen numerous compounds and identify new therapeutic agents is highlighted, demonstrating its significant contribution to addressing these infectious diseases.

Difference in Baseline Antimicrobial Prescription Patterns of Hospitals According to Participation in the National Antimicrobial Monitoring and Feedback System in Korea.

This study aimed to evaluate the differences in the baseline characteristics and patterns of antibiotic usage among hospitals based on their participation in the Korea National Antimicrobial Use Analysis System (KONAS). We obtained claims data from the National Health Insurance for inpatients admitted to all secondary- and tertiary-care hospitals between January 2020 and December 2021 in Korea. 15.9% (58/395) of hospitals were KONAS participants, among which the proportion of hospitals with > 900 beds (31.0% vs. 2.6%, P < 0.001) and tertiary care (50.0% vs. 5.2%, P < 0.001) was higher than that among non-participants. The consumption of antibiotics targeting antimicrobial-resistant gram positive bacteria (33.7 vs. 27.1 days of therapy [DOT]/1,000 patient-days, P = 0.019) and antibiotics predominantly used for resistant gram-negative bacteria (4.8 vs. 3.7 DOT/1,000 patient-days, P = 0.034) was higher in KONAS-participating versus -non-participating hospitals. The current KONAS data do not fully represent all secondary- and tertiary-care hospitals in Korea; thus, the KONAS results should be interpreted with caution.

Human ß-defensins: The multi-functional natural peptide.

The increasing threat of antibiotic resistance among pathogenic microorganisms and the urgent demand for new antibiotics require immediate attention. Antimicrobial peptides exhibit effectiveness against microorganisms, fungi, viruses, and protozoa. The discovery of human ß-defensins represents a major milestone in biomedical research, opening new avenues for scientific investigation into the innate immune system and its resistance mechanisms against pathogenic microorganisms. Multiple defensins present a promising alternative in the context of antibiotic abuse. However, obstacles to the practical application of defensins as anti-infective therapies persist due to the unique properties of human ß-defensins themselves and serious pharmacological and technical challenges. To overcome these challenges, diverse delivery vehicles have been developed and progressively improved for the conjugation or encapsulation of human ß-defensins. This review briefly introduces the biology of human ß-defensins, focusing on their multistage structure and diverse functions. It also discusses several heterologous systems for producing human ß-defensins, various delivery systems created for these peptides, and patent applications related to their utilization, concluding with a summary of current challenges and potential solutions.

Burden and Management of Multi-Drug Resistant Organism Infections in Solid Organ Transplant Recipients Across the World: A Narrative Review.

Solid organ transplant (SOT) recipients are particularly susceptible to infections caused by multidrug-resistant organisms (MDRO) and are often the first to be affected by an emerging resistant pathogen. Unfortunately, their prevalence and impact on morbidity and mortality according to the type of graft is not systematically reported from high-as well as from low and middle-income countries (HIC and LMIC). Thus, epidemiology on MDRO in SOT recipients could be subjected to reporting bias. In addition, screening practices and diagnostic resources may vary between countries, as well as the availability of new drugs. In this review, we aimed to depict the burden of main Gram-negative MDRO in SOT patients across HIC and LMIC and to provide an overview of current diagnostic and therapeutic resources.

Leading Paediatric Infectious Diseases-Current Trends, Gaps, and Future Prospects in Oral Pharmacotherapeutic Interventions.

Paediatric infectious diseases contribute significantly to global health challenges. Conventional therapeutic interventions are not always suitable for children, as they are regularly accompanied with long-standing disadvantages that negatively impact efficacy, thus necessitating the need for effective and child-friendly pharmacotherapeutic interventions. Recent advancements in drug delivery technologies, particularly oral formulations, have shown tremendous progress in enhancing the effectiveness of paediatric medicines. Generally, these delivery methods target, and address challenges associated with palatability, dosing accuracy, stability, bioavailability, patient compliance, and caregiver convenience, which are important factors that can influence successful treatment outcomes in children. Some of the emerging trends include moving away from creating liquid delivery systems to developing oral solid formulations, with the most explored being orodispersible tablets, multiparticulate dosage forms using film-coating technologies, and chewable drug products. Other ongoing innovations include gastro-retentive, 3D-printed, nipple-shield, milk-based, and nanoparticulate (e.g., lipid-, polymeric-based templates) drug delivery systems, possessing the potential to improve therapeutic effectiveness, age appropriateness, pharmacokinetics, and safety profiles as they relate to the paediatric population. This manuscript therefore highlights the evolving landscape of oral pharmacotherapeutic interventions for leading paediatric infectious diseases, crediting the role of innovative drug delivery technologies. By focusing on the current trends, pointing out gaps, and identifying future possibilities, this review aims to contribute towards ongoing efforts directed at improving paediatric health outcomes associated with the management of these infectious ailments through accessible and efficacious drug treatments.

Metal copper and silver revealed potent antimicrobial activity for treating Caenorhabditis elegans infected with carbapenemase-producing Klebsiella pneumonia.

OBJECTIVES: The increasing issue of bacterial resistance, coupled with inadequate progress in developing new antibiotics, necessitates exploring alternative treatments. Antibacterial biomaterials, such as silver and copper, possess advantageous properties such as heat resistance, durability, continuity, and safety. Particularly, they can effectively eliminate pathogenic bacteria while preserving cellular integrity, emphasizing the necessity of identifying optimal metal ion concentrations for practical application. Caenorhabditis elegans (C. elegans) can serve as a noteworthy model in this context. This study employed a C. elegans infection model to assess the efficacy of antibacterial metal ions. METHODS: Hematoxylin-eosin (HE) staining and inductively coupled plasma mass spectrometry (ICP-MS) assay were utilized to determine the toxic levels of metal ions in mice. Additionally, RNA sequencing (RNA-seq) and assessment of reactive oxygen species (ROS) production in the C. elegans model were conducted to elucidate the mechanisms underlying metal ion toxicity. RESULTS: Silver ion concentrations ranging from 10-6 to 10-7 M and copper ion concentrations ranging from 10-4 to 10-5 M exhibited antimicrobial properties without eliciting cytotoxic effects. Analysis of the transcriptome data derived from mRNA isolated from C. elegans indicated that CRKP infection activated the FoxO signaling pathway, potentially leading to ROS accumulation and C. elegans demise. CONCLUSIONS: In conclusion, C. elegans serves as a comprehensive infection model for assessing antibacterial metal ions.

Safety of carrageenan-based gels as preventive microbicides: a narrative review.

BACKGROUND: Carrageenan-containing gels researched for the prevention of sexually transmitted infections (STIs) have shown promising results for human papillomavirus prevention in women, but not in men. We conducted a narrative review to assess the safety of these gels for genital use. METHODS: We searched PubMed using MeSH terms and keywords on 5 November 2023. Title/abstract of articles were screened to identify relevant ones. Full-text screening determined eligibility: empirical study evaluating safety of carrageenan-containing gel(s) for genital use. RESULTS: Of the 125 identified records, 15 were eligible, comprising 14 (10 randomised controlled trials and 4 cohorts) unique study populations. Studies included women only (n=11), men only (n=1) or both (n=3); number of participants ranged from 4 to 6202. Safety was assessed for vaginal (n=13), penile (n=3) and anal use (n=2). Most studies assessed safety of Carraguard (53%), followed by Divine9 (14%), and one each of iota-carrageenan gel, lambda-carrageenan gel, Carvir, PC-6500 (griffithsin and carrageenan) and PC-1005 (MIV-150/zinc acetate/carrageenan). Safety assessment relied on self-report (80.0%), testing for STIs (53.3%), investigator-identified genital findings (93.3%) and/or testing for changes in genital flora (60.0%). Adverse events (AEs) were described by investigators as mostly mild, (mostly) comparable between groups, not observed and/or not significant for vaginal and penile use. Only one study, assessing anal use of carrageenan, reported a significantly higher proportion of AEs in the carrageenan compared with placebo group. CONCLUSIONS: Carrageenan-based gels are generally well tolerated for vaginal and penile, but not anal use. Studies on carrageenan gel's safety for anal use are scarce.