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.

Antimicrobial efficacy and bonding properties of orthodontic bonding systems enhanced with silver nanoparticles: a systematic review with meta-analysis.

The aim of this systematic review was to assess the antimicrobial effectiveness of silver nanoparticles (AgNPs) incorporated to different orthodontic bonding systems. Additionally, the review investigated the impact of AgNPs on the bonding properties of these materials. The hypothesis posed that the addition of AgNPs would enhance the antimicrobial efficacy of orthodontic bonding systems while maintaining their bonding properties. The systematic review employed a PICO-based search strategy, targeting in vitro studies focusing on the integration of nano silver particles into orthodontic bonding systems with potential antimicrobial activity. The intervention involved the use of nano silver in orthodontic bonding systems, with a comparison to systems lacking nano silver. The primary outcomes assessed were antimicrobial activity and shear bond strength (SBS). The search process, conducted without publication date restrictions, yielded 551 potential articles: 34 from PubMed, 360 from PubMed Central, 42 from Embase, 54 from Scopus, and 61 from Web of Science. Ultimately, a qualitative synthesis was conducted on 13 papers. The PRISMA diagram, visually represented the search strategy, screening process, and inclusion criteria. The study protocol was registered in PROSPERO CRD42023487656 to enhance transparency and adherence to systematic review guidelines. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale, revealing that the 13 articles meeting the inclusion criteria demonstrated a high level of evidence. Seven studies were included in the meta-analysis regarding shear bond strength. In summary, the synthesized findings from these studies strongly underscore the promising potential of orthodontic materials modified with AgNPs. These materials exhibit effective resistance against cariogenic bacteria without compromising bonding properties below clinical acceptability. Such innovative materials hold significant implications for advancing oral health within the realm of orthodontics.

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.

An Analysis of the Use of Topical Ocular Anti-Infectives in Galicia (Spain) between 2020 and 2023.

Eye infections are a global health and economic problem that affect people of both sexes at any age. Topical application of anti-infectives is widely used in the treatment of these types of infections. However, little is known about the current status and trends of the use of topical ocular anti-infectives in Spain. In the present work, we evaluated the use of this type of drug in the Spanish autonomous community of Galicia and described the variability in its consumption between Galician provinces between 2020 and 2023. In addition, the possible existence of a deviation in consumption at a seasonal level was evaluated, as well as possible changes during the study period. A descriptive, cross-sectional and retrospective study of the use of drugs belonging to the subgroups S01A (anti-infectives) and S01C (anti-inflammatory agents and anti-infectives in combination) of the Anatomic Therapeutic Chemical Classification was carried out. This work demonstrated that the most used topical ocular anti-infective in Galicia was tobramycin and that the use of these types of drugs in our region varied according to the provinces. This study also revealed that the consumption of these medications has remained stable during the period 2020-2023, with no significant seasonal differences observed.

Unveiling the promise: Exosomes as game-changers in anti-infective therapy.

Extracellular vesicles (EVs)-based intercellular communication (through exosomes, microvesicles, and apoptotic bodies) is conserved across all kingdoms of life. In recent years, exosomes have gained much attention for targeted pharmaceutical administration due to their unique features, nanoscale size, and capacity to significantly contribute to cellular communication. As drug delivery vehicles, exosomes have several advantages over alternative nanoparticulate drug delivery technologies. A key advantage lies in their comparable makeup to the body's cells, which makes them non-immunogenic. However, exosomes vesicles face several challenges, including a lack of an effective and standard production technique, decreased drug loading capacity, limited characterization techniques, and underdeveloped isolation and purification procedures. Exosomes are well known for their long-term safety and natural ability to transport intercellular nucleic acids and medicinal compounds across the blood-brain-barrier (BBB). Therefore, in addition to revealing new insights into exosomes' distinctiveness, the growing availability of new analytical tools may drive the development of next-generation synthetic systems. Herein, light is shed on exosomes as drug delivery vehicles in anti-infective therapy by reviewing the literature on primary articles published between 2002 and 2023. Additionally, the benefits and limitations of employing exosomes as vehicles for therapeutic drug delivery are also discussed.

Acute Cystitis in a Transfeminine Patient: Assessment and Treatment of Urinary Tract Symptoms.

Management of acute cystitis in a transfeminine patient is discussed as an example of treatment of urinary tract infections (UTIs). The case is an introduction for clinicians who typically care for cisgender women and wish to expand the populations they serve to include care of gender-diverse individuals. This is supportive of the 2021 American College of Nurse-Midwives Position Statement on Health Care for Transgender and Gender Non-Binary People. Possible differential diagnoses for urinary symptoms in transfeminine patients are discussed, as well as relevant history taking, examination skills, and treatment guidelines for acute cystitis of patients with penises along with discussion of basic care for transgender individuals seeking midwifery or primary care services.

ß-Carboline-3-carboxamide Antimalarials: Structure-Activity Relationship, ADME-Tox Studies, and Resistance Profiling.

The development of parasite resistance to both artemisinin derivatives and their partner drugs jeopardizes the effectiveness of the artemisinin combination therapy. Thus, the discovery of new antimalarial drugs, with new mechanisms of action, is urgently needed. We recently disclosed that ß-carboline 1a was orally efficacious in Plasmodium berghei-infected mice and that it showed low cross-resistance between susceptible Plasmodium falciparum and four different drug-resistant strains. In this report, we describe the synthesis and in vitro antimalarial evaluation of 91 new derivatives of 1a. The asexual blood stage growth inhibition data show a clear preference for a 3,4-dihalogenated, 3,5-dihalogenated, 3,4,5-trichloro-, or 4-trifluoromethyphenyl ring at the C1-position. The most potent compound, 3,4,5-trichlorophenyl-substituted 42a, is twice as potent as 1a. Six potent analogues were assessed for their drug-like properties, and four of these were subjected to in vitro barcoded cross-resistance profiling. Compounds 1a, 1m, 42a, and 42m showed no cross-resistance to 32 resistance mutations on the Dd2 genetic background and 10 resistance mutations on the 3D7 genetic background. These data suggest that compounds in this scaffold possess a novel mechanism of antimalarial action.

Drugs Targeting Sirtuin 2 Exhibit Broad-Spectrum Anti-Infective Activity.

Direct-acting anti-infective drugs target pathogen-coded gene products and are a highly successful therapeutic paradigm. However, they generally target a single pathogen or family of pathogens, and the targeted organisms can readily evolve resistance. Host-targeted agents can overcome these limitations. One family of host-targeted, anti-infective agents modulate human sirtuin 2 (SIRT2) enzyme activity. SIRT2 is one of seven human sirtuins, a family of NAD+-dependent protein deacylases. It is the only sirtuin that is found predominantly in the cytoplasm. Multiple, structurally distinct SIRT2-targeted, small molecules have been shown to inhibit the replication of both RNA and DNA viruses, as well as intracellular bacterial pathogens, in cell culture and in animal models of disease. Biochemical and X-ray structural studies indicate that most, and probably all, of these compounds act as allosteric modulators. These compounds appear to impact the replication cycles of intracellular pathogens at multiple levels to antagonize their replication and spread. Here, we review SIRT2 modulators reported to exhibit anti-infective activity, exploring their pharmacological action as anti-infectives and identifying questions in need of additional study as this family of anti-infective agents advances to the clinic.

An insight into pharmacokinetics and dose optimization of antimicrobials agents in elderly patients.

The global elderly population is on the rise, and infections tend to have a higher mortality rate among older individuals. Aging is associated with the progressive impairment of multi-organ function, which can impact the pharmacokinetics of antimicrobials, potentially leading to the failure of anti-infective therapy. With the increasing life expectancy, a significant growth in the elderly demographic, and the escalating costs of healthcare, gaining a thorough understanding of pharmacokinetic changes in the elderly holds crucial clinical significance. This review compiles findings from published studies, offering a comprehensive overview of the pharmacokinetics of various antimicrobials in both adults and the elderly. Furthermore, it delves into advancements in pharmacokinetic methods specific to the elderly population.

From clove oil to bioactive agents: synthetic routes, antimicrobial and antiparasitic activities of eugenol derivatives.

Eugenol, a natural compound found in essential oils such as clove oil, has been extensively studied for its diverse biological activities including the therapeutic potential against microbial and parasitic infections. This review provides an overview of the synthetic strategies (shown in Supplementary Material) employed to develop bioactive derivatives and analogues derived from eugenol and related compounds (e.g., dihydroeugenol and isoeugenol), focusing on biological activity of more than 100 bioactive eugenol derivatives against bacterial, fungal, viral and protozoal pathogens. Through a comprehensive survey of literature, this paper shows the impact of structural modifications of these phenylpropanoids on antimicrobial and antiparasitic activity. Key findings highlight promising candidates for further development in antimicrobial drug discovery, suggesting directions for future research in the pursuit of effective therapeutic agents.

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[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.

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.

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.

Formulation of three tailed bacteriophages by spray-drying and atomic layer deposition for thermal stability and controlled release.

Deep infection is the second most common complication of arthroplasty following loosening of the implant. Antibiotic-loaded bone cements (ALBCs) and high concentrations of systemic broad-spectrum antibiotics are commonly used to prevent infections following injury and surgery. However, clinical data fails to show that ALBCs are effective against deep infection, and negative side effects can result following prolonged administration of antibiotics. Additionally, the rise of multidrug resistant (MDR) bacteria provides an urgent need for alternatives to broad-spectrum antibiotics. Phage therapy, or the use of bacteriophages (viruses that infect bacteria) to target pathogenic bacteria, might offer a safe alternative to combat MDR bacteria. Application of phage therapy in the setting of deep infections requires formulation strategies that would stabilize bacteriophage against chemical and thermal stress during bone-cement polymerization, that maintain bacteriophage activity for weeks or months at physiological temperatures, and that allow for sustained release of phage to combat slow-growing, persistent bacteria. Here, we demonstrate the formulation of three phages that target diverse bacterial pathogens, which includes spray-drying of the particles for enhanced thermal stability at 37 °C and above. Additionally, we use atomic layer deposition (ALD) to coat spray-dried powders with alumina to allow for delayed release of phage from the dry formulations, and potentially protect phage against chemical damage during bone cement polymerization. Together, these findings present a strategy to formulate phages that possess thermal stability and sustained release properties for use in deep infections.

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.