Obtenção e caracterização de sistemas particulados de quitosana para liberação gástrica de amoxicilina

The infection caused by Helicobacter pylori (H. pylori) is associated with gastroduodenal inflammation can lead to the development of gastritis, gastric or duodenal ulcer and gastric cancer (type 1 carcinogen for stomach cancer). Amoxicillin is used as first-line therapy in the treatment of H. pylori associated to metronidazole or clarithromycin, and a proton pump inhibitor. However, the scheme is not fully effective due to inadequate accumulation of antibiotics in gastric tissue, inadequate efficacy of ecological niche of H. pylori, and other factors. In this context, this study aimed to obtaining and characterization of particulate systems gastrorretentivos chitosan - amoxicillin aiming its use for treatment of H. pylori infections. The particles were obtained by the coacervation method / precipitation using sodium sulfate as precipitating agent and crosslinking and two techniques: addition of amoxicillin during preparation in a single step and the sorption particles prior to amoxycillin prepared by coacervation / precipitation and spray drying. The physicochemical characterization of the particles was performed by SEM, FTIR, DSC, TG and XRD. The in vitro release profile of amoxycillin free and incorporated in the particles was obtained in 0.1 N HCl (pH = 1.2). The particles have higher encapsulation efficiency to 80% spherical shape with interconnected particles or adhered to each other, the nanometric diameter to the systems obtained by coacervation / precipitation and fine for the particles obtained by spray drying. The characterization by FTIR, DSC and XRD showed that the drug was incorporated into the nanoparticles dispersed in the polymeric matrix. Thermal analysis (TG and DSC) indicated that encapsulation provides greater heat stability to the drug. Amoxicillin encapsulated in nanoparticles had slower release compared to free drug. The particles showed release profile with a faster initial stage (burst effect) reaching a maximum at 30 minutes 35% of amoxicillin for the system in 1: 1 ratio relative to the polymer and 80% for the system in the ratio 2: 1. Although simple and provide high encapsulation efficiency of amoxicillin, the process of coacervation, precipitation in one step using sodium sulfate as precipitant / cross-linker must be optimized in order to adjust the release kinetics according to the intended application.

Prevalence and control of Clostridium difficile in patients with cystic fibrosis

The aim of this thesis was to investigate the high prevalence of Clostridium difficile in patients with cystic fibrosis (CF), and to control its dissemination. To determine the carriage rate of C. difficile in CF patients, 60 patients were tested for C. difficile and its toxin. In total, 50% of patients were found to be asymptomatic carriers of C. difficile despite toxin being detected in 31.66% of patients. Ribotyping of the C. difficile isolates revealed 16 distinct ribotypes, including the hyper virulent RT078. All isolates were sensitive to both Vancomycin and Metronidazole. The effect of CF and its treatment on the gut microbiota of CF patients was assessed by 16s sequencing of the gut microbiota of 68 CF patients. When compared to a healthy control group, CF patient gut microbiota was found to be less diverse and had an increased Firmicutes to Bacteriodetes ratio. Interestingly, CF patients who were carriers of C. difficile had a less diverse gut microbiota than C. difficile negative CF patients. Multilocus sequence typing was found to be comparable to PCR-ribotyping for typing C. difficile isolates from high risk patient groups. The sequence type ST 26 is potentially associated with CF patients as all seven isolates were found in this group and this sequence type has been previously reported in CF patients in a geographically distinct study. The bacteriophage ФCD6356 was assessed as a targeted antimicrobial against C. difficile in an ex-vivo model of the human distal colon. Despite reducing viable C. difficile by 1.75 logs over 24 hours, this bacteriophage was not suitable due to its lysogenic nature. Following treatment, all surviving C. difficile were immune to reinfection due to prophage integration. However, the ФCD6356 encoded endolysin was capable of reducing viable C. difficile by 2.9 over 2 hours in vitro after being cloned and expressed in Escherichia coli.

Use of oral rehydration therapy in the treatment of childhood diarrhoea in Douala, Cameroon

Introduction The use of oral rehydration solutions in our context remains limited. This study was conducted to analyze the rate of this use in Douala, Cameroon and thereby determine the factors associated with it. Method A cross-sectional survey was administered to parents of children aged five years and younger during a six-month study period. The studied variables focused on the socio-demographic data of the population, data on diarrhoea and its severity, data on oral rehydration salts (ORS), and data related to other interventions for diarrhoea. The chi-square test was used to qualify associations between variables, with the significance level being set at 5%. Results Overall, 672 people agreed to participate in the study. Among them, 418 (62.2%) correctly defined diarrhoea. When their children develop diarrhoea, the majority of the parents (348, 51.8%) reported seeking hospital assistance before any intervention, while 225 parents (33.5%) preferred the use of ORS first. Four hundred seventy-five parents (70.7%) had heard of ORS and among them 313 (65.9%) had actually given ORS to their children as treatment during these children’s most recent episodes of diarrhoea. Of the parents who had given their children ORS, 217 (69.3%) knew how to prepare it, and 122 (39.0%) knew how to administer it. One hundred thirty-five parents (20.1%) had administered metronidazole to treat their children’s diarrhoea. The age of the children, the parents’ level of education, and the number of children in the household significantly influenced the use or non-use of ORS (respectively, p < 0.001, p = 0.003 and p < 0.0001). Rehydration was correctly identified by 234 parents (34.8%) as the purpose of administering ORS. Conclusion The knowledge and the use of ORS in diarrhoea by the study sample was insufficient. The role of ORS was poorly known. Awareness campaigns can be carried out in order to improve the use of this effective intervention for diarrhoea.

A review of patients with advanced cervical cancer presenting to palliative care services at Queen Elizabeth Central Hospital in Blantyre, Malawi

Background Cervical cancer is the commonest cancer affecting women in Malawi, which has the highest rate of this disease in the world. Most cases are diagnosed at an advanced stage. Aim To describe the symptom burden, palliative care interventions, and outcomes of cervical cancer patients who entered care at Tiyanjane Clinic in Blantyre, Malawi, between January and December 2012. Methods We reviewed the case files of 72 patients presenting to our hospital-based palliative care service over one year. Results The mean age was 49.5 years. Twenty-six patients (36%) were HIVpositive and the majority of these (n = 22; 85%) were on antiretroviral medication at presentation to palliative care. Pain (n = 66; 92%), vaginal discharge (n = 44; 61%), and unpleasant odour (n = 37; 51%) were commonly reported. Over a third of patients (n = 26; 36%) reported pain in two or more sites. Fourteen patients (19%) reported vaginal bleeding. Spousal breakdown (through widowhood or divorce) was noted in over half (n = 41; 57%) of all cases. Pain relief was provided to 69 (96%) of the patients (morphine to 40 patients; 56%). Common interventions provided included metronidazole tablets (used vaginally), sanitary items, and counselling. At the end of the study period, 18 patients (25%) were still under the care of palliative services. Conclusions Access to medications such as morphine, metronidazole and tranexamic acid can improve quality of life, even when radiotherapy is limited. Health care teams require necessary skills and training, including how to perform a comprehensive assessment, with an emphasis on the provision of psychosexual counselling, to assist with the complexity of symptoms occurring in this vulnerable group.

Emerging pathogens in the central nervous system: a cerebral abscess by Streptococcus porcinus

Brain abscesses can cause an incapacitating neurological deicit in up to 50% of patients, thus the reduction of these sequelae becomes the main goal of its timely and speciic surgical and medical treatment. With technological advances in bacteriological identiication and diagnostic imaging, the clinical suspicion can be conirmed, and the speciic etiological agent can be identiied in a larger number of cases. New pathogens have emerged through this process, such as Streptococcus porcinus, in which the ability to affect the central nervous system has not been documented. A clinical case is presented of a brain abscess in an immunocompetent patient, and its favorable response to surgical drainage t hrough a skull burr h ole and nee dle aspiration with antibiotic therapy (ceftriaxone, metronidazole and vancomycin) is discussed.

Primary Antibiotic Resistance to Helicobacter pylori Strains Isolated From Children in Northern Iran: A Single Center Study

Background: Initial resistance to antibiotics is the main reason for the failure of Helicobacter pylori (H. pylori) eradication in children. Objectives: As we commonly face high antibiotic resistance rates in children, we aimed to determine the susceptibility of H. pylori to common antibiotics. Patients and Methods: In this cross-sectional in vitro study, 169 children younger than 14 years with clinical diagnosis of peptic ulcer underwent upper gastrointestinal endoscopy. Biopsy specimens from stomach and duodenum were cultured. In isolated colonies, tests of catalase, urease, and oxidase as well as gram staining were performed. After confirming the colonies as H. pylori, the antibiogram was obtained using disk diffusion method. Results: Culture for H. pylori was positive in 12.3% of the specimens, urease test in 21.3%, serological test in 18.9% and stool antigen test was positive in 21.9%. We could show high specificity but moderate sensitivity of both histological and H. pylori stool antigen tests to detect H. pylori. The overall susceptibility to metronidazole was 42.9%, amoxicillin 95.2%, clarithromycin 85.7%, furazolidone 61.9%, azithromycin 81.0%, and tetracycline 76.2% with the highest resistance to metronidazole and the lowest to clarithromycin. Conclusions: In our region, there is high resistance of H. pylori to some antibiotics including metronidazole and furazolidone among affected children. To reduce the prevalence of this antibiotic resistance, more controlled use of antibiotics should be considered in children.

Australasian Society of Infectious Diseases updated guidelines for the management of Clostridium difficile infection in adults and children in Australia and New Zealand

The incidence of Clostridium difficile infection (CDI) continues to rise, whilst treatment remains problematic due to recurrent, refractory and potentially severe nature of disease. The treatment of C. difficile is a challenge for community and hospital-based clinicians. With the advent of an expanding therapeutic arsenal against C. difficile since the last published Australasian guidelines, an update on CDI treatment recommendations for Australasian clinicians was required. On behalf of the Australasian Society of Infectious Diseases, we present the updated guidelines for the management of CDI in adults and children.

Utilización de antimicrobianos en las infecciones odontogénicas en niños y adolescentes: análisis farmacocinético/farmacodinámico (PK/PD)

El objetivo de este estudio es evaluar la eficacia de los tratamientos más utilizados en infecciones odontogénicas en niños y adolescentes aplicando criterios farmacocinéticos/farmacodinámicos (PK/PD). Se han simulado las curvas de concentración plasmática libre-tiempo a partir de parámetros farmacocinéticos medios de amoxicilina, amoxicilina-ácido clavulánico, cefuroxima axetilo, espiramicina, clindamicina, azitromicina y metronidazol. Para los antibióticos con actividad dependiente del tiempo, se ha calculado el tiempo durante el cual las concentraciones permanecen por encima de la concentración inhibitoria mínima (CIM90) de los microorganismos (T>CIM). Para los antimicrobianos con actividad dependiente de la concentración, se ha calculado el cociente entre el área bajo la curva y la CIM90 (ABC/CIM90). Con amoxicilina-ácido clavulánico (80 mg/kg/día) se han obtenido índices de eficacia adecuados frente a los microorganismos estudiados (T > CIM > 40%), excepto paraVeillonella spp. Clindamicina (40 mg/kg/día) también ha presentado índices PK/PD adecuados frente a la mayoría de los patógenos, excepto Lactobacillus, Actinobacillus actinomycetemcomitans, Peptostreptococcus resistente a penicilina y Eikenella corrodens. Con dosis altas de amoxicilina los resultados no han sido satisfactorios frente a varias especies bacterianas. Con azitromicina y metronidazol no se han alcanzado valores adecuados frente a la mayoría de patógenos (ABC/CIM90 < 25). En conclusión, el tratamiento empírico más adecuado en infecciones odontogénicas en niños y adolescentes es amoxicilina-ácido clavulánico en altas dosis de amoxicilina, aunque se puede utilizar como alternativa clindamicina. Sería conveniente confirmar estos resultados mediante ensayos clínicos, para cuyo diseño y evaluación podría ser de gran utilidad la aplicación de estudios PK/PD.