Estudio clínico comparativo de la eficacia de azitromicina frente a amoxicilina/Ac. Clavulánico en el tratamiento de infecciones orales.

Fundamentos: el objetivo de este estudio fue comparar la eficacia. seguridad y tolerancia de la azitromicina frente a amoxicilina/ac. clavulánico en el tratamiento de pacientes con infecciones bucales agudas de origen odontogénico. Pacientes y Método: en este estudio abierto, comparativo y multicéntrico, se incluyeron 208 pacientes con infección bucal aguda de origen odontogénico, asignados aleatoriamente a dos grupos; 102 pacientes recibieron azitromicina, y 106 pacientes recibieron amoxicilina/ac. clavulánico. Se realizaron una historia clínica y una exploración física, y se tomaron muestras de sangre y orina. En cada una de las visitas, se recogieron los signos y síntomas característicos de la infección. Resultados: el nivel de respuesta fue similar en ambos grupos terapéuticos, obteniéndose un porcentaje de curación o mejoría superior al 90%. Azitromicina fue mejor tolerada y tuvo mejor cumplimiento que amoxicilina/ac. clavulánico. Los efectos adversos fueron en su mayoría gastrointestinales. Conclusión: Azitromicina y amoxicilina/clavulánico fueron igualmente efectivos en el tratamiento de infecciones agudas de origen odontogénico.

Role of Inflammatory Monocytes in Vaccine-Induced Reduction of Helicobacter felis Infection.

Despite the proven ability of immunization to reduce Helicobacter infection in mouse models, the precise mechanism of protection has remained elusive. In this study, we evaluated the role of inflammatory monocytes in the vaccine-induced reduction of Helicobacter felis infection. We first showed by using flow cytometric analysis that Ly6C(low) major histocompatibility complex class II-positive chemokine receptor type 2 (CCR2)-positive CD64(+) inflammatory monocytes accumulate in the stomach mucosa during the vaccine-induced reduction of H. felis infection. To determine whether inflammatory monocytes played a role in the protection, these cells were depleted with anti-CCR2 depleting antibodies. Indeed, depletion of inflammatory monocytes was associated with an impaired vaccine-induced reduction of H. felis infection on day 5 postinfection. To determine whether inflammatory monocytes had a direct or indirect role, we studied their antimicrobial activities. We observed that inflammatory monocytes produced tumor necrosis factor alpha and inducible nitric oxide synthase (iNOS), two major antimicrobial factors. Lastly, by using a Helicobacter in vitro killing assay, we showed that mouse inflammatory monocytes and activated human monocytes killed H. pylori in an iNOS-dependent manner. Collectively, these data show that inflammatory monocytes play a direct role in the immunization-induced reduction of H. felis infection from the gastric mucosa.

Oxidative stress in gastric mucosa of asymptomatic humans infected with Helicobacter pylori: effect of bacterial eradication.

BACKGROUND: Inducible nitric oxide synthase (iNOS) and interleukin 8 (IL-8) are positive in approximately 50% of Helicobacter pylori-related diseases but it is not clear whether oxidative stress is also present in H. pylori asymptomatic humans. Our aim was to study the expression of iNOS, superoxide dismutase, catalase and IL-8 production in H. pylori-infected asymptomatic humans, and to investigate the effect of eradication of H. pylori. MATERIALS AND METHODS: Biopsies of corpus and antrum of asymptomatic H. pylori positive and negative humans served for determination of the gastritis score and H. pylori status; iNOS was measured by reverse transcriptase polymerase chain reaction and immunohistochemistry and superoxide dismutase and catalase by immunohistochemistry. IL-8 in biopsies was assessed by enzyme-linked immunosorbent assay. RESULTS: Immunostaining of iNOS, catalase and superoxide dismutase was significantly associated with H. pylori infection and was localized to inflammatory cells. IL-8 concentrations were greater in the H. pylori positive than H. pylori negative group and decreased after bacterial eradication. A decrease in staining for iNOS and catalase was observed after H. pylori eradication. CONCLUSIONS: INOS and antioxidant enzymes are present in gastric biopsies of asymptomatic H. pylori positive humans. Eradication caused a significant decrease in staining for iNOS and catalase. These results indicate that oxidative stress occurs in asymptomatic patients and can be modulated by H. pylori eradication.

Tómese unos minutos para revisar sus conocimientos sobre Transmisión de infecciones. Autoprotección del personal sanitario

En la transmisión de infecciones se mezclan las evidencias científicas, los miedos y las valoraciones personales del riesgo de contagio, en ocasiones inadecuadas, dado que el concepto"riesgo" es siempre subjetivo y difícil de definir. Todo ello puede generar conceptos erróneos o no totalmente ciertos. Esta autoevaluación es una pequeña contribución para separar"los mitos y/o leyendas sanitarias" de las realidades en relación con los riesgos de transmisión de algunas infecciones al personal sanitario.

Tómese unos minutos para revisar sus conocimientos sobre Transmisión de infecciones. Autoprotección del personal sanitario

En la transmisión de infecciones se mezclan las evidencias científicas, los miedos y las valoraciones personales del riesgo de contagio, en ocasiones inadecuadas, dado que el concepto"riesgo" es siempre subjetivo y difícil de definir. Todo ello puede generar conceptos erróneos o no totalmente ciertos. Esta autoevaluación es una pequeña contribución para separar"los mitos y/o leyendas sanitarias" de las realidades en relación con los riesgos de transmisión de algunas infecciones al personal sanitario.

How to get rid of a pathobiontic bacterium from the stomach mucosa : role of inflammatory monocytes and IL-22 in the vaccine-induced reduction of helicobacter infection

Helicobacter pylori is a bacterium colonizing the human stomach. To prevent or cure this potentially detrimental infection, vaccination might be a suitable alternative to antibiotic therapies. Recently, a study has demonstrated that a vaccine efficiently prevented H pylori infection in human. However, the mechanisms leading to protection remain elusive. In mice, the vaccine-induced protective response relies on CD4+ T cells and especially on Thl7 response. Nevertheless, the factors mediating the reduction of H pylori infection are not fully characterized. Hence, the aim of my thesis was to characterize the factors associated with the Thl7 response. In the context of the vaccine-induced reduction of Helicobacter infection, I first focused on the role of inflammatory monocytes. I showed that CDllb+Ly6CLOW inflammatory monocytes accumulated in the stomach of vaccinated mice in association with the reduction of Helicobacter infection. Remarkably, the depletion of inflammatory monocytes delayed the vaccine-induced protective response. Concerning the role of these cells, I demonstrated that inflammatory monocytes extracted from the stomach of vaccinated mice produced iNOS and killed H pylori in vitro. In a next step, I evaluated the role of IL-22 during the vaccine-induced response. IL-22, which is linked to the Thl7 response, increases innate defense mechanisms of epithelial cells. I demonstrated that IL-22 produced by antigen- specific Thl7 was increased in the stomach of vaccinated mice during the protective response. Interestingly, neutralization of IL-22 was associated with an impaired vaccine-induced protective response. Then, I demonstrated that IL-22 induced antimicrobial peptides (AMPs) secretion by epithelial cells. These AMPs killed H pylori in vitro. In conclusion, I showed that both inflammatory monocytes and IL-22 participated to the vaccine induced reduction of Helicobacter infection. In addition, I demonstrated that the epithelium along with inflammation induced by Thl7 response is a critical factor mediating reduction of Helicobacter infection.

Susceptibilidad antibiótica de las bacterias causantes de infecciones odontogénicas

Objetivos: Identificar la flora bacteriana y su susceptibilidad a varios antibióticos utilizados en infecciones odontogénicas de localización periapical y en las pericoronaritis del tercer molar inferior, para poder adaptar convenientemente el tratamiento antibiótico a las exigencias de tales infecciones, y evitar así los efectos secundarios y los sobretratamientos con antibióticos. Material y métodos: Se han seleccionado con unos criterios de inclusión y de exclusión a 64 pacientes que presentaban una infección odontogénica. Se recogieron muestras de las lesiones en condiciones de máxima asepsia, evitando la contaminación por flora saprófita bucal. Las muestras se sembraron en medios de cultivo apropiados y se incubaron en condiciones aeróbicas y anaeróbicas; finalmente se procedió a la identificación de los microorganismos aislados y a la determinación de su susceptibilidad antibiótica, los resultados se analizaron estadísticamente mediante la prueba t-Student (para muestras aparejadas y para una muestra). Resultados: Se aislaron un total de 184 cepas bacterianas, incluyendo cocos Gram positivo anaerobios facultativos (68%), bacilos Gram negativo anaerobios estrictos (30%), y bacilos Gram positivo anaerobios facultativos (2%). Independientemente del origen de la infección odontogénica los antibióticos que obtuvieron los mejores resultados en cuanto a mayor sensibilidad y menor resistencia estadísticamente significativos fueron respectivamente la amoxicilina/clavulánico y la amoxicilina (p<0,05). Discusión: Cada vez hay más estudios que indican el alto índice de resistencias a antibióticos en poblaciones bacterianas patógenas que producen infecciones en territorios no bucodentales. A pesar de ello, los niveles de resistencia a los antibióticos en las infecciones odontogénicas no han seguido la misma tendencia, aunque se ha detectado para ciertos antibióticos un alto índice de resistencia. En nuestro trabajo hemos encontrado que los antibióticos de uso común que han obtenido mayor sensibilidad y menor resistencia han sido la amoxicilina en combinación con ácido clavulánico seguido de la amoxicilina.

Infecciones Respiratorias en el Enfermo Inmunodeprimido

El paciente inmunodeprimido se define como aquel que presenta un déficit congénito o adquirido de su respuesta inmune, integrada por neutrófilos e inmunidad humoral y celu- lar. El sistema defensivo del niño puede verse seriamente comprometido por un amplio abanico de situaciones congénitas y adquiridas ...

Targeted vs. standard treatment against Helicobacter pylori: safety assessment clinical trial

Helicobacter pylori (H. pylori) is a gram negative bacteria that represents a considerable global burden in the world and is related to many gastrointestinal diseases (peptic ulcer, gastric MALT lymphoma or gastric cancer). Currently the triple standard therapy is less used as there is an increase of the clarithromycin resistance. Therefore patients have to receive several lines of treatment with the consequence of adverse events and the possibility to interrupt the treatment. This is why the main objective is to determine if making a culture and antibiogram to do a targeted treatment cause less adverse events with the same eradication than making an empirical treatment to eradicate H. pylori. The secondary objective is to determine the prevalence of resistance to clarithromycin in the province of GironaThis is a multicentre clinical trial without blinding; patients are selected by non-probabilistic sampling, with a total sample of 868 patients randomized in two equal groups of 434 patients in each group. The study will last 2 years. The endpoints will be to evaluate the adverse events and eradication of each group of patients. Also it will be evaluated the resistance to clarithromycin

Avaliação da prevalência da infecção por helicobacter pylori em pacientes portadores de câncer gástrico

OBJETIVO: Nos últimos anos, evidências de associação entre Helicobacter pylori e câncer gástrico têm sido relatadas por inúmeros estudos. Este trabalho objetiva investigar a prevalência da infecção por este microorganismo em pacientes com câncer gástrico, oriundos do Hospital de Câncer Napoleão Laureano (João Pessoa - PB) e determinar o risco relativo para o desenvolvimento desta neoplasia nos pacientes infectados. MÉTODO: Com esta finalidade, 16 pacientes com diagnóstico confirmado de adenocarcinoma gástrico foram submetidos à endoscopia digestiva alta para coleta de fragmentos da mucosa gástrica, para realização do teste da urease, sendo então, pareados com um grupo de 16 controles com exames endoscópicos normais. RESULTADOS: Dos 16 portadores de câncer, 28,1% estavam infectados, versus 25% para os do grupo controle. Nos indivíduos infectados, houve maior prevalência da infecção nos portadores de lesões gástricas distais (43,8%), nos tumores Borrmann III (37,6%), e moderadamente diferenciados (37,6%). Houve associação estatisticamente significante entre o grau de diferenciação e a presença da infecção pelo H. pylori (p<0,10). O risco relativo estimado para a associação entre câncer gástrico e infecção pelo H. pylori foi de 1,28% (odds ratio = 1,28%). CONCLUSÃO: Estes resultados permitem concluir que a infecção pelo H. pylori é um fator de risco relativo para o desenvolvimento do adenocarcinoma gástrico.

Câncer de coto gátrico em ratos: papel da associação de Helicobacter pylori e refluxo êntero-gástrico

OBJETIVOS: Avaliar a relação entre o refluxo êntero-gástrico e Helicobacter pylori na gênese de neoplasias epiteliais e seus precursores, no rato submetido a gastrectomia subtotal com reconstrução a Billroth II. MÉTODO: Foram operados 20 ratos machos da raça Wistar, divididos igualmente em dois grupos: um grupo controle submetido à laparotomia exploradora e outro submetido à gastrectomia subtotal a BII. Após nove meses de operados, os animais foram mortos e seus estômagos estudados quanto à quantificação de H. pylori por glândula gástrica e à alterações epiteliais neoplásicas ou pré-neoplásicas. RESULTADOS: Os animais gastrectomizados tiveram percentual maior de colonização por H. pylori, assim como de alterações epiteliais que variaram do aumento do número de mitoses ao carcinoma invasor. CONCLUSÃO: O comprometimento glandular por H. pylori aumenta com o refluxo êntero-gástrico proporcionado pela gastectomia parcial, e está associado ao desenvolvimento de adenocarcinoma de coto gástrico em ratos.

Serodiagnosis of Helicobacter pylori infection by Cobas Core ELISA in adults from Minas Gerais, Brazil

We evaluated the accuracy of a 2nd generation ELISA to detect Helicobacter pylori infection in adults from a developing country in view of variations in sensitivity and specificity reported for different populations. We studied 97 non-consecutive patients who underwent endoscopy for evaluation of dispeptic symptoms. The presence of H. pylori was determined in antral biopsy specimens by culture, by the preformed urease test and in carbolfuchsin-stained smears. Patients were considered to be H. pylori positive if at least two of the three tests presented a positive result or if the culture was positive, and negative if the three tests were negative. Sixty-five adults (31 with peptic ulcer) were H. pylori positive and 32 adults were H. pylori negative. Antibodies were detected by Cobas Core anti-H. pylori EIA in 62 of 65 H. pylori-positive adults and in none of the negative adults. The sensitivity, specificity and positive and negative predictive values of the test were 95.4, 100, 100 and 91.4%, respectively. The Cobas Core anti-H. pylori EIA presented high sensitivity and specificity when employed for a population in Brazil, permitting the use of the test both to confirm the clinical diagnosis and to perform epidemiologic surveys.

A study of the interaction between Helicobacter pylori and components of the human fibrinolytic system

The interaction of plasminogen, tissue plasminogen activator (t-PA) and urokinase with a clinical strain of Helicobacter pylori was studied. Plasminogen bound to the surface of H. pylori cells in a concentration-dependent manner and could be activated to the enzymatic form, plasmin, by t-PA. Affinity chromatography assays revealed a plasminogen-binding protein of 58.9 kDa in water extracts of surface proteins. Surface-associated plasmin activity, detected with the chromogenic substrate CBS 00.65, was observed only when plasminogen and an exogenous activator were added to the cell suspension. The two physiologic plasminogen activators, t-PA and urokinase, were also shown to bind to and remain active on the surface of bacterial cells. epsilon-Aminocaproic acid caused partial inhibition of t-PA binding, suggesting that the kringle 2 structure of this activator is involved in the interaction with surface receptors. The activation of plasminogen by t-PA, but not urokinase, strongly depended on the presence of cells and a 25-fold enhancer effect on the initial velocity of activation by t-PA compared to urokinase was established. Furthermore, a relationship between cell concentration and the initial velocity of activation was demonstrated. These findings support the concept that plasminogen activation by t-PA on the bacterial surface is a surface-dependent reaction which offers catalytic advantages.

Eradication of Helicobacter pylori infection in patients with duodenal ulcer and non-ulcer dyspepsia and analysis of one-year reinfection rates

Helicobacter pylori (HP) infection is endemic worldwide. The proposed treatment is expensive and there are few reports regarding reinfection rates in Brazil. The aim of this study was to compare the eradication rates obtained with two therapeutic options and to evaluate reinfection one year after treatment. This was a prospective randomized trial with 55 patients. Thirty-nine patients had active duodenal ulcer (DU) and 16 non-ulcer dyspepsia (NUD), and all tested positive for HP. Diagnosis was based on at least two positive tests: ultrarapid urease test, histology and/or culture. Patients were randomized to two groups: group OMC treated with 40 mg omeprazole (once a day), 500 mg metronidazole and 250 mg clarithromycin (twice daily) for 7 days, or group NA treated with 300 mg nizatidine (once a day) and 1000 mg amoxicillin (twice daily) for 14 days. Those patients in whom HP was eradicated were followed up for one year to evaluate reinfection. Twenty-five patients were randomized for OMC and 30 for NA. HP eradication occurred in 20/25 patients (80%) treated with OMC and 13/30 (43%) treated with NA (P = 0.01). After reallocation because of initial treatment failure, the overall eradication rate was 44/51 patients (86%). After an average follow-up of one year, we evaluated 34 patients (23 with DU and 11 with NUD). Reinfection occurred in 3/34 patients (7.6%). We conclude that OMC is effective for HP eradication, and that NA should not be used. Reinfection occurs in 7.6% of the patients in the first year after eradication.

The effect of CagA status on response to Helicobacter pylori eradication therapy in Western Turkey

If cytotoxin-associated gene A (CagA) status affects the response rates of therapy, then it may be possible to predict Helicobacter pylori eradication rates. We aimed to evaluate the response to eradication treatment of H. pylori infection in CagA-positive and CagA-negative patients. A total of 184 patients (93 males, 91 females, mean age 42.6 ± 12.8 years) with H. pylori-positive chronic gastritis were studied. Subjects underwent a gastroscopy and biopsy specimens were taken from the gastric antrum, body, and fundus. Before the eradication therapy was given all patients were tested for CagA, TNF-alpha and gastrin levels. They were then prescribed lansoprazole (30 mg bid), clarithromycin (500 mg bid), and amoxicillin (1.0 mg bid) for one week. On the 8th week a second endoscopy was performed and further biopsy specimens were obtained from the same sites as in the initial endoscopy. One hundred and twenty-seven patients (69.1%) were found to be CagA positive and 57 patients (30.9%) were CagA negative. The total eradication rate was 82.6%. In the CagA-positive group this rate was 87.4%, and in the CagA-negative group it was 71.9% (P = 0.019). TNF-alpha levels were higher in the CagA-positive than in the CagA-negative group (P = 0.001). However, gastrin levels were not different between groups (P = 0.421). Our findings revealed that CagA-negative status might be a risk factor for failure of H. pylori triple therapies. The CagA pathogenicity island gives a growth advantage to H. pylori strains and has been associated with an increase in the inflammatory response at the gastric mucosal level. These properties could make CagA-positive H. pylori strains more susceptible to antibiotics.