A pilot study evaluating high dose esomeprazole, bismuth subcitrate and amoxicillin for eradicating Helicobacter pylori infection in Iran.

BACKGROUND: Helicobacter pylori (H. pylori) is strongly associated with peptic ulcer disease and gastric cancer. We evaluated two triple therapy regimens comprising esomeprazole, high dose bismuth, and different doses of amoxicillin for first-line H. pylori eradication. MATERIALS AND METHODS: Two hundred patients with dyspepsia and naive H. pylori infection were randomly assigned into two groups (n = 100). Both groups were treated for 14 days similarly with esomeprazole (40 mg, twice daily) and bismuth subcitrate (240 mg, three times daily), but the dose of amoxicillin was varied between Groups A (750 mg) and B (1000 mg) three times daily. Treatment compliance and side effect were evaluated following the therapies and after 8 weeks, a negative test of stool H. pylori antigen confirmed eradication. RESULTS: The two groups were comparable with respect to sex and age. According to intention to treat analysis, eradication rates were 80% (95% CI: 77.2%-82.8%) and 90% (95% CI: 84.1%-95.9%) in A and B groups, respectively (p = 0.22). Per-protocol eradication rates were 87% (95% CI: 80.4%-93.6%) and 92.8% (95% CI: 87.7%-97.9%), respectively (p = 0.23). Severe adverse effects were 3% and 2%, respectively (p = 0.34). CONCLUSION: High dose esomeprazole, amoxicillin and bismuth achieved 92.8% cure rates per protocol in a country with a high background rate of resistance. Additional studies are needed to ascertain whether this therapy can be further improved. Until then, it can be recommended as a first-line H. pylori eradication in north of Iran.

Acidente de hipoclorito de sódio durante retratamento endodôntico / Sodium hypochlorite accident during endodontic retreatment / Accidente con hipoclorito de sodio durante retratamiento

O retratamento endodôntico é uma intervenção executada em um dente que já apresenta um tratamento realizado anteriormente que foi mal sucedido clínica e/ou radiograficamente. O objetivo deste trabalho foi o de relatar um caso de retratamento endodôntico na clínica de Atenção Básica III da Faculdade de Odontologia de Pernambuco devido ao desconforto estético do incisivo lateral superior que estava fraturado e necessitando de prótese fixa. Após anamnese, exames extra e intra-oral e exames radiográficos, constatou-se o canal do dente 12 havia sido tratado endodonticamente há aproximadamente quatro anos. A remoção da gutta percha contaminada foi realizada com as limas rotatórias EasyLogic RT® 25mm sequência 30.10 torque 4N e 900 RPM, 25.08 torque 4Ne 900 RPM. Após remoção da guta-percha, realizou-se o protocolo de irrigação com solução de hipoclorito de sódio a 2,5% (Biodinâmic). A odontometria foi realizada com localizador apical e confirmada por radiografia periapical e o repreparo do canal radicular confeccionado com a Lima EasyLogic 2® de número 35.06 e posterior irrigação com a solução de Labarraque. Nesse momento, o paciente relatou dor e após aspiração com sugador endodôntico, notou-se sangramento abundante, correspondendo ao extravasamento do hipoclorito de sódio (Enfizema por hipoclorito de sódio. O paciente foi medicado com Amoxacilina 875mg de 12 em 12 horas durante sete dias, Predisin 20mg ­ Corticóide - um comprimido pela manhã por 4 dias e Nimesulida 100mg de 12 em 12 horas durante 5 dias. Após 24 horas o paciente não relatou dor nem edema. Na segunda sessão, 10 dias após o acidente, a obturação foi realizada com cone único de guta-percha 35.06 HBassi (Easy, associado ao cimento Bio C Sealer Fillapex (Angelus®). Concluiu-se que a conduta terapêutica imediata instituída para este caso, foi efetiva para o controle da dor e prevenção de complicações adicionais após injeção acidental de hipoclorito de sódio.

Endodontic retreatment is an intervention performed on a tooth that already has a previously performed treatment that was clinically and/ or radiographically unsuccessful. The objective of this study was to report a case of endodontic retreatment at the Primary Care Clinic III of the Faculty of Dentistry of Pernambuco due to the aesthetic discomfort of the maxillary lateral incisor that was fractured and required a fixed prosthesis. After anamnesis, extra and intraoral exams and radiographic exams, it was found that the root canal of tooth 12 had been endodontically treated for approximately four years. Removal of contaminated gutta percha with those performed with EasyLogic RT® 25mm rotary files sequence 30.10 torque 4N and 900 RPM, 25.08 torque 4N and 900 RPM. After removing the gutta-percha, the irrigation protocol was performed with a 2.5% sodium hypochlorite solution (Biodynamic). Odontometry was performed with an apex locator and confirmed by periapical radiography and root canal re-preparation made with EasyLogic 2® File number 35.06 and subsequent irrigation with Labarraque's solution. At that moment, the patient reported pain and after aspiration with an endodontic sucker, there was profuse bleeding, corresponding to sodium hypochlorite extravasation (Sodium hypochlorite emphysema. The patient was medicated with Amoxicillin 875mg every 12 hours for seven days, Predisin 20mg - Corticosteroid - one tablet in the morning for 4 days and Nimesulide 100mg every 12 hours for 5 days. After 24 hours the patient did not report pain or swelling. In the second session, 10 days after the accident, the filling was performed with a single cone of gutta-percha 35.06 HBassi (Easy, associated with Bio C Sealer Fillapex cement (Angelus®). It was concluded that the immediate therapeutic approach instituted for this case was effective for pain control and prevention of complications. additional doses after accidental injection of sodium hypochlorite.

El retratamiento endodóntico es una intervención que se realiza sobre un diente que ya tiene un tratamiento realizado previamente que resultó clínica y/o radiográficamente fallido. El objetivo de este estudio fue relatar un caso de retratamiento endodóntico en la Clínica de Atención Básica III de la Facultad de Odontología de Pernambuco debido a la incomodidad estética del incisivo lateral maxilar que estaba fracturado y requirió prótesis fija. Después de anamnesis, exámenes extraorales, intraorales y exámenes radiográficos, se encontró que el conducto radicular del diente 12 había sido tratado endodónticamente durante aproximadamente cuatro años. Eliminación de gutapercha contaminada con las realizadas con limas rotatorias EasyLogic RT® 25mm secuencia 30.10 torque 4N y 900 RPM, 25.08 torque 4N y 900 RPM. Tras retirar la gutapercha, se realizó el protocolo de irrigación con una solución de hipoclorito de sodio al 2,5% (Biodynamic). Se realizó odontometría con localizador de ápices y se confirmó mediante radiografía periapical y repreparación del conducto radicular realizada con EasyLogic 2® File número 35.06 y posterior irrigación con solución de Labarraque. En ese momento el paciente refirió dolor y luego de aspiración con ventosa endodóntica presentó sangrado profuso, correspondiente a extravasación de hipoclorito de sodio (Enfisema por hipoclorito de sodio. El paciente fue medicado con Amoxicilina 875mg cada 12 horas por siete días. Predisin 20mg - Corticosteroide - una tableta por la mañana por 4 días y Nimesulida 100mg cada 12 horas por 5 días, luego de 24 horas el paciente no refirió dolor ni hinchazón, en la segunda sesión, 10 días después del accidente, se realizó el relleno con un solo cono de gutapercha 35.06 HBassi (Easy, asociado al cemento Bio C Sealer Fillapex (Angelus®). Se concluyó que el abordaje terapéutico inmediato instituido para este caso fue eficaz para el control del dolor y la prevención de complicaciones. dosis adicionales después de accidente inyección de hipoclorito de sodio.

Podcast POEMs (BVS APS): Em crianças com pneumonia que não precisam de hospitalização, o tratamento de 5 dias com altas doses de amoxicilina é comparável ao tratamento de 10 dias?

Neste episódio vou apresentar um estudo realizado no Canadá, onde pesquisadores propuseram comparar o tratamento de 5 dias com amoxicilina com o tradicional tratamento de 10 dias para pneumonia em crianças não hospitalizadas. Também vou comentar sobre alguns aspectos metodológicos a respeito dos estudos de não inferioridade, do cegamento nos ECR e das análises por intenção de tratar.

Fiebre tifoidea: una etiología poco frecuente de síndrome febril prolongado en pediatría / Typhoid fever: a rare etiology of prolonged febrile illness in pediatrics / Febre tifoide: uma etiología rara de síndrome febril prolongada em pediatría

Introducción: Las infecciones representan la etiología más frecuente del síndrome febril prolongado (SFP). Si bien las fiebres entéricas constituyen una causa posible, en Uruguay su prevalencia ha disminuido significativamente con la mejora de las condiciones socio sanitarias. Objetivo: Comunicar el caso de un adolescente con una etiología actualmente excepcional de SFP. Caso clínico 14 años, sano, zona suburbana. Comienza 2 semanas previo al ingreso con dolor en hemiabdomen superior. Agrega cefalea holocraneana leve y vómitos ocasionales. 5 días previos al ingreso fiebre 40°C axilar, un pico diario, sin otra sintomatología. Tránsito digestivo bajo y urinario normal. Examen físico: lúcido, buen aspecto general, abdomen doloroso a la palpación profunda en epigastrio. Sin irritación peritoneal. Resto normal. Analítica: Leucocitos 5200mm3, Proteína C reactiva 71.4mg/dL, hemocultivo sin desarrollo. Ecografía abdominal, radiografía de tórax y ecocardiograma normales. Serologías para Virus Epstein Barr, Citomegalovirus, y Bartonella henselae negativas. Orina normal, urocultivo sin desarrollo. Persiste con fiebre, agrega exantema macropapular evanescente en tronco, sin otros síntomas. Al 7° día de internación nuevo hemocultivo: Salmonella Typhi sensible a ampicilina que recibe por 14 días. Buena evolución. Discusión: La fiebre tifoidea es una enfermedad infectocontagiosa, aguda, potencialmente mortal. Las condiciones socioeconómicas son determinantes en su transmisión. La sensibilidad del hemocultivo es mayor durante la primera semana de enfermedad, por lo que en ocasiones es necesario reiterarlo. Sus manifestaciones clínicas inespecíficas y la baja incidencia hacen que esta etiología no sea habitualmente sospechada en nuestro medio. Por tanto, es importante aumentar el índice de sospecha y considerar entre los diagnósticos diferenciales de SFP esta etiología.

Introduction: Infections are the most frequent etiology of prolonged febrile illness (PFI). Although enteric fevers are a possible cause, their prevalence has significantly diminished in Uruguay, due to improved socio-sanitary conditions. Objective: To communicate the case of an adolescent with a currently exceptional etiology of PFI. Clinical case: 14 years old, healthy, suburban area. Two days prior to admission the patient has pain in upper hemi abdomen. Adds mild holocranial headache and occasional vomiting. 5 days prior to admission axilary temperature of 40°C, one daily peak, without other symptoms. Normal lower digestive and urinary transit. Physical examination: lucid, good general aspect, pain at deep palpation in epigastrium. No peritoneal irritation. Rest is normal. Laboratory: leukocytes 5200 mm3, C-reactive protein 71.4mg/dL, blood culture shows no growth. Abdominal sonogram, thoracic X-ray and echocardiogram are normal. Negative serology for Epstein Barr Virus, Cytomegalovirus and Bartonella henselae. Normal urine, urine culture with no growth. Fever persists, adds evanescent macropapular exanthema in on the trunk, without other symptoms. On the 7th day in hospital a new blood culture shows Salmonella Typhi sensitive to ampicillin, which he receives for 14 days. Good evolution. Discussion: Typhoid fever is an acute, life-threatening, infectious disease. Socioeconomic conditions are determinant in its transmission. Blood culture sensitivity is greater during the first week of the disease, that is why it must occasionally be repeated. Its unspecific clinical manifestations and low incidence make this etiology not be usually suspected in our surroundings. It is therefore important to increase our suspicion and to consider it amongst differential diagnosis in PFI.

Introdução: As infecções representam a etiologia mais frequente da síndrome febril prolongada (SFP). Embora as febres entéricas sejam uma causa possível, no Uruguai sua prevalência diminuiu significativamente com a melhoria das condições sociossanitárias. Objetivo: Relatar o caso de um adolescente com etiologia atualmente excepcional de SFP. Caso clínico 14 anos, saudável, zona suburbana. Começa 2 semanas antes da admissão com dor no abdome superior. Adiciona dor de cabeça holocraniana leve e vômitos ocasionais. 5 dias antes da admissão febre 40°C axilar, pico diário, sem outros sintomas. Trânsito digestivo inferior e trânsito urinário normais. Exame físico: lúcido, bom aspecto geral, abdome doloroso à palpação profunda no epigástrio. Sem irritação peritoneal. Resto normal. Análise: Leucócitos 5200mm3, proteína C reativa 71,4mg/dL, hemocultura sem desenvolvimento. Ultrassonografia abdominal, radiografia de tórax e ecocardiograma foram normais. As sorologias para vírus Epstein Barr, Citomegalovírus e Bartonella henselae foram negativas. Urina normal, urocultura sem desenvolvimento. Persiste com febre, acrescenta erupção macropapular evanescente no tronco, sem outros sintomas. No 7º dia de internação, nova hemocultura: Salmonella Typhi sensível à ampicilina, que recebeu por 14 dias. Boa evolução. Discussão: A febre tifóide é uma doença infecciosa aguda, potencialmente fatal. As condições socioeconômicas são decisivas na sua transmissão. A sensibilidade da hemocultura é maior durante a primeira semana da doença, por isso às vezes é necessário repeti-la. Suas manifestações clínicas inespecíficas e baixa incidência fazem com que essa etiologia não seja usualmente suspeitada em nosso meio. Portanto, é importante aumentar o índice de suspeição e considerar essa etiologia entre os diagnósticos diferenciais da SFP.

Duodenitis, la gran desconocida / Duodenitis, the great unknown

Debido a la relación que mantiene el duodeno con el resto de los órganos vecinos, el abordaje de la duodenitis implica realizar un amplio diagnóstico diferencial. Las patologías de este sector del intestino delgado son muy diversas e incluyen procesos congénitos, inflamatorios, traumáticos y neoplásicos. En el presente caso, comentamos una duodenitis erosiva secundaria a una infección por H. pylori (AU)

Due to the relationship of the duodenum with all other adjacent organs, the approach to duodenitis requires a broad differential diagnosis. Diseases in this part of the small intestine are diverse and include congenital, inflammatory, traumatic and malignant processes. Here, we discuss a case of erosive duodenitis secondary to Helicobacter pylori infection. (AU)

En niños, ¿se puede acortar el tratamiento de la neumonía adquirida en la comunidad a 3 días? / Is it possible to use a shortened 3-day course of treatment for community-acquired pneumonia in children?

Conclusiones de los autores del estudio: en relación con la necesidad de retratamiento con antibióticos en niños con neumonía adquirida en la comunidad dados de alta de un servicio de urgencias hospitalarias o de la planta de hospitalización tras ingreso de menos de 48 horas de duración, el uso de dosis bajas de amoxicilina no fue inferior frente a dosis altas, al igual que la duración de 3 días no fue inferior frente a 7 días. Conclusiones de los revisores: los datos de este estudio invitan a revisar en nuestro entorno las pautas que se utilizan en niños en el tratamiento de neumonía en la comunidad, en cuanto a la menor duración del tratamiento y dosificación que podría conllevar beneficios, pero hay limitaciones de este estudio para que sus conclusiones sean aplicables a nuestro país (AU)

Authors' conclusions: as concerns the need for antibiotic retreatment in children with community-acquired pneumonia discharged from the emergency department or inpatient ward within 48 hours of admission, lower-dose outpatient oral amoxicillin was non-inferior to high-dose amoxicillin, and a 3-day course was non-inferior to a 7-day course.Reviewers' conclusions: the data from this study invite a revision of the guidelines used in our region for the treatment of community-acquired pneumonia in children, with the purpose of clarifying if a shorter duration of treatment and lower dose could be beneficial, but there are limitations to the study for its conclusions to be applicable in our country. (AU)

Efficacy and Safety of Antofloxacin-Based Triple Therapy for Helicobacter pylori Eradication Failure in China.

AIMS: Quinolone-containing triple therapy has been considered as the second-line therapy for eradication of Helicobacter pylori (H. pylori). At present, there are no data to show the efficacy and safety of antofloxacin-based rescue therapy for the eradication of H. pylori, and this pilot clinical trial was designed. METHODS: A total of 196 patients who failed H. pylori eradication using the clarithromycin-based or metronidazole-based triple or bismuth quadruple therapy were randomly allocated to one of the following rescue eradication therapy groups: AEA group (antofloxacin 200 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days, or LEA group (levofloxacin 500 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days. The minimal inhibitory concentrations were tested by the E-test method. The gyrA mutation was analyzed by sequencing. Follow-up 13/14C-urea breath test was examined at 1 month after discontinuation. RESULTS: A total of 178 eligible patients were included in this study. The eradication rate was significantly higher in AEA group than in LEA group according to both ITT (87.6% vs. 68.5%; P = 0.002) and PP analyses (90.7% vs. 70.1%; P = 0.001). ITT analyses indicated that the eradication rate was significantly higher in AEA group than in LEA group with Asn87 mutation (78.9% vs. 31.3%; P = 0.005) and levofloxacin-resistant strains (76.9% vs. 44.2%; P = 0.003). Two groups exhibited similar adverse event rates (AEA 14.6% vs. LEA 20.2%, P = 0.323). CONCLUSIONS: The findings showed that antofloxacin may be a promising candidate in rescue therapy for H. pylori eradication failure in China.

Diagnosis of non-immediate hypersensitivity to amoxicillin in children by skin test and drug provocation tests: A retrospective case-series study.

BACKGROUND: Skin rash often occurs upon oral administration of amoxicillin in children, due to non-immediate hypersensitivity. However, information on delayed hypersensitivity to amoxicillin is scarce. Moreover, the appropriate diagnostic method and actual diagnostic rate of delayed hypersensitivity to amoxicillin among Japanese children are unclear. We conducted intradermal tests (IDTs) and drug provocation tests (DPTs) and retrospectively investigated the proportion of children with a definitive diagnosis of non-immediate hypersensitivity to amoxicillin. We then evaluated the characteristics of patients with a positive allergic workup. METHODS: We enrolled children referred for suspected findings of mild or moderate non-immediate hypersensitivity to amoxicillin between August 2018 and March 2020. If the IDT in the delayed phase was negative, DPT with amoxicillin (60-90 mg/kg/day) was performed for 7 days. Non-immediate hypersensitivity to amoxicillin was defined when IDT or DPT was positive. We evaluated the potential of the drug-induced lymphocyte stimulation test (DLST) to reveal hypersensitivity to amoxicillin. RESULTS: This study enrolled 27 children. Fourteen children (52%) had hypersensitivity to amoxicillin, of whom 12 had positive IDTs and two had positive DPTs. No differences in age, sex, history of allergic disease, days from oral use to symptom onset, type of rash at symptom onset, generalized rash, and DLST results were observed between the hypersensitivity and non-hypersensitivity groups. CONCLUSIONS: Examination should be performed for children with mild or moderate reactions because positive cases have no significant features and half of the suspected cases are negative.

The influence of pretreatment with PPI on Helicobacter pylori eradication: A systematic review and meta-analysis.

BACKGROUND: In this meta-analysis, we aimed to comprehensively investigate the impact of pretreatment with proton pump inhibitor (PPI) on Helicobacter pylori (H. pylori) eradication and provide novel inspiration to clinical practice. METHODS: Relevant studies were selected through PubMed, Embase, and Cochrane Library from inception to March 2021. Two reviewers performed the selection independently. The primary outcome of the meta-analysis was the eradication rate. A modified Jadad scale was used to evaluate literature quality quantitatively. RESULTS: Ten studies were included in this research. The results showed no significant difference between PPI pretreatment and standard treatment on eradication of H. pylori [relative risk (RR): 1.17, 95% confidence interval (95% CI): 0.0.73-1.88]. There was no significant difference between the PPI pretreatment group and the standard therapy group for conventional triple therapy, PPI and amoxicillin and clarithromycin (RR: 1.29, 95% CI: 0.60-2.77). Similar results were obtained in the therapy strategy of PPI and amoxicillin and metronidazole (RR: 3.01, 95% CI: 0.62-14.74). Interestingly, for the therapy regimen of PPI and clarithromycin and metronidazole, PPI pretreatment indicated superiority on H. pylori eradication rate (RR: 0.48, 95% CI: 0.23-0.97, P < .05). CONCLUSION: PPI pretreatment did not affect the H. pylori eradication rates, regardless of the various types of bacteriostatic antibiotic, except the therapy regimen of PPI and clarithromycin and metronidazole.

Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children With Community-Acquired Pneumonia: The CAP-IT Randomized Clinical Trial.

Importance: The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear. Objective: To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days. Design, Setting, and Participants: Multicenter, randomized, 2 × 2 factorial noninferiority trial enrolling 824 children, aged 6 months and older, with clinically diagnosed CAP, treated with amoxicillin on discharge from emergency departments and inpatient wards of 28 hospitals in the UK and 1 in Ireland between February 2017 and April 2019, with last trial visit on May 21, 2019. Interventions: Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg/kg/d; n = 410) or higher dose (70-90 mg/kg/d; n = 404), for a shorter duration (3 days; n = 413) or a longer duration (7 days; n = 401). Main Outcomes and Measures: The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization. The noninferiority margin was 8%. Secondary outcomes included severity/duration of 9 parent-reported CAP symptoms, 3 antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates. Results: Of 824 participants randomized into 1 of the 4 groups, 814 received at least 1 dose of trial medication (median [IQR] age, 2.5 years [1.6-2.7]; 421 [52%] males and 393 [48%] females), and the primary outcome was available for 789 (97%). For lower vs higher dose, the primary outcome occurred in 12.6% with lower dose vs 12.4% with higher dose (difference, 0.2% [1-sided 95% CI -∞ to 4.0%]), and in 12.5% with 3-day treatment vs 12.5% with 7-day treatment (difference, 0.1% [1-sided 95% CI -∞ to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P = .63). Of the 14 prespecified secondary end points, the only significant differences were 3-day vs 7-day treatment for cough duration (median 12 days vs 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P = .04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P = .03). Among the subgroup of children with severe CAP, the primary end point occurred in 17.3% of lower-dose recipients vs 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, -∞ to10%]; P value for interaction = .18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, -∞ to 7.4%]; P value for interaction = .73). Conclusions and Relevance: Among children with CAP discharged from an emergency department or hospital ward (within 48 hours), lower-dose outpatient oral amoxicillin was noninferior to higher dose, and 3-day duration was noninferior to 7 days, with regard to need for antibiotic re-treatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideration when interpreting the findings. Trial Registration: ISRCTN Identifier: ISRCTN76888927.

Single Dose of Oral Azithromycin With or Without Amoxicillin to Prevent Peripartum Infection in Laboring, High-Risk Women in Cameroon: A Randomized Controlled Trial.

OBJECTIVE: To compare the effectiveness of single-dose azithromycin, with or without amoxicillin, with placebo to prevent peripartum infection in laboring women. METHODS: We conducted a multicenter, three-group, double-blind randomized controlled trial of women with viable term nonanomalous pregnancies with either prolonged labor of 18 hours or longer or rupture of membranes for 8 hours or longer in Cameroon. Women with chorioamnionitis before randomization, study drug contraindications, or planned cesarean births were excluded. Women were randomized to oral azithromycin 1 g-placebo (group 1), oral azithromycin 1 g-oral amoxicillin 2 g (group 2), or placebo-placebo (group 3). All groups received usual care, including antibiotics given at the health care professional's discretion. The primary outcome was a composite of maternal peripartum infection or death from any cause up to 6 weeks postpartum. Two primary comparisons (group 1 vs group 3 and group 2 vs group 3) were planned. We estimated that 241 women per group (planning for 750 total) would provide 80% power at two-sided α=0.05 (0.025 per comparison) to detect a 50% effect size assuming 20% baseline composite infection rate. RESULTS: From January 6, 2018, to May 15, 2020, 6,531 women were screened, and 756 (253 in group 1, 253 in group 2, and 250 in group 3) were randomized. Baseline characteristics (including body mass index, duration of rupture of membranes or labor, and parity) were balanced across groups, except for maternal age. More than 60% of women in each group received usual-care antibiotics: more than 90% penicillin and approximately 50% for prolonged rupture of membranes across all study groups. Composite outcome incidences were similar in antibiotic groups 1 (6%) and 2 (7%) compared with placebo group 3 (10%) (RR 0.6, 95% CI 0.3-1.2; 0.7, 95% CI 0.4-1.3, respectively). Chorioamnionitis and wound infection were significantly lower in group 2 (3.2% vs 0.4% and 4% vs 0.8% respectively, both P=.02) compared with group 3. There were no differences in other maternal or neonatal outcomes including neonatal infection. CONCLUSION: A single dose of oral azithromycin with or without amoxicillin for prolonged labor or rupture of membranes at term did not reduce maternal peripartum or neonatal infection. Observed lower than expected infection rates and frequent usual-care antibiotic use may have contributed to these findings. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03248297. FUNDING SOURCE: Merck for Mothers Investigator Studies Program grant.

Comparative Evaluation for Controlled Release of Amoxicillin from RSM-CCD-Optimized Nanocomposites Based on Sodium Alginate and Chitosan-Containing Inclusion Complexes.

Amoxicillin (AMX) is a semisynthetic antibiotic, an analogue of ampicillin, with a wide spectrum of bacterial activity against many microorganisms but possesses some limits. To increase the drug effectiveness, supramolecule nanocomposites composed of ß-cyclodextrin (ß-CD) and chitosan/sodium alginate/GO were chosen in the present study as a sustained release formulation. Nanocomposites of chitosan (CH), sodium alginate (ALG), and graphene oxide (GO) were synthesized at 50 °C. The inclusion complexes (ICs) were processed via the physical mixture (PM), kneading (KM), microwave (MW) method, or coprecipitation (CP) and directly loaded into the nanocomposite. To confirm the formation of true ICs, the ICs were analyzed by DSC, SEM, 1H NMR, 2D NMR ROESY, and XRD. A drug release study was performed to find out which method is best for the controlled release of drugs in different environments of pH 2, 7, and 7.4 at 37 °C. From the observed drug release data, it was found that PM and KM showed a burst release of drugs and the microwave method was the most suitable method to prepare exact ICs of AMX and ß-CD for sustained release of drugs. Kinetics of drug release was analyzed by various kinetic models, and it was observed that the Korsmeyer-Peppas and Peppas-Sahlin models were best fit for drug release in all cases. A Phase solubility study was carried out to find the stoichiometry of IC formation and the complexation constant. The drug release was controlled and pH-dependent, confirming that nanocomposites are pH-sensitive. From drug release analysis, it was acknowledged that ß-CD is capable of causing sustained drug release.

Pretreatment with Ranitidine Bismuth Citrate May Improve Success Rates of Helicobacter pylori Eradication: A Prospective, Randomized, Controlled and Open-Label Study.

Effective Helicobacter pylori (H. pylori) eradication is a major public health concern; however, eradication failure rates with the standard triple therapy remain high. We aimed to investigate the effectiveness and tolerability of ranitidine bismuth citrate (RBC) pretreatment before standard triple therapy for H. pylori eradication. A prospective, randomized, controlled, and open-label clinical trial was conducted from June to December 2019. H. pylori eradication rate, safety, and tolerability were compared between the standard treatment group (esomeprazole, amoxicillin, and clarithromycin for 7 days) and RBC pretreatment group (RBC for 2 weeks before standard triple therapy). This trial ended earlier than estimated owing to the N-nitrosodimethylamine concerns with ranitidine. Success rates of H. pylori eradication were 80.9% and 67.3% in the RBC pretreatment (n = 47) and standard treatment (n = 52) (p = 0.126) groups, respectively. Our trial was discontinued earlier than planned; however, a statistical significance would be achieved by expansion of our data (p = 0.031) if patient enrollment numbers reached those initially planned. Adverse event rates were comparable between groups (25.5% in the pretreatment group vs. 28.8% in the standard treatment group), without serious event. Tolerability was excellent in both groups, recorded as 97.9% and 100% in the pretreatment and standard treatment groups, respectively. Compared with the standard triple regimen, RBC pretreatment for 2 weeks may achieve higher H. pylori eradication rates, with excellent safety and tolerability. However, this study necessitates further validation as it was discontinued early owing to the N-nitrosodimethylamine issues of ranitidine.

Antibiotics for lower respiratory tract infection in children presenting in primary care in England (ARTIC PC): a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Antibiotic resistance is a global public health threat. Antibiotics are very commonly prescribed for children presenting with uncomplicated lower respiratory tract infections (LRTIs), but there is little evidence from randomised controlled trials of the effectiveness of antibiotics, both overall or among key clinical subgroups. In ARTIC PC, we assessed whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) LRTI in primary care, overall and in key clinical subgroups. METHODS: ARTIC PC was a double-blind, randomised, placebo-controlled trial done at 56 general practices in England. Eligible children were those aged 6 months to 12 years presenting in primary care with acute uncomplicated LRTI judged to be infective in origin, where pneumonia was not suspected clinically, with symptoms for less than 21 days. Patients were randomly assigned in a 1:1 ratio to receive amoxicillin 50 mg/kg per day or placebo oral suspension, in three divided doses orally for 7 days. Patients and investigators were masked to treatment assignment. The primary outcome was the duration of symptoms rated moderately bad or worse (measured using a validated diary) for up to 28 days or until symptoms resolved. The primary outcome and safety were assessed in the intention-to-treat population. The trial is registered with the ISRCTN Registry (ISRCTN79914298). FINDINGS: Between Nov 9, 2016, and March 17, 2020, 432 children (not including six who withdrew permission for use of their data after randomisation) were randomly assigned to the antibiotics group (n=221) or the placebo group (n=211). Complete data for symptom duration were available for 317 (73%) patients; missing data were imputed for the primary analysis. Median durations of moderately bad or worse symptoms were similar between the groups (5 days [IQR 4-11] in the antibiotics group vs 6 days [4-15] in the placebo group; hazard ratio [HR] 1·13 [95% CI 0·90-1·42]). No differences were seen for the primary outcome between the treatment groups in the five prespecified clinical subgroups (patients with chest signs, fever, physician rating of unwell, sputum or chest rattle, and short of breath). Estimates from complete-case analysis and a per-protocol analysis were similar to the imputed data analysis. INTERPRETATION: Amoxicillin for uncomplicated chest infections in children is unlikely to be clinically effective either overall or for key subgroups in whom antibiotics are commonly prescribed. Unless pneumonia is suspected, clinicians should provide safety-netting advice but not prescribe antibiotics for most children presenting with chest infections. FUNDING: National Institute for Health Research.

Assessment of Immune Response and Efficacy of Essential Oils Application on Controlling Necrotic Enteritis Induced by Clostridium perfringens in Broiler Chickens.

Necrotic enteritis (NE) caused by Clostridium perfringens is one of the most important enteric diseases in poultry. The antibacterial activity of two different essential oil (EO) blends against C. perfringens was investigated both in vitro and in vivo. Additionally, the immunological response to EO treatment was assessed. In the in vitro study, the antibacterial activity of EO formulas and commonly used antibiotics was evaluated against C. perfringens using disk diffusion assay, minimum inhibitory concentration (MIC) assay, and minimum bactericidal concentration (MBC) assay. In the in vivo study, NE experimental infection was performed on 440 Ross broiler chicks at 19 days of age for 4 continuous days. The chicks were treated with either EOs or amoxicillin at 22 days of age for 5 continuous days. One day after the end of treatment, the birds' performance was evaluated by calculating the feed conversion ratio. Serum samples from 120 birds were collected to measure the levels of IL-1ß, IFN-γ, IL-8, IL-10, and IL-17. After that, all birds were slaughtered, and their small intestines were subjected to gross and histopathological evaluation. In addition, bacterial counts in the small intestines were evaluated. In the in vitro study, EOs showed higher antimicrobial activities in comparison with antibiotics against C. perfringens. In the in vivo study, birds treated with EOs showed a significant decrease in bacterial counts, a significant decrease in intestinal lesions, and a significant improvement in performance compared with untreated birds (p < 0.05). Moreover, treating birds with EOs directed the immune system toward an anti-inflammatory pathway. None of the treated birds died due to NE compared with the 10% mortality rate in untreated birds. In conclusion, EOs might be an effective and safe alternative to antibiotics in the treatment of chicken NE.

Amoxicillin chewable tablets intended for pediatric use: formulation development, stability evaluation and taste assessment.

To cover the unpleasant taste of amoxicillin (250 mg), maize starch (baby food) and milk chocolate were co-formulated. The raw materials and the final formulations were characterized by means of Dynamic Light Scattering (DLS), Differential Scanning Calorimetry (DSC) and Fourier-Transform Infrared (FT-IR) spectroscopy. To evaluate the taste masking two different groups of volunteers were used, according to the Ethical Research Committee of the Aristotle University of Thessaloniki. The optimization of excipients' content in the tablet was determined by experimental design methodology (crossed D-optimal). Due to the matrix complexity, amoxicillin was extracted using liquid extraction and analyzed isocratically by HPLC. The developed chromatographic method was validated (%Recovery 98.7-101.3, %RSD = 1.3, LOD and LOQ 0.15 and 0.45 µg mL-1 respectively) according to the International Conference on Harmonization (ICH) guidelines. The physicochemical properties of the tablets were also examined demonstrating satisfactory quality characteristics (diameter: 15 mm, thickness: 6 mm, hardness <98 Newton, loss of mass <1.0%, disintegration time ∼25min). Additionally, dissolution (%Recovery >90) and in vitro digestion tests (%Recovery >95) were carried out. Stability experiments indicated that amoxicillin is stable in the prepared formulations for at least one year (%Recovery <91).