Bovine Lactoferrin in the Prevention of Antibiotic-Associated Diarrhea in Children: A Randomized Clinical Trial.

Introduction: Antibiotic-associated diarrhea (AAD) is a common adverse reaction to antibiotic treatment affecting up to 21% of children. The aim of the study is to evaluate whether bovine lactoferrin (bLf) might be used for AAD prevention. Materials and Methods: In this prospective, randomized, double-blind, placebo-controlled, single-center study, we enrolled 156 children aged between 1 and 18 years, treated with antibiotic due to acute respiratory or urinary tract infection. We randomly allocated children 1:1 to receive 100 mg of bLf or a placebo twice a day orally for the whole period of antibiotic therapy. The primary outcome was the occurrence of antibiotic-associated diarrhea during and up to 2 weeks after antibiotic therapy. The secondary endpoint was intravenous rehydration or antibiotic withdrawal due to diarrhea. We performed intention-to-treat analysis. Results: We included 150 patients in intention-to-treat analysis. AAD occurred in 16 of 75 (21.3%) patients in bLf group and in 7 of 75 (9.3%) individuals in placebo group [OR = 2.6, (95% CI: 1.01-6.84), p = 0.04]. Relative risk was 2.29 (95% CI: 0.89-5.88). The need for intravenous rehydration occurred in one patient in the placebo group (p = 0.3). We observed no adverse effects in neither of the groups. Discussion: The trial indicated that bLf is not effective in AAD prevention. The risk for AAD was higher in bovine lactoferrin group as compared with placebo. We registered the study protocol on ClinicalTrials.gov (NCT02626104).

A Two-Week Fecal Microbiota Transplantation Course in Pediatric Patients with Inflammatory Bowel Disease.

Dysbiosis plays a major role in the etiology of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) is a new promising option for IBD treatment. We aimed to assess the effectiveness of a two-week FMT course in children with IBD. Ten patients, 10-17 years of age with moderate to severe IBD received a course of eight doses of freshly prepared FMT via a naso-duodenal tube or gastroscopy. All of the patients had pancolitis. There were eight cases of ulcerative colitis (UC) and two of Crohn's disease (CD). Disease activity was evaluated using the Pediatric UC Activity Index (PUCAI) and Pediatric CD Activity Index (PCDAI) for UC and CD, respectively, CRP, and fecal calprotectin on the day before the first infusion and then on the day before the next course of FMT. Clinical response, defined as a decrease of 15 points in either index, was observed in 9/10 patients (seven UC and two CD). Clinical remission, defined as a PCDAI score ≤ 10 and PUCAI score < 10 measured at the same time point, was observed in 3/8 UC patients and 2/2 CD patients. Side effects observed were self-limiting and benign. We conclude that a short, intensive course of FMT has a beneficial effect on UC and CD colitis. FMT was well-tolerated and safe. Nonetheless, an optimal protocol of FMT administration is crucial for treatment efficacy.

Serotype-Specific Pneumococcal Status prior to PCV 13 Administration in Children and Adolescents with Inflammatory Bowel Disease.

The aim of this study was to evaluate the serotype-specific pneumococcal status of children and adolescents with inflammatory bowel disease (IBD) who were naïve to pneumococcal vaccination before administering the 13-valent pneumococcal conjugate vaccine (PCV 13). This was an open, prospective study on children and adolescents aged 5-18 years who had IBD and were naïve to pneumococcal vaccination. A single dose of PCV 13 was administered to each patient. The geometric mean concentrations (GMCs) were measured for all 13 serotypes. A total of 122 subjects completed the study. Prevaccination GMCs ranged from 0.55 µg/ml (serotype 4) to 4.26 µg/mI (serotype 19A). Prior to the administration of PCV 13, high GMCs were detected in older children and adolescents who had IBD and were naïve to pneumococcal vaccination.

Value of Antral Nodularity for the Diagnosis of Helicobacter pylori Infection in Children.

BACKGROUND: The aim of this study was to confirm the role of antral nodularity in the diagnosis of Helicobacter pylori (H. pylori) infection in children. MATERIAL AND METHODS: This prospective study included 107 children (58 male; 54.2%), between the ages of 3 and 18 years, infected with H. pylori, which was confirmed if the patient had at least 2 of 4 positive test results (urea breath test, urease test in gastric biopsy, histopathology - positive hematoxylin and eosin and Giemsa staining, and/or monoclonal stool ELISA test - Amplified IDEIA™ Hp StAR™). The control group consisted of 234 children with abdominal pain, of similar age, in whom urease test in gastric tissue and histopathology were negative. In both groups, photographs of the gastric antrum taken during endoscopy were evaluated for nodularity by 3 independent endoscopists, blinded to the results of other tests. Sensitivity, specificity, and negative and positive predictive value of nodularity were assessed. Indication for upper endoscopy was chronic abdominal pain not considered to be functional. RESULTS: There were no statistical differences between groups regarding sex (chi-square test with Yates's correction: p=0.8763) or age (mean ±SD) 11.77±3.49 and 12.43±3.32, study and control groups, respectively (Mann-Whitney test: p=0.1352). The sensitivity of the presence of nodularity as an indication of H. pylori infection was 91.6% and specificity was 91%. PPV of gastric nodularity was 81% and NPV was 96%. CONCLUSIONS: Antral nodularity is reliable test. Physicians could start treatment of H. pylori infection whenever gastric nodularity is observed and the urease test result is positive, without waiting for histopathology results.

Immunogenicity of 13-Valent Pneumococcal Conjugate Vaccine in Pediatric Patients with Inflammatory Bowel Disease.

BACKGROUND: There are only a few studies on immune response to pneumococcal vaccines in patients with inflammatory bowel disease (IBD); all of them assessed polysaccharide vaccines only. The aim of the study was to evaluate the immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) in IBD pediatric patients compared with healthy controls. METHODS: This was a multicenter, prospective, and controlled study on children and adolescents aged 5 to 18 years with IBD with no history of pneumococcal immunization. The subjects for the study belonged to one of the following groups: patients with IBD on no immunosuppressive therapy (group A), those on tumor necrosis factor agents or immunomodulators (group B), and healthy controls (group C). The study population received 1 intramuscular injection of PCV13. The primary outcome measure was adequate vaccine response defined as postvaccination titer ≥0.35 µg/mL to all 13 serotypes. Geometric mean titers and geometric mean titer rises were measured for all serotypes. The evidence of local and systemic adverse effects for 5 days after the vaccine was registered. RESULTS: A total of 178 subjects (122 patients and 56 controls) completed the study course. There was no significant difference in the rate of adequate vaccine response between patients with IBD and controls measured 4 to 8 weeks after vaccination (90.4% versus 96.5%, P = 0.5281). Children in group A had higher geometric mean titer rises than children in group B (P = 0.0369). There were no serious adverse events related to PCV13 during the study. CONCLUSIONS: PCV13 is both immunogenic and safe in pediatric patients with IBD.

Sequential therapy compared with standard triple therapy for Helicobacter pylori eradication in children: a double-blind, randomized, controlled trial.

OBJECTIVE: To determine the effectiveness of sequential therapy compared with standard triple therapy for Helicobacter pylori eradication in children. STUDY DESIGN: In 107 children with H pylori infection confirmed with 2 of 3 tests ((13)C-urea breath test, histopathology, rapid urease test), we conducted a double-blind, randomized, controlled trial comparing a sequential treatment (amoxicillin and omeprazole for 5 days followed by clarithromycin, tinidazole, and omeprazole for 5 days) to a 7-day standard triple eradication regimen (amoxicillin and clarithromycin plus omeprazole) followed by placebo for 3 days. RESULTS: In the experimental group (n=52) compared with the control group (n=51), there was a significant difference in the H pylori eradication rate at 6 to 8 weeks after the completion of treatment (primary outcome), as confirmed with negative results on (13)C-urea breath test (45/52 or 86.5% versus 35/51 or 68.6%; relative risk, 1.26; 95% CI, 1.02-1.60). Groups did not differ in any of the secondary outcomes (ie, adverse effects, the need for discontinuation of the H pylori therapy, compliance with therapy). CONCLUSIONS: In children with H pylori infection, sequential eradication therapy compared with standard triple therapy resulted in a higher eradication rate, although the difference was of borderline statistical significance.

Immunogenecity of hepatitis A vaccine in pediatric patients with inflammatory bowel disease.

BACKGROUND: There are only a few studies on immune response to routine vaccinations in children with inflammatory bowel disease (IBD), despite a strong need for this kind of study. The aim of the study was to evaluate the immunogenicity of an inactivated hepatitis A vaccine (HAV) in IBD pediatric patients compared with healthy controls. METHODS: This was an open, prospective, and controlled study on anti-HAV-negative children and adolescents age 2-18 years with IBD. HAV using 720 enzyme-linked immunosorbent assay (ELISA) units were administered at 0 months and at 6-12 months. Seroconversion and geometric mean titers were measured after each vaccine dose. The evidence of local and systemic adverse effects for 3 days after the first and second dose of vaccine was registered. RESULTS: A total of 134 subjects (66 patients and 68 controls) completed the whole study course consisting of two doses of vaccine and six serum samples. There was no significant difference in the rate of seroconversion between IBD patients and controls when measured after the second dose of vaccine (97% versus 100%, P = 0.2407), but the rate was significantly lower in the IBD group when measured after the first dose (39% versus 64%, P = 0.00001). The mean geometric titers were statistically significantly lower in the IBD group than in the control group at all of the measured timepoints. There were no serious adverse events related to HAV during the study. CONCLUSIONS: HAV is both immunogenic and safe in pediatric patients with IBD.