Antibiotic-associated Diarrhea In Children Research Articles

Can the Evidence-Based Use of Probiotics (Notably Saccharomyces boulardii CNCM I-745 and Lactobacillus rhamnosus GG) Mitigate the Clinical Effects of Antibiotic-Associated Dysbiosis?

Dysbiosis corresponds to the disruption of a formerly stable, functionally complete microbiota. In the gut, this imbalance can lead to adverse health outcomes in both the short and long terms, with a potential increase in the lifetime risks of various noncommunicable diseases and disorders such as atopy (like asthma), inflammatory bowel disease, neurological disorders, and even behavioural and psychological disorders. Although antibiotics are highly effective in reducing morbidity and mortality in infectious diseases, antibiotic-associated diarrhoea is a common, non-negligible clinical sign of gut dysbiosis (and the only visible one). Re-establishment of a normal (functional) gut microbiota is promoted by completion of the clinically indicated course of antibiotics, the removal of any other perturbing external factors, the passage of time (i.e. recovery through the microbiota's natural resilience), appropriate nutritional support, and-in selected cases-the addition of probiotics. Systematic reviews and meta-analyses of clinical trials have confirmed the strain-specific efficacy of some probiotics (notably the yeast Saccharomyces boulardii CNCM I-745 and the bacterium Lactobacillus rhamnosus GG) in the treatment and/or prevention of antibiotic-associated diarrhoea in children and in adults. Unusually for a probiotic, S.boulardii is a eukaryote and is not therefore directly affected by antibiotics-making it suitable for administration in cases of antibiotic-associated diarrhoea. A robust body of evidence from clinical trials and meta-analyses shows that the timely administration of an adequately dosed probiotic (upon initiation of antibiotic treatment or within 48h) can help to prevent or resolve the consequences of antibiotic-associated dysbiosis (such as diarrhoea) and promote the resilience of the gut microbiota and a return to the pre-antibiotic state. A focus on the prescription of evidence-based, adequately dosed probiotics should help to limit unjustified and potentially ineffective self-medication.

Use of Saccharomyces boulardii to Prevent Antibiotic-associated Diarrhea in Children with Pneumonia and Bronchitis

In recent years, an increase in the prevalence of antibiotic-associated diarrhea (AAD) in children has been registered. In modern conditions, there are changes in the microbial spectrum of AAD pathogens and their sensitivity to antimicrobial drugs. This indicates the need for further research on the effectiveness and safety of the use of antidiarrheal drugs, in particular Saccharomyces boulardii (SB), in clinical practice. The objective: to analyze the clinical effectiveness and safety of the use of SB in the prevention of AAD manifestations in children. Materials and methods. The results of examination and treatment of 84 children aged 1 to 16 years with pneumonia (n=50) and acute bronchitis of bacterial etiology (n=34) were analyzed. Patients comparable in age, gender, etiology and clinical form of acute respiratory disease were divided into two research groups: I (main) group – 44 children who received SB for a course of 10–12 days in complex treatment (antibacterial and symptomatic therapy) and II (control) group – 40 patients who received only antibiotic therapy and did not take probiotic drugs. During the study, the condition of the digestive tract (appetite, presence of nausea and vomiting, frequency and severity of diarrhea), skin (dryness, drowsiness), nervous system (sleep disturbances, restlessness) was assessed. Results. At the beginning of the study there was no statistical difference between the frequency of pathological symptoms in the research groups. In the course of treatment, positive dynamics of clinical manifestations of respiratory tract lesions were observed in children in the groups. In the patients of the I group who received SB, on the 10th day all patients had formed stools, while in the II group, on the 10th day diarrhea was detected in 12 (30%) of 40 children (p<0.01). In the dynamics of treatment on the 10th–12th day, the decrease in the number of bifidobacteria (<1010) was found in 2 (6.7%) of 30 children of the I group and in 15 (60%) of the 25 children of the II group (р<0.01). A decrease in the number of lactobacilli (<107) was found in 1 (3.3%) of 30 children of group I and in 9 (36.0%) of 25 patients of group II (p<0.05). On the 10th–12th day, it was possible to achieve complete normalization of intestinal function in almost all children of the I group. There were no side effects during the use of the drug. Conclusions. The use of SB simultaneously with antibacterial therapy made it possible to reliably reduce flatulence and intestinal colic in 86.4–88.6% of children on the 5th day of complex treatment. In the main group the frequency and consistency of bowel movements quickly normalized. Such dynamics of clinical symptoms was not observed in the comparison group.

Probiotics in the Management of Antibiotic-Associated Diarrhea in Children

This review aimed to evaluate probiotic use to prevent antibiotic-associated diarrhea in children. A total of 1564 studies of randomized clinical trials published in English were found using PubMed, Cochrane, and Virtual Health Library (MEDLINE/LILACS). A meta-analysis included 4 trials in subgroup Lactobacillus rhamnosus (95% confidence interval [CI]: 0.17-0.49; P < .00001), 2 trials in subgroup L reuteri (95% CI: 0.51-1.77; P = .87), and 5 groups in subgroup association of species of probiotics (95% CI: 0.21-1.71; P = .33). The findings suggest that L rhamnosus alone may be useful in preventing antibiotic-associated diarrhea in children.

Multispecies Probiotic Can Prevent Antibiotic-Associated Diarrhea in Children.

According to this study: Although a multispecies probiotic didn't reduce the risk of antibiotic-associated diarrhea in children when the most stringent definition of the condition was used, it did, however, have a beneficial effect on the overall risk of diarrhea during and seven days after antibiotic treatment.The authors point out that the cause of diarrhea may not be relevant so long as the preventive intervention is effective.

Effect of Traditional Chinese Medicine on Treating Antibiotic-Associated Diarrhea in Children: A Systematic Review and Meta-Analysis.

Background Due to the limited treatment options in antibiotic-associated diarrhea (AAD) in children, more effective treatments should be explored. Traditional Chinese medicine (TCM) has a long history in China, which has produced a pretty effect in clinical practice. Many randomized clinical trials (RCTs) have explored the effect of traditional Chinese medicine on treating AAD in children. However, there has been no systematic review or meta-analysis on the impact of TCM on AAD in children. The aim of this study was to systematically review RCTs on the effect of TCM in children with AAD. Methods RCTs in the past ten years on TCM for AAD in children were included. We searched Electronic databases as much as possible. This paper was registered in PROSPERO (CRD42022301034). Results 26 studies were included in this systematic review. 25 studies reported the effects of TCM interventions on the total effective rate (RR = 1.20, CI 1.16 to 1.24; p < 0.001). 7 studies reported the effects of TCM interventions on the time to change the shape of feces (MD = −1.37, CI −1.67 to −1.07; p < 0.001). 17 studies reported the effects of TCM interventions (MD = −1.43, CI −1.71 to −1.15; p < 0.001). The pooled results showed that there were no significant differences between the two groups in CD3+, CD4+, CD8+, CD4 : CD8, time for bowel sounds to return to normal, hs-CRP, and IgM. There was a significant difference between the two groups in frequency of diarrhea on the third day after TCM intervention, vomiting improvement time, diamine oxidase, IL-8, TNF, IgA, IgG, and average hospital stay. Conclusions TCM interventions combined with conventional therapy can improve the therapeutic effect of AAD in children. However, future studies are still needed for the low methodological quality.

Characteristics and management of children with Clostridioides difficile infection at a tertiary pediatric hospital in China

BackgroundClostridiodes difficile infection (CDI) is one of the most common causes of antibiotic-associated diarrhea in children. Conventional antibiotics and emerging fecal microbiota transplantation (FMT) are used to treat CDI.MethodsChildren with CDI admitted to the Shanghai Children's Hospital, from September 2014 to September 2020, were retrospectively included to this observational study. Pediatric patients were assigned as initial CDI and recurrent CDI (RCDI), and symptoms, comorbidities, imaging findings, laboratory tests, and treatments were systematically recorded and analyzed.ResultsOf 109 pediatric patients with CDI, 58 were boys (53.2%), and the median age was 5 years (range, 2-9 years). The main clinical symptoms of CDI children were diarrhea (109/109, 100%), hematochezia (55/109, 50.46%), abdominal pain (40/109, 36.70%); fever, pseudomembrane, vomit, and bloating were observed in 39 (35.78%), 33 (30.28%), and 24 (22.02%) patients, respectively. For the primary therapy with conventional antibiotics, 68 patients received metronidazole, and 41 patients received vancomycin. RCDI occurred in 48.53% (33/68) of those initially treated with metronidazole compared with 46.33% (19/41) of those initially treated with vancomycin (p=0.825). The total resolution rate of FMT for RCDI children was significantly higher than with vancomycin treatment (28/29, 96.55% vs 11/23, 47.83%, p < 0.001). There were no serious adverse events (SAEs) reported after two months of FMT.ConclusionsThe major manifestations of children with CDI were diarrhea, hematochezia, and abdominal pain. The cure rate of FMT for pediatric RCDI is superior to vancomycin treatment.

Multispecies Probiotic for the Prevention of Antibiotic-Associated Diarrhea in Children

The efficacy of multispecies probiotic formulations in the prevention of antibiotic-associated diarrhea (AAD) remains unclear. To assess the effect of a multispecies probiotic on the risk of AAD in children. This randomized, quadruple-blind, placebo-controlled trial was conducted from February 2018 to May 2021 in a multicenter, mixed setting (inpatients and outpatients). Patients were followed up throughout the intervention period. Eligibility criteria included age 3 months to 18 years, recruitment within 24 hours following initiation of broad-spectrum systemic antibiotics, and signed informed consent. In total, 646 eligible patients were approached and 350 patients took part in the trial. A multispecies probiotic consisting of Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Lactobacillus acidophilus W37, L acidophilus W55, Lacticaseibacillus paracasei W20, Lactiplantibacillus plantarum W62, Lacticaseibacillus rhamnosus W71, and Ligilactobacillus salivarius W24, for a total dose of 10 billion colony-forming units daily, for the duration of antibiotic treatment and for 7 days after. The primary outcome was AAD, defined as 3 or more loose or watery stools per day in a 24-hour period, caused either by Clostridioides difficile or of otherwise unexplained etiology, after testing for common diarrheal pathogens. The secondary outcomes included diarrhea regardless of the etiology, diarrhea duration, and predefined diarrhea complications. A total of 350 children (192 boys and 158 girls; mean [range] age, 50 [3-212] months) were randomized and 313 were included in the intention-to-treat analysis. Compared with placebo (n = 155), the probiotic (n = 158) had no effect on risk of AAD (relative risk [RR], 0.81; 95% CI, 0.49-1.33). However, children in the probiotic group had a lower risk of diarrhea regardless of the etiology (RR, 0.65; 95% CI, 0.44-0.94). No differences were observed between the groups for most of the secondary outcomes, including adverse events. A multispecies probiotic did not reduce the risk of AAD in children when analyzed according to the most stringent definition. However, it reduced the overall risk of diarrhea during and for 7 days after antibiotic treatment. Our study also shows that the AAD definition has a significant effect on clinical trial results and their interpretation. ClinicalTrials.gov Identifier: NCT03334604.

Variety of effects of silicon dioxide colloid in the treatment of antibiotic-associated diarrhea in children

Antibiotic-associated diarrhea (AAD) is a key aspect of pediatrics concerning antibiotic therapy Purpose. The article aims at investigating the effects of colloidal silicon dioxide in the treatment of antibiotic-associated diarrhea in children. Materials and methods. Using parametric and nonparametric methods of analysis, 83 patients were examined (treatment group — 41 children who used colloidal silicon dioxide and the control group — 42 children) of both sexes (mean age (13.7 ± 2.6) years) with pathology of the lower respiratory tract (acute bronchitis or community-acquired pneumonia), who developed AAD against the background of ABT. Results. When using colloidal silicon dioxide in 75.6% of children, diarrhea decreased by the 2nd day and stopped by the 4th day (median — 0 points). Against the background of taking the drug throughout the treatment, there was a marked 3-fold decrease in all AAD values. The assessment of the efficacy and safety of the drug according to the data of medical researchers was 3.4 points. Analysis of subjective data on the tolerability of the drug showed «excellent» and «good». Against the background of the full course of treatment with colloidal silicon dioxide, a 2 times more pronounced decrease in the characteristics of AAD was noted. Conclusion. The presented data are intended to focus the attention of pediatricians on the rational use of ABT, timely diagnosis of an unwanted drug reaction in the form of AAD and its correction. The studied drug showed high efficacy and safety, which makes it possible to recommend it as a symptomatic treatment of diarrhea that developed against the background of ABT treatment in the complex therapy of diseases of the lower respiratory tract in children.

Clinical effects of Saccharomyces boulardii combined with aluminum phosphate in treatment of acute antibiotic-associated diarrhea in children

Clinical effects of <i>Saccharomyces boulardii</i> combined with aluminum phosphate in treatment of acute antibiotic-associated diarrhea in children

Донецкий национальный медицинский университет им. М. Горького, г. Красный Лиман

В статье рассмотрены проблемные вопросы нерационального назначения антибактериальных средств у детей, развития побочных патологических реакций и осложнений, в частности антибиотик­ассоциированных диарей. Представлены современные средства для профилактики и лечения данной категории заболеваний, в частности применение пробиотиков.

Обзор материалов экспертного совета «Дифференциальная диагностика диарейного синдрома в зависимости от его патогенеза в практике врача-педиатра, роль пробиотических лекарственных средств в его лечении»

On November 10, 2021, an online meeting of the expert council was held on the conference platform of the First Medical Channel. The subject was “Diarrhea differential diagnosis depending on its pathogenesis in pediatric practice, the role of probiotic medications in its treatment”. Leading Russian experts in the field of clinical pharmacology, gastroenterology, pediatrics, infectious diseases, and allergology-immunology took part in this meeting. As a result of the meeting, the main principles of diagnosis, treatment, and prevention of diarrhea in children were formulated, and an algorithm for using probiotics to treat diarrhea in children was developed. Conclusion. It is preferable to prescribe medicinal probiotics (with registration status) than a dietary supplement containing probiotic bacteria. Medicinal products containing a combination of strains of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12, vitamins B1 and B6, which are approved for use in pediatric practice, are recommended for administration in diarrhea and in suspected antibiotic-associated diarrhea in children, regardless of etiology and pathogenesis, both during the acute period and the next 4 weeks as well as during the entire recovery period (the period of repair and convalescence). Key words: antibiotics, children, diarrhea, treatment, prophylaxis, strain-specific probiotics, Lactobacillus rhamnosus GG, Bifidobacterium animalis subsp. lactis BB-12

Approaches to prevention of antibiotic-associated diarrhea in children

The incidence of antibiotic-associated diarrhea, according to various authors, ranges from 5 to 39% and depends on the patient’s age and other contributing factors. Antibiotic-associated diarrhea can be caused by any antibiotic, regardless of dosage form or route of administration. In the pediatric population, the prevalence of antibiotic-associated diarrhea ranges from 6 to 70%. An urgent problem is the development of this disease against the background of a course of H. pylori eradication therapy, which significantly complicates tolerance and adherence to therapy. This article presents current data on the pathogenesis and risk factors of antibiotic-associated diarrhea in children. The clinical picture ranges from idiopathic enteritis to antibiotic-associated diarrhea caused by Cl. difficile - pseudomembranous colitis.The main principle of antibiotic-associated diarrhea treatment is cancellation of the antibacterial medicine that caused the diarrhea, or reducing its dose (if the course of the disease allows it). In complex treatment sorbents are used, correction of water-electrolyte balance is carried out. The use of probiotics seems quite logical for the treatment and prevention of antibiotic-associated diarrhea in terms of the pathogenesis of this condition. To correct dysbiosis, drugs are used to maintain and restore the quantitative and qualitative composition of the intestinal microbiota.Taking into account modern recommendations the main groups of drugs (probiotics, prebiotics, synbiotics) used for correction of intestinal microbiocenosis are presented. The mechanism of action of probiotics and mechanisms of their effect on intestinal microflora are considered. The basic requirements for bacterial strains that are part of the probiotic drugs are presented.The results of various randomized clinical trials and meta-analyses confirming the necessity of including probiotic complexes in antibiotic-associated diarrhea treatment regimens are presented from an evidence-based medicine perspective. The clinical effects of strains of Lactobacillusspp., Bifidobacterium spp.,Streptococcusspp. and Lactococcusspp. on the digestive tract microbiota are considered. The role of a synbiotic containing 9 probiotic strains of 4.5 * 109 CFU in one capsule and the prebiotic component fructooligosac-charides in the prevention of antibiotic-associated diarrhea in children is discussed separately. The results of microbiological studies confirmed the presence of microorganisms of genera Bifidobacterium, Lactobacillus, Streptococcus in the product, and the content of bacteria in one dose of the product was not less than 2 x 1010 CFU.

Використання розчину для оральної регідратації (оральної регідратаційної солі) з додаванням пробіотичного штаму для лікування дітей із гострою інфекційною патологією

Актуальність. На тлі гострої інфекційної патології в дітей існує ймовірність розвитку дегідратації, для ліквідації якої можливо використовувати розчини для оральної регідратації (оральна регідратаційна сіль — ОРС). При призначенні антибактеріальної терапії в 11–40 % дітей спостерігається антибіотик-асоційована діарея (ААД). Для профілактики розвитку ААД рекомендують застосовувати пробіотичні препарати. Мета: вивчити ефективність та переносимість розчину для оральної регідратації (Регідрон Біо) для підтримання водно-електролітного балансу та запобігання дисбіотичним порушенням у дітей із гострими інфекційними захворюваннями. Матеріали та методи. Було проведено спостереження за 60 дітьми віком від 3 до 14 років, які перебували на стаціонарному лікуванні на клінічній базі кафедри дитячих інфекційних хвороб НМУ ім. О.О. Богомольця й отримували антибактеріальну терапію. Основну групу становили 30 дітей, яким у комплексній терапії призначався розчин ОРС Регідрон Біо. Групу порівняння становили 30 дітей, які отримували стандартну терапію й компенсація втрат рідини яким проводилась традиційними засобами (чай, питна вода тощо). Результати. Серед симптомів зневоднення найчастіше виявлялись спрага та сухість слизових оболонок, які були присутні в 40–63 % хворих при надходженні до стаціонару. Відновлення водно-електролітного балансу за рахунок введення води та основних мінеральних речовин забезпечує швидке зникнення симптомів дегідратації. Діарея на тлі застосування антибактеріальної терапії спостерігалась у 10,0 % хворих, додаткове введення пробіотичного штаму Lactobacillus rhamnosus GG запобігало розвитку цього ускладнення. Висновки. Застосування оральної регідратаційної терапії препаратом ОРС Регідрон Біо є ефективним засобом корекції водно-електролітних порушень при гострих інфекційних захворюваннях у дітей. Наявність у складі ОРС Регідрон Біо пробіотичного штаму Lactobacillus rhamnosus GG дозволяє застосовувати його для профілактики ААД у дітей, які отримують антибіотики при інфекційних діареях.

Пробіотики при антибіотик-асоційованiй діареї в дітей: обґрунтований вибір

Призначення пробіотичних штамів для профілактики антибіотик-асоційованої діареї (ААД) у дорослих і дітей на сьогодні є стандартною схемою як віт­чизняних, так і європейських протоколів лікування. Сахароміцети Saccharomyces boulardii належать до дріжджових пробіотиків. Їх принциповою відмінністю від бактеріальних пробіотиків (Lactobacіllus та ін.) є стійкість до дії антибіотиків. У зв’язку з цим Saccharomyces boulardii можуть застосовуватися одночасно з антибіотиками для профілактики виникнення побічних явищ з боку травного тракту, викликаних антибіотикотерапією (перш за все ААД). Вибір у цій ситуації бактеріального пробіотика менш вдалий, оскільки антибіотики можуть пригнічувати активність введених бактерій. Важливо зазначити, що Saccharomyces boulardii не здатні передавати стійкість до дії антибіотиків патогенним бактеріям, у той час як у бактеріальних пробіотиків такий потенціал існує. Результати виконаних клінічних досліджень свідчать про високу ефективність та безпечність Saccharomyces boulardii в профілактиці та лікуванні антибіотик-асоційованої діареї в дітей. В Україні цей пробіотик представлений лікарським засобом Ентерол®.

Порушення травлення у дітей з антибіотик-асоційованою діареєю

Актуальність. Найбільш відчутною проблемою широкого використання антибіотиків є зміни мікробної екології, порушення рівноваги біоценозу кишечника, поява антибіотикорезистентних штамів мікроорганізмів з патогенними властивостями та виникнення у зв’язку з цим патологічних змін в кишечнику, що й обумовлюють симптоми порушення травлення у хворих з антибіотик-асоційованою діареєю. Мета дослідження. Визначення проявів синдрому мальабсорбції для удосконалення діагностики антибіотик-асоційованої діареї в дітей. Матеріали й методи. Об’єкт дослідження становили 116 хворих, які отримували антибіотики, віком від 6 місяців до 18 років. Обстеження дітей включало загальноклінічні, біохімічні, бактеріологічні, імуноферментні, імунохроматографічні, інструментальні, математичні методи дослідження. Результати. При розвитку діареї у хворих за умов негативних тестів на клостридіальні токсини кваліфікували ці випадки як ідіопатичну антибіотик-асоційовану діарею, при позитивних — як кишкову інфекцію Clostridium difficilе. У ході дослідження були виявлені вірогідні відмінності за копрологічними показниками між дітьми з гострою ідіопатичною й обумовленою клостридіальною інфекцією антибіотик-асоційованою діареєю. При мікроскопічному та біохімічному дослідженні випорожнень виявлено маніфестні ознаки порушення травлення та всмоктування жирів і вуглеводів, які проявляються клінічними симптомами мальабсорбції. Усім дітям з антибіотик-асоційованою діареєю притаманні підвищені концентрації вуглеводів у випорожненнях. Виявлені ознаки порушення травлення з розвитком мальабсорбції ліпідів у дітей з антибіотик-асоційованою діареєю, і в першу чергу обумовленою інфекцією Clostridium difficile. Висновки. Порушення травлення та всмоктування вуглеводів та ліпідів, а також показники запальної реакції кишечника (лейкоцити, прихована кров, слиз) є маркерами антибіотик-асоційованої діареї та можуть використовуватися для її ранньої діагностики, у тому числі в разі інфекції Clostridium difficile.

Досвід використання пробіотичних штамів Lactobacillus acidophilus R0052 та Lactobacillus rhamnosus R0011 у дітей з опіковою травмою

На сьогодні опіки посідають друге місце серед усіх травм дітей. Основною причиною летальних наслідків у випадку виражених та глибоких опіків є інфекція, що виникає у 23–82 % усіх випадків опіків. Раціональна антибактеріальна терапія має велике значення в боротьбі з генералізованою інфекцією. Метою цього дослідження було ретельне вивчення епідеміології та характеристики антибіотик-асоційованої діареї (ААД) у хворих дітей з опіками, а також можливість запобігання цій діареї, що виникала внаслідок антибактеріальної терапії в пацієнтів Обласного опікового відділення м. Запоріжжя. Протягом 2012–2015 років ми спостерігали 438 дітей з опіковими травмами, які приймали антибіотики. У цих госпіталізованих дітей було знайдено специфічні для ААД Clostridium difficile токсини А + В у фекаліях. Це дозволило діагностувати Clostridium difficile-ентероколіт, пов’язаний з прийомом хворими антимікробних препаратів (A4.07, МКБ‑10). Розроблено профілактичні методи AAД, а саме призначення з перших годин перебування в стаціонарі per os пробіотичного засобу Lactobacillus acidophilus R0052 і Lactobacillus rhamnosus R0011 у складі препарату Lacidofil®. Використання пробіотичних штамів з антитоксичною активністю щодо Clostridium difficile скорочує в 3,4 раза число випадків антибіотик-асоційованої діареї в дітей з опіками та зменшує тяжкість її симптомів.

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).

Systematic review: clinical evidence of probiotics in the prevention of antibiotic-associated diarrhoea

Antibiotic-associated diarrhoea (AAD) is the most common intestinal side effect of an antibiotic therapy. Various probiotics or probiotic combinations are often used preventively while taking antibiotics for the prevention of AAD. This review is based on a systematic literature research in MEDLINE and EMBASE. 7 probiotics are presented with regard to their effectiveness and evidence in the prevention of AAD. Only preparations classified by the World Gastroenerology Organization (WGO) with evidence levels 1-3 for the prevention of AAD were taken into account. 37 clinical studies, including 33 RCTs, were evaluated. Saccharomyces (S.) boulardii CNCM I-745 is the most extensively studied probiotic regarding the prevention of AAD. It has shown evidence-based efficacy in all patient groups (outpatients and hospitalized children and adults). Lactobacillus rhamnosus GG also has a good evidence regarding the prevention of AAD in children and outpatient adults. The other probiotics and probiotic combinations evaluated in the present study only show efficacy in hospitalized patients or only show very limited evidence regarding their efficacy in the prevention of AAD due to the underlying study design or the small number of patients. The effect of probiotics is strain-specific, no general statement can be made about the efficacy of probiotics in the prevention of AAD. In principle, it is advisable to select a probiotic with an evidence-based effect such as S. boulardii CNCM I-745 or Lactobacillus rhamnosus GG to prevent AAD.

Modern approaches to the prevention and rehydration therapy of antibiotic-associated diarrhea affected by ARI in children

The use of antibiotic drugs (ABDs) has significantly reduced the number of severe bacterial infectious diseases and mortality in children, especially in infants. But the widespread and unnecessary use of ABDs, including reserve antibiotics (the use of carbapenems increased by 45%, polymyxins – by 13%), to treat uncomplicated acute respiratory infections is open to many hazards, such as increased antibiotic resistance of pathogens. Antibiotic-associated diarrhea is one of the common complications of antibiotic therapy. According to various authors, the incidence of antibiotic-associated diarrhea is 6–80% among patients treated with antibiotics, on average 35% of patients (approximately every third patient) receiving antibiotics report symptoms of antibiotic-associated diarrhea. Disruptive changes in the qualitative and quantitative composition of the intestinal microbiota are accompanied by a decrease in the protective functions of the intestinal mucosa and contribute to the growth of pathogenic and opportunistic microorganisms (Clostridium spp., Candida spp., Salmonella spp., Staphyloccus aureus). The findings of most studies obtained on a large sample of paediatric population, as well as the clinical guidelines of the World Association of Gastroenterologists recommend the use of L. rhamnosus GGprobiotic strain (level of evidence 1) to prevent antibiotic-associated diarrhea in children. L. rhamnosus GGpresents chromosomal resistance to a range of antibiotics, which varies with species and strain. They do not contain plasmid DNA, which is dangerous for the spread of antibiotic resistance among other bacteria, which enables their wide therapeutic and prophylactic use. Clinical case studies of the course of antibiotic-associated diarrhea in children are presented to demonstrate the variability of clinical symptoms. Fever in children with ARI, particularly in tender-age infants, requires special attention from parents and doctors, as its main risk lies with a dehydration due to significant water loss during breathing, and especially increased sweating (including sweating induced by antipyretics). Therefore, oral rehydration therapy is an important method for treating infectious diseases in children. Complications that develop in patients, especially in children, after administration of antibiotics, diseases that can lead to water and electrolyte imbalance are life-threatening conditions that require immediate medical attention. Correction of water and electrolyte balance, timely restoration of intestinal microflora improve prognosis in such patients and promote faster recovery.

Профилактика дисбиотических нарушений и антибиотик- ассоциированной диареи у детей с острыми респираторными заболеваниями на фоне антибиотикотерапии

Aim: to develop a method of dysbiotic abnormality prevention after antibiotic therapy (ABT) in early childhood. Patients and Methods: the study enrolled 90 children aged 12–60 months who were admitted to the hospital with complicated acute respiratory infections (ARIs) and received ABT. The children were randomized into three groups (each comprised of 30 children). The children received either a probiotic with Lactobacillus rhamnosus GG and Bifidobacterium BB-12 (group 1) or a cytomucoprotector, gelatin tannate (group 2) to prevent antibiotic-associated diarrhea (AAD). Group 3 children received ABT only. To assess microbiocenosis, short-chain fatty acids (SCFAs) in stool were measured by gas-liquid chromatography. Results: AAD was reported in 23.3% of group 1 children, 17% of group 2 children, and 46.7% of group 3 children (p=0.03). In group 2, the duration of diarrhea was significantly lower. Baseline stool concentration of SCFAs was 2.5-times lower compared to normal ranges. Further reduction in the total absolute level of SCFAs was reported in group 3 after treatment. An increase in total SCFA level, a significant increase in the relative amounts of acetic acid, and a reduction in propionic acid and (to a lesser degree) butyric acid were reported in groups 1 and 2 compared to group 3. Conclusions: an improvement in stool SCFA levels was reported in group 1 and 2 children who received probiotics or cytomucoprotector. Incorporation of these medications and ABT in the complex treatment for ARIs in children stabilized metabolic activity of microbiota through preserving the pool of indigenous microorganisms producing butyrate. KEYWORDS: antibiotic, antibiotic-associated diarrhea, acute respiratory viral infections, microbiota, short-chain fatty acids, probiotic, gelatin tannate. FOR CITATION: Mazankova L.N., Perlovskaya S.G., Ardatskaya M.D. et al. Prevention of dysbiosis and antibiotic-associated diarrhea in children with acute respiratory infections after antibiotic therapy. Russian Medical Inquiry. 2021;5(11):712–720 (in Russ.). DOI: 10.32364/2587-6821-2021-5-11-712-720.