Prevention Of Antibiotic-associated Diarrhea 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.

The Efficacy of a Mix of Probiotics (Limosilactobacillus reuteri LMG P-27481 and Lacticaseibacillus rhamnosus GG ATCC 53103) in Preventing Antibiotic-Associated Diarrhea and Clostridium difficile Infection in Hospitalized Patients: Single-Center, Open-Label, Randomized Trial.

Antibiotic-associated diarrhea is a condition reported in 5-35% of patients treated with antibiotics, especially in older patients with comorbidities. In most cases, antibiotic-associated diarrhea is not associated with serious complications, but it can prolong hospitalization and provoke Clostridium difficile infection. An important role in the prevention of antibiotic-associated diarrhea is carried out by some probiotic strains such as Lactobacillus GG or the yeast Saccharomyces boulardii that showed good efficacy and a significant reduction in antibiotic-associated diarrhea. Similarly, the Limosilactobacillus reuteri DSM 17938 showed significant benefits in acute diarrhea, reducing its duration and abdominal pain. The aim of this study was to test the efficacy of a mix of two probiotic strains (Limosilactobacillus reuteri LMG P-27481 and Lacticaseibacillus rhamnosus GG ATCC 53103; Reuterin GG®, NOOS, Italy), in association with antibiotics (compared to antibiotics used alone), in reducing antibiotic-associated diarrhea, clostridium difficile infection, and other gastrointestinal symptoms in adult hospitalized patients. We enrolled 113 (49M/64F, mean age 69.58 ± 21.28 years) adult patients treated with antibiotics who were hospitalized at the Internal Medicine Department of the San Carlo di Nancy Hospital in Rome from January 2023 to September 2023. Patients were randomized to receive probiotics 1.4 g twice/day in addition with antibiotics (Reuterin GG® group, total: 56 patients, 37F/19M, 67.16 ± 20.5 years old) or antibiotics only (control group, total: 57 patients, 27F/30 M, 71 ± 22 years old). Patients treated with Reuterin GG® showed a significant reduction in diarrhea and clostridium difficile infection. In particular, 28% (16/57) of patients in the control group presented with diarrhea during treatment, compared with 11% (6/56) in the probiotic group (p < 0.05). Interestingly, 7/57 (11%) of patients treated only with antibiotics developed clostridium difficile infection compared to 0% in the probiotic group (p < 0.01). Finally, 9% (5/57) of patients in the control group presented with vomiting compared with 2% (1/56) in the probiotic group (p < 0.05). Our study showed, for the first time, the efficacy of these two specific probiotic strains in preventing antibiotic-associated diarrhea and clostridium difficile infection in adult hospitalized patients treated with antibiotic therapy. This result allows us to hypothesize that the use of specific probiotic strains during antibiotic therapy can prevent dysbiosis and subsequent antibiotic-associated diarrhea and clostridium difficile infection, thus resulting in both patient and economic health care benefits.

Применение пробиотиков, содержащих комбинацию штаммов Lactobacillus acidophilus LA-5 и Bifidobacterium animalis subsp. lactis BB-12: метаанализ эффективности для профилактики антибиотик-ассоциированной диареи и в схемах эрадикационной терапии Helicobacter pylori

Применение пробиотиков, содержащих комбинацию штаммов Lactobacillus acidophilus LA-5 и Bifidobacterium animalis subsp. lactis BB-12: метаанализ эффективности для профилактики антибиотик-ассоциированной диареи и в схемах эрадикационной терапии Helicobacter pylori

Unlocking the Power of Probiotics: A Comprehensive Review on Safeguarding Hospitalised Patients from Clostridium Difficle Infection

Antibiotic-associated diarrhea (AAD) is a commoncomplication of antibiotic therapy, with Clostridiumdifficile infection (CDI) being a major cause of severeAAD. CDI is associated with high morbidity, mortality,and healthcare costs. The administration of probiotics isa promising strategy for the prevention of AAD and CDI,as they can create a favorable gut environment andalter the composition of the intestinal flora. Thissystematic review evaluated the use of probiotics inpreventing CDI in hospitalized adult patients. Thereview of 12 randomized controlled trials involving3,586 patients found that probiotics reduced theincidence of CDI in hospitalized adult patients by up to70%. Specifically, the probiotic strains Lactobacillusrhamnosus GG and Saccharomyces boulardii werefound to be effective in preventing CDI. However,further research is needed to establish optimal dosingregimens and to identify the most effective probioticstrains for CDI prevention. Nonetheless, the use ofprobiotics appears to be a promising strategy forreducing the incidence of CDI in hospitalized adultpatients receiving antibiotics.

Qualitative Analysis of the Efficacy of Probiotic Strains in the Prevention of Antibiotic-Associated Diarrhea.

Antibiotic-associated diarrhea is often managed by the withdrawal of the culprit antibiotics or the administration of alternative antibiotics when a Clostridium difficile infection (CDI) is suspected, an infection that tends to be the most common causative agent of the disease. Probiotics are also gaining popularity as alternative therapies, and it was hypothesized in this article that a Lactobacillus strain is the most efficacious probiotic for the prevention of antibiotic-associated diarrhea. This article conducted a literature review investigating the relative efficacy of the Lactobacillus, Bifidobacterium, and Saccharomyces probiotic strains as effective alternative therapies for antibiotic-associated diarrhea. The literature searched was from the PubMed database. The inclusion filters were: random control trials (RCTs), clinical trials, meta-analysis, last 10 years, full-text articles available in English, and all articles published in peer-reviewed journals. All three probiotic genera had strains that demonstrated significant efficacy in the prevention of antibiotic-associated diarrhea. However, Saccharomyces boulardii I-745 tends to outperform all the strains as the most effective and the one with the fewest, if any, adverse effects. Whenever probiotics are considered for the prevention of antibiotic-associateddiarrhea (AAD) in both pediatric and adult patients, S. boulardii I-745 should probably be prioritized.

Pathogenetic aspects of the development and treatment of antibiotic-associated diarrhea: the choice of a synbiotic from the standpoint of evidence-based medicine

Introduction. In recent years, diarrheal syndrome is the most common clinically significant negative effect of the antibiotic therapy (ABT), which constitutes a first-priority medical and social problem. The prescription of any antibiotic for any duration of treatment may cause a potential risk of developing antibiotic-associated diarrhea (AAD). In that regard, there is a need for the systematization of the main pathogenetic aspects of the deveopment of AAD and the rationale for the use of probiotics to prevent its development and treatment. Aim. To conduct a comparative evaluation of the efficacy, adherence and tolerability of a synbiotic Floriosa containing Bifidobacterium lactis Bl-04, Lactobacillus acidophilus La-14, Lactobacillus rhamnosus Lr-32, inulin, B vitamins, and an eubiotic Bifiform containing Enterococcus faecium, Bifidobacterium longum for the prevention of the development of AAD during and after the use of ABT in inpatients. Materials and methods. A total of 60 patients, which was used for the ABT in the hospital settings, were included in the study: the 1st group (30 patients) received a synbiotic, the 2nd group (30 patients) received an eubiotic. The efficacy of the preventive administration of drugs was assessed by Day 12 and 28 of the therapy. The methods included the patients’ assessment of the efficacy and satisfaction with treatment, an assay of short-chain fatty acids (SCFAs) in feces via gas-liquid chromatography and a Clostridium difficile Toxin A + B rapid test. Results. No cases of AAD were detected in both groups. The study drugs were comparable in terms of their efficacy assessment by the doctor and patients. A trend towards a higher assessment of the therapeutic effect and satisfaction with synbiotic therapy was observed. Changes in the absolute and relative content of SCFAs in the patients’ feces from the baseline level were established. More pronounced positive changes in the quantitative and qualitative composition of acids due to the treatment were identified in the patients who received the synbiotic and had more than 3 risk factors. Conclusions. The synbiotic Floriosa and probiotic Bifiform are effective drugs to prevent AAD. The synbiotic has advantages in terms of the overall assessment of the efficacy of the treatment and patient satisfaction, provides a pronounced protective effect on the intestinal microbiocenosis status during and after the ABT (as evidenced by the changes in SCFAs level in the feces), can be the drug of choice for the prevention of AAD, including AAD associated with C. difficile in individuals with more than 3 risk factors for the development of AAD.

Probiotics for the Management of Pediatric Gastrointestinal Disorders: Position Paper of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications.

Probiotics, defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, are widely used despite uncertainty regarding their efficacy and discordant recommendations about their use. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Special Interest Group on Gut Microbiota and Modifications provides updated recommendations for the use of probiotics for the management of selected pediatric gastrointestinal disorders. All systematic reviews and/or meta-analyses, as well as subsequently published randomized controlled trials (RCTs) (until December 2021), that compared the use of probiotics in all delivery vehicles and formulations, at any dose, with no probiotic (ie, placebo or no treatment), were eligible for inclusion. The recommendations were formulated only if at least 2 RCTs on a similar well-defined probiotic strain were available. The modified Delphi process was used to establish consensus on the recommendations. Recommendations for the use of specific probiotic strains were made for the management of acute gastroenteritis, prevention of antibiotic-associated diarrhea, nosocomial diarrhea and necrotizing enterocolitis, management of Helicobacter pylori infection, and management of functional abdominal pain disorders and infant colic. Despite evidence to support the use of specific probiotics in some clinical situations, further studies confirming the effect(s) and defining the type, dose, and timing of probiotics are still often required. The use of probiotics with no documented health benefits should be discouraged.

Indian Academy of Pediatrics Consensus Guidelines for Probiotic Use in Childhood Diarrhea

Several probiotic species and strains, single or combined, have been evaluated in childhood diarrheal disorders, and recommendations have ever been changing as newer trials are published. Therefore, there is a need to develop a guideline for Indian children describing the current role of probiotics in clinical practice. To develop a guideline for the use of probiotics in children with diarrhea. A national consultative group (NCG) was constituted by the Indian Academy of Pediatrics (IAP), consisting of subjects experts. Sub-topics were allotted to various experts as paired groups for detailed review. Members reviewed the international and Indian literature for existing guidelines, systematic reviews, meta-analyses and trials. Thereafter, two virtual structured meetings of the group were held on 2nd and 22nd August, 2020. The management guidelines were formulated by the group and circulated to the participants for comments. The final guidelines were approved by all experts, and adopted by the IAP executive board. The NCG suggests Lactobacillus GG as a conditional recommendation with low-to-moderate level evidence or Saccharomyces boulardii as a conditional recommendation with very low-to-low level evidence as adjuvant therapy in acute diarrhea. The NCG also recommends the use of combination probiotics in neonatal necrotizing enterocolitis (NEC), as these reduce the risk of NEC stage II and above, late-onset sepsis, mortality and also time to achieve full feeds. The NCG does not recommend the use of any kind of probiotics in the therapy of acute dysentery, persistent diarrhea, Clostridium difficile diarrhea and chronic diarrheal conditions such as celiac disease, diarrhea-predominant irritable bowel syndrome and inflammatory bowel disease in children. Risk of antibiotic-associated diarrhea (AAD) is high with some antibiotics and most of these cases present as mild diarrhea. The NCG recommends probiotics only in special situations of AAD. L. rhamnoses GG or S. boulardii may be used for the prevention of AAD. VSL#3, a combination probiotic, may be used as an adjuvant in active pouchitis, prevention of recurrences and maintenance of remission in pouchitis.

До питання профілактики антибіотикоасоційованої діареї у дітей

У статті подані результати власних досліджень терапевтичної та профілактичної ефективності симбіотичного препарату Коліфагіна ПРО на фоні антибактеріальної терапії у дітей з респіраторною патологією. Необхідність корекції дисбіотичних порушень у супроводі антибіотикотерапії не викликає сумніву. Включення до комплексної терапії з антибіотиками пробіотичної корекції симбіотиком Коліфагіна ПРО у дітей із гострою респіраторною патологією дозволило профілактувати антибіотикоасоційовану діарею та сприяло більш швидкому регресу основних симптомів захворювання, нормалізації характеру і частоти випорожнень.

Probiotics: relevant during the coronavirus (COVID-19) infection pandemic?

The review presents modern views on the role of probiotics in the treatment and prevention of complications of the novel coronavirus COVID-19 infection. This infection can be complicated, for example, by the development of diarrhea after the use of antibacterial drugs in case of secondary bacterial infection, extrapulmonary viral infections, viremia, and the so-called «cytokine storm». The emphasis has been placed on such potentially beneficial effects of probiotics as а prevention of antibioticassociated diarrhea, prevention of intestinal damage induced directly by viral replication, prevention of leaky gut syndrome and immunomodulation in case of coronavirus COVID-19 infection. It has been shown that the use of probiotics alongside antibiotic therapy significantly reduces the risk of developing antibiotic-associated diarrhea, including such a severe variant as pseudomembranous colitis. The use of a probiotic during a viral respiratory disease reduces the risk of a severe disease course due to the positive modulation of inflammation and direct antiviral effects. Selected data showed the positive effect of probiotics on the tight junction stability of the intestine, which potentially protects against viremia and the penetration of immunogenic molecules into the internal environment of the body. In order to address the challenges adequately, a probiotic should meet certain requirements in terms of product quality, safety, evidence of efficacy, composition and understanding of the strains. The article presents data on the successful use of a multi-strain immuno-probiotic as an example demonstrating the therapeutic potential of modern multi-strain probiotics as a nonspecific immunomodulatory agent for the prevention of acute respiratory diseases.

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.

Analysis of information asymmetry in the instructions for medical use on the example of Enterol

There may be variations in the texts of instructions for medical use of medicines (hereinafter – the instructions) containing the same active pharmaceutical ingredient, and registered in the pharmaceutical markets of different countries. First of all this applies to medicines manufactured in one country and distributed to other countries. Therefore, there are questions related to incorrect use of medicines due to the existing asymmetry of information. This problem is especially relevant in connection with tourist activity and labour migration.&#x0D; The aim of the study was to identify discrepancies in the instructions of Enterol, registered in different countries.&#x0D; The materials of the study were the registers of medicines in France, Ukraine, Belarus, Bulgaria, Poland, the Czech Republic and Russia, as well as the texts of instructions of Enterol (Biocodex, France), registered in the above countries. Methods of generalization, systematization, as well as contextual and comparative analysis were used.&#x0D; It was found that the original (French) instruction has two indications for the use of Enterol (treatment of acute diarrhea in children under 12 years old; prevention of antibiotic-associated diarrhea caused by Clostridium difficile or recurrence of diarrhea caused by Clostridium difficile), while Belarusian and Russian instructions have one indication. Polish instruction contains 5 indications, while Bulgarian and Czech – 8. The largest number of indications for the use of Enterol (11) is given in Ukrainian instruction.&#x0D; A contradictory information is in the sections «Therapeutic Indications», «Posology and method of administration», «Contraindications», «Undesirable effects», «Special warnings and precautions for use», including «Pregnancy and lactation». In the text of one instruction there is no information available in the text of another, and none of the instructions is identical to the instructions of Enterol, registered in France (country of manufacture). Actually, these information discrepancies, as well as the patient's perception of information, can lead to improper use of medicines and, as a consequence, drug-related problems. Thus, to minimize the asymmetry of information, the applicant during the registration of the drug must submit a notarized translation of the manufacturer's instructions.

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®.

Особенности применения пробиотиков при антибиотикоассоциированной диарее у детей

Антибиотикоассоциированная диарея (ААД) возникает тогда, когда антибиотик нарушает экологию микробиоты кишечника, изменяя разнообразие и количество бактерий в нем. Эти изменения могут повлиять на способность резидентной микробиоты противостоять вторжению патогенных микроорганизмов или росту условно-патогенных видов, которые эндогенно присутствуют в микробиоме. Поэтому AAД может привести к длительной госпитализации, увеличению расходов и ухудшению качества жизни. Диарея чаще всего связана с применением антибиотиков широкого спектра действия. Пробиотики — это «живые микроорганизмы, которые при применении в достаточном количестве приносят пользу здоровью хозяина». Многочисленные клинические исследования изучают эффективность Lactobacillus rhamnosus GG для предотвращения ААД. Целью работы было изучить эффективность применения препарата Пробиолог Бейби у детей в возрасте от 4 мес. до 9 лет жизни с диагнозом антибиотикоассоциированной диареи, а также исследовать его влияние на дисбиотические изменения кишечника. Под нашим наблюдением находилось 28 детей в возрасте от 4 мес. до 9 лет (средний возраст — 4,6 ± 1,9 года) с диагнозом антибиотикоассоциированной диареи, среди них 57 % мальчиков и 43 % девочек. Дети получали Пробиолог Бейби по 1 стику в день в течение 10 дней. Через 10 дней только у 2 детей (7,2 %) были жалобы на диарею против 100 % в начале наблюдения. Применение штамма Lactobacillus rhamnosus GG (АТСС 53103) у детей с антибиотикоассоциированной диареей способствует уменьшению диареи, колик, вздутия живота, тошноты, рвоты, беспокойства и плохого сна. Принимая во внимание комплексное воздействие штамма Lactobacillus rhamnosus GG, можно утверждать, что Пробиолог Бейби увеличивает уровень бифидобактерий и лактобактерий в кале, а также уменьшает рост грибов рода Candida и патогенной кишечной флоры.

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).

Potential Roles for Probiotics in the Treatment of COVID-19 Patients and Prevention of Complications Associated with Increased Antibiotic Use.

Medical care for patients hospitalized with COVID-19 is an evolving process. Most COVID-19 inpatients (58–95%) received empiric antibiotics to prevent the increased mortality due to ventilator-associated pneumonia and other secondary infections observed in COVID-19 patients. The expected consequences of increased antibiotic use include antibiotic-associated diarrhea (AAD) and Clostridioides difficile infections (CDI). We reviewed the literature (January 2020–March 2021) to explore strategies to reduce these consequences. Antimicrobial stewardship programs were effective in controlling antibiotic use during past influenza epidemics and have also been shown to reduce healthcare-associated rates of CDI. Another potential strategy is the use of specific strains of probiotics shown to be effective for the prevention of AAD and CDI prior to the pandemic. During 2020, there was a paucity of published trials using these two strategies in COVID-19 patients, but trials are currently ongoing. A multi-strain probiotic mixture was found to be effective in reducing COVID-19-associated diarrhea in one trial. These strategies are promising but need further evidence from trials in COVID-19 patients.

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.

Clinical evaluation of the synbiotic Prodefen Plus® in the prevention of the antibiotic-associated diarrhoea in subjects requiring antibiotic treatment.

Prodefen® is a dietary food supplement formulated as a synbiotic that has shown additional benefit to the standard supportive therapy in the management of acute viral diarrhoea in children. There is scarce evidence of this synbiotic in adults. The objective of this randomised double blind placebo-controlled clinical trial was to evaluate the efficacy and safety of Prodefen Plus® in the prevention of antibiotic-associated diarrhoea (AAD) in an adult population requiring either antibiotic treatment for an oral infection or antibiotic prophylaxis for a dental surgical procedure in a dental consultation. 151 subjects were randomised to the active (synbiotic) or control arm (placebo) for 14 days. There was a significantly higher reduction in the AAD incidence, and an improvement in the stool consistency in the active group. A higher reduction in both the frequency and duration of the diarrhoea episodes in the active group was also observed, as it was an improved perception of the diarrhoea severity. Overall, the study medication was well tolerated. In conclusion, results from this study confirm the beneficial effect of the synbiotic administered as adjuvant therapy in preventing the antibiotic-associated diarrhoea.

Effect of Limosilactobacillus reuteri LRE02-Lacticaseibacillus rhamnosus LR04 Combination on Antibiotic-Associated Diarrhea in a Pediatric Population: A National Survey.

Probiotics are living microorganisms, which, upon oral ingestion, may prevent antibiotic-associated diarrhea (AAD) through the normalization of an unbalanced gastrointestinal flora. The objective of this study was to evaluate the benefits of a probiotic combination (Limosilactibacillus reuteri LRE02-DSM 23878 and Lacticaseibacillus rhamnosus LR04-DSM 16605) on the prevention of AAD in an outpatient pediatric setting. Questionnaires were delivered to pediatricians by each patient/parent during the visits after antibiotics and probiotics treatment to monitor physiological parameters. The primary outcome of both groups (probiotics and no probiotics treated) was the evaluation of the prevalence of AAD between the two groups. Evaluation of stool consistency using the Bristol Stool Scale (BSS) score was performed, as well as the evaluation of AAD duration, frequencies of daily evacuation, and the beginning of diarrhea and weight loss during AAD in both groups and related to antibiotic categories. Results indicated that probiotics, at the recommended dosage of 1.2 × 109 CFU (Colony Forming Unit) per day for 30 days, are associated with lower rates of AAD and a decreased number of days with diarrhea, independent of the type of antibiotic used. Moreover, the use of probiotics resulted in a normal stool consistency in a shorter time period, as evaluated by the BSS.