Development Of Antibiotic-associated Diarrhea Research Articles

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.

Antibiotic-Associated Syndrome in Clinical Practice

Purpose of Research: Establishing clinical features of an antibiotic- associated diarrhea and extra-intestinal manifestations of an antibiotic- associated syndrome in children Patients and Methods: In 2017-2019 on the basis of GBUZ Infectious clinical hospital No. 2 DZ of Moscow a prospective clinical surveillance was carried out 200 patients aged 3 months to 13 years who were hospitalized with a diagnosis of acute pneumonia and received antibacterial therapy. All patients were evaluated for antibiotic-associated diarrhea (development of diarrhea, vomiting, dyspepsia, stomatitis) and manifestations of antibiotic-associated syndrome in children (condition of the skin and appendages of the skin, nervous system, development of inflammatory changes in the external genitals) within a month after antibiotic therapy. Comparative analysis of the effectiveness of probiotic prevention of antibiotic-associated syndrome was conducted in two groups: group 1 (23 children who received a drug containing Lactobacillus acidophilus, polysaccharide of kefir fungus in parallel with antibacterial therapy), group 2 (122 patients who received a medication containing Lactobacillus acidophilus, Bifidobacterium infantis, Enterococcus faecium). Results: 29% of patients had symptoms of antibiotic-associated syndrome. AAD symptoms were diagnosed in 13% of patients. Abdominal pain (32.8%), dyspepsia symptoms (22.4%), bad breath (17.2%), flatulence (17.2%), stomatitis (10.3%), and constipation (1.7%) associated with antibiotic therapy were found among the manifestations of antibiotic-associated gastrointestinal syndrome. Dry skin was observed in 15.5% of patients, diaper rash-3.4%, brittle nails-15.5%, peeling of the skin-3.4% of patients, increased irritability in 17.2%, inflammatory changes in the external genitals-in 1.7% of patients. Comparative analysis of various probiotic prophylaxis of AAD showed that 1 group patients were significantly more likely to have stomatitis (p<0.01) and dry skin (p<0.05) than patients in group 2. Summary: New term “ antibiotic-associated syndrome» implies the development of a wider range of clinical manifestations associated with the use of antibacterial agents than the development of antibiotic-associated diarrhea. The use of probiotic prophylaxis with a medication containing Lactobacillus acidophilus, Bifidobacterium infantis, Enterococcus faecium demonstrates high efficiency compared to the comparison group.

Prophylactic use of Saccharomyces boulardii probiotics in preventing antibiotic-associated diarrhea: a single center hospital-based case-control study in Serbia


 Background. Antibiotic-associated diarrhea (AAD) develops through the loss of normal bacterial intestinal flora. We have conducted a case-control study in order to assess whether prophylactic administration of Saccharomyces boulardii (S. boulardii) prevents occurrence of AAD among adult hospitalized patients.
 Methods. Single-center hospital based case-control study was conducted in University Clinic “Dr Dragisa Misovic-Dedinje”, Belgrade, Serbia. Hospital records were screened in order to identify all the patients developing AAD in period January 1. 2010 – August 31. 2015. For every case, one age and gender matched control was randomly selected among patients hospitalized at the same time at the same department who were administered with antibiotics and did not develop AAD. For both cases and controls data were extracted on demographics, medical history, indication for use of antibiotics, antibiotics used, and prophylactic use of S.boulardii probiotics. The relationship between occurrence of AAD and putative risk factors were measured using the odds ratios (ORs) and their 95% confidence interval (CI) derived from logistic regression analysis.
 Results. Number of 59 cases and 59 controls were included in the study. Most of AAD cases were associated with old age (mean age of 78.05), and almost half (49.15%) were hospitalized on geriatrics department. Most prescribed class of antibiotics among cases was III generation cephalosporins (50.85%), followed by fluoroquinolones (28.81%) and trimethoprim-sulfamethoxazole (20.34%). Significantly more cases than controls were treated with carbapenems (16.95% vs. 5.08% respectively, p=0.04). Significantly less cases were administered with prophylactic S. boulardii probiotics (18.64% vs. 42.37% p=0.005). We identified prophylactic use of S. boulardii to act protectively against development of AAD from both univariate (OR: 0.31, 95% CI: 0.14-0.72) and multivariate analysis (OR:0.36, 95% CI: 0.14-0.80). Use of carbapenems was borderline significant risk factor for development of AAD in univariate (OR: 3.81, 95% CI: 0.99-14.64) as well as multivariate analysis (OR: 3.82, 0.91-16.08) (Table 3). Conclusion. Prophylactic use of probiotics containing Saccharomyces boulardii acts protectively against antibiotic-associated diarrhea among hospitalized patients. 

Патогенетические особенности антибиотик-ассоциированного синдрома на примере биологической модели

Antibiotic therapy is an integral part of current therapeutic practice to save patients’ lives. However, as with any therapeutic intervention, the development of adverse events is possible, one of which is the antibiotic-associated syndrome (AAS). Objective. To study the pathogenetic features of AAS extraintestinal manifestations using a biological model as an example. Materials and methods. This study was conducted using the biological model (outbred male mice) between 2019 and 2020 on the basis of the Central Research Institute of Epidemiology of Rospotrebnadzor. Experimental animals were injected with amoxicillin/clavulanic acid and cefotaxime in two therapeutic doses, average and maximum. The recalculation of drug doses was carried out depending on the animal’s body weight. The comparison was performed in four study groups and one control group, which were distinguished according to the dose and type of antibacterial agent. The histological examination of internal organs (large intestine, small intestine, liver, pancreas, kidney, lung, heart, testicles, spleen, stomach, duodenum, skin, bladder) was conducted at two time points: 24 hours after antibiotic administration and 7 days after the end of antibiotic therapy. Results. The results of histological examination at the first time point (24 hours after antibiotic administration) demonstrated that the use of the studied antibacterial agents at the average therapeutic dose did not cause significant morphological changes in the organs of mice, while the administration of maximum dose led to the development of reactive changes, primarily in the vascular system. The results of histological examination in the experimental groups at the second control time point (7 days after the end of antibiotic therapy) showed a systemic reaction in the organs of mice, expressed primarily in perivascular leukocyte infiltration. Similar changes were registered in the group of experimental animals that were injected with average therapeutic doses of antibacterial agents. Conclusion. AAS is characterized by systemic and homogeneous pathomorphological changes in various tissues, which explains not only the development of antibiotic-associated diarrhea, but also its extraintestinal symptoms. Our findings allow to suggest that antibiotics, especially when used irrationally, increase the risks of pathology associated with a systemic inflammatory response, in particular atherosclerosis and obesity, at the population level. Key words: antibiotic-associated diarrhea, antibiotic-associated syndrome

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.

Gut Ruminococcaceae Levels Correlate with Risk of Antibiotic-Associated Diarrhea

Antibiotic-associated diarrhea (AAD) affects a significant proportion of patients receiving antibiotics. We sought to understand if differences in the gut microbiome would influence the development of AAD. We administered a 3-day course of amoxicillin-clavulanate to 30 healthy adult volunteers, and analyzed their stool microbiome, using 16S rRNA gene sequencing, at baseline and up to 4-weeks post-antibiotic administration. Lower levels of gut Ruminococcaceae were significantly and consistently observed from baseline till Day 7 in participants who developed AAD. Overall, participants who developed AAD experienced a greater decrease in microbial diversity. The probability of AAD could be predicted based on qPCR-derived levels of Faecalibacterium prausnitzii . Our findings suggest that a lack of gut Ruminococcaceae influences development of AAD. Quantification of F. prausnitzii in stool prior to antibiotic administration may help identify patients at risk of AAD, and aid clinicians in devising individualised treatment regimens to minimise such adverse effects.

Comparison of clinical-metabolic efficacy of pre- and probiotics in the conducted optimized protocols of eradication therapy of Helicobacter pylori infection

The purpose of this study was to study the comparative effect on the clinical effectiveness of eradication therapy (ET) of Helicobacter pylori infection and metabolic changes in the colon microbiota of additional inclusion in the optimized treatment regimen of the combined prebiotic Zakofalk (inulin + butyrate) with probiotics (lacto- and bifidobacteria in an amount of at least 1017 СFU). 120 patients with chronic gastroduodenal diseases and infected H. pylori were еxamined. A comparative analysis of the effect of a combined prebiotic and lacto-bifid-containing probiotics on improving the effectiveness of the optimized ET scheme and improving its tolerability, as well as on the quantitative and qualitative content of short-chain fatty acids (SFA) in feces. The success of eradication was controlled by a 13C urease breath test. According to the results of the study in randomized groups of patients, an excellent percentage of eradication (95%) was achieved in patients who performed ET with the addition of the prebiotic Zakofalk. In the same group of patients, there was an increase in the absolute content of SFA and a significant increase in the concentration of butyric acid. In the group of patients who received ET with the addition of probiotics, an acceptable level of eradication was achieved (85.7%), but no changes in SFA were found indicating an increase in the number or activity of the butyrate-producing flora. Patients who performed ET without the addition of pre-probiotics did not achieve the target percentage of successful eradication (83.3%), and a significant quantitative decrease in SFA was found with a significant decrease in the proportion of butyric acid. The inclusion of Zakofalk in the ET scheme, in comparison with probiotics, significantly increases the probability of successful eradication, more effectively restores the metabolic potential of the microbiota, and prevents the development of AAD.

What methods are currently available to prevent and treat antibiotic-associated diarrhoea in children?

Unwanted drug reactions of the gastrointestinal tract (GIT), often with the development of antibiotic-associated diarrhoea (AAD), are the most frequent adverse effects of antibacterial therapy in outpatient practice. This review presents the most current data on antibiotic-associated intestinal lesions. It provides up-to-date information on the epidemiology and etiology of microbial factors of AAD and pseudomembranous colitis. The authors cite clinical forms of AAD, which range from idiopathic with a picture of enteritis to pathogen-specific AAD (antibiotic-associated colitis). A comprehensive approach to AAD verification and patient management tactics makes it possible to significantly reduce the number and severity of possible complications. AAD, including C. difficile-associated diarrhoea/colitis, should be suspected in any patient with diarrhoea who has received antibiotics in the previous 2 months. In addition to clinical signs, laboratory tests confirming clostridial infection should be evaluated. The article presents the algorithm of the comprehensive approach to the treatment of antibiotic-associated diarrhea (AAD), which along with the use of metronidazole and vancomycin places a high priority on the probiotics, which not only prevents relapse, but also protects from this pathology. The article presents general characteristics of probiotic preparations, mechanisms of action of probiotics: antagonistic influence on pathogenic and opportunistic bacteria of microbiota, strengthening of mucous barrier of gastrointestinal tract, and also influence on modulation of immune response, as a result of which the chain of mechanisms of immunological protection starts. On the basis of publications of domestic and foreign researchers, the possibilities of using various probiotic strains of bacteria, and in particular, the prospects of using Lactobacillus reuteri, have been considered.

Role of Probiotics in Mycoplasma pneumoniae Pneumonia in Children: A Short-Term Pilot Project.

Mycoplasma pneumoniae is one of the most common pathogens causing community-acquired pneumonia in children. Mycoplasma pneumoniae pneumonia (MPP) can be successfully treated with azithromycin; however, antibiotic-associated diarrhea (AAD) is a common adverse effect. Increasing evidence suggests that some probiotics may prevent the development of AAD. The present study determined the effects of probiotics (live Clostridium butyricum plus Bifidobacterium infantis) on the prevention and treatment of AAD in children with MPP when co-administered with intravenous azithromycin. Fifty-five children with MPP were enrolled and received azithromycin (10 mg/kg/day; once daily for 7 days) combined with probiotics (starting on the third day of azithromycin treatment; 1,500 mg three times daily); 50 healthy children served as controls. At the end of the trial, the incidence of AAD, fecal microbiota, intestinal mucosal barriers, and systemic inflammation were analyzed using recommended systems biology techniques. No cases of AAD or other adverse events occurred in children with MPP after co-administration of probiotics with azithromycin. A live C. butyricum plus B. infantis preparation partly reconstructed the gut microbiota, especially restoration of bacterial diversity. The indicators of intestinal mucosal barrier function, such as D-lactate, endotoxin, and diamine oxidase, were significantly improved and the systemic inflammation (interleukin 10) was attenuated after probiotic therapy. The present study indicated that co-administration of probiotics with azithromycin is a promising therapy for MPP treatment which could prevent and treat AAD effectively.

PECULIARITIES OF ANTIBIOTIC-ASSOCIATED DIARRHEA DEVELOPMENT IN CHILDREN WITH ACUTE RESPIRATORY INFECTIONS

Introduction: Acute respiratory infections (ARI) are the main cause of morbidity in most countries. The probability of complications and age determine antibiotics administration. Antibiotic associated diarrhea (AAD) is one of the side effects of antibiotics. The aim: The study of the prevalence rate of AAD and the characteristics of its development in children with ARI. Materials and methods: The study included 75 children aged from 1 to 12 y diagnosed with ARI, who were treated with age-specific doses of antibiotics. The influence of children's anamnesis, parents' health on the development of AAD was studied with odds ratio calculation (OR). Results: In general, AAD incidence was 52%. The highest frequency 59.3% was observed in children under 3 y. AAD most often developed in children treated with amoxicillin - 92%. The greatest dependence of AAD development was connected with breastfeeding less than 6 months - OR was 7.65, preterm birth - 2.9, functional GIT disorders in anamnesis - up to 3.14, allergy - 2.33. The risk of AAD development increased with the age of parents more than 35 y - 5.03, at the age of parents less than 18 and older than 35 y - 4.09, parents' allergies - 3.74 and parents smoking - 2.43. Conclusions: The most important factors of AAD development on antibiotics therapy in children with ARI are breastfeeding less than 6 months, functional GIT disorders and allergic conditions in anamnesis. Suboptimal age and parents' health (GIT disorders, allergic conditions and unhealthy habits) also increase the risk of AAD development.

Enzyme Inhibitor Antibiotics and Antibiotic-Associated Diarrhea in Critically Ill Patients.

BackgroundThis study aimed to analyze the factors associated with the development of antibiotic-associated diarrhea (AAD) in critically ill patients receiving enzyme inhibitor antibiotics.Material/MethodsA retrospective study of patients with and without AAD admitted to the intensive care unit (ICU) of the First Teaching Hospital of Xi’an Jiaotong University from February 1, 2014, to January 31, 2016, was undertaken. Relevant clinical data underwent univariate or multivariate regression analysis.ResultsOf 184 patients who received enzyme inhibitor antibiotic therapy, 70 patients (38.04%) developed AAD, with a mean duration of onset of 6.97±3.64 days. AAD was associated with the use of enzyme inhibitor antibiotic therapy alone (OR, 1.142; 95% CI, 1.038–1.256; P=0.007), and in combination with antifungal agents (OR, 2.449; 95% CI, 1.116–5.372; P=0.025), quinolones (OR, 5.219; 95% CI, 1.746–15.601; P=0.003), and oxazolidinones (OR 2.895; 95% CI, 1.183–7.083; P=0.020). The mean duration of ICU stay was significantly increased in patients with AAD (19.00±11.49 days vs. 9.60±6.76 days) (P<0.001). Mean duration of antibiotic therapy (14.09±8.82 days vs. 8.10±4.91 days) (P<0.001) and duration of enzyme inhibitor antibiotic therapy (9.26±5.06 days vs. 6.61±3.24 days) (P<0.001) were significantly increased in patients with AAD.ConclusionsDuration of use of enzyme inhibitor antibiotic therapy and the combined use of antifungals, quinolones, and oxazolidinones increased the incidence and duration of AAD and increased the length of stay in ICU.

Этиологическая структура антибиотико-ассоциированной диареи у пациентов с заболеваниями толстой кишки

Aim. Determine the etiological structure of antibiotic-associated diarrhea in Russia. Materials and methods. The study included 746 patients in inpatient treatment. 502 patients were examined at the stage of admission and discharge from the hospital, and 305 patients with the clinical picture of Clostridioides difficile-associated infection (CDI), among them 163 (46.6%) men and 142 (53.4%) women. The age of the patients was 48-67 years. All patients were examined luminal feces upon admission to the hospital, upon discharge from the hospital and in the case of a clinical picture of CDI. Results. Analysis of the etiological factor of clostridial infection showed that in 253 (83.2%) cases, the causative agent of antibiotic-associated diarrhea was C. difficile. Other types of clostridia were found in almost all CDI cases (97.7%). At the same time, C. perfringens remained the dominant type of clostridia in the same way as in patients upon admission to the clinic. The average dissemination of C. difficile was higher (p <0.05) compared with the value of the indicator in patients on admission and was 10 * 7 CFU / g; the titer of dissemination with other types of clostridia remained at the level of 10 * 5 CFU / g. - 10 * 7 CFU / g., Median 10 * 6 CFU / g. Analysis of the clinical picture of clostridial colitis revealed its similarity, regardless of the etiologically significant microorganism being detected. In 52 (16.8%) of 305 patients, the clinical picture was due to other members of the genus Clostridium (Clostridium perfringens, C. paraputrificum, C. tertium, C. novyi). Also, as with CDI, diarrhea syndrome occurred in 100% of cases, hyperthermia occurred in 82%, flatulence in 42%, vomiting in 13%, and abdominal pain in 11%. The severity of Clostridium spp. Diarrhea varied widely. So, in 26 (50%) of 52 patients with preserved anal defecation, the median stool frequency was 10 (5; 14) times / day, which is comparable with the data obtained in colitis caused by C. difficile. Conclusions. An analysis of the etiological factor in the development of CDI showed that, in addition to the known etiological factor of antibiotic-associated diarrhea - toxigenic C. difficile with the leading virulence factor production of toxin B, in 52 (16.9%) cases, other representatives of this genus were an etiological factor of diarrhea (Clostridium perfringens, C. paraputrificum, C. tertium, C. novyi). The development of antibiotic-associated diarrhea, caused by representatives of other types of clostridia, must be considered when prescribing therapy for clostridial colitis.

Use of antibiotics and the prevalence of antibiotic-associated diarrhoea in patients with spinal cord injuries: an international, multi-centre study

Little is known about the use of antibiotics and the extent of antibiotic-associated diarrhoea (AAD) in patients with spinal cord injuries (SCIs). To record the use of antibiotics, establish the prevalence of AAD and Clostridium difficile infection (CDI), and assess if there was any seasonal variation in antibiotic use and incidence of AAD in patients with SCIs. A retrospective study was conducted in six European SCI centres between October 2014 and June 2015. AAD was defined as two or more watery stools (Bristol Stool Scale type 5, 6 or 7) over 24 h. In total, 1267 adults (median age 54 years, 30.7% female) with SCIs (52.7% tetraplegia, 59% complete SCI) were included in this study. Among the 215 (17%) patients on antibiotics, the top three indications for antibiotics were urinary tract infections (UTIs), infected pressure ulcers and other skin infections. Thirty-two of these 215 (14.9%) patients developed AAD and two patients out of the total study population (2/1267; 0.16%) developed CDI. AAD was more common in summer than in spring, autumn or winter (30.3% vs 3.8%, 7.4% and 16.9%, respectively; P<0.01). AAD was associated with age ≥65 years, tetraplegia, higher body mass index, hypoalbuminaemia, polypharmacy, multiple antibiotic use and high-risk antibiotic use. Summer and winter seasons and male sex were identified as independent predictors for the development of AAD. This survey found that AAD is common in patients with SCIs, and UTI is the most common cause of infection. Summer and winter seasons and male sex are unique predictors for AAD. Both AAD and UTIs are potentially preventable; therefore, further work should focus on preventing the over-use of antibiotics, and developing strategies to improve hospital infection control measures.

ANTIBIOTIC-ASSOCIATED DIARRHEA AND CL. DIFFICILE-INFECTION IN CHILDREN: RISK FACTORS

The review of literature presents data on the incidence and characteristics of the current development of antibiotic-associated diarrhea (AAD) in children. Presented research materials of Russian and foreign scientists on risk factors activation toxigenic strains Cl. difficile, showed the relationship between the depth microecologi-cal metabolomical violations and Cl. difficile-infection in children.

Efficacy of Bacillus probiotics in prevention of antibiotic‐associated diarrhoea: a randomized, double‐blind, placebo‐controlled clinical trial

Introduction: Antibiotic‐associated diarrhoea (AAD) is one of the most common side effects of antibiotic therapy. The main mechanism associated with the development of AAD is significant changes in the composition and quantity of the gut microbiota during the treatment with antibiotics. Probiotic bacteria have been shown to stabilize the gut microbiota and can be used to prevent diarrhoea associated with antibiotic therapy. Case presentation: We present the results of a single‐centre, randomized, double‐blinded, placebo‐controlled clinical trial. Patients were randomized into three groups: probiotic group 1 received a probiotic containing strains Bacillus subtilis 3 and Bacillus licheniformis 31; probiotic group 2 received a probiotic, containing B. subtilis 3; and the placebo group received an inert composition in vials, formulated to be indistinguishable from the vials with probiotics. Participants received one vial twice a day. Probiotic treatment significantly reduced incidents of AAD in the patients. Among 91 patients in group 1 treated with probiotic mix, nine developed AAD. In group 2, seven patients out of 90 who received only one probiotic strain developed AAD. A considerably higher incidence of AAD was registered in the placebo group – 23 from 90 patients (P<0.001 vs groups 1 and 2). Both probiotics demonstrated a significant effect in the prevention of nausea, bloating, vomiting and abdominal pain. Conclusion: Treatment with Bacillus probiotics during antibiotic therapy significantly decreased the incidence of AAD and adverse effects related to the use of antibiotics. Both probiotics were well tolerated by the patients without side effects. No significant difference was found in the efficacy of the two probiotics.

Антибиотикоассоциированная диарея в клинической практике

Modern data on an urgent clinical problem — antibiotic-associated diarrhea — are summarized in the article. In development of antibiotic-associated diarrhea the main role is played by disturbances in microbiocenosis and immune response of the organism. Along with usage of metronidazole and vancomycin probiotics have great importance in treatment of these conditions. Probiotics also play a certain part in prevention of relapses and prophylaxis of antibiotic-associated diarrhea. Complex approach to verification of antibioticassociated diarrhea and management of patients allows significant decreasing of prevalence and severity of possible complications.

Probiotics for preventing antibiotic-associated diarrhea

Probiotics for preventing antibiotic-associated diarrhea

Saccharomyces boulardii for the Prevention of Antibiotic-Associated Diarrhea in Adult Hospitalized Patients: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Trial

Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Probiotics were effective in preventing AAD and CDAD in several randomized controlled trials. This study was aimed at testing the effect of Saccharomyces boulardii on the occurrence of AAD and CDAD in hospitalized patients. A single-center, randomized, double-blind, placebo-controlled, parallel-group trial was performed. Patients being prescribed antibiotics or on antibiotic therapy for <48 h were eligible. Exclusion criteria were ongoing diarrhea, recent assumption of probiotics, lack of informed consent, inability to ingest capsules, and severe pancreatitis. Patients received a capsule containing S. boulardii or an indistinguishable placebo twice daily within 48 h of beginning antibiotic therapy, continued treatment for 7 days after antibiotic withdrawal, and were followed for 12 weeks after ending antibiotic treatment. Of 562 consecutive eligible patients, 275 patients aged 79.2 ± 9.8 years (134 on placebo) were randomized and 204 aged 78.4 ± 10.0 years (98 on placebo) completed the follow-up. AAD developed in 13.3% (13/98) of the patients receiving placebo and in 15.1% (16/106) of those receiving S. boulardii (odds ratio for S. boulardii vs. placebo, 1.16; 95% confidence interval (CI), 0.53-2.56). Five cases of CDAD occurred, 2 in the placebo group (2.0%) and 3 in the probiotic group (2.8%; odds ratio for S. boulardii vs. placebo, 1.40; 95% CI, 0.23-8.55). There was no difference in mortality rates (12.7% vs. 15.6%, P=0.60). In elderly hospitalized patients, S. boulardii was not effective in preventing the development of AAD.

Antibiotic-associated diarrhoea

Diarrhoea is a common complication of antimicrobial therapy. The term antibiotic-associated diarrhoea (AAD) is often considered synonymous with Clostridium difficile. In fact, AAD can develop through a variety of mechanisms and manifest through a broad range of clinical signs and symptoms. For improved prevention and recognition of AAD, it is important to understand the pathophysiology and risk factors for AAD. Although Clostridium difficile continues to be the most common identifiable pathogen of AAD, many patients with AAD can be managed through a variety of conservative measures. This review focuses on some of the important distinctions between nonspecific AAD and antibiotic-associated colitis. In addition, the most recent data on important risk factors for the development of AAD are summarised. Given its pathogenicity, there will be an emphasis on the early diagnosis, treatment and prevention of Clostridium difficile-associated diarrhoea. AAD is a common clinical problem that can progress to severe, life-threatening disease if not recognised quickly. Better awareness of risk factors can lead to the most efficacious treatment of this disorder: primary prevention.

Saccharomyces Boulardii in the Prevention of Pseudomembranous Colitis

Objective To evaluate the efficacy of the yeast Saccharomyces boulardii in the prevention of pseudomembranous colitis (PMC). Data Sources A MEDLINE search (January 1966–April 2000, updated July 2001) of English-language medical literature was conducted. Key search terms included Saccharomyces boulardii, pseudomembranous colitis, antibiotic-associated diarrhea, and Clostridium difficile. Additional information was obtained from pathophysiology and medical textbooks. Data Synthesis S. boulardii is a nonpathogenic yeast used to treat and prevent antibiotic-associated diarrhea, including PMC, a serious, sometimes refractory complication of antibacterial drug therapy. A literature search was conducted to determine its efficacy in preventing PMC. Conclusions When administered in combination with standard treatments, S. boulardii does not appear to prevent the first relapse but does appear to reduce subsequent recurrences of probable PMC in patients experiencing antibiotic-associated diarrhea. It has also shown promise as monotherapy in preventing the development of antibiotic-associated diarrhea in patients not experiencing diarrhea. Further well-designed, controlled studies are needed.