Treatment Of Acute Intestinal Infections Research Articles

Оценка эффективности применения бактериофагов при лечения острых кишечных инфекций, вызванных условно-патогенными микроорганизмами, у детей первого года жизни

Acute intestinal infections caused by opportunistic microflora (OPM) are a pressing problem in infants. The purpose of this research was to investigate the treatment of enterocolitis caused by OPM in infants using antibacterial drugs and their detection by bacteriophages. Materials and methods used: a single-center retrospective cohort study of 106 pediatric patients aged 1 month to 1 year old with mild to moderate severity of acute intestinal infections caused by OPM and treated with an antibacterial drug (nifuroxazide), a bacteriophage (complex liquid pyophage) or a combination thereof, who were divided into the three groups as follows: G1 (“Nifuroxazide,” n=39), G2 (“Pyophage,” n=33) and G3 (“Combined drugs,” n=34), was conducted at the Scientific and Research Institute for Children’s Infections of the Russian Federal Biomedical Agency (Saint Petersburg, Russia) in 2018-2021. Data on pathogen elimination and duration of symptoms in patients were analyzed. The criteria for the effectiveness of therapy were the normalization of temperature, stool and coprograms and a decrease in the OPM titer in feces to a level of ≤104 CFU/g. Results: achievements of all applications of successful therapy occurred more often in G3 compared to G1 (0.007). An increased risk of treatment failure was evidenced by patients having OPM in a stool at the level of over 109 CFU/g (RR=14,09 [2,84; 69,96]) and the “visible entire” presence of erythrocytes (RR=6.26 [2.51; 15.62]) and leukocytes (RR=5,51 [2,22; 13,67]) in a coprogram. The probability of a response to therapy when using the active substances Nifuroxazide+Pyophage was lower (0.120 [0.037, 0.389]) than with monotherapy with Pyophage (0.227 [0.074, 0.692]) or Nifuroxazide (2.678 [1.14, 6.297]) alone. Conclusion: combined therapy of acute intestinal infections caused by OPM in infants using the antibacterial drugs coupled with Pyophage increases the effectiveness of OPM elimination and the disease’s clinical and laboratory symptoms’ relief.

General characteristics, results and prospects for the clinical application of bacteriophage therapy

Viruses are the most numerous biological creatures in the biosphere of the globe. Their number is huge ~ 1031, and bacteriophages are the most numerous group of environmental viruses. It is not surprising that in such an environment and in the human body and on its skin, a large community of various viruses has formed, representing a viral metagenome (virome). This virome includes not only viruses that penetrate into the cells of the human body and replicate in them using cell material, but also viruses that target only bacteria, namely bacteriophages. The ability of lytic bacteriophages with high specificity to kill certain bacteria was discovered in the 1920s. XX century. In this regard, lytic bacteriophages have been proposed and successfully used for the treatment of acute intestinal infections. However, the advent of antibiotics, the use of which was initially more effective for the treatment of bacterial infections, has led to the abandonment of phage therapy in Western countries. The return of attention of scientists and practical healthcare professionals to the use of bacteriophages as drugs occurred due to the formation and spread of multidrug resistance of pathogenic bacteria to the most commonly used antibacterial drugs. The incidence of various bacterial infections is not decreasing. This review provides information on a number of successful clinical and experimental applications of bacteriophage preparations in various diseases that are caused by bacteria, or bacterial inflammation has arisen as a complication of the underlying disease. It is very important that bacteriophages have a synergistic effect with antibacterial drugs. Bacteriophage therapy is considered as a potentially effective method of treatment.

THE PROBLEM OF INCIDENCE OF ACUTE INTESTINAL INFECTIONS IN CHILDREN DURING WARTIME IN UKRAINE

The relevance of this pathology today is due to the increased incidence of acute intestinal infections in children. The purpose of our work was the analysis of modern views on the diagnosis and treatment of acute intestinal infections in children during the wartime period in Ukraine. Materials and methods: the data of the scientific literature were analyzed using the bibliosemantic method of research and a clinical case of the medical history was proposed, which caused some difficulties for the doctors at the initial stage. Research results and their discussion. The range of possible human etiological agents continues to expand as previously unknown viruses are isolated. The diseases caused by them are less studied, since their detection was carried out mainly in the framework of scientific research. The most frequent pathogens of intestinal infections are rotaviruses, enteroviruses, adenoviruses, and coronaviruses. Episodes of acute diarrheal diseases in European countries in children under 3 years of age were noted up to 2 times a year, but in countries with limited resources or military operations, on average, up to 6 times a year (in particular, in Ukraine by 2022). The war led to an increase in viral etiology and an increase in the share of children with secondary bacterial complications, and accordingly, the share of the use of antibacterial agents increased. The most common nosology of the gastrointestinal tract was acute gastroenterocolitis, which was characterized by any combination of diarrhea, fever, vomiting, and abdominal pain. Diarrhea is the second leading cause of child mortality in the world, especially in countries where there are military conflicts or a low social standard of living. The authors give an example of a clinical case of a girl, born in 2018, who was treated in the children's infectious disease department in the summer of 2022. and referred to persons forcibly resettled due to military operations.
 Isolation and identification of the causative agent usually takes at least 48 hours, and therefore the possibility of choosing a therapy decreases. Virological research in routine practice is rarely available due to the high cost of research. Therefore, it should be noted that there is immunoprophylaxis, in particular, of rotavirus infection. In the world, since 2006, vaccination has been introduced in more than 100 countries, which made it possible to significantly reduce the level of morbidity among children under 2 years of age. Two vaccines against rotavirus are registered in Ukraine. The first - is used in 2 doses at the age of 6 to 24 weeks, and the second - at the age of 6 to 32 weeks. Protection against severe rotavirus gastroenteritis is approximately 90-95%. But in our country, this vaccination is not yet included in the calendar of mandatory vaccinations. The authors give an example of a clinical case of a girl who was treated in the children's infectious disease department of the 1st Medical Center of Poltava in the summer of 2022.
 Conclusion. Thus, acute intestinal infections in childhood are a complex pathological process. Treatment should be timely, complex and justified from the etiopathogenetic point of view.

Сучасні підходи до антибактеріальної терапії гострих кишкових інфекцій

Гострі кишкові інфекції залишаються актуальною проблемою медицини через високий рівень захворюваності й летальності. У світі щорічно реєструється близько 1,7 мільярда випадків діарейних захворювань у дітей, від яких помирає 525 тисяч дітей віком до п’яти років. У статті наведені рекомендації з лікування гострих кишкових інфекцій з урахуванням міжнародних рекомендацій.

Нифуроксазид в стартовой терапии острых кишечных инфекций у взрослых

The article presents the results of the meta-analysis of the effectiveness of nifuroxazide in the treatment of acute intestinal infections in adults. Objective. To summarize the results of studies evaluating the efficacy and safety of nifuroxazide in acute intestinal infections in adults. Materials and methods. A search was carried out in electronic databases and among paper-based information in accordance with modern requirements for conducting meta-analysis. We selected high-quality randomized and non-randomized clinical trials, in which nifuroxazide was compared with placebo, an alternative antibiotic, or with the absence of antibacterial therapy in the treatment of acute intestinal infections in adults from 18 to 90 years of age. In most studies, the compared medications were prescribed together with other therapies: formulations for rehydration, enterosorbents, and probiotics. Results. A total of 1999 people participated in the studies selected for analysis (541 – in the main group, 1458 – in the comparison group). It was shown that nifuroxazide significantly reduced the duration of diarrhea in acute intestinal infections adults, on average, by 1,35 days. When prescribing nifuroxazide, there was no increase in intoxication, symptoms of gastrointestinal mucosa irritation (nausea, vomiting), and allergic reactions. Conclusion. The meta-analysis confirmed the effectiveness of nifuroxazide in acute intestinal infections in adults. Key words: antibacterial therapy, adults, diarrhea, intoxication, fever, nifuroxazide, acute intestinal infections

Ранняя диагностика нарушения функции почек у детей при острых кишечных инфекциях

In recent years, significant breakthroughs have been made in the study of etiology, pathogenesis, and the development of accessible diagnostic methods, as well as in the treatment of acute intestinal infections, resulting in a significantly lower frequency of their severe course and adverse outcomes and in reducing the frequency and duration of hospitalization. At the same time, the emergence of modern biochemical markers of injury of different organs and systems makes it possible to investigate new pathological conditions that were previously detected in the stage of clinical manifestations. These include the problem of early diagnosis of acute kidney injury in children, the frequency and timing of which have not yet been studied. Objective. Comparative evaluation of the diagnostic value of glomerular filtration rate and serum cystatin C levels for early diagnosis of kidney failure in children with acute intestinal infections (AII). Patients and methods. This study included 80 children with acute intestinal infection who were hospitalized in G.N.Speransky Children’s Clinical Hospital No 9. In all cases the course of disease was moderate-to-severe without developing hemolyticuremic syndrome. To assess kidney function in the acute period of intestinal infection, we studied glomerular filtration rate (GFR) by the “bedside” Schwartz equation, as well as serum cystatin C levels. Results. In the acute period of AII in children under 3 years of age, GFR was 98.56 ± 2.84 mL/min/1.73 m2 according to the “bedside” Schwartz equation of 2009. In the group of children over 3–7 years of age, these values were 108.85 ± 3.84 mL/min/1.73 m2, differences are statistically significant (p < 0.001). High (>950 ng/mL) serum cystatin C levels were found in 22% of patients. In other patients, cystatin C levels remained within or below the normal range. The analysis showed that 10% of children in the age group of 1–3 years and 2.5% of children in the age group of 3–7 years were at risk of developing acute kidney injury in AII, according to the GFR estimation based on the Schwartz “bedside” equation and cystatin C-based equation. When assessing the risk of developing acute kidney injury according to the GFR estimation using the cystatin C-based equation, the proportion of such patients in the age group of 1–3 years was 20% and in the age group of 3–7 years – 22%, and when assessing GFR according to the Schwartz “bedside” equation only, the proportion of children was 7.5% and 7.5%, respectively. Conclusion. Determination of cystatin C levels in children in the early period of acute intestinal infections of moderate severity is an earlier and more accurate marker of acute kidney injury, regardless of age and sex of patients, in comparison with the evaluation of glomerular filtration rate. Inclusion of cystatin C in laboratory test plan allows timely identification of patients who are in the risk group of developing acute kidney injury. Key words: children, kidney failure, acute intestinal infection, acute kidney injury, cystatin C, glomerular filtration rate

Пробиотики в терапии острых кишечных инфекций у детей

Пробиотики в терапии острых кишечных инфекций у детей

Technological and pharmacoeconomic aspects of the development of drug for the complex therapy of acute intestinal infections

Today combination drugs are widely used to treat acute intestinal infections (AII). Acute intestinal infections requiring comprehensive treatment with antimicrobial drugs, enterosorbents, pro- and prebiotics and immune drugs. We have developed the composition and technology of drug wchich contain nifuroxazide and plant substance plantaglucid. This combination is a modern treatment of AII, because it combination has high efficiency, safety, availability and comfortable use.The purpose of the research was development of composition and technological scheme of the original combined drug in the form of capsules “Diaplant” for the complex treatment AII and the study of its pharmacoeconomic aspects.Results and discussion. The combination of nifuroxazide with plantaglucid, which has additional microbiological and pharmacological effects, was justified. To develop of the composition and technology this combined drug, the technology of separate preparation of masses for encapsulation with using excipients of different groups was used. The technological scheme of production of “Diaplant” capsules is developed and the specification for quality control of capsules is made. ATC/DDD-methodology showed that the cost for DDD of “Diaplant” was 14,54 UAH. The total cost of the average recommended daily doses of separate drugs (nifuroxazide and Plantaglucidum) ranged from 22,13 to 38,05 UAH. The use of “Diaplant” in clinical practice allows reducing the cost of pharmacotherapy of AII from 152 to 262 %.Conclusion. The technological scheme of production of the domestic drug in capsules “Diaplant” that contains nifuroxazide and Plantaglucidum was developed for pharmacotherapy of acute intestinal infections. The developed drug “Diaplant” has high antimicrobial, anti-inflammatory, antispasmodic and detoxic activity, normalizes intestinal motility and helps to restore the intestinal microflora.

Энтеросорбция в комплексной терапии острых кишечных инфекций у взрослых

Objective. To evaluate the efficacy and tolerability of the dietary supplement ‘Complex with pectin Liquid Charcoal’ used for the treatment of acute intestinal infections (AIIs) in adults. Patients and methods. This study included 40 patients aged between 18 and 59 years diagnosed with AIIs of unknown etiology (moderate gastroenteritis) and treated in the Republican Clinical Hospital for Infectious Diseases in Kazan in 2019. Participants were divided into two groups according to their treatment scheme. Patients in the experimental group (n = 20) received dietary supplement “Complex with pectin Liquid Charcoal” as a part of their basic therapy (1 sachet × 3 times a day 1 hour before meals), while patients in the control group received activated charcoal at a dose of 0.1 g/kg/day divided into 3 portions. Data analysis was performed using the Microsoft Office Excel 2007 and STATISTICA 10.0 software and included Student t-test. Results. In patients receiving “Complex with pectin Liquid Charcoal”, intoxication syndrome was 1.5 days (31.3%) shorter than that in patients receiving activated charcoal (р < 0.001). Moreover, the duration of gastroenteritis syndrome among patients from the experimental group was 0.5 days (15.4%) shorter than that in the controls (р < 0.05). “Complex with pectin Liquid Charcoal” ensured a 28% shortening of total disease duration compared to the control group (3.6 ± 0.16 days vs 5.0 ± 0.17 days) (р < 0.001). Conclusion. Our findings suggest high clinical efficacy of the dietary supplement “Complex with pectin Liquid Charcoal” in the treatment of AIIs in adults. The supplement has also shown good safety profile and ensured high patient compliance. Key words: dietary supplement “Complex with pectin Liquid Charcoal”, acute intestinal infection, pectin, sorbents

Нифуроксазид в терапии острых кишечных инфекций у детей: результаты мета-анализа

Key words: nifuroxazide, acute intestinal infections, diarrhea, intoxication, children

Некоторые особенности терапии острых кишечных инфекций у взрослых и детей

Некоторые особенности терапии острых кишечных инфекций у взрослых и детей

Probiotic properties of heterofermented milk products

Information is presented on the study of the probiotic properties of fermented milk products of heteroenzymatic fermentation, namely their antimutagenic, hypocholesterolemic, antioxidant activity, and the ability to suppress pathogenic and conditionally pathogenic bacteria. Data on the effective use of koumiss, kefir, chegen, kurunga in the treatment of acute intestinal infections, their ability to limit the intensity of peroxide metabolism are presented. Thus, their bactericidal action against tubercle Bacillus, Escherichia coli, Bacillus fastidiosus, Pseudomonas aeruginosa, Leuconostoc mesenteroides, Candida albicans, Staphylococcus aureus, etc. was established.the data of clinical trials proving their influence on the normalization of human lipid metabolism are Presented. Antioxidant effect is associated with the action of vitamins C, E, polyunsaturated fatty acids, etc. produced by the microflora of dairy products. Many researchers indicate that multicomponent probiotics have a high adaptive potential in the conditions of the gastrointestinal tract. Thus, artificially created communities of lactobacilli isolated from spontaneously formed microflora of "artisanal" fermented milk products exhibit antimirobial action against pathogenic microflora.

How do the intestinal infections proceeding with the haemocolitis syndrome influence anthropometrical indicators of the nutritional status of children?

This article presents the results of a study of the nutritional status of children with acute intestinal infections (AII) occurring with hemocolitis syndrome. It was found that the nutritional status reflects the severity of the pathological process, and its dynamics allows to evaluate the effectiveness of therapy. The aim of the work was to study the changes in anthropometric indicators of nutritional status in the treatment of AII with hemocolitis syndrome in children. 50 patients with AII with hemocolitis syndrome aged from 5 months to 8 years were observed in an infectious hospital. Patients were divided by age: group 1 – breast age (n = 10), group 2 – early age (n = 27), group 3 – preschool age (n = 10), group 4 – school age (n = 3). The nutritional status of patients was studied in dynamics on the 1st and 7th day of inpatient treatment according. Analysis of research data was performed using Studentʼs t-test, U-Mann-Whitney test, Kruskal-Wallis criterion. The level and harmony of physical development of children in all groups at the time of admission to the hospital did not differ significantly. In the course of treatment, positive dynamics was noted in group 1 by the values of body mass index (BMI) (p = 0.05), Z-score BMI (p = 0.04), body weight deviation by height (in %) (p = 0.05); in group 2 – by the values of body weight by height (p = 0.05). Positive dynamics of nutrition indicators in group 1 was combined with a high frequency of diagnosis of unspecified forms of AII (60%). The negative dynamics of most indicators was observed in group 3, which was accompanied by a high frequency of diagnosis of refined (bacterial) etiological forms of AII (90%). The obtained data show that the dynamics of nutritional status of patients with AII with hemocolitis syndrome during therapy was more favorable in infants and young children and less favorable in preschool children, depended on the etiology of the disease and reflected its impact on metabolism.

Experience in the use and evaluation of the effectiveness of gelatino tannatG in the treatment of acute intestinal infections in children

A clinical study was conducted to evaluate the effectiveness of Adiarin ^ Ыте tannat е ) in infants and young children with acute intestinal infections (AII) of various etiologies. As a result of the study, reliable positive dynamics of the main clinical symptoms of acute intestinal infections (reduction of the duration of diarrhea, normalization of stool frequency and nature) were established when the drug Adiarin ^ Ыте tannat е ) was used in the acute period of the disease, which indicates its effectiveness.

Experience in clinical using normobact l sinbiotic in combination therapy of acute intestinal infections of virus etiology in children

The article presents the results of using Normobact L Synbiotic for the treatment of acute intestinal infections (AII) in children. The study included 60 children aged between 6 months and 6 years with a clinical diagnosis of AII, acute gastroenteritis of viral etiology. The average age of patients enrolled was 2.6 years, with 46.7% (28/60) girls. The treatment of AII was carried out in accordance with the clinical guidelines for the management of acute intestinal infections and included pathogenetic and symptomatic therapy. In addition, the study groupa recieved the biologically active additive (BAA) Normobact L (manufacturer Akrikhin, Russia) containing a probiotic strain Lactodacillus rhamnosus GG. According to the ESPGHAN guidelines, this strain has the largest evidence base of efficacy in the treatment of AII [8]. Synbiotic Normobact L was used at a dose of 1 sachet once daily for 7 days. In the comparison group, the patients received Bifidumbacterin in the amount 15 doses divided into 3 daily intakes for 7 days in addition to pathogenetic and symptomatic therapy. The obtained data analysis showed that diarrheal syndrome ceased earlier in the group of children who received Normobact L. The stool became normal 1.19 days sooner than in the group of children receiving Bifidumbacterin. In general, the period of normalization of stools in Group 1 (Normobact L) was significantly less than in Group 2 (Bifidumbacterin): 3.24 ± 0.4 days and 4.43 ± 0.2 days, respectively. It was also found that the period of normalization of temperature in Group 1 (Normobact L) was significantly less than in Group 2 (Bifidumbacterin): 53.00 ± 1.98 and 78.3 ± 2.44 h respectively. The body temperature in 100% of patients in the group of children receiving Normobact L became normal on Day 5, in the group of children receiving Bifidumbacterin on Day 7.

Rationality of the using of photochromotherapy in the complex treatment of acute intestinal infections in children

Aim. The objective of the study was to substantiate the rationality of using monochromatic polarized incoherent optical radiation (photochromotherapy) on the abdomen as a supplement to the standard program for the treatment of acute intestinal infections in children. Material and methods. Twenty-six children with acute intestinal infections from 6 months to 12 years old were observed during inpatient treatment. In the comparison group (n = 11), children received standard therapy, including diet therapy, rehydration, sorbents, probiotics or prebiotics, as well as indications for etiotropic drugs. In the main group, patients (n = 15) in addition to standard therapy received photochromotherapy as an effect on the abdomen with monochromatic polarized incoherent optical radiation from the Bioptron apparatus with a blue filter at a distance of 5 cm labile along the bowel. The duration of photochromotherapy was 5 minutes, the course of treatment included 4-5 sessions 1 time per day. The effectiveness of the therapy regimens used in the groups was assessed by the duration of the disease, the length of inpatient treatment, the dynamics of changes in the clinical blood test at the time of discharge. Results. The advantage of the technique with the addition of standard treatment of acute intestinal infections by photochromotherapy was established. In the main group of patients, the duration of the disease was significantly shorter (9,1±0,8 days) compared to the comparison group (10,2±1,5 days, p=0,02) against the background of a significant decrease in the severity of inflammatory manifestations in the hemogram in form of a decrease in thrombocytosis. Conclusion . The obtained data make it possible to recommend the method of photochromotherapy in the complex therapy of intestinal infections of various etiologies in children older than 6 months.

EXPERIMENTAL STUDY OF THE EFFECTIVENESS OF THE JOINT THERAPEUTIC ACTION OF LACTOGLOBULIN AND SALLMONELLA BACTERIOPHAGE

The wide spread of drug-resistant forms of the pathogens, complicating prevention and treatment of acute intestinal infections, determines the feasibility of using bacteriophages and immune lactoglobulins for antibacterial therapy of these diseases. The aim of this study was to investigate the antibacterial efficacy of the joint use of immune lactoglobulin and Salmonella bacteriophage in the treatment of experimental salmonellosis in mice. The experimental Salmonella infection was reproduced by means of a single intragastric administration of 2LD50 of daily agar culture of S.typhimurium. As a result, the development of Salmonella infection lasting up to 14 days was noted. The animals were divided into four groups according to the pattern of the treatment. The following preparations were used for the treatment of animals: «Lactoglobulin against opportunistic bacteria and Salmonella» dry cow, «Lactoglobulin» liquid, bacteriophage of Salmonella ABCDE groups, liquid. The preparations were daily administered to mice orally after the infection for 7 days. In the study of the joint therapeutic effect of the lactoglobulin and bacteriophage the special attention was paid to the terms of elimination of the pathogen from animal organs. Analysis of the data showed that in all four groups a positive dynamics of excretion of the pathogen of mice was revealed. In groups of animals that were treated with both drugs, the elimination of Salmonella out of organs occurred 1.5 times faster than in the control groups of mice. At the same time in the experimental groups on the third day of treatment with preparations the statistically significant decrease in the number of S.typhimurium in the contents of the large intestine of animal was revealed. The study found that immune lactoglobulin used simultaneously with Salmonella phage for 7 days reduced the severity and duration of the disease course and blocked the further development of the infectious process, promoted the efficient and rapid cleansing of animals organism of the pathogen, increased the survival of mice. The obtained data suggest the applicability of joint use of immune lactoglobulin preparations and bacteriophages in the treatment of acute intestinal infections caused by antibiotic-resistant strains of Salmonella.

The marketing research of medicines used in complex treatment of acute intestinal infections of viral etiology in children

The marketing research of medicines used in complex treatment of acute intestinal infections of viral etiology in children

CLINICAL AND MICROBIOLOGICAL EFFICACY OF ANTIBIOTIC THERAPY OF ACUTE INTESTINAL INFECTIONS WITH INVASIVE TYPE OF DIARRHEA IN CHILDREN

In the article results of a randomized comparative multicenter study of the clinical and microbiological efficacy and safety of azithromycin (Sumamed) and cefixime (Suprax) 185 children aged 1—14 years with moderate (70.8%) and severe forms (29.2%) of acute intestinal infections with invasive type of diarrhea. Etiological diagnosis microbiological method was detected in 48 (25.9%) patients, including salmonellosis in 85.4% of cases sonnei shigellosis or Flexner in 14.6% of patients. Found that both drugs have a high clinical efficacy (of 86.2% and 87.2%, respectively). While, microbiological efficacy of azithromycin was significantly higher (83.3%) than of cefixime (58.3%) (p < 0.001), including, when salmonellosis she reached 81.8% and that of cefixime, only 52.6% of patients. A clinical study confirmed the safe use of these antimicrobial agents in the treatment of acute intestinal infections in children.

DIETARY CORRECTION IN TREATMENT OF ACUTE INTESTINAL INFECTIONS IN YOUNG CHILDREN

Acute intestinal infections (AII) are still one of the main challenges in pediatrics because of their high prevalence, polyetiology, high rate of severe and complicated forms, especially in young children. The perfect feeding for infants is breast milk. The child feeding with artificial formulas must be supplied with appropriate balanced feeding, assisting not only in physical and mental development, but also in recovery. The article provides information on dietary correction in treatment of AII with formulas containing probiotics.