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ЭКОЛОГИЯ И ГИГИЕНА
© КОЛЛЕКТИВ АВТОРОВ, 2017
UDC 616.9 -053.2 +616.34 -008.314.4
R. Kh. Begaydarova, A. M. Izteleuova, G. M. Omarova, Kh. D. Talipbekova, V. R. Atakishiyeva
ROLE OF ENTEROL (SACCHAROMYCES BOULARDII) IN PREVENTION AND TREATMENT OF ANTIBIOTIC-ASSOCIATED DIARRHEA IN CHILDREN
Department of children's infectious diseases of Karaganda state medical university (Karaganda, Kazakhstan)
Among the diversity of the etiological factors of antibiotic-associated diarrhea, the greatest importance is attached to C. difficile, a gram-positive aerobic spore-forming bacterium that is resistant to most antibiotics. Probiotics have a good effect in the prevention of antibiotic-associated diarrhea, Enterol (Saccharomyces boulardii) is the most successful in the ratio of efficacy.
120 children with diagnosed intestinal infections were under supervision, of whom children under 6 months were 20 (16.7%); from 6 months. up to 1 year - 60 (50,0%), over the year - 40 (33,3%). The syndrome of gastroenteritis was noted in 14 (11.6%) children, in 72 (60.0%) - gastroenterocolitis syndrome, in 30 (25.0%) - enterocolitis. In order to select the optimal treatment regimen and evaluate its clinical effectiveness, Enterol (Saccharomyces boulardii) prescribed to children up to 1 packet 1 time per day, children over the age of 1 packet 1-2 times a day. The course of treatment was 5 days. The use of Enterol (Saccharomyces boulardii) had a positive effect on the duration of the main clinical symptoms in diarrhea syndrome. The use of Enterol (Saccharomyces boulardii) at age dosages for 5 days prevents the development of antibiotic-associated diarrhea in children.
Key words: children, antibiotic-associated diarrhea, C. difficile, Enterol, Saccharomyces boulardii
Antibiotic-associated diarrhea (AAD) is diarrhea that develops in patients receiving antibiotics or when not identified other reasons that manifested from mild self-limited diarrhea to pseudomembranous inflammation of the intestine.
For the given data of a number of authors: the occurrence of symptoms of antibiotic-associated diarrhea, both during antibiotic treatment and after treatment for 2 months was observed in 5-62% of patients [2, 3, 6, 7]. In children who received antibiotic therapy broad-spectrum, diarrheal syndrome met in more than 11% cases and in some cases 42% [2, 4, 5, 7]. The most common reason for the development of intestinal dysbiosis in children can be the use of antibiotics, which could lead to antibiotic-associated diarrhea that can be linked to the negative impact of waste products of Clostridium difficile [1].
Estimates on the prevalence of antibiotic-associated prevalence of diarrhea in children in the scientific literature are presented very poorly, making it impossible to assess the problem. Analysis of scientific literature showed that the prevalence of AAD in children in different countries varies from 6.2% to 80% and is associated with intake of amoxicillin/clavulanate. The risk of AAD increases in children at a younger age [1].
It is therefore apparent the need for continuous improvement of the performances of doctors in different fields about the role of the normal microbiota, etiological factors, leading to its pathological changes, approaches to the correc-
tion of dysbiotic disorders. Clinical studies have shown a preventive effect of several probiotics (Bifidobacterium /acts, Bifidobacterium longum, Enterococcus faecium, Lactobacillus GG, Lactobacillus acidophilus, Saccharomyces boulardii) to prevent the development antibiotic-associated diarrhea [1].
The meta-analysis demonstrates reduced risk of AAD by 53% thanks to the use of S. bou-lardii. This is established in children and adult patients. Included in the review clinical studies have not shown side effects due to the intake of S. boulardii, However, the use of probiotics cannot be considered totally devoid of risk in specific groups of patients (with immune deficiency and severe systemic diseases) [8].
The use of Saccharomyces boulardii in the clinical studies included 1 117 children demonstrated: reduced risk of iarrhea lasting longer than 4 days, reducing the duration of iarrhea by an average of 1 day, decrease the risk of iarrhea on the third day, decrease the duration of hospitalization [9, 10].
In one of the latest recommendations for probiotics in 2015 in the journal (Journal Clinical Gastroenterology) published the recommendations of the group for the study of probiotics Yale University (Yale/Harvard) on the use of probiotics. That is Saccharomyces boulardii has the highest level of recommendations for the prevention and treatment of disorders of the intestines. Thus, prevention of complications from antibiotic therapy for Saccharomyces boulardii, in treatment of diarrhea Saccharomyces boulardii has
level of evidence A.
Objective of the clinical study was to assess the clinical efficacy of the probiotic Enterol (saccharomyces boulardii) in children with intestinal infections.
MATERIAL AND METHODS
The study included 120 children with enteric infections, from them children till 6 months, there were 20 cases (16.7%); from 6 months to 1 year - 60 (50,0%), over the year - 40 (33.3%) of which were in Regional infectious diseases hospital (RID) of Karaganda city.
Additional laboratory examination of children was carried out using the following methods: General clinical (General analysis of blood, urine, coprogram), biochemical (electrolytes, total protein and protein fractions), culture of feces for pathogenic flora, conducting enzyme immunoas-say (EIA) for detection of rotavirus antigen in feces.
The diagnosis of intestinal infection from all the sick children was confirmed bacteriologically. Allocated coproculture Ps. Aerogenosa was in 1 (0,8%), Salmonella Enterttidis - 2 (1,7%), Proteus Vulgaris - 3 (2,5%), Enterobacter cloacae -7 (5,8%), Cttrobacter diversus - 7 (5,8%), Klebsiella iarrhea - 8 (6,7%), Morganella Morganii - 9 (7,5%), Proteus Mirabllis - 10 (8,3%), Cttrobacter former - 12 (10%), acute enteric infection unspecified etiology in 61 (50.8%).Detection of rotavirus antigen in the feces was in 12 (10%) of the studied patients.
Syndrome of gastroenteritis was in 14 (11,6%) patient, 72 (60,0%) and 30 (25,0%) had enterocolitis. Signs of dehydration were not expressed in 39 (32,5%) examined children. Exsicosis of the I degree was in 78 (65,0%) patients, of the II degree - in 3(2,5%).
Pathogenetically based basic therapy included infusion therapy with glucose - salt solutions. Fluid were appointed with the purpose of rehydration was calculated in the volume of physiological needs and pathological losses. To select the optimal plan of treatment and evaluation of its clinical effectiveness Enterol (Saccharomyces boulardii) were administered to children under the age of 1 year by 1 sachet 1 times a day, and over 1 year by 1 sachet 1-2 times a day. The course of treatment was 5 days.
Have observed patients in the dynamics were evaluated the severity and duration of main clinical symptoms of the disease such as intoxication, the temperature reaction, vomiting, diarrhe-al syndrome.
Statistical processing of the results of the clinical study. Statistical analysis was performed
using the program STATISTICA.
N-number of patients, p% - percentage, t - Student's test, p-level - statistical significance 95%, CI - from and to the percent within the 95% CI.
If p is less than (<0,05) that the received changes are statistically significant, if more (>0,05) that the received changes are statistically insignificant.
RESULTS AND DISCUSSION
Results and discussion: At admission all studied sick children was expressed intoxicating syndrome: fever, intoxication, loss of appetite, drowsiness, lethargy, hypodynamia. Dyspeptic syndrome was manifested by vomiting, flatulence, rumbling stomach, loose stools. However, the frequency of occurrence of clinical symptoms has been mixed. Appetite were absent or reduced in 116 (96,7%), is safed in 4(3.3%), thirst was expressed in 81(67,5%), was absent in 39(32,5 per cent), or repeated vomiting after every drink and food were observed in 52(43,3%), vomiting was observed in 68(56,7%) of patients.
Table 1 presents the results of clinical symptoms in the studied patients at admission to the hospital.
One of the manifestations of the syndrome of dehydration was sunken eyeballs - in 81 (67,5%) children, condition of skin folds, which goes back immediately - in 39 (32,5%), less than in 2 seconds - in 78 (65,0%), more than in 2 seconds - in 3 (2,5%).
Visible mucous membranes were dry in 81 (67.5%), wet in 39 (32.5%), tongue dry, the saliva viscid, 81 (6,5%), wet in 39 (32.5%). In palpation iarrhe swollen and painful, 112 (93,3%), soft and painless in 8 (6.7%), thin stool with pathological impurities in 109 (90.8%), porridgelike stool without pathological impurities in 11 (9.2%).
Interpretation of complete blood cell count revealed inflammatory changes in 115 (95.8%) of sick children. In scatoscopy mucus was detected in 120 (100%), the leukocyte count to 20 in the field of view in 56 (46.7%), more than 20 in 64 (53,3%), indicating that the invasive nature of the diarrhea syndrome in the studied patients. The data presented in table 2.
According to the results of the study after treatment was shown only in 1 (08%) of the 120 children's appetite was reduced, 119 (99.2%) recovered fully. Symptoms of toxicosis and dehydration completely arrested all 120 surveyed children (vomiting, thirst, sunken eyeballs, skin fold, visible mucous membranes, tongue). Thin stool with pathological impurities was observed only in
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Table 1 - Characteristics of clinical symptoms in the studied patients before treatment
Clinical symptoms BEFORE TREATMENT
n p% 95%ДИ 95%ДИ
Appetite
is absent or reduce 116 96,7 93,5 99,9
saved 4 3,3 0,1 6,5
Thirst
severe 81 67,5 59,1 75,9
is absent 39 32,5 24,1 40,9
Vomiting
repeated or after each meal drink and food 52 43,3 34,5 52,2
is absent 68 56,7 47,8 65,5
Eyeballs
sunken eyes 81 67,5 59,1 75,9
no sunken eyes 39 32,5 24,1 40,9
Skin fold
goes back immediately 39 32,5 24,1 40,9
less than 2 second 78 65,0 56,5 73,5
more than 2 seconds 3 2,5 0,0 5,3
Visible mucous membranes
are dry 81 67,5 59,1 75,9
are moist 39 32,5 24,1 40,9
Tongue
is dry, saliva viscid 81 67,5 59,1 75,9
is moist 39 32,5 24,1 40,9
Abdominal palpation
swollen and painful 112 93,3 88,9 97,8
soft and painless 8 6,7 2,2 11,1
The nature of the stool
Thin stool with pathological impurities 109 90,8 85,7 96,0
porridge-like stool, without pathological impurities 11 9,2 4,0 14,3
Table 2 - Characteristics of additional laboratory data in the studied patients before treatment
Complete blood cell count
inflammatory changes 115 95,8 92,3 99,4
no inflammatory changes 5 4,2 0,6 7,7
Scatoscopy
mucus 120 100,0 100,0 100,0
the leukocyte count to 20 in the field/ vision 56 46,7 37,7 55,6
more than 20 in the field/vision 64 53,3 44,4 62,3
2 (1.7%) patients. By the end of treatment these adverse phenomena in children disappeared.
Bloating in the form of flatulence was before treatment in 112 (93.3%) children, and after treatment the abdomen was soft, painless in all examined children. Table 3 presents the results of clinical symptoms in the studied patients after treatment.
Table 3 - Dynamics of clinical symptoms in the studied patients after treatment
Clinical symptom After treatment t p-level
n p% m2 95%CI 95%CI
Appetite
is absent or reduce 1 0,8 0,7 0,0 2,5 52,174 0,000
saved 119 99,2 0,7 97,5 100,8 52,174 0,000
Thirst
severe 0 0,0 0,0 0,0 0,0 15,787 0,000
is absent 100 83,3 11,6 76,7 90,0 9,303 0,000
Vomiting
repeated or after each meal drink and food 0 0,0 0,0 0,0 0,0 9,579 0,000
is absent 120 100,0 0,0 100,0 100,0 9,579 0,000
Eyeballs
sunken eyes 0 0,0 0,0 0,0 0,0 15,787 0,000
no sunken eyes 120 100,0 0,0 100,0 100,0 15,787 0,000
Skin fold
goes back immediately 120 100,0 0,0 100,0 100,0 15,787 0,000
less than 2 second 0 0,0 0,0 0,0 0,0 14,928 0,000
more than 2 seconds 0 0,0 0,0 0,0 0,0 1,754 0,083
Visible mucous membranes
are dry 0 0,0 0,0 0,0 0,0 15,787 0,000
are moist 120 100,0 0,0 100,0 100,0 15,787 0,000
Tongue
is dry, saliva viscid 0 0,0 0,0 0,0 0,0 15,787 0,000
is moist 120 100,0 0,0 100,0 100,0 15,787 0,000
Abdominal palpation
swollen and painful 0 0,0 0,0 0,0 0,0 40,988 0,000
soft and painless 120 100,0 0,0 100,0 100,0 40,988 0,000
The nature oft he stool
Thin stool with pathological impurities 2 1,7 1,4 0,0 4,0 30,942 0,000
porridge-like stool, without pathological impurities 118 98,3 1,4 96,0 100,6 30,942 0,000
Interpretation of the complete blood cell count revealed a positive dynamics in 110 (91.7%) and only 10(8.3%) of children were retained inflammatory changes. In scatoscopy mucus and leukocytes to 20 per field of view were detected only in 2 (1%). The data presented in table 4.
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Table 4 - Characteristics of additional laboratory data in the studied patients after treatment.
Complete blood cell count
inflammatory changes 10 8,3 6,4 3,4 13,3 28,104 0,000
no inflammatory changes 110 91,7 6,4 86,7 96,6 28,104 0,000
Scatoscopy
mucus 2 1,7 1,4 0,0 4,0 84,143 0,000
the leukocyte count to 20 in the field/vision 2 1,7 1,4 0,0 4,0 9,571 0,000
more than 20 in the field/ vision 0 0,0 0,0 0,0 0,0 11,711 0,000
Thus, the analysis of the clinical course of intestinal infections in children in this study showed that inclusion in complex therapy of Enteral (Saccharomyces boulardii) reduced the duration of the main manifestations of the disease, improved overall health and well-being in the form of reduced weakness, almost all patients have improved appetite, normalized nature of the stool. The use of Enterol (Saccharomyces boulardii) had a positive impact on the duration of basic clinical symptoms in the diarrheal syndrome. The use of Enterol (Saccharomyces boulardii) in the age dosages within 5 days prevents the development antibioticassociated diarrhea in children.
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6 McFarland L. V. Epidemiology, risk factors and treatments for antibiotic-associated diarrhea //Dig. Dis. - 1998. - №16. - P. 292-307.
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8 Szajewska H. Saccharomyces boulardii for treating acute gastroenteritis in children: updated meta-analysis of randomized controlled trials /H. Szajewska, A. Skorka //Aliment. Pharmacol. Ther. - 2009. - №30. - P. 955-963.
9 Szajewska H. Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea /H. Szajewska, M. Kotodziej //Aliment. Pharmacol. Ther. - 2015. - №42(7) . - P. 793-801.
10 Urbanska M. The efficacy of Lactobacillus reuteri DSM 17938 in infants and children: a review of the current evidence /M. Urbanska, H. Szajewska //Eur. J. Pediatr. - 2014. - №173. - P. 1327-1337.
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1 Surkov A. N. Rol' probiotikov v profil-aktike i lechenii antibiotikoassociirovannoj diarei u detej //Pediatricheskaja farmakologija. - 2014. -T. 11, №4. - S. 41-45.
2 Usenko D. V. Vozmozhnosti prime-nenija probiotikov v profilaktike antibiotikoassociirovannoj diarei //Rus. med. zhurn. - 2008. - №1. - S. 36.
3 Frequency of antibiotic-associated iarrhea in 2462 antibiotic-treated hospitalized patients: a prospective study /J. Wistrom, S. R. Norrby, E. B. Myhre et al. //J. Antimicrob. Chemother. - 2001. - №47. - P. 43-50.
4 Incidence and risk factors for of oral antibiotic-associated diarrhea in an outpatient pediatric population /D. Turck, J. P. Bernet, J. Marx et al. //J. Pediatr. Gastroenterol. Nutr. -2003. - №7. - P. 22-26.
5 Lack of relationship of Clostridium difficile to antibiotic-associated diarrhea in children /C. L. Elstner, A. N. Lindsay, L. S. Book et
al. //Pediatr. Inf. Dis. - 1983. - №2. - P. 364-366.
6 McFarland L. V. Epidemiology, risk factors and treatments for antibiotic-associated diarrhea //Dig. Dis. - 1998. - №16. - P. 292-307.
7 Prevention of antibiotic-associated diarrhea with Lactobacillus sporogens and fructo-oligosaccharides in children: a multi-centric double-blind vs. placebo study /M. LaRosa, G. Botta-ro, N. Gulino et al //Minerva Pediatr. - 2003. -№5. - P. 47-52.
8 Szajewska H. Saccharomyces bou-lardii for treating acute gastroenteritis in children: updated meta-analysis of randomized controlled
trials /H. Szajewska, A. Skorka //Aliment. Pharmacol. Ther. - 2009. - №30. - Р. 955-963.
9 Szajewska H. Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea /H. Szajewska, M. Kotodziej //Aliment. Pharmacol. Ther. - 2015. - №42(7) . - Р. 793-801.
10 Urbanska M. The efficacy of Lactobacillus reuteri DSM 17938 in infants and children: a review of the current evidence /M. Urbanska, H. Szajewska //Eur. J. Pediatr. - 2014. - №173. - Р. 1327-1337.
Поступила 10.10.2017
Р. Х. Бегайдарова, А. М. Изтелеуова Г. М. Омарова, Х. Т. Талипбекова, В. Р. Атакишиева
БАЛАЛАРДАЕЫАНТИБИОТИКПЕНАССОЦИАЦИЯЛАНЕАНДИАРЕЯЛАРДЬЩ ЕМ1 МЕНАЛДЫНАЛУДА ЭНТЕРОЛДЬЩ (SACCHAROMYCES BOULARDII) РОЛ1
ААД эртYрлi этиологиялык факторларынын шнде ен маныздысы C. difficile - грамон аэробты спора TY3ymi, антибиотиктердН кепштИне туракты бактериялар. ААД алдын алуда пробиотиктер тшмд^ онын шнде тшмдшп бойынша ен сэтпа Энтерол (Saccharomyces boulardii) болып табылады, элемдег пробиотиктердщ ^н-де №1. 1шек инфекцияларымен аyырFан барлыFы 120 бала, олардын iшiнде 6 аЙFа дейiнгi сэбилердщ саны 20 (16,7%); 6 айдан 1 жаска дейiнгi - 60 (50,0%), бiр жастан аскандары - 40(33,3%). Гастроэнтерит синдромы 14 (11,6%) балада, 72 (60,0%) - гастроэнтероколит синдромы, ал 30 (25,0%) - энтероколит байкалFан. Оптималды емдеу жоспарын тандау жэне онын клиникалык тшмдшИн баFалаy максатында Энтерол (Saccharomyces boulardii) 1 жаска дешнп балаларFа 1 пакеттен кYнiне 1 рет, ал бiр жастан аскан балаларFа 1 пакеттен кYнiне 1-2 рет таFайындалды. Емдеу курсы 5 ^н. Использование Энтеролды (Saccharomyces boulardii) колдану диарея син-дромында негiзгi клиникалык симптомдарынын узакть^ына он эсерiн типздк Энтеролды (Saccharomyces boulardii) балаларFа жас шамасына карай мелшерлеп 5 ^ бергенде антибиотикпен ассоциирленген диареялардын алдын алyFа болады.
Клт сездер: балалар, антибиотикпен ассоциирленген диарея, C. difficile, Энтерол, Saccharomyces boulardii
Р. Х. Бегайдарова, А. М. Изтелеуова, Г. М. Омарова, Х. Т Талипбекова, В. Р. Атакишиева
ЭНТЕРОЛ (SACCHAROMYCES BOULARDII) В ПРОФИЛАКТИКЕ И ЛЕЧЕНИИ АНТИБИОТИК-АССОЦИИРОВАННОЙ
ДИАРЕИ У ДЕТЕЙ
Карагандинский государственный медицинский университет (Караганда, Казахстан)
Среди разнообразия этиологических факторов антибиотик-ассоциированной диареи наибольшее значение придается C. dffficile - грамположительной аэробной спорообразующей бактерии, обладающей устойчивостью к большинству антибиотиков. Хорошим эффектом при профилактике антибиотик-ассоциированной диареи обладают пробиотики, причем наиболее удачными по соотношению эффективности является Энтерол (Saccharomyces boulardii).
Под наблюдением находились 120 детей с диагностированными кишечными инфекциями, из них детей до 6 месяцев было 20 (16,7%); от 6 мес. до 1 года - 60 (50,0%), старше года - 40 (33,3%). Синдром гастроэнтерита отмечался у 14 (11,6%) детей, у 72 (60,0%) - синдром гастроэнтероколита, у 30 (25,0%) - энтероколит. С целью выбора оптимальной схемы лечения и оценки ее клинической эффективности Энтерол (Saccharomyces boulardii) назначали детям до года по 1 пакетику 1 раз в сут, детям старше года - по 1 пакетику 1-2 раза в сут. Курс лечения составил 5 сут. Использование Энтерола (Saccharomyces boulardii) оказало положительное влияние на длительность основных клинических симптомов при диарейном синдроме. Использование Энтерола (Saccharomyces boulardii) в возрастных дозировках в течение 5 сут предупреждает развитие антибиотикоассоци-ированной диареи у детей.
Ключевые слова: дети, антибиотикоассоциированная диарея, C. dffficile, Энтерол, Saccharomyces boulardii
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