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

Fu, Shunlian; Sun, Lisha; Chen, Yiding; Zhou, Qian; Yuan, Lijun; Li, Zinan; Chen, Qiu

doi:https://doi.org/10.1155/2022/6108772

Evidence-Based Complementary and Alternative Medicine

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Abstract Introduction Materials and Methods Results Discussion Conclusions Data Availability Conflicts of Interest Authors’ Contributions Acknowledgments References Copyright Related Articles

Review Article | Open Access

Volume 2022 | Article ID 6108772 | https://doi.org/10.1155/2022/6108772

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

Shunlian Fu,¹Lisha Sun,¹Yiding Chen,¹Qian Zhou,¹Lijun Yuan,¹Zinan Li,¹and Qiu Chen¹

Academic Editor: Chan-Yen Kuo

Received28 Feb 2022

Revised30 Jul 2022

Accepted10 Aug 2022

Published22 Sept 2022

Abstract

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

1. Introduction

As one of the most widely used drugs in subjects between birth and 18 years of age, oral or intravenous antibiotics are applied to more than half of those subjects, resulting in many adverse events, such as antibiotic-associated diarrhea (AAD) [1, 2]. AAD is a common complication in up to a third of all patients treated with antibiotics, and in particular in 11–62% of children and in up to 80% of hospitalized toddlers [3–5]. AAD may result in withdrawing antibiotics, rehydrating by vein, or receiving treatment in hospital, complexing the treatment of underlying infection [6]. At present, about the treatment of AAD in children, suggestions are recommended as follows: discontinuation and adjustment of antibiotics, probiotics, treatment of specific pathogens, fecal microbiota transplantation, symptomatic and supportive treatment, surgical operation, and control of infection in hospital [7]. However, there are some limitations to the present treatments mentioned above. Opportunistic infections and translocations can be caused through the gastrointestinal tract when using probiotic bacteria, which may further become the causative agent of many severe human infections, including bacteremia, meningitis, and endocarditis [1]. Discontinuation and modulation of antibiotics may also aggravate the primary disease. Due to the immature technology of fecal microbiota transplantation, promotions are limited [8]. In addition, individual variability can always make an influence the therapeutic effect for patients [9]. Therefore, more effective treatments and alternative therapies need to be forced and explored.

As a primary complementary and alternative medicine, traditional Chinese medicine (TCM) has been widely used for thousands of years in China, which also has been accepted by more and more countries. Based on unique theories accumulated through phenotypic and individualized evidence in long-term clinical trials, TCM has been confirmed to play a crucial part in diarrhea and evidence also has been demonstrated from some systematic reviews and meta-analyses in recent years [10–14]. Recently, a series of randomized clinical trials (RCTs) have explored the effect of traditional Chinese medicine on treating AAD in children. However, no systematic review or meta-analysis has been conducted on the impact of TCM on AAD in children so far. The aim of this study was to systematically and comprehensively summarize RCTs of TCM interventions involving patients with AAD in children and to evaluate the efficacy of TCM in improving AAD.

2. Materials and Methods

We conducted this systematic review by reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement [15]. This paper were registered in PROSPERO (CRD42022301034).

2.1. Eligibility Criteria

We checked each article by following inclusion criteria as follows: (1) participants: the participants were patients with AAD in children; (2) interventions: on the basis of the control treatment, TCM interventions were given by oral administration in the experimental group; the interventions in the experimental group included any structured and conceptualized traditional Chinese medicine (TCM), such as Chinese herbal compounds, Chinese patent medicine, and single Chinese medical herbs, administered in the form of decoctions, granules, or powders [9, 16]. We did not restrict the dose, frequency, or duration; (3) comparison: the comparison was set as conventional western medicine treatment; (4) outcome: the primary outcomes were the total effective rate; the secondary outcomes were indicators associated with improvement of diarrhea symptoms, such as the time to change the shape of feces, antidiarrheal time, immune-related indicators, inflammatory biomarkers, average hospital stay, and diamine oxidase. All RCTs were published in the past ten years. The diagnosis of AAD is diarrhea after being exposed to antibiotics, whether on antibiotics or after discontinuing antibiotics for two months or longer [4, 5]. Etiologies for pediatric AAD may be in connection with viruses or C. difficile, but may also be related to osmotic imbalances in the intestines after antibiotic exposure and microbiota disruption [17].

The exclusion criteria were as follows: studies were excluded when the interventions in the experimental group were herb extracts, or any nondrug therapy combined with TCM, such as Chinese herb point application therapy, traditional Chinese medical massage, Chinese medicine rectal drops, and moxibustion. The control group included individuals treated with either Western medicine or placebo or treated with no intervention. If the intervention in the experimental group was based on Western medicine, the use of Western medicine in the control group should be consistent. Studies were excluded when the purpose of the study was to investigate the prevention of antibiotic-associated diarrhea by TCM. Articles about conferences, abstracts, and correspondence were excluded. Articles without complete data after consulting corresponding authors were excluded.

2.2. Search Strategy

Electronic databases were searched as follows: Web of Science, PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Information-Chinese Scientific Journal Database from inception to February 24th, 2022 in the English and Chinese languages. Key terms were “traditional Chinese medicine,” “randomized controlled trial,” “effective rate,” and “antibiotic-associated diarrhea.” Search terms are shown in Table 1. Grey literature were also included. When necessary, for collecting missing data on the main endpoints or consulting unclear information, the corresponding authors of the included systematic reviews were contacted.

2.3. Selection of Studies

All the search results based on the predefined search terms were imported into Endnote X9 (a reference management software). Two authors manually and independently screened the relevant literature by reading titles and abstracts, and then evaluated the full text on the basis of the eligibility criteria using a study-selection form. Any disagreements were solved by consulting a third researcher.

2.4. Quality Assessment

Two reviewers independently assessed the quality of all included studies by using the Cochrane Collaborations tool [18]. Criteria were as follows: random sequence generation, allocation concealment, blinding of outcome assessment or participant, incomplete outcome data, selective reporting, and other bias. The evaluation of each item was classified as low, high, or unclear risk according to the descriptions of the method in each study. Any disagreement was settled by discussing with the third author.

2.5. Data Extraction

Two authors independently extracted the data as follows: name of researcher, the included population, published year, the number of people included in the intervention group and in the control group, characteristics of participants, study types, intervention and dosage of TCM, treatment course, control group, baseline, treatment outcomes, adverse events, and other information. A third author checked the data extracted again. Disagreements were settled by discussing with the third author. When necessary, additional information were contacted with the corresponding authors of the studies. Two authors independently assessed the methodological quality and risk of bias (ROB) of all included studies by using the Cochrane Collaboration’s tool.

2.6. Data Synthesis and Statistical Analyses

When the reported data for included outcomes were sufficient, we performed meta-analysis. Meta-analysis was conducted for the primary outcomes and the secondary outcomes,which were managed by using Review Manager (version 5.4; Cochrane Collaboration). In addition to total effective rate, risk ratio (RR) was used as the pooled effect size, and other outcome measures used mean difference as the pooled effect size(95% CI). When values were less than 0.05, the results were considered statistically significant. Heterogeneity was evaluated by using I² statistics: if I² < 50%, a fixed-effect (FE) model was used; if I² ≥ 50%, the random-effect (RE) model was used. The Chi-square test () was also used to evaluate the heterogeneity. When there was heterogeneity, subgroup analysis was conducted. Exploration of publication bias was conducted when the included trials were more than ten in outcomes.

3. Results

In all, 1000 potentially relevant studies were yielded through the initial target databases search. After removing duplicates and eliminating ineligible studies, 114 articles were remained. After the full-text review, 88 studies were excluded, whose contents were irrelevant with our outcomes. The study selection process is shown in Figure 1. At last, 26 RCTs [19–44] were included in this systematic review.

3.1. Characteristics of the Trials Included in the Study

The total number of participants across the included studies was 2636, and the sample size in each study ranged from 50 to 165 participants. All included studies were published in China and the ethnicity of the participants were not reported. Treatment course ranged from 3 days to 2 weeks. In the included studies, 22 articles were reported about Chinese patent medicine, including Shenling Baizhu granule, Xingpi Yanger granule, Erxieting granules, Weichangan pill, modified Yigong Powder, Xiaoer Fuxie powder, Yiersan, Guben Yichang tablets, Buzhong Yiqi particles, and Qiweibaizhu powder. Details are shown in Table 2.

4. Methodological Quality

According to the results of Cochrane Collaboration risk of bias tool, the method of randomization and allocation concealment was described clearly in all included studies. The bias for each trial is shown in Figure 2, and the bias summary is shown in Figure 3.

4.1. Effect of TCM Combined with Conventional Therapy on the Total Effective Rate

By a comparison of total effective rate, a total of 25 trials [19–30], [32–44] showed that TCM combined with conventional therapy was more effective than conventional therapy alone. There was no heterogeneity of the 25 trials by comparing total effective rate (Heterogeneity: Chi² = 30.72, df = 24 (); I² = 22%) with the fixed-effects model (RR = 1.20, CI 1.16 to 1.24; ) used (Figure 4). The funnel plot showed that there might be a publication bias for the outcome of total effective rate (Figure 5). Subgroup analysis was performed by the commonly used Chinese medicine formulations to explore the possible source of heterogeneity. The results of subgroup analysis for Shenling Baizhu granule, Xingpi Yanger granule, Weichangan pill, and other Chinese medicine formulations were, respectively, RR = 1.17 (CI 1.08 to 1.27; , I² = 22%, ), RR = 1.19 (CI 1.12 to 1.27; , I² = 3%, ), RR = 1.20 (CI 1.09 to 1.31; , I² = 0%, ), and RR = 1.20 (CI 1.09 to 1.31; , I² = 0%, ). From the results mentioned above, we can conclude that the total effective rate of TCM in the treatment of AAD was significant, and the results are stable and reliable.

4.2. Effect of TCM Combined with Conventional Therapy on the Time to Change the Shape of Feces

By a comparison of the time to change the shape of feces, a total of 7 trials [23–25, 30–32, 34] showed that TCM combined with conventional therapy was more effective than conventional therapy alone. There was high heterogeneity of the 7 trials by comparing the time to change the shape of feces (Heterogeneity: Tau² = 0.13; Chi² = 47.05, df = 6 (); I² = 87%) with the random-effects model (MD = −1.37, CI −1.67 to −1.07; ) used (Figure 6). Due to the limited number of included studies, we did not detect the publication bias and did not conduct subgroup analysis.

4.3. Effect of TCM Combined with Conventional Therapy on Antidiarrheal Time

By a comparison of antidiarrheal time, a total of 17 trials [19, 20], [22–31], [33, 35, 37, 38, 40] showed that TCM combined with conventional therapy was more effective than conventional therapy alone. There was high heterogeneity of the 17 trials by comparing the antidiarrheal time (Heterogeneity: Tau² = 0.29; Chi² = 209.80, df = 16 (); I² = 92%) with the random-effects model (MD = −1.43, CI −1.71 to −1.15; ) used (Figure 7). The funnel plot showed that there was no publication bias for the outcome of the antidiarrheal time (Figure 8).

According to the commonly used Chinese medicine formulations and the intervention time, we conducted subgroup analysis. When the intervention time was two weeks, the result was RR = −1.49 (CI −2.94 to −0.05; , I² = 98%, ). The result was RR = −1.41 (CI −1.65 to −1.17; , I² = 87%, ). We performed a subgroup analysis by the time of intervention, but the heterogeneity was not reduced. Subgroup analysis by the commonly used Chinese medicine formulations showed that the results for Weichangan pill, Xingpi Yanger granule, and Shenling Baizhu granule were, respectively, RR = −0.68 (CI −0.96 to −0.40; , I² = 0%, ), RR = −1.96 (CI −2.20 to −1.72; , I² = 95.7%, ), and RR = −1.65 (CI −1.93 to −1.37; , I² = 92.6%, ). Therefore, subgroup analysis by the Chinese medicine formulations and the time of intervention hardly reduced the heterogeneity.

4.4. Effect of TCM Combined with Conventional Therapy on Other Indices

The pooled results showed that there were no significant difference between the two groups in CD3+, CD4+, CD8+, CD4 : CD8, time for bowel sounds to return to normal, hs-CRP, and IgM. There was significant difference between the two groups in frequency of diarrhea on the third day after TCM intervention, vomiting improvement time, diamine oxidase, IL-8, TNF, IgA, IgG, and average hospital stay. The details are shown in Table 3. There was no report about the adverse events.

5. Discussion

This systematic review was aimed at evaluating the effect of TCM combined with conventional therapy on treating AAD in children. Two systematic reviews have reported that TCM interventions combined with conventional therapy can be more effective than conventional therapy alone on treating AAD [45, 46]. However, there has been no systematic review and meta-analysis of TCM interventions treating AAD in children. In our systematic review of 26 RCTs involving 2636 children with AAD, it was demonstrated that TCM interventions combined with conventional therapy could effectively treat AAD in children.

With the overuse of antibiotics, a series of side effects are caused, such as antibiotic-associated diarrhea (AAD), which imposes more economic burden on the patient [47]. To our knowledge, the cause of AAD is commonly identified as intestinal flora disturbance [48]. As one of the oldest medical practices in human history, TCM has been widely used in diagnosing and treating diseases, which can improve the imbalance of intestinal flora [49, 50]. By conducting a systematic review, Zheng et al. [9] found that TCM can make an influence on modulating gut microbiota and improving glucose metabolisms in T2DM patients. Guo et al. [47] have demonstrated that Buzhongyiqi decoction (BD), Sijunzi decoction (SD), and Shenlingbaizhu decoction (SHD) can alleviate diarrhea symptoms induced by ceftriaxone sodium in animal experiments by balancing intestinal flora and improving villi structure. Hui et al. [48] reported that Qiweibaizhusan can restore and adjust the diversity of bacteria in mice intestine with diarrhea syndrome caused by administrating the mixture of gentamycin sulfate and cefradine. It is consistent with the results obtained by our systematic review that Shenling Baizhu granule, Xingpi Yanger granule, Erxieting granules, Huangqi Jianzhong decoction, Weichangan pill, Jianpi Bushen decoction, Modified Yigong powder, Xiaoer Fuxie powder, Guben Yichang tablets, Qiweibaizhu powder, and Buzhong Yiqi particles can significantly improve total effective rate and shorten the time to change the shape of feces, vomiting improvement time, time for bowel sounds to return to normal, and antidiarrheal time. Those outcomes above reflected the changes of AAD symptoms. The shortening of those outcomes could be associated with the reducing of average hospital stay and contribute to the enhancement of total effective rate in AAD. In addition, those herbal formulas are consisted of some typical herbs commonly used for tonifying Qi. Those are consistent with reports in previous studies that a major proportion of AAD is composed of the spleen deficiency type [51, 52]. All in all, the results have demonstrated that TCM could be used as an alternative therapeutic approach to treat AAD in children by balancing intestinal flora. However, the potential publication bias and heterogeneity may reduce the reliability of the results.

AAD is often accompanied by systemic inflammation, characterized by a significant increase in proinflammatory factors and a significant decrease in anti-inflammatory factors [53]. Changes in proinflammatory cytokines include tumor necrosis factor and interleukins, both of which play a primary role in communicating with immune cells and reflect inflammatory infiltration in the host [54]. Therefore, the levels of inflammatory cytokines are evaluated in AAD, including TNF and IL-8. In our results, TCM can improve some inflammation factors, such as TNF and IL-8, while TCM makes no difference in hs-CRP, which is consistent with the results reported by Ya-Nan et al. [55]. However, due to the limited study number, we cannot draw a definite conclusion about the results so far. In addition, due to the complexity of the chemical components in the formulas of herbs, it is difficult to make it clear about the mechanisms, restricting its clinical application at this stage.

The damage of intestinal mucosal barrier dysfunction can be also an important reason for AAD [47]. As one of the marker enzymes in many mammalian intestinal mucosal epithelial villus cells, DAO levels can objectively present the degree of intestinal mucosal damage [56]. Our results show that TCM can significantly reduce the level of diamine oxidase, which is the same with the results reported by Li et al. [57]. However, the small number of included studies limit the reliability of the results so far.

Intestinal immunity in the intestinal mucosa is the largest and most complex part of the overall immune system, accounting for at least 80% of all antibodies in adults [58]. As immune proteins are secreted by B lymphocytes when they differentiate into plasma cells, IgM, IgG, and IgA are important members of body humoral immunity, and their levels are positively correlated with body immunity [59]. As the body’s immune system of the major groups of cells, T cell subgroup of CD4+ cells activate macrophages, CD8+ cells, by contrast, have inhibitory effect on cell activation [60]. AAD is closely linked to the disturbance of intestinal immunity [58]. In our systematic review, CD3+, CD4+, CD8+, CD4 : CD8, IgM, IgA, and IgG are summarized about the effect of TCM on AAD. However, the results in our systematic review indicate that TCM makes no significant difference on those outcomes. This may be associated with the small sample sizes in the included literature.

5.1. Limitations

In our systematic review, we focused on the effect of TCM on AAD in children. Nevertheless, the methodological quality scores were low and may restrict the generalizability of the results, which was the one of the main limitations in this systematic review. In addition, the studies were conducted in China, and the effect has not been established for other ethnic groups, which deserves further study. The publication bias and high heterogeneity may further reduce the reliability of the results. Therefore, more standard and large randomized controlled trials are needed in the future.

6. Conclusions

According to this systematic review, TCM interventions combined with conventional therapy can effectively alleviate AAD by improving diarrhea symptoms and reducing some inflammatory biomarkers in children. However, for the methodological quality is low which may reduce the reliability of the results, large and multicenter randomized controls are needed in the future.

Data Availability

The datasets used in the present review are available from the corresponding author on reasonable request.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors’ Contributions

Shunlian Fu, Qiu Chen, Lisa sun, Yiding Chen, and Qian Zhou designed the study and drafted the manuscript. Lijun Yuan and Zinan Li contributed to literature search, figures, data collection, and data analysis. Qiu Chen provided guidance on the methodology. All authors read and approved the final manuscript.

Acknowledgments

This study was funded by Regional Promotion and Application of Intelligent Management Innovation System of TCM for Metabolic Diseases Based on Internet of Things Technology (CKY2021088).

References

C. Mantegazza, P. Molinari, E. D’Auria, M. Sonnino, L. Morelli, and G. V. Zuccotti, “Probiotics and antibiotic-associated diarrhea in children: a review and new evidence on Lactobacillus rhamnosus GG during and after antibiotic treatment,” Pharmacological Research, vol. 128, pp. 63–72, 2018.
View at: Publisher Site | Google Scholar
M. K. Gibson, T. S. Crofts, and G. Dantas, “Antibiotics and the developing infant gut microbiota and resistome,” Current Opinion in Microbiology, vol. 27, pp. 51–56, 2015.
View at: Publisher Site | Google Scholar
F. Barbut and J. L. Meynard, “Managing antibiotic associated diarrhoea,” BMJ, vol. 324, no. 7350, pp. 1345-1346, 2002.
View at: Publisher Site | Google Scholar
Q. Guo, J. Z. Goldenberg, C. Humphrey, R. El Dib, and B. C. Johnston, “Probiotics for the prevention of pediatric antibiotic-associated diarrhea,” Cochrane Database of Systematic Reviews, vol. 4, no. 4, Article ID Cd004827, 2019.
View at: Publisher Site | Google Scholar
L. V. McFarland, M. Ozen, E. C. Dinleyici, and S. Goh, “Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections,” World Journal of Gastroenterology, vol. 22, no. 11, pp. 3078–3104, 2016.
View at: Publisher Site | Google Scholar
E. A. Suniega and J. Frasca, “Probiotics to prevent antibiotic-associated diarrhea in children,” American Family Physician, vol. 101, no. 5, 2020.
View at: Google Scholar
Y. J. Zheng, Q. B. Wu, F. Fang et al., “Expert consensus on diagnosis, treatment and prevention of antibiotic-associated diarrhea in children,” Chinese Journal of Practical Pediatrics, vol. 36, no. 6, pp. 424–430, 2021.
View at: Google Scholar
R. Bernard, S. K. Hourigan, and M. R. Nicholson, “Fecal microbiota transplantation and microbial therapeutics for the treatment of clostridioides difficile infection in pediatric patients,” Journal of the Pediatric Infectious Diseases Society, vol. 10, no. 3, pp. S58–s63, 2021.
View at: Publisher Site | Google Scholar
Y. Zheng, Q. Ding, Y. Wei et al., “Effect of traditional Chinese medicine on gut microbiota in adults with type 2 diabetes: a systematic review and meta-analysis,” Phytomedicine, vol. 88, Article ID 153455, 2021.
View at: Publisher Site | Google Scholar
B. Wu, M. Liu, H. Liu et al., “Meta-analysis of traditional Chinese patent medicine for ischemic stroke,” Stroke, vol. 38, no. 6, pp. 1973–1979, 2007.
View at: Publisher Site | Google Scholar
Z. X. Yan, Y. M. Liu, T. Ma et al., “Efficacy and safety of retention enema with traditional Chinese medicine for ulcerative colitis: a meta-analysis of randomized controlled trials,” Complementary Therapies in Clinical Practice, vol. 42, Article ID 101278, 2021.
View at: Publisher Site | Google Scholar
Y. Mao, G. Hu, Q. Meng et al., “Efficacy of Shenling Baizhu San on stable chronic obstructive pulmonary disease patients: a systematic review and meta-analysis,” Journal of Ethnopharmacology, vol. 272, Article ID 113927, 2021.
View at: Publisher Site | Google Scholar
L. Gao, C. Jia, and H. Huang, “Paediatric massage for treatment of acute diarrhoea in children: a meta-analysis,” BMC Complementary and Alternative Medicine, vol. 18, no. 1, p. 257, 2018.
View at: Publisher Site | Google Scholar
X. Du, L. Shi, W. Cao, B. Zuo, and A. Zhou, “Add-on effect of Chinese herbal medicine in the treatment of mild to moderate COVID-19: a systematic review and meta-analysis,” PLoS One, vol. 16, no. 8, Article ID e0256429, 2021.
View at: Publisher Site | Google Scholar
L. Shamseer, D. Moher, M. Clarke et al., “Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation,” BMJ, vol. 349, no. 1, Article ID g7647, 2015.
View at: Publisher Site | Google Scholar
N. Wang, D. D. Qin, Y. H. Xie et al., “Traditional Chinese medicine strategy for patients with tourette syndrome based on clinical efficacy and safety: a meta-analysis of 47 randomized controlled trials,” BioMed Research International, vol. 2021, Article ID 6630598, 11 pages, 2021.
View at: Publisher Site | Google Scholar
S. J. Newberry, S. J. Newberry, A. R. Maher et al., “Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis,” JAMA, vol. 307, no. 18, pp. 1959–1969, 2012.
View at: Publisher Site | Google Scholar
J. P. T. Higgins, D. G. Altman, P. C. Gøtzsche et al., “The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials,” BMJ, vol. 343, no. 2, Article ID d5928, 2011.
View at: Publisher Site | Google Scholar
X. D. Ruan, “Treatment of antibiotic related diarrhea in children with Chinese and Western combination,” Jilin Traditional Chinese Medicine, vol. 39, no. 9, pp. 1202–1204, 2019.
View at: Google Scholar
B. Jin, C. Huang, and B. Zhang, “Effects of Xiaoer Diarrheal powder combined with live Clostridium butyricum powder on hs-CRP, IL-8, IL-12 and TNF-α in children with antibiotic-associated diarrhea,” Shaanxi Traditional Chinese Medicine, vol. 38, no. 7, pp. 837-838, 2017.
View at: Google Scholar
H. Zhu, “Effect of Shenling Baizhu granule combined with Saccharomyces boulardii powder and vitamin C on antibiotic related diarrhea in children,” Primary Medical Forum, vol. 24, no. 32, pp. 4693–4695, 2020.
View at: Publisher Site | Google Scholar
M. Z. Zhang, “Clinical observation on 39 cases of antibiotic associated diarrhea in children treated with integrated traditional Chinese and Western medicine,” Chinese National and Folk Medicine, vol. 27, no. 15, pp. 106–108, 2018.
View at: Google Scholar
F. Zhang, L. A. N. Li, and M. Wan, “Clinical observation on the treatment of antibiotic - associated diarrhea in children with pneumonia by Erxierting granules,” Modern Distance Education of Traditional Chinese Medicine, vol. 19, no. 14, pp. 85-86, 2021.
View at: Google Scholar
C.-G. Yuan and C. Li-fang, “Huangqi Jianzhong decoction combined with conventional western medicine to treat 60 children with antibiotic related diarrhea,” Chinese Medicine Technology, vol. 29, no. 01, pp. 141-142, 2022.
View at: Google Scholar
N. Yao, “Clinical effect of Shenling Baizhu granules combined with Bifidobacterium triple enteric-soluble capsule in the treatment of neonatal antibiotic-associated diarrhea,” Chinese Institute of Sanatorium Medicine, vol. 28, no. 6, pp. 651-652, 2019.
View at: Google Scholar
L. P. Yang, J. Y. Ma, L. X. Jia, and X. N. Guo, “Efficacy of Weigang an pill combined with Bifidobacterium triple viable capsule in the treatment of children with antibiotic-associated diarrhea,” Journal of Modern Integrated Traditional Chinese and Western Medicine, vol. 25, no. 26, pp. 2858–2860, 2016.
View at: Google Scholar
L. Yang, J. Y. Ma, X. N. Guo, and X. H. Wang, “Treatment of 58 children with antibiotic-associated diarrhea with Weiji’ an pill,” Henan Traditional Chinese Medicine, vol. 36, no. 5, pp. 871–873, 2016.
View at: Google Scholar
C. Yang and R. Zhou, “Clinical observation of Jianpi Bushen Gushu Decoction in the treatment of children with antibiotic related diarrhea,” Guangming Traditional Chinese Medicine, vol. 32, no. 22, pp. 3255–3257, 2017.
View at: Google Scholar
Y. J. Xu, “Effect of Sijunzi decoction on infant β-lactam antibiotic-associated diarrhea,” Zhejiang Journal of Integrated Traditional Chinese and Western Medicine, vol. 25, no. 02, pp. 162-163, 2015.
View at: Google Scholar
S. Wang and G. Yuan, “Effect of Xingpi Yanger granule on antibiotic related diarrhea,” Henan Medical Research, vol. 29, no. 03, pp. 471-472, 2020.
View at: Google Scholar
F. H. Wang, C. X. Zeng, D. W. Zhang, L. Y. Wu, and J. Q. Yu, “Effects of ShenlingBaizhu granules on intestinal barrier function and immune function in children with antibiotic-associated diarrhea,” Today Pharmacy, vol. 30, no. 7, pp. 489–492, 2020.
View at: Google Scholar
X. F. Tu, Z. Q. Wu, X. P. Chen, and W. H. Zhu, “Clinical study of Jiawei Yigong powder combined with conventional therapy in the treatment of children with antibiotic-associated diarrhea,” The new Chinese medicine, vol. 52, no. 15, pp. 32–35, 2020.
View at: Google Scholar
T. Tian, F. Jing, and X. Gao, “Clinical study of Xingpi Yanger granule in the adjuvant treatment of infant antibiotic related diarrhea,” Shaanxi Traditional Chinese Medicine, vol. 39, no. 8, pp. 1112–1114, 2018.
View at: Google Scholar
H. Qi, “Xingpi Yanger granule combined with probiotics in the treatment of children with antibiotic-related diarrhea,” Clinical application of integrated Chinese and Western Medicine, vol. 20, no. 4, pp. 47-48, 2020.
View at: Google Scholar
X. P. Ma, T. T. Hao, S. P. Liu, and J. Cheng, “Clinical study of Gubenyichang tablets combined with Saccharomycete Boulardi powder and vitamin C in the treatment of children with antibiotic-associated diarrhea,” Modern Medicine and Clinical, vol. 31, no. 9, pp. 1412–1416, 2016.
View at: Google Scholar
J. Ma and L. Yang, “Effect of Weigang an pill on antibiotic related diarrhea in children with bronchopneumonia,” Clinical Journal of Rational Drug Use, vol. 10, no. 11, pp. 69-70, 2017.
View at: Google Scholar
L. Luo, “Clinical observation on ShenlingBaizhu granules combined with Bifidobacterium triple live enteric-soluble capsule in the treatment of 60 cases of neonatal antibiotic-associated diarrhea,” Hebei Traditional Chinese Medicine, vol. 36, no. 6, pp. 860-861, 2014.
View at: Google Scholar
H.-J. Liu, H. U. A. N. G. Chun-xia, and N. I. U. Yan-hui, “Clinical effect of Chinese and Western medicine on antibiotic related diarrhea in infants with bronchopneumonia,” Proprietary Chinese medicine, vol. 39, no. 5, pp. 1103–1105, 2017.
View at: Google Scholar
J. Lin, “Clinical observation of Xingpi Yanger granule in treating antibiotic-associated diarrhea secondary to bronchopneumonia,” Chinese Folk Therapy, vol. 27, no. 07, pp. 34-35, 2019.
View at: Google Scholar
R. Li, “Effect of Xingpi Yanger granule combined with live Clostridium butyricum tablets in the treatment of infant antibiotic-associated diarrhea,” Clinical application of integrated Chinese and Western Medicine, vol. 20, no. 02, pp. 94-95, 2020.
View at: Google Scholar
J. Fan and H. Chen, “Effect of Buzhong Yiqi granule on antibiotic associated diarrhea in children with pneumonia,” Contemporary Medicine, vol. 27, no. 15, pp. 175–177, 2021.
View at: Google Scholar
C. Li-Fang and C. Qi-Xin, “Clinical observation of Yier Powder in the treatment of 43 children with antibiotic related diarrhea,” The new Chinese medicine, vol. 47, no. 9, pp. 159-160, 2015.
View at: Google Scholar
C. Li-Fang and C. Qi-Xin, “Treatment of 45 cases of antibiotic related diarrhea in children with Qiwei Baizhu Powder,” Zhejiang Journal of Traditional Chinese Medicine, vol. 50, no. 8, p. 603, 2015.
View at: Google Scholar
F. Cao, “Treatment of 100 cases of infant antibiotic-associated diarrhea with erxie stop combined with probiotics,” Modern Distance Education of Chinese Medicine, vol. 14, no. 20, pp. 91–93, 2016.
View at: Google Scholar
Q. Chen, “Systematic review of the efficacy of traditional chinese medicine in the treatment of adult antibiotic-associated diarrhea,” Liaoning University of Traditional Chinese Medicine, Shenyang, Chinna, 2018, Master’s thesis.
View at: Google Scholar
X. L. Liu, “Systematic review of chinese medicine and integrated chinese and western medicine in the treatment of antibiotic-associated diarrhea,” Chengdu University of Traditional Chinese Medicine, Chengdu, China, 2009, Master’s thesis.
View at: Google Scholar
X. Guo, Z. Yan, J. Wang et al., “Effect of traditional Chinese medicine (TCM) and its fermentation using Lactobacillus plantarum on ceftriaxone sodium-induced dysbacteriotic diarrhea in mice,” Chinese Medicine, vol. 17, no. 1, p. 20, 2022.
View at: Publisher Site | Google Scholar
H. Hui, Y. Wu, T. Zheng, S. Zhou, and Z. Tan, “Bacterial characteristics in intestinal contents of antibiotic-associated diarrhea mice treated with qiweibaizhu powder,” Medical Science Monitor, vol. 26, Article ID e921771, 2020.
View at: Publisher Site | Google Scholar
W. Feng, H. Ao, C. Peng, and D. Yan, “Gut microbiota, a new Frontier to understand traditional Chinese medicines,” Pharmacological Research, vol. 142, pp. 176–191, 2019.
View at: Publisher Site | Google Scholar
Y. Z. Chen, M. Y. Yuan, Y. L. Chen et al., “The gut microbiota and traditional Chinese medicine: a new clinical frontier on cancer,” Current Drug Targets, vol. 22, no. 11, pp. 1222–1231, 2021.
View at: Publisher Site | Google Scholar
X. M. Wang, X. B. Li, and Y. Peng, “Impact of Qi-invigorating traditional Chinese medicines on intestinal flora: a basis for rational choice of prebiotics,” Chinese Journal of Natural Medicines, vol. 15, no. 4, pp. 241–254, 2017.
View at: Publisher Site | Google Scholar
S. M. Xie, “Study on the syndrome distribution and medication rule of antibiotic-associated diarrhea,” Tianjin University of Traditional Chinese Medicine, 2020, Master’s thesis.
View at: Google Scholar
R. Chandrasekaran and D. B. Lacy, “The role of toxins in Clostridium difficile infection,” FEMS Microbiology Reviews, vol. 41, no. 6, pp. 723–750, 2017.
View at: Publisher Site | Google Scholar
B. Xu, S. Liang, J. Zhao et al., “Bifidobacterium animalis subsp. lactis XLTG11 improves antibiotic-related diarrhea by alleviating inflammation, enhancing intestinal barrier function and regulating intestinal flora,” Food & Function, vol. 13, no. 11, pp. 6404–6418, 2022.
View at: Publisher Site | Google Scholar
G. Ya-Nan, W. Jun, Z. Hao-Jun, J. Hong-Bing, L. Ping, and L. Xin-Zhu, “Traditional Chinese medicine QPYF as preventive treatment for Clostridium difficile associated diarrhea in a mouse model,” Evidence-based Complementary and Alternative Medicine, vol. 2016, pp. 1–7, 2016.
View at: Publisher Site | Google Scholar
J. W. Ning, Y. Zhang, M. S. Yu et al., “Emodin alleviates intestinal mucosal injury in rats with severe acute pancreatitis via the caspase-1 inhibition,” Hepatobiliary and Pancreatic Diseases International, vol. 16, no. 4, pp. 431–436, 2017.
View at: Publisher Site | Google Scholar
X. Li, Y. Wu, Z. Xu et al., “Effects of hetiao Jianpi decoction on intestinal injury and repair in rats with antibiotic-associated diarrhea,” Medical Science Monitor, vol. 26, Article ID e921745, 2020.
View at: Publisher Site | Google Scholar
J. Ramirez, F. Guarner, L. Bustos Fernandez, A. Maruy, V. L. Sdepanian, and H. Cohen, “Antibiotics as major disruptors of gut microbiota,” Frontiers in Cellular and Infection Microbiology, vol. 10, Article ID 572912, 2020.
View at: Publisher Site | Google Scholar
S. Zhang and K. Yang, “Clinical effect of bifidobacterium quadruple viable tablets in the treatment of children with antibiotic-associated diarrhea,” Clinical Medical Research and Practice, vol. 7, no. 13, pp. 63–65, 2022.
View at: Google Scholar
X. Li, X. Yang, and L. Qiu, “Efficacy of bifidobacterium quadruple viable tablets in the treatment of children with antibiotic-associated diarrhea,” Chinese Journal of Anorectal Diseases, vol. 42, no. 3, pp. 51-52, 2022.
View at: Google Scholar

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Copyright © 2022 Shunlian Fu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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