The Impact of Zinc and Probiotics in Preventing Pediatric Antibiotic-Associated Diarrhea in Southern Iran.

doi:10.21203/rs.3.rs-4932813/v1

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The Impact of Zinc and Probiotics in Preventing Pediatric Antibiotic-Associated Diarrhea in Southern Iran.

https://doi.org/10.21203/rs.3.rs-4932813/v1

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Background

Antibiotic-associated diarrhea (AAD) is a frequently encountered complication that arises from the administration of antimicrobial agents.

Objective:

The aim of this study was to evaluate and compare the impacts of zinc and probiotics on the prevention of antibiotic-associated diarrhea (AAD).

Patients and methods:

This is a randomized clinical trial involving 165 children referred to Bandar Abbas Children's Hospital, which necessitated antibiotics for any given reason. They were randomly assigned to three groups of equal size, exclusively receiving the standard antibiotic regimen or the zinc and probiotics groups. Age, sex, length of hospital stay, treatment duration, type of antibiotic, and incidence of antibiotic-associated diarrhea (AAD) were documented for all patients.

Results:

Among the 165 children who participated in the survey, AAD occurred in 12.7% of the zinc group, 9.1% of the probiotics group, and 10.9% of the control group; however, the difference among the groups was not statistically significant (P = 0.829). There was no significant association between AAD and age, sex, hospital length of stay, type of antibiotic, or patient grouping.

Conclusions:

Despite the lower incidence of AAD, duration of hospital stay and duration of treatment in children in the probiotic group, these findings were not statistically significant.

antibiotic-associated diarrhea

children

zinc

probiotics

In the past two decades, many studies have demonstrated the clinical benefit and safety of a wide range of probiotics for the prevention and control of gastrointestinal diseases(1, 2, 3). Probiotics have been increasingly used as preventive measures against AAD in children. AAD is a common side effect of antibiotic use and can lead to significant discomfort and complications(4). Two types of probiotics, Lactobacillus rhamnosus GG and Saccharomyces boulardii, have been recommended for preventing pediatric AAD (5). Lactobacillus rhamnosus GG is a probiotic strain that has been shown to reduce the incidence and duration of AAD in children. According to a previous study, children who received Lactobacillus rhamnosus GG had a significantly lower risk of developing AAD than did those who received a placebo (6). Saccharomyces boulardii is another probiotic strain that has been found to be effective in preventing AAD in children. (6, 8). In terms of dosage, a higher dose range of 5–40 billion colony-forming units per day has been reported to be the most efficacious in trials (6). Probiotics are generally considered safe for healthy children, but rare serious adverse events have been documented in severely debilitated or immunocompromised children (7). In conclusion, probiotics, specifically Lactobacillus rhamnosus GG and Saccharomyces boulardii, can be effective in preventing antibiotic-associated diarrhea in children. (5).

Zinc supplementation has shown promising results in the prevention and treatment of AAD in children(9). AAD is a common side effect of antibiotic use, and the role of zinc in reducing the severity and duration of diarrhea has been investigated in multiple studies. (10) Zinc is an essential micronutrient that plays crucial roles in immune function, cell growth, and protein synthesis. It has been shown to improve the absorption of water and electrolytes in the intestine, which helps to reduce the duration and severity of diarrhea(11). Zinc supplementation has also been found to prevent subsequent infections for 2–3 months after administration. Zinc supplementation is generally accepted by both children and caregivers and is effective regardless of the type of common zinc salt used (zinc sulfate, zinc acetate, or zinc gluconate) (12).

The aim of this study was to evaluate and compare the effects of zinc and probiotics on AAD children aged 3 months to 12 years in southern Iran. While zinc supplementation and probiotics have shown promising results in the management of diarrhea, more research is needed to determine their efficacy, specifically in preventing and treating AAD in children.

3,1. Study Design

This study was a randomized controlled trial of 165 children that was conducted in pediatric hospitals in the southern region of Iran. The participants will be children aged 3 months to 3 years who are prescribed antibiotics for various medical conditions. They were randomly assigned to one of three groups: a zinc group, a probiotics group, or a control group. The zinc group received oral zinc supplementation; 2.5 ml every 12 hours for children aged < 1 year and 5 ml every 12 hours for older children; the probiotics group received oral probiotics; 1 probiotic sachet (KidiLact: Lacticaseibacillus rhamnosus, Lactobacillus reuteri, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus acidophilus, Bifidobacterium bifidum and Streptococcus thermophilus); and the control group received nothing. The incidence and severity of AAD were assessed and compared among the three groups. Other parameters, such as the duration of hospital stay and the occurrence of complications, were evaluated.

3,2. Data collection and statistical analysis

After the desired information was collected, it was entered into SPSS software version 26 and then analyzed via descriptive statistics. Chi-square tests and Fisher's exact tests were used to compare the qualitative variables between the study groups. Owing to the nonnormality of the distribution of quantitative variables in the Kolmogorov‒Smirnoff test, the Kruskal‒Wallis and Mann‒Whitney tests were used to compare quantitative variables between groups. Logistic regression was also used to determine the factors affecting the incidence of AAD.

3,3. Ethical considerations

This study was conducted in accordance with the tenets of the Declaration of Helsinki and was ethically approved by the Ethics Committee of Hormozgan University of Medical Sciences (Approval ID: IR.HUMS.REC.1399.579). Informed consent was obtained from the children and their parents. Clinical trial number is not applicable.

In this study, a total of 165 children aged between 3 months and 12 years were investigated. The participants had an average age of 45.65 ± 41.46 months. Among the total sample, 84 (50.9%) were boys, and 81 (49.1%) were girls. AAD was detected in 12.7% of the samples in the zinc group, 9.1% of those in the probiotics group, and 10.9% of those in the control group. However, there was no statistically significant difference among the groups (P = 0.829). The length of hospital stay and duration of treatment did not differ between the zinc and probiotic groups and the control group (P = 0.098 and P = 0.061, respectively). Nevertheless, both were significantly shorter with probiotics than with zinc (P < 0.001). Ampicillin consumption was observed in 16.4% of the probiotics group, 3.6% of the control group, and 1.8% of the zinc group (P = 0.013). Additionally, vancomycin consumption was observed in 10.9% of the control group and 7.3% of the zinc group, whereas no patients in the probiotics group received vancomycin (P = 0.037). No significant differences were found among the groups in terms of the consumption of ceftriaxone, meropenem, cefotaxime, or clindamycin. There was no significant association between AAD and age, sex, hospital length of stay, type of antibiotic, or patient grouping.

The results of this study revealed that the rate of AAD was lower in the probiotic group than in the zinc group. However, the difference between the groups was not statistically significant. The control group had an AAD that fell between those of the other two groups.

On the other hand, the probiotic group had significantly shorter hospitalization and treatment durations than did the zinc group. This finding contrasts with that of Kodam's study, which revealed that, compared with probiotics, zinc was more effective at reducing diarrhea recovery time (13). Both treatments had similar effects on stool consistency and frequency, but zinc was more effective overall. Similarly, Ahmadpour et al. reported that zinc was more effective than probiotics in treating acute diarrhea in children. Additionally, the side effects of zinc treatment are less severe than those of probiotics(14).

Hassan et al. investigated the effectiveness of oral zinc and probiotics on AAD in children(15). Their study included a third group that received both zinc and probiotics. These results were inconsistent with those of the present study, as they reported that the combination treatment was more effective than either treatment alone. These studies had designs similar to those of the present study, which compared zinc and probiotics in separate groups(13, 14, 15). However, there were differences in the entry and exit criteria, demographics, dosage and form of zinc, content of probiotics, and type of diarrhea being studied. These variations, along with differences in the studies' purposes (prevention or treatment of diarrhea), likely explain the contrasting findings.

The probiotics used in the present study contained different types of bacteria, which may explain why they were more effective than zinc. The findings of Huang et al. support this idea, as they reported that a combination of probiotics was more effective at reducing the duration of diarrhea than a single probiotic was (16).

Importantly, neither zinc nor probiotics were superior to the control group in terms of hospital stay and duration of treatment. A systematic review and meta-analysis by Huang et al. revealed that probiotics shortened the duration of diarrhea and reduced the effectiveness of two-day treatment. The probiotic group also had shorter hospitalization (16).

In another study, Azim et al. compared the combination of zinc and probiotics to zinc alone in treating acute gastroenteritis in children. The combination treatment was significantly more effective. Hassan et al. reported similar results, suggesting that the combination treatment was more effective than either treatment alone!17).

These findings suggest that the combination of zinc and probiotics may be a better option for treatment or prevention than either treatment alone. Future studies should consider including a zinc-containing probiotic arm in addition to zinc, probiotics, and control arms to provide more conclusive results.

Xiang et al. reported that zinc in combination with probiotics was more effective than probiotics alone in treating antibiotic-induced diarrhea caused by pneumonia in children(18).

Tai et al.'s clinical trial revealed that zinc supplementation reduced the duration of AAD in hospitalized children but did not affect disease severity except on the sixth day(19). Zarin Far et al. reported that Lactobacillus probiotics did not significantly reduce AAD but did alleviate colitis symptoms(20).

5.1. Conclusion

In summary, this study contributes to the literature by examining the effectiveness of zinc and probiotics in treating AAD in children. The combination of zinc and probiotics may be more effective than either treatment alone. However, further research is needed to provide more definitive conclusions. The findings of the present study revealed that the prevalence of AAD was lower in the probiotic group than in the zinc group. Importantly, however, the disparity between the two groups did not reach statistical significance.

Ethics approval and consent to participate : This study was conducted in accordance with the tenets of the Declaration of Helsinki and was ethically approved by the Ethics Committee of Hormozgan University of Medical Sciences (Approval ID: IR.HUMS.REC.1399.579).

Consent for publication: All authors are satisfied their consent for publication.

Availability of data and material: The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.

Competing interests: The authors had no conflicts of interest to declare in relation to this article..

Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. This article is the result of Resident theses No: 990707.

Authors' contributions: M.B.R. , S.H.T. and M.A. wrote the main manuscript text, M.B.R, R.K collected data, S.H.T. wrote analysis and interpretation and M.B.R, M.A. edited the main manuscript text . All authors reviewed the manuscript.

Acknowledgements: We gratefully acknowledge the dedicated efforts of the investigators, the coordinators, the volunteer patients who participated in this study, and the Clinical Research Development Unit (CRDU) of Bandar Abbas Pediatric Hospital.

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No competing interests reported.

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You are reading this latest preprint version

The Impact of Zinc and Probiotics in Preventing Pediatric Antibiotic-Associated Diarrhea in Southern Iran.

Status:

Version 1

Abstract

Background

Objective:

Patients and methods:

Results:

Conclusions:

1. Introduction

2. Objectives

3. Materials and methods

3,1. Study Design

3,2. Data collection and statistical analysis

3,3. Ethical considerations

4. Results

5. Discussion

5.1. Conclusion

Declarations

References

Additional Declarations

Status:

Version 1