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Use of Probiotics for Prophylaxis of Urinary Tract Infection Recurrence in Children; A Randomized Controlled Trial

Khedijeh Ghassemi

1

, Sahar Montazeri

2

*, Mohammad Saber Moghateli

3

, Nader Shakibazad

4

, Mohammadreza Fariborzi

5

1 Associate professor of pediatric nephrology, Bushehr university of medical sciences, Bushehr, Iran.

2 Assistant professor of pathology, department of pathology, Razi hospital, Tehran university of medical sciences, Tehran, Iran.

3 General practitioner, Bushehr university of medical sciences, Bushehr, Iran.

4 Department of pediatric hematology and oncology, Bushehr university of medical sciences, Bushehr, Iran.

5 Department of pediatric gastroenterology, Bushehr university of medical sciences, Bushehr, Iran.

*Corresponding Author

ABSTRACT

Introduction; Urinary tract infection (UTI) is a prevalent bacterial infection which can cause many complications such as cystitis, abscess formation, fistula, bacteremia, sepsis, pyelonephritis and kidney dysfunction if not treated appropriately.

Probiotics have been proposed to be used as an alternative option to prevent recurrence of urinary tract infection with controversial results. Therefore, we decided to examine the potential of probiotics to prevent recurrence of urinary tract infection in children.

Methods and Materials; This was a randomized controlled trial. Ninety-four children (1 to 12 years old) were randomly divided into two groups of probiotics and placebo. All patients received a routine antibiotic regimen for UTI. Children in the probiotics group also received a probiotic and the placebo group received a placebo after antibiotic therapy. Children were followed up for six months for UTI recurrence. Regression was used to analyze the effect of probiotics for recurrent UTI.

Data entered SPSS and analyzed.

Results; Ninety-four children entered the study, 47 in each group. The mean age of children in the probiotic and placebo groups were 4.7 ± 2.56 and 3.4 ± 2.34 years, respectively. There were statistically significant differences between the two groups regarding age (P value = 0.009) and body weight (P value = 0.018). In total, 39 of 47 patients (83%) in the placebo group and 44 of 47 patients (93.6%) in the probiotic group did not experience a recurrence. A logistic regression was performed to investigate the relationship between probiotic use and recurrence with the control of age and weight variables.

The results showed that probiotics use had a significant preventive effect on disease recurrence (P value= 0.04). The probability of recurrence in patients who did not receive probiotics was more than five times higher than those who received it.

Discussion; Probiotic use was effective to reduce the probability of UTI recurrence in children. However, more studies with combination of probiotics and antibiotics are recommended to yield clearer results regarding probiotics prophylactic effect in urinary tract infection.

Keywords

Urinary Tract Infection; Probiotics; Recurrence; Complications

Introduction

Urinary tract infection (UTI) is an important and common disease among children (1), which can lead to significant complications such as cystitis (2), abscess formation (3), pyelonephritis (4), bacteremia (5), fistula (2), sepsis (6, 7) and renal dysfunction (8). Mortality rates from urinary tract infections have been reported to be 1% in boys and 3%

in girls due to urosepsis (2). The most common disease-causing microorganism is Escherichia coli (54-80% of cases) followed by Klebsiella, Proteus, Enterobacter and Citrobacter in the gram-negative group. Causative gram-positive pathogens include Staphylococcus saprophyticus, Enterococcus and rarely Staphylococcus aureus (9, 10). Renal scars (11), hypertension (12), chronic kidney disease or end stage renal disease could occur following UTI (13).

Pediatric urinary tract infections impose more than 180 million USD annually on the health care system and leads to more than 5.1 million doctor visits a year. Therefore, proper diagnosis and treatment is of great importance to prevent long-term complications (14, 15).

Administration of low-dose of antibiotics for recurrent UTI is an acceptable practice. Despite the fact, long-term antibiotic use would increase bacterial resistance or lead to adverse effects (16). A promising alternative is to use probiotics to prevent recurrence. The main mechanisms of benefit of probiotics include nutritional competition with

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other bacteria, production of bacteriocin as well as lactic acid and consequently lowering the pH of the environment, which in turn prevents the growth of other bacteria (17, 18). There are some controversial reports regarding the effect of probiotics in the prevention of UTI. Therefore, we tried to assess the effect of probiotics to prevent the recurrence of urinary tract infection in children with first time simple UTI.

Methods and Materials

This was a randomized controlled trial. The prophylactic effect of probiotics compared with placebo was investigated in children aged 1 to 12 years with the first time simple urinary tract infection regarding further recurrence. Patients were hospitalized or referred to the emergency department and pediatric ward of Shohadeye- Khalij-Fars Hospital, Bushehr from 2019 to 2020.

Randomization was performed using R statistical software by block randomization. Patients were randomly divided into two groups of probiotics and placebo. Then, during 6 months, patients in both groups were followed regarding the recurrence of urinary tract infection by checking a urine culture. Children information were recorded in a researcher made checklist including demographic data, physical examination, laboratory findings (BUN, Cr, CBC) and imaging results (Ultrasonography).

Patients in probiotic group received a Prokid capsule daily containing 109 colony-forming unit (CFU) (0.5g)/10 mL of Lactobacillus and 0.5 mL (25 mg)/kg Bifidobacterium strains with maximum daily dosage of 20 ml. The capsule was dissolved in water and given to children before sleep. However, the placebo group received the same amount of water every night. All children received a standard treatment for urinary tract infection as well.

Ethical consideration

The study protocol was explained to all participants’ legal guardians before enrolment. A written informed consent was also obtained. All participants were free to leave the study at any time without affecting their routine care. All the steps of study were performed according to Helsinki Declaration. The study protocol was approved by the ethics committee of Bushehr University of Medical Sciences (code; IR. BPUMS. REC. 1398.134). the study protocol was also registered in Iranian Registry for Clinical Trials (IRCT). Patient anonymity was ensured and all data were kept confidential.

Statistical analysis

Data entered SPSS version 22 (SPSS. Inc. Chicago, Il, The USA) and analyzed. The normality of data was determined using the Kolmogorov-Smirnov test. Descriptive data were reported using frequency and Mean ± SD. To compare the recurrence rate of urinary tract infections between the two probiotics and placebo groups, Fisher exact test was used. Besides, logistic regression model was used to investigate the effect of probiotics on urinary tract recurrence by controlling other confounding factors. P value below 0.05 was considered as statistically significant.

Results

Ninety-four children entered the study, 47 in each group. The mean age of children in the probiotic and placebo groups were 4.7 ± 2.56 and 3.4 ± 2.34 years, respectively. From 47 children in the probiotic group, 4 were males and 43 females, also, in the placebo group, 5 were males and 42 females. Gender did not differ between the two groups significantly using Fisher exact test. According to Kolmogorov-Smirnov test, age and weight variables did not follow the normal distribution; therefore, Mann-Whitney test was used to compare the variables between probiotics and placebo groups. There were statistically significant differences between the two groups regarding age (P value = 0.009) and body weight (P value = 0.018).

In overall, 39 patients (83%) in the placebo group and 44 patients (93.6%) in the probiotics group did not experience a recurrence in six-month follow-up. Due to the significance of confounding variables such as age and weight between the two groups, logistic regression was used to investigate the relationship between probiotic use and UTI recurrence with the control of age and weight. The results showed that probiotic use had a significant effect to reduce

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the recurrence (P value= 0.04). In fact, the probability of recurrence in patients who did not receive probiotics was five times more than those who received probiotics (Table 1).

Table 1. Regression analysis to control age and weight variable The

regression coefficient

Standard error

Odds ratio 95% confidence interval P value Upper limit Lower limit

Age 0.024 0.316 0.977 1.814 0.526 0.940

Weight 0.137 0.126 1.147 1.469 0.895 0.408

Placebo group

1.639 0.799 5.151 24.363 1.077 0.04

In addition, all the three patients with recurrence in the probiotics group occurred after two months by the pathogens the same as the primary infection (Two cases E. coli and one Citrobacter). All the three children were females aged 6 to 10 years and had the same antibiogram as the primary UTI. On the other hand, in cases of recurrence in the placebo group (8 patients), the recurrence occurred from one to three months after the initial infection, and the pathogens were the same microbes as the primary infection except for two. In one, the primary pathogen was Klebsiella and E. coli in the recurrence; In another, the primary pathogen was Proteus and Pseudomonas in the recurrence. Of eight recurrences in this group, seven were girls and one was a boy in the age range of 1 to 6 years. There was no significant difference in the primary and recurrence antibiogram in the placebo group, however, some cases of antibiotic resistance were reported.

Discussion

Urinary tract infection is an important and common disease among children and if not treated appropriately, may cause significant complications. Therefore, the need to treat UTI and prevent further recurrence is of outmost importance. In this study, the effect of probiotics as a prophylaxis was assessed in children with simple urinary tract infection regarding further recurrence. Logistic regression model showed that probiotic consumption had a significant association with the prevention of urinary tract infections recurrence. In patients who did not receive probiotics, the probability of recurrence was five times higher than those who received it. Despite the fact, there are controversial results in different studies and the prophylactic role of probiotics cannot be stated with certainty.

For instance, a systemic review was published in 2015 by Schwenger EM et al. regarding the prophylactic role of probiotics in the prevention of urinary tract infections in adults and children. They included a total of 735 patients from nine studies. They finally concluded that no substantial benefit was found for probiotics compared with placebo or no treatment, despite the fact, probiotics efficacy cannot be ignored as data were few, and extracted from studies with low sample size and a weak methodological status. Moreover, there were few data regarding probable adverse effects of probiotics in these trials. They failed to indicate a positive effect of probiotics to prevent UTI recurrence (19). Their conclusion is against our findings, however, they preferred not to come to a definite conclusion regarding the effect of probiotics to reduce the risk of UTI recurrence and suggested to perform more delicate clinical trials with better design. They believed that there is lack of RCTs in this regard and there is still a long way to find an answer the question whether probiotics are effective in UIT recurrences.

On the other hand, Ilke Beyitler et al. in a systematic review indicated that the use of probiotics should be considered valuable in the prevention of urinary tract infections in children. They nominated several beneficial mechanisms for probiotics including nutrients and receptor competition, direct killing, immunomodulation and making inhibitory factors by probiotics for other pathogens. Lactobacillus sp., Bifidobacterium were among the most common probiotics studied in the literature in this review, which were used in our study as well (20). Their result supports our findings. Moreover, in another study, 85 children were followed for three years, and probiotics were considered as a useful factor in the prevention of urinary tract infections (21). Furthermore, Mohammad Javad Mohseni et al. In 2013 concluded that combination of antibiotics and probiotics in the prevention of recurrence of febrile urinary tract infections in children are more effective than antibiotics alone (17).

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However, a meta-analysis conducted by Mostafa Hosseini et al. In 2017 on the prophylactic effect of probiotics on recurrence of urinary tract infections in children, concluded that probiotics have little beneficial effect in preventing recurrence of urinary tract infections; However, in combination with antibiotics, they can play a minor role as a prophylactic agent (22). The results of this study are not in line with our findings.

Despite all these controversial findings there are several investigations regarding the beneficial biological properties of probiotics. It is reported that probiotics prevent other pathogens from adhesions to cells and penetrate the defense mechanism (23). Pathogens have a challenge to find nutrition in the presence of probiotics. Probiotics also help in the production of different cytokines and IgA, hydrogen peroxide (24), bacteriocins (25), acetic acid and etc. (26-28).

These effects have been probably effective in lowering the risk of UTI recurrence in our patients.

Despite the fact, lactobacilli have been shown to produce bacteriocin and prevent pathogens to adhere to the epithelium of the urinary tract thus inhibiting UTI recurrence as observed in our investigation. There are several reports showing the benefits of lactobacilli in prevention of urinary tract infection with different mechanisms (29- 31).

Conclusion

Based on the above mentioned characteristics of probiotics and comparing the results with some similar studies, it can be said that probiotics are useful in preventing the recurrence of urinary tract infections in children; However, a definite statement requires more extensive studies. Larger sample size trials by controlling confounding factors are suggested to yield more accurate results.

Funding and support

This study was supported by Bushehr University of Medical Sciences as part of a thesis to obtain medical final diploma.

Disclosure None

Conflict of interest

There was no conflict of interest to indicate.

References

[1] Leung AK, Wong AH, Leung AA, Hon KL. Urinary tract infection in children. Recent patents on inflammation & allergy drug discovery. 2019;13(1):2-18.

[2] Schwenger EM, Tejani AM, Loewen PS. Probiotics for preventing urinary tract infections in adults and children. Cochrane Database of Systematic Reviews. 2015(12).

[3] Olson PD, McLellan LK, Hreha TN, Liu A, Briden KE, Hruska KA, et al. Androgen exposure potentiates formation of intratubular communities and renal abscesses by Escherichia coli. Kidney international.

2018;94(3):502-13.

[4] Morello W, La Scola C, Alberici I, Montini G. Acute pyelonephritis in children. Pediatric Nephrology.

2016;31(8):1253-65.

[5] Honkinen O, Jahnukainen T, Mertsola J, Eskola J, Ruuskanen O. Bacteremic urinary tract infection in children. The Pediatric infectious disease journal. 2000;19(7):630-4.

[6] Dani C, Biadaioli R, Bertini G, Martelli E, Rubaltelli FF. Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. Neonatology. 2002;82(2):103-8.

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[7] Tehrani FHE, Moradi M, Ghorbani N. Bacterial etiology and antibiotic resistance patterns in neonatal sepsis in Tehran during 2006-2014. Iranian journal of pathology. 2017;12(4):356.

[8] Nordenström J, Sjöström S, Sillén U, Sixt R, Brandström P. The Swedish infant high-grade reflux trial: UTI and renal damage. Journal of pediatric urology. 2017;13(2):146-54.

[9] Chen P-C, Chang L-Y, Lu C-Y, Shao P-L, Tsai I-J, Tsau Y-K, et al. Drug susceptibility and treatment response of common urinary tract infection pathogens in children. Journal of Microbiology, Immunology and Infection. 2014;47(6):478-83.

[10] Karimpour HA, Mohamadi S. The study of frequency and antibiotic resistance pattern of urinary tract infection pathogens in children of Kermanshah in 2015. Razi Journal of Medical Sciences.

2017;24(155):20-7.

[11] Park YS. Renal scar formation after urinary tract infection in children. Korean journal of pediatrics.

2012;55(10):367.

[12] Kapur G, Baracco R. Evaluation of hypertension in children. Current hypertension reports. 2013;15(5):433- 43.

[13] Isert S, Müller D, Thumfart J. Factors associated with the development of chronic kidney disease in children with congenital anomalies of the kidney and urinary tract. Frontiers in Pediatrics. 2020;8:298.

[14] Behrman RE, Vaughan III VC. Nelson textbook of pediatrics: WB Saunders company; 1983.

[15] Schmidt B, Copp HL. Work-up of pediatric urinary tract infection. Urologic Clinics. 2015;42(4):519-26.

[16] Craig JC, Simpson JM, Williams GJ, Lowe A, Reynolds GJ, McTaggart SJ, et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. New England Journal of Medicine. 2009;361(18):1748-59.

[17] Mohseni M-J, Aryan Z, Emamzadeh-Fard S, Paydary K, Mofid V, Joudaki H, et al. Combination of probiotics and antibiotics in the prevention of recurrent urinary tract infection in children. Iranian journal of pediatrics. 2013;23(4):430.

[18] Hosseini M, Yousefifard M, Ataei N, Oraii A, Razaz JM, Izadi A. The efficacy of probiotics in prevention of urinary tract infection in children: A systematic review and meta-analysis. Journal of pediatric urology.

2017;13(6):581-91.

[19] Schwenger EM, Tejani AM, Loewen PS. Probiotics for preventing urinary tract infections in adults and children. Cochrane Database Syst Rev. 2015(12):Cd008772.

[20] Beyitler I, Kavukcu S. Probiotics for prophylaxis and treatment of urinary tract infections in children.

Iranian Journal of Pediatrics. 2017;27(2).

[21] Sihra N, Goodman A, Zakri R, Sahai A, Malde S. Nonantibiotic prevention and management of recurrent urinary tract infection. Nature Reviews Urology. 2018;15(12):750-76.

[22] Hosseini M, Yousefifard M, Ataei N, Oraii A, Mirzay Razaz J, Izadi A. The efficacy of probiotics in prevention of urinary tract infection in children: A systematic review and meta-analysis. J Pediatr Urol.

2017;13(6):581-91.

[23] Tuo Y, Song X, Song Y, Liu W, Tang Y, Gao Y, et al. Screening probiotics from Lactobacillus strains according to their abilities to inhibit pathogen adhesion and induction of pro-inflammatory cytokine IL-8.

Journal of dairy science. 2018;101(6):4822-9.

[24] Seth A, Yan F, Polk DB, Rao R. Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC-and MAP kinase-dependent mechanism. American Journal of Physiology- Gastrointestinal and Liver Physiology. 2008;294(4):G1060-G9.

[25] Dobson A, Cotter PD, Ross RP, Hill C. Bacteriocin production: a probiotic trait? Applied and environmental microbiology. 2012;78(1):1-6.

[26] Galdeano CM, Cazorla SI, Dumit JML, Vélez E, Perdigón G. Beneficial effects of probiotic consumption on the immune system. Annals of Nutrition and Metabolism. 2019;74(2):115-24.

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[27] Milajerdi A, Mousavi SM, Sadeghi A, Salari-Moghaddam A, Parohan M, Larijani B, et al. The effect of probiotics on inflammatory biomarkers: a meta-analysis of randomized clinical trials. European journal of nutrition. 2020;59(2):633-49.

[28] Nomoto K. Prevention of infections by probiotics. Journal of bioscience and bioengineering.

2005;100(6):583-92.

[29] Ng QX, Peters C, Venkatanarayanan N, Goh YY, Ho CYX, Yeo W-S. Use of Lactobacillus spp. to prevent recurrent urinary tract infections in females. Medical hypotheses. 2018;114:49-54.

[30] Kim J-M, Park Y-J. Lactobacillus and urine microbiome in association with urinary tract infections and bacterial vaginosis. Urogenital Tract Infection. 2018;13(1):7-13.

[31] Falah F, Vasiee A, Behbahani BA, Yazdi FT, Moradi S, Mortazavi SA, et al. Evaluation of adherence and anti-infective properties of probiotic Lactobacillus fermentum strain 4-17 against Escherichia coli causing urinary tract infection in humans. Microbial pathogenesis. 2019;131:246-53.

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