Lactobacillus rhamnosus PL1 and Lactobacillus plantarum PM1 versus placebo as a prophylaxis for recurrence urinary tract infections in children: a study protocol for a randomised controlled trial

Maria Daniel, Hanna Szymanik-Grzelak, Agnieszka Turczyn, Małgorzata Pańczyk-Tomaszewska, Maria Daniel, Hanna Szymanik-Grzelak, Agnieszka Turczyn, Małgorzata Pańczyk-Tomaszewska

Abstract

Background: Urinary tract infections (UTIs) are one of the most common bacterial infections in children. In children < 7 years of age, the prevalence of one episode of symptomatic UTI has been estimated at 3-7% in girls and 1-2% in boys, whereas 8-30% of them will have one or more episodes of UTI. The use of some probiotics appears to reduce the risk of recurrence of UTIs. Since the effects of probiotics are strain-specific, the efficacy and safety of each strain has to be assessed. The main aim of this study is to determine whether probiotics (containing Lactobacillus rhamnosus PL1 and Lactobacillus plantarum PM1) therapy are effective in preventing UTI in children compared to placebo.

Method: A superiority, double-blind, randomised, controlled trial is being conducted. One hundred and six patients aged 3 to 18 years with recurrent UTIs in last year (defined as: ≥ 2 episodes of UTI with acute pyelonephritis/upper UTI; or 1 episode of UTI with acute pyelonephritis and ≥ 1 episodes of UTI with cystitis/lower UTI; or ≥ 3 episodes of UTI with cystitis/lower UTI) or children with ≥ 1 infection in the upper urinary tract and ≥ 1 of recurrent UTIs risk factors (congenital anomalies of the kidney and urinary tract, constipation, bladder dysfunction, myelomeningocele, sexual activity in girls) will be randomly assigned to receive a 90-day prophylaxis arm (probiotic containing L. rhamnosus PL1 and L. plantarum PM1) or a 90-day placebo arm. The primary outcome measure will be the frequency of recurrence of UTI during the intervention and in the period 9 months after the intervention.

Discussion: The findings of this randomised controlled trial (RCT), whether positive or negative, will contribute to the formulation of further recommendations on prevention of recurrent UTIs in children.

Trial registration number: NCT03462160, date of trial registration 12th March 2018.

Keywords: Children; Lactobacillus plantarum PM1; Lactobacillus rhamnosus PL1; Probiotics; Prophylaxis; RCT; Recurrent UTI.

Conflict of interest statement

The Miralex company had no input into the design of the trial. The authors have no competing financial or no-financial interests.

References

    1. Simões Silva AC, Oliviera EA. Update on the approach of urinary tract infection in childhood. J Pediatr (Rio J) 2015;91(6 Suppl 1):S2–S10. doi: 10.1016/j.jped.2015.05.003.
    1. Hellström A, Hanson E, Hansson S, Hjälmås K, Jodal U. Association between urinary symptoms at 7 years old and previous urinary tract infection. Arch Dis Child. 1991;66:232–234. doi: 10.1136/adc.66.2.232.
    1. Conway PH, Cnaan A, Zaoutis T, Brandon VH, Grundmeier RW, Keren R. Recurrent urinary tract infections in children risk factors and association with prophylactic antimicrobials. JAMA. 2007;298(2):179–186. doi: 10.1001/jama.298.2.179.
    1. National Institute for Health and Care Excellence. Urinary tract infections in children and young people. 2013. .
    1. Stein R, Dogan HS, Hoebeke P, Kočvara R, Nijman RJ, Radmayr C, Tekgül S, European Association of Urology. European Society for Pediatric Urology Urinary tract infections in children: EAU/ESPU guidelines. Eur Urol. 2015;67(3):546–558. doi: 10.1016/j.eururo.2014.11.007.
    1. Żurowska A, Wasilewska A, Jung A, Kiliś-Pstrusińska K, Pańczyk-Tomaszewska M, Sikora P, Tkaczyk M, Zagożdżon I. Zalecenia Polskiego Towarzystwa Nefrologii Dziecięcej dotyczące postępowania z dzieckiem z zakażeniem układu moczowego. Forum Medycyny Rodzinnej. 2016;10(4):159–178.
    1. Subcommittee on Urinary Tract Infection Reaffirmation of AAP clinical practice guideline: the diagnosis and management of the initial urinary tract infection in febrile infants and young children 2–24 months of age. Pediatrics. 2016;128:595–610. doi: 10.1542/peds.2011-1330.
    1. Garin EH, Olavarria F, Garcia Nieto V, Valenciano B, Campos A, Young L. Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. Pediatrics. 2006;117(3):626–632. doi: 10.1542/peds.2005-1362.
    1. Amdekar S, Singh V, Singh DD. Probiotic therapy: immunomodulating approach toward urinary tract infection. Curr Microbiol. 2011;63(5):484–490. doi: 10.1007/s00284-011-0006-2.
    1. Lee SJ, Cha J, Lee JW. Probiotics prophylaxis in pyelonephritis infants with normal urinary tracts. World J Pediatr. 2016;12(4):425–429. doi: 10.1007/s12519-016-0013-2.
    1. Mohseni MJ, Aryan Z, Emamzadeh-Fard S, Paydary K, Mofid V, Joudaki H, Kajbafzadeh AM. Combination of probiotics and antibiotics in the prevention of recurrent urinary tract infection in children. Iran J Pediatr. 2013;23(4):430–438.
    1. Tewary K, Narchi H. Recurrent urinary tract infections in children: preventive interventions other than prophylactic antibiotics. World J Methodol. 2015;5(2):13–19. doi: 10.5662/wjm.v5.i2.13.
    1. Lee SJ, Shim YH, Cho SJ, Lee JW. Probiotics prophylaxis in children with persistent primary vesicoureteral reflux. Pediatr Nephrol. 2007;22(9):1315–1320. doi: 10.1007/s00467-007-0507-1.
    1. Lee SJ, Lee JW. Probiotics prophylaxis in infants with primary vesicoureteral reflux. Pediatr Nephrol. 2015;30(4):609–613. doi: 10.1007/s00467-014-2988-z.
    1. Reid G, Bruce AW. Probiotics to prevent urinary tract infections: the rationale and evidence. World J Urol. 2006;24(1):28–32. doi: 10.1007/s00345-005-0043-1.
    1. Grin PM, Kowalewska PM, Alhazzan W, Fox-Robichaud AE. Lactobacillus for preventing recurrent urinary tract infections in women: meta-analysis. Can J Urol. 2013;20(1):6607–6614.
    1. Ng QX, Peters C, Venkatanarayanan N, Goh YY, Ho CYX, Yeo WS. Use of Lactobacillus spp. to prevent recurrent urinary tract infections in females. Med Hypotheses. 2018;114:49–54. doi: 10.1016/j.mehy.2018.03.001.
    1. Schwenger EM, Tejani AM, Loewen PS. Probiotics for preventing urinary tract infections in adults and children. Cochrane Database Syst Rev. 2015 doi: 10.1002/14651858.CD008772.pub2.
    1. 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):581–591. doi: 10.1016/j.jpurol.2017.08.018.
    1. Gupta V, Nag D, Garg P. Recurrent urinary tract infections in women: How promising is the use of probiotics? Indian J Med Microbiol. 2017;35(3):347–354. doi: 10.4103/ijmm.IJMM_16_292.
    1. Rodríguez JM. The origin of human milk bacteria: is there a bacterial entero-mammary pathway during late pregnancy and lactation? Adv Nutr. 2014;5:779–784. doi: 10.3945/an.114.007229.
    1. Bouchard DS, Seridan B, Saraoui T, Rault L, Germon P, Gonzalez-Moreno C, Nader-Macias FME, Baud D, François P, Chuat V, Chain F, Langella P, Nicoli J, Loir YL, Even S. Lactic acid bacteria isolated from bovine mammary microbiota: potential allies against bovine mastitis. PLoS ONE. 2015;10(12):e0144831. doi: 10.1371/journal.pone.0144831.
    1. Cerbo A, Palmieri B, Aponte M, Morales-Medina JC, Iannitti T. Mechanisms and therapeutic effectiveness of lactobacilli. J Clin Pathol. 2016;69:187–203. doi: 10.1136/jclinpath-2015-202976.
    1. Manzoor A, Ul-Haq I, Baig S, Qazi JI, Seratlic S. Efficacy of locally isolated lactic acid bacteria against antibiotic-resistant uropathogens. Jundishapur J Microbiol. 2016;9(1):e18952. doi: 10.5812/jjm.18952.
    1. Salvetti E, O'Toole PW. The genomic basis of lactobacilli as health-promoting organisms. Microbiol Spectr. 2017 doi: 10.1128/microbiolspec.BAD-0011-2016.
    1. Salah RB, Trabelsi I, Hamden K, Chouayekh H, Bejar S. Lactobacillus plantarum TN8 exhibits protective effects on lipid, hepatic and renal profiles in obese rat. Anaerobe. 2013;23:55–61. doi: 10.1016/j.anaerobe.2013.07.003.
    1. Sadeghi-bojd S, Naghshizadian R, Mazaheri M, Ghane Sharbaf F, Assadi F. Efficacy of probiotic prophylaxis after the first febrile urinary tract infection in children with normal urinary tracts. J Pediatric Infect Dis Soc. 2019 doi: 10.1093/jpids/piz025.
    1. Beerepoot MA, ter Riet G, Nys S, van der Wal WM, de Borgie CA, de Reijke TM, et al. Lactobacilli versus antibiotics to prevent urinary tract infections: a randomized, double-blind, noninferiority trial in postmenopausal women. Arch Intern Med. 2012;172:704–712. doi: 10.1001/archinternmed.2012.777.
    1. Urinary tract infection (recurrent): antimicrobial prescribing NICE guideline. 2018. .

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner