Vaginal treatment with lactic acid gel delays relapses in recurrent urinary tract infections: results from an open, multicentre observational study.


Journal

Archives of gynecology and obstetrics
ISSN: 1432-0711
Titre abrégé: Arch Gynecol Obstet
Pays: Germany
ID NLM: 8710213

Informations de publication

Date de publication:
08 2021
Historique:
received: 24 11 2020
accepted: 17 03 2021
pubmed: 28 3 2021
medline: 29 10 2021
entrez: 27 3 2021
Statut: ppublish

Résumé

The main objective of this open, prospective, multicentre, observational study is to investigate the relapse rate and tolerability of lactic acid gels in adult female patients with recurrent urinary tract infections during routine practice. Data were collected from patients undergoing intermittent short courses of intravaginal treatment with lactic acid gel for prevention of recurrent urinary tract infections. The observation period for individual patients was 4 months, aimed at covering four short courses of intravaginal treatment. Data on UTI relapses, tolerability, handling and satisfaction with the treatment were collected via patient diaries and physician assessments and comprised any adverse events (AEs). In total, 72 patients were treated. During the last 12 months prior to the study, patients had on average 4.0 UTIs. In the 4 months after commencing treatment, 63.5% of patients had no recurrence of UTI symptoms. Overall efficacy was rated by physicians as 'excellent/good' for 96.7% of patients. The patients' overall acceptance of local treatment was high with 94.1% being '(very) satisfied'. Similarly, handling was rated as '(very) easy' by 94.2% of patients. The tolerability was assessed as 'highly tolerable/tolerable' by over 98% of patients and physicians alike. Safety analyses reported six AEs of mild intensity, all of which had resolved by the end of the study. Treatment with lactic acid gel may increase resilience against uropathogens, possibly preventing the need for antibiotic prevention of recurrent urinary tract infections. Treatment was positively assessed by the patients. The physician assessments corroborate these findings. DRKS00016760, 18.02.2019.

Identifiants

pubmed: 33772330
doi: 10.1007/s00404-021-06040-8
pii: 10.1007/s00404-021-06040-8
pmc: PMC8277613
doi:

Substances chimiques

Anti-Bacterial Agents 0
Gels 0
Lactic Acid 33X04XA5AT

Banques de données

DRKS
['DRKS00016760']

Types de publication

Journal Article Multicenter Study Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

409-417

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2021. The Author(s).

Références

Foxman B (2014) Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin N Am 28(1):1–13
doi: 10.1016/j.idc.2013.09.003
Deutsche Gesellschaft für Urologie (DGU), Epidemiologie, Diagnostik, Therapie, Prävention und Management unkomplizierter, bakterieller, ambulant erworbener Harnwegsinfektionen bei erwachsenen Patienten. S-3 Leitlinie Langfassung [AWMF-Register-Nr. 043/044]. Stand: 30.04.2017
O’Brien VP et al (2016) Drug and vaccine development for the treatment and prevention of urinary tract infections. Microbiol Spectr 4(1):589–646. https://doi.org/10.1128/microbiolspec.UTI-0013-2012
doi: 10.1128/microbiolspec.UTI-0013-2012
Wawrysiuk S et al (2019) Prevention and treatment of uncomplicated lower urinary tract infections in the era of increasing antimicrobial resistance—non-antibiotic approaches: a systemic review. Arch Gynecol Obstet 300(4):821–828
pubmed: 31350663 pmcid: 6759629 doi: 10.1007/s00404-019-05256-z
Naber KG et al (2008) Surveillance study in Europe and Brazil on clinical aspects and antimicrobial resistance epidemiology in females with cystitis (ARESC): implications for empiric therapy. Eur Urol 54(5):1164–1178
pubmed: 18511178 doi: 10.1016/j.eururo.2008.05.010
Bonkat G et al (2017) Urological infections. EAU Guidelines London: European Association of Urology, pp 857–920
O’Mahony C et al (2008) Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation. PLoS Pathog 4(8):e1000112
pubmed: 18670628 pmcid: 2474968 doi: 10.1371/journal.ppat.1000112
Smith AL et al (2018) Treatment and prevention of recurrent lower urinary tract infections in women: a rapid review with practice recommendations. J Urol 200(6):1174–1191
pubmed: 29940246 doi: 10.1016/j.juro.2018.04.088
Wagenlehner F et al (2018) Social and economic burden of recurrent urinary tract infections and quality of life: a patient web-based study (GESPRIT). Expert Rev Pharmacoecon Outcomes Res 18(1):107–117
pubmed: 28737469 doi: 10.1080/14737167.2017.1359543
Stapleton AE (2016) The vaginal microbiota and urinary tract infection. Microbiol Spectr 4(6):79–86. https://doi.org/10.1128/microbiolspec.UTI-0025-2016
doi: 10.1128/microbiolspec.UTI-0025-2016
Bauer HW (1998) Epidemiologie, urogenitale infektionen. Springer Verlag
Enzyklopädie, H., Hagers enzyklopädie. Dih-Eti. Vol. 6.
Ejrnaes K (2011) Bacterial characteristics of importance for recurrent urinary tract infections caused by Escherichia coli. Dan Med Bull 58(4):B4187
pubmed: 21466767
Hanson L et al (2016) Probiotics for treatment and prevention of urogenital infections in women: a systematic review. J Midwifery Womens Health 61(3):339–355
pubmed: 27218592 doi: 10.1111/jmwh.12472
Schwenger EM, Tejani AM, Loewen PS (2015) Probiotics for preventing urinary tract infections in adults and children. Cochrane Database Syst Rev 12:73–99. https://doi.org/10.1002/14651858
doi: 10.1002/14651858
Swidsinski A et al (2012) Positive effects of local therapy with a vaginal lactic acid gel on dysuria and E.coli bacteriuria question our current views on recurrent cystitis. Arch Gynecol Obstet 285(6):1619–1625
pubmed: 22218825 doi: 10.1007/s00404-011-2196-z
Instruction for use KadeFungin® Milchsäurekur, September 2018. Available from: https://www.kade.de/media/Produkte/Gebrauchsinformationen/kadefungin-milchsaeurekur-GI-20200427.pdf . Accessed 14 Mar 2021
World Medical Association, Declaration of Helsinki. Ethical principles for medical research involving human subjects. https://www.wma.net/wp-content/uploads/2018/07/DoH-Oct2008.pdf , 2008. Accessed 14 Mar 2021
International Organization for Standardization/Technical Committee 194(ISO/TC194), Clinical investigation of medical devices for human subjects: Good clinical practice. Second edition February 2011 (ISO 14155:2011). Official Journal of the European Union (OJ). 2012/C123/02:2012-04-27
Bundesärztekammer, (Muster-)Berufsordnung für die in Deutschland tätigen Ärztinnen und Ärzte—MBO-Ä 1997—in der Fassung der Beschlüsse des 121. Deutschen Ärztetages 2018 in Erfurt geändert durch Beschluss des Vorstandes der Bundesärztekammer am 14.12.2018
European Commission. Guidelines on Medical Devices—Clinical Investigations: Serious Adverse Event Reporting under Directives 90/385/EEC and 93/42/EEC. MEDDEV 2.7/3 revision 3 (May 2015) Available from: https://ec.europa.eu/docsroom/documents/13053/attachments/1/translations/en/renditions/pdf . Accessed 14 Mar 2021
Hintze J (2011) PASS 11. NCSS, LLC. Kaysville, Utah, USA. https://www.ncss.com . Accessed 14 Mar 2021
Czaja CA et al (2009) Prospective cohort study of microbial and inflammatory events immediately preceding Escherichiacoli recurrent urinary tract infection in women. J Infect Dis 200(4):528–536
pubmed: 19586416 doi: 10.1086/600385
Bruce AW et al (1973) Recurrent urethritis in women. Can Med Assoc J 108(8):973–976
pubmed: 4633489 pmcid: 1941341
Gupta K et al (1998) Inverse association of H
pubmed: 9697725 doi: 10.1086/515635
O’Hanlon DE, Moench TR, Cone RA (2013) Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. PLoS ONE 8(11):e80074
pubmed: 24223212 pmcid: 3819307 doi: 10.1371/journal.pone.0080074
Hudson PL et al (2020) Effect of vaginal lactobacillus species on Escherichiacoli growth. Female Pelvic Med Reconstr Surg 26(2):146–151
pubmed: 31990804 doi: 10.1097/SPV.0000000000000827
Stapleton AE et al (2011) Randomized, placebo-controlled phase 2 trial of a lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clin Infect Dis 52(10):1212–1217
pubmed: 21498386 pmcid: 3079401 doi: 10.1093/cid/cir183
Pfau A, Sacks T (1981) The bacterial flora of the vaginal vestibule, urethra and vagina in premenopausal women with recurrent urinary tract infections. J Urol 126(5):630–634
pubmed: 7029007 doi: 10.1016/S0022-5347(17)54661-3
Tachedjian G et al (2017) The role of lactic acid production by probiotic Lactobacillus species in vaginal health. Res Microbiol 168(9):782–792
pubmed: 28435139 doi: 10.1016/j.resmic.2017.04.001
Alakomi HL et al (2000) Lactic acid permeabilizes Gram-negative bacteria by disrupting the outer membrane. Appl Environ Microbiol 66(5):2001–2005
pubmed: 10788373 pmcid: 101446 doi: 10.1128/AEM.66.5.2001-2005.2000
Boeke AJ et al (1993) Effect of lactic acid suppositories compared with oral metronidazole and placebo in bacterial vaginosis: a randomised clinical trial. Genitourin Med 69(5):388–392
pubmed: 8244360 pmcid: 1195125
Andersch B et al (1986) Treatment of bacterial vaginosis with an acid cream: a comparison between the effect of lactate-gel and metronidazole. Gynecol Obstet Invest 21(1):19–25
pubmed: 3485071 doi: 10.1159/000298923
Decena DCD et al (2006) Metronidazole with lactacyd vaginal gel in bacterial vaginosis. J Obstet Gynaecol Res 32(2):243–251
pubmed: 16594932 doi: 10.1111/j.1447-0756.2006.00383.x
Andersch B et al (1990) Bacterial vaginosis and the effect of intermittent prophylactic treatment with an acid lactate gel. Gynecol Obstet Invest 30(2):114–119
pubmed: 2245947 doi: 10.1159/000293230
Plummer EL et al (2021) Lactic acid containing products for bacterial vaginosis and their impact on the vaginal microbiota: a systematic review. PLoS ONE. https://doi.org/10.1371/journal.pone.0246953
pubmed: 33571286 pmcid: 7877752 doi: 10.1371/journal.pone.0246953
Tidbury FD et al (2020) Non-antibiotic treatment of bacterial vaginosis—a systematic review. Arch Gynecol Obstet 303:1–9
Barrons R, Tassone D (2008) Use of Lactobacillus probiotics for bacterial genitourinary infections in women: a review. Clin Ther 30(3):453–468
pubmed: 18405785 doi: 10.1016/j.clinthera.2008.03.013
Falagas ME et al (2006) Probiotics for prevention of recurrent urinary tract infections in women: a review of the evidence from microbiological and clinical studies. Drugs 66(9):1253–1261
pubmed: 16827601 doi: 10.2165/00003495-200666090-00007
Ng QX et al (2018) Use of Lactobacillus spp to prevent recurrent urinary tract infections in females. Med Hypotheses 114(9):49–54
pubmed: 29602464 doi: 10.1016/j.mehy.2018.03.001
Reid G, Bruce AW (2006) Probiotics to prevent urinary tract infections: the rationale and evidence. World J Urol 24(1):28–32
pubmed: 16389539 doi: 10.1007/s00345-005-0043-1
Borges S, Silva J, Teixeira P (2014) The role of lactobacilli and probiotics in maintaining vaginal health. Arch Gynecol Obstet 289(3):479–489
pubmed: 24170161 doi: 10.1007/s00404-013-3064-9
Heinemann C et al (2000) Purification and characterization of a surface-binding protein from Lactobacillus fermentum RC-14 that inhibits adhesion of Enterococcus faecalis 1131. FEMS Microbiol Lett 190(1):177–180
pubmed: 10981710 doi: 10.1111/j.1574-6968.2000.tb09282.x
Velraeds MM et al (1996) Inhibition of initial adhesion of uropathogenic Enterococcus faecalis by biosurfactants from Lactobacillus isolates. Appl Environ Microbiol 62(6):1958–1963
pubmed: 8787394 pmcid: 167974 doi: 10.1128/aem.62.6.1958-1963.1996
Trivedi D et al (2013) Partial purification and characterization of a bacteriocin dt24 produced by probiotic vaginal Lactobacillus brevis dt24 and determination of its anti-uropathogenic Escherichiacoli potential. Probiotics Antimicrob Proteins 5(2):142–151
pubmed: 26782739 doi: 10.1007/s12602-013-9132-4
Leccese Terraf MC et al (2017) In vitro effect of vaginal Lactobacilli on the growth and adhesion abilities of uropathogenic Escherichiacoli. Arch Microbiol 199(5):767–774
pubmed: 28280842 doi: 10.1007/s00203-016-1336-z
Juárez Tomás MS et al (2003) Growth and lactic acid production by vaginal Lactobacillusacidophilus CRL 1259, and inhibition of uropathogenic Escherichiacoli. J Med Microbiol 52(12):1117–1124
pubmed: 14614071 doi: 10.1099/jmm.0.05155-0
Baerheim A, Larsen E, Digranes A (1994) Vaginal application of lactobacilli in the prophylaxis of recurrent lower urinary tract infection in women. Scand J Prim Health Care 12(4):239–243
pubmed: 7863140 doi: 10.3109/02813439409029247
Czaja CA et al (2007) Phase I trial of a Lactobacillus crispatus vaginal suppository for prevention of recurrent urinary tract infection in women. Infect Dis Obstet Gynecol. https://doi.org/10.1155/2007/35387
pubmed: 18288237 pmcid: 2216064 doi: 10.1155/2007/35387
Kontiokari T et al (2001) Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ 322(7302):1571–1573
pubmed: 11431298 pmcid: 33514 doi: 10.1136/bmj.322.7302.1571
Reid G et al (2003) Oral use of Lactobacillus rhamnosus GR-1 and Lfermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol Med Microbiol 35(2):131–134
pubmed: 12628548 doi: 10.1016/S0928-8244(02)00465-0
Reid G, Bruce AW, Taylor M (1992) Influence of three-day antimicrobial therapy and Lactobacillus vaginal suppositories on recurrence of urinary tract infections. Clin Ther 14(1):11–16
pubmed: 1576619
Beerepoot MA et al (2012) Lactobacilli vs antibiotics to prevent urinary tract infections: a randomized, double-blind, noninferiority trial in postmenopausal women. Arch Intern Med 172(9):704–712
pubmed: 22782199 doi: 10.1001/archinternmed.2012.777

Auteurs

Ruth Diebold (R)

Dr. Kade Pharmazeutische Fabrik GmbH, Berlin, Germany. ruth.diebold@kade.de.

Bettina Schopf (B)

Pharmalog Institut für klinische Forschung GmbH, Ismaning, Germany.

Holger Stammer (H)

Pharmalog Institut für klinische Forschung GmbH, Ismaning, Germany.

Werner Mendling (W)

German Centre for Infections in Obstetrics and Gynecology, Wuppertal, Germany.

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