Risk-factors for Multidrug-resistant Bacteria Colonization Among Patients at High Risk of STIs (BMR-IST)

• ClinicalTrials.gov Identifier: NCT03767374
• Recruitment Status: Unknown
• First Posted: December 6, 2018
• Last Update Posted: December 9, 2019
• Sponsor: Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
• Collaborator: ANRS, Emerging Infectious Diseases
• Information provided by (Responsible Party): Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba

Study Description

Brief Summary:

The aim of this study is to identify risk factors and prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria colonization among patients at high risk of STIs

Condition or disease	Intervention/treatment
Bacterial Infections; HIV Infections	Procedure: Inguinal swab sample; Procedure: Anal swab sample; Procedure: Fecal sample; Other: Risk factor assessment

Detailed Description:

The spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria have become a worldwide public health concern. Infection with MDR/XDR bacteria is associated with increased morbidity, increased risk of therapeutic failure and healthcare costs. The largest burden is from extended-spectrum betalactamase-producing enterobacteriaceae (ESBL) and carbapenem-resistant enterobacteriaceae (CRE).

The World Health Organization (WHO) has considered the epidemic of MDR/XDR bacteria as a major health concern and has registered these bacteria in the "priory pathogens list." This list includes pathogens for which new antibiotics are urgently needed. Moreover, in their recent report on ESBL, the French National Authorities of Health (HAS) has recommended that additional studies be conducted to improve knowledge about colonization risk factors.

Some risk factors have been already identified: antibiotic intake and travel to countries with high MCR/XDR bacteria prevalence; however, many others are poorly identified. Patients visiting the CeGIDD (free information, screening and diagnosis center for sexually transmitted infections) and those receiving pre-exposure prophylaxis (PrEP) to prevent HIV infection are more exposed to STIs (including methicillin-resistant staphylococcus aureus, MRSA) and receive antibiotics for STI treatment. Moreover, an increase of STIs has been recently observed in men who have sex with men and in patients receiving PrEP. As antibiotic use is likely considerably increased in this population, we anticipate a high proportion with MDR/XDR colonization.

The objective of the "BMR-IST" study is to identify risk-factors (i.e. sexual behaviors, HIV status, antiretroviral PrEP, STIs, antibiotic use and travel to epidemic countries) of MDR/XDR bacteria colonization among patients at high risk of acquiring STIs and to determine the prevalence of MDR colonization in the studied population.

Study Design

• Study Type: Observational
• Actual Enrollment: 2186 participants
• Observational Model: Cohort
• Time Perspective: Cross-Sectional
• Official Title: Risk-factors for Multidrug-resistant (MDR) and Extensively Drug-resistant (XDR) Bacteria Colonization Among Patients at High Risk of STIs
• Actual Study Start Date: May 11, 2018
• Actual Primary Completion Date: June 30, 2019
• Estimated Study Completion Date: December 31, 2019

Groups and Cohorts

Group/Cohort	Intervention/treatment
Main study group (HIV-negative); 2000 HIV-negative individuals seeking care at the STI clinic of Saint-Antoine Hospital; Inguinal swab sample; Anal swab sample; Fecal sample; Risk factor assessment	Procedure: Inguinal swab sample; Inguinal samples using swab at cross-sectional visit; Other Name: ESwab; Procedure: Anal swab sample; Anal samples using swab at cross-sectional visit and at 6-month visit (for those with ESBL and/or CRE colonization); Other Name: ESwab; Procedure: Fecal sample; Fecal sample at cross-sectional visit and at 6-month visit (for those with ESBL and/or CRE colonization); Other: Risk factor assessment; Patients will be asked questions on risk factors associated with MDR/XDR colonization at cross-sectional visit and at 6-month visit (for those with ESBL and/or CRE colonization
Exposure-matched group (HIV-positive); 500 HIV-positive men who have sex with men from the Infectious Diseases Unit of Saint- Antoine Hospital. These individuals will be compared to 500 HIV-negative MSM from the main study group, matching on age (+/-5 years).; Inguinal swab sample; Anal swab sample; Fecal sample; Risk factor assessment	Procedure: Inguinal swab sample; Inguinal samples using swab at cross-sectional visit; Other Name: ESwab; Procedure: Anal swab sample; Anal samples using swab at cross-sectional visit and at 6-month visit (for those with ESBL and/or CRE colonization); Other Name: ESwab; Procedure: Fecal sample; Fecal sample at cross-sectional visit and at 6-month visit (for those with ESBL and/or CRE colonization); Other: Risk factor assessment; Patients will be asked questions on risk factors associated with MDR/XDR colonization at cross-sectional visit and at 6-month visit (for those with ESBL and/or CRE colonization

Outcome Measures

Primary Outcome Measures :

1. Prevalence of ESBL and/or CRE colonization [ Time Frame: 0 months ]
   Proportion of participants with ESBL and/or CRE colonization

Secondary Outcome Measures :

1. Loss of ESBL and/or CRE colonization after 6 months [ Time Frame: 6 months ]
   Proportion of ESBL and/or CRE colonized participants no longer colonized at 6 months
2. STI prevalence [ Time Frame: 0 months ]
   Proportion of participants with an STIs
3. Prevalence of ESBL and/or CRE colonization in the HIV-negative MSM group [ Time Frame: 0 months ]
   Proportion of HIV-negative MSM participants with ESBL and/or CRE colonization
4. Prevalence of ESBL and/or CRE colonization in the HIV-positive MSM group [ Time Frame: 0 months ]
   Proportion of HIV-positive MSM participants with ESBL and/or CRE colonization
5. Prevalence of ESBL and/or CRE colonization in the PrEP group [ Time Frame: 0 months ]
   Proportion of participants undergoing PrEP with ESBL and/or CRE colonization
6. Prevalence of ESBL and/or CRE colonization in those with previous antibiotic exposure [ Time Frame: 0 months ]
   Proportion of participants having previous antibiotic exposure with ESBL and /or CRE colonization

Biospecimen Retention:   Samples Without DNA

Inguinal (at inclusion) and anal swab samples (at inclusion and after 6 months) Fecal sample (at inclusion and after 6 months, only for patients identified with ESBL and/or CRE colonization)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Cohort 1: HIV-negative individuals at high risk of STI infection seeking care at a STI testing center in Paris, France

Cohort 2: HIV-positive individuals seeking care at a university hospital in Paris, France

Criteria

Cohort 1 -

Inclusion Criteria:

• Age ≥ 18 years
• Consulting at the STI clinic of Saint-Antoine Hospital
• Signed the informed consent form

Non-inclusion criteria:

- No fluency in French

Cohort 2 -

Inclusion criteria:

• Men who have sex with men
• Seeking care at Saint-Antoine Hospital
• HIV-positive

Non-inclusion criteria:

- No fluency in French

Contacts and Locations

Locations

France

CeGIDD and Infections Diseases Unit

Paris, France, 75012

Sponsors and Collaborators

Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba

ANRS, Emerging Infectious Diseases

Investigators

• Principal Investigator: Laure Surgers, MD; Saint-Antoine Hospital, Paris, France 75012

More Information

Publications:

Ben-Ami R, Rodríguez-Baño J, Arslan H, Pitout JD, Quentin C, Calbo ES, Azap OK, Arpin C, Pascual A, Livermore DM, Garau J, Carmeli Y. A multinational survey of risk factors for infection with extended-spectrum beta-lactamase-producing enterobacteriaceae in nonhospitalized patients. Clin Infect Dis. 2009 Sep 1;49(5):682-90. doi: 10.1086/604713.

Cantón R, Coque TM. The CTX-M beta-lactamase pandemic. Curr Opin Microbiol. 2006 Oct;9(5):466-75. Epub 2006 Aug 30. Review.

Coque TM, Baquero F, Canton R. Increasing prevalence of ESBL-producing Enterobacteriaceae in Europe. Euro Surveill. 2008 Nov 20;13(47). pii: 19044. Review. Erratum in: Euro Surveill. 2008 Nov 27;13(48). pii: 19051.

Diep BA, Chambers HF, Graber CJ, Szumowski JD, Miller LG, Han LL, Chen JH, Lin F, Lin J, Phan TH, Carleton HA, McDougal LK, Tenover FC, Cohen DE, Mayer KH, Sensabaugh GF, Perdreau-Remington F. Emergence of multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus clone USA300 in men who have sex with men. Ann Intern Med. 2008 Feb 19;148(4):249-57. Epub 2008 Jan 30.

Gaudreau C, Pilon PA, Sylvestre JL, Boucher F, Bekal S. Multidrug-Resistant Campylobacter coli in Men Who Have Sex with Men, Quebec, Canada, 2015. Emerg Infect Dis. 2016 Sep;22(9):1661-3. doi: 10.3201/eid2209.151695.

Harris AD, McGregor JC, Johnson JA, Strauss SM, Moore AC, Standiford HC, Hebden JN, Morris JG Jr. Risk factors for colonization with extended-spectrum beta-lactamase-producing bacteria and intensive care unit admission. Emerg Infect Dis. 2007 Aug;13(8):1144-9.

Jean SS, Lee WS, Lam C, Hsu CW, Chen RJ, Hsueh PR. Carbapenemase-producing Gram-negative bacteria: current epidemics, antimicrobial susceptibility and treatment options. Future Microbiol. 2015;10(3):407-25. doi: 10.2217/fmb.14.135. Review. Erratum in: Future Microbiol. 2017 Apr;12 :456.

Livermore DM, Canton R, Gniadkowski M, Nordmann P, Rossolini GM, Arlet G, Ayala J, Coque TM, Kern-Zdanowicz I, Luzzaro F, Poirel L, Woodford N. CTX-M: changing the face of ESBLs in Europe. J Antimicrob Chemother. 2007 Feb;59(2):165-74. Epub 2006 Dec 6. Review.

Livermore DM. Has the era of untreatable infections arrived? J Antimicrob Chemother. 2009 Sep;64 Suppl 1:i29-36. doi: 10.1093/jac/dkp255. Review.

Molina JM, Capitant C, Spire B, Pialoux G, Cotte L, Charreau I, Tremblay C, Le Gall JM, Cua E, Pasquet A, Raffi F, Pintado C, Chidiac C, Chas J, Charbonneau P, Delaugerre C, Suzan-Monti M, Loze B, Fonsart J, Peytavin G, Cheret A, Timsit J, Girard G, Lorente N, Préau M, Rooney JF, Wainberg MA, Thompson D, Rozenbaum W, Doré V, Marchand L, Simon MC, Etien N, Aboulker JP, Meyer L, Delfraissy JF; ANRS IPERGAY Study Group. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection. N Engl J Med. 2015 Dec 3;373(23):2237-46. doi: 10.1056/NEJMoa1506273. Epub 2015 Dec 1.

Landry MM, Sarma DP. In-situ chondrosarcoma of the foot arising in a solitary enchondroma. J Foot Surg. 1990 Jul-Aug;29(4):324-6.

Nicolas-Chanoine MH, Gruson C, Bialek-Davenet S, Bertrand X, Thomas-Jean F, Bert F, Moyat M, Meiller E, Marcon E, Danchin N, Noussair L, Moreau R, Leflon-Guibout V. 10-Fold increase (2006-11) in the rate of healthy subjects with extended-spectrum β-lactamase-producing Escherichia coli faecal carriage in a Parisian check-up centre. J Antimicrob Chemother. 2013 Mar;68(3):562-8. doi: 10.1093/jac/dks429. Epub 2012 Nov 9.

Osthoff M, McGuinness SL, Wagen AZ, Eisen DP. Urinary tract infections due to extended-spectrum beta-lactamase-producing Gram-negative bacteria: identification of risk factors and outcome predictors in an Australian tertiary referral hospital. Int J Infect Dis. 2015 May;34:79-83. doi: 10.1016/j.ijid.2015.03.006. Epub 2015 Mar 11.

Rodríguez-Baño J, López-Cerero L, Navarro MD, Díaz de Alba P, Pascual A. Faecal carriage of extended-spectrum beta-lactamase-producing Escherichia coli: prevalence, risk factors and molecular epidemiology. J Antimicrob Chemother. 2008 Nov;62(5):1142-9. doi: 10.1093/jac/dkn293. Epub 2008 Jul 18.

Ruppé E, Lixandru B, Cojocaru R, Büke C, Paramythiotou E, Angebault C, Visseaux C, Djuikoue I, Erdem E, Burduniuc O, El Mniai A, Marcel C, Perrier M, Kesteman T, Clermont O, Denamur E, Armand-Lefèvre L, Andremont A. Relative fecal abundance of extended-spectrum-β-lactamase-producing Escherichia coli strains and their occurrence in urinary tract infections in women. Antimicrob Agents Chemother. 2013 Sep;57(9):4512-7. doi: 10.1128/AAC.00238-13. Epub 2013 Jul 8.

Schwaber MJ, Navon-Venezia S, Kaye KS, Ben-Ami R, Schwartz D, Carmeli Y. Clinical and economic impact of bacteremia with extended- spectrum-beta-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2006 Apr;50(4):1257-62.

Szumowski JD, Wener KM, Gold HS, Wong M, Venkataraman L, Runde CA, Cohen DE, Mayer KH, Wright SB. Methicillin-resistant Staphylococcus aureus colonization, behavioral risk factors, and skin and soft-tissue infection at an ambulatory clinic serving a large population of HIV-infected men who have sex with men. Clin Infect Dis. 2009 Jul 1;49(1):118-21. doi: 10.1086/599608.

Tumbarello M, Sanguinetti M, Montuori E, Trecarichi EM, Posteraro B, Fiori B, Citton R, D'Inzeo T, Fadda G, Cauda R, Spanu T. Predictors of mortality in patients with bloodstream infections caused by extended-spectrum-beta-lactamase-producing Enterobacteriaceae: importance of inadequate initial antimicrobial treatment. Antimicrob Agents Chemother. 2007 Jun;51(6):1987-94. Epub 2007 Mar 26. Erratum in: Antimicrob Agents Chemother. 2007 Sep;51(9):3469.

Woerther PL, Burdet C, Chachaty E, Andremont A. Trends in human fecal carriage of extended-spectrum β-lactamases in the community: toward the globalization of CTX-M. Clin Microbiol Rev. 2013 Oct;26(4):744-58. doi: 10.1128/CMR.00023-13. Review.

• Responsible Party: Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
• ClinicalTrials.gov Identifier: NCT03767374
• Other Study ID Numbers: IMEA 52
• First Posted: December 6, 2018
• Last Update Posted: December 9, 2019
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: Will be decided later by the scientific committee at the end of the study.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba:

MDR, XDR, ESBL, ESBL, MRSA, CRE; HIV, PrEP, CeGIDD, STI, bacteria colonization

Additional relevant MeSH terms:

Infections; Communicable Diseases; Bacterial Infections; Disease Attributes; Pathologic Processes; Bacterial Infections and Mycoses