Rifampicin Resistance in S. Aureus During and After Treatment for Latent Tuberculosis

July 12, 2024 updated by: Anton Reepalu, Region Skane

Acquisition and Persistence of Rifampicin Resistance in Staphylococcus Aureus During and After Treatment for Latent Tuberculosis

Two commonly used treatments for latent tuberculosis infection are either 4 months rifampicin or 6-9 months isoniazid. The invistigators will study the risk of acquisition of rifampicin resistance in commensal Staphylococcus aureus in persons treated with rifampicin versus in persons treated with isoniazide. Through repeated swab cultures before, during, and after treatment the investigators will also investigate potential accumulation of mutations associated with rifampicin resistance over time. Finally, household contacts to persons with rifampicin-resistant S. aureus will be examined to investigate whether onward transmission of rifampicin-resistant S. aureus occurs within households.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The use of rifampicin for treatment of latent tuberculosis has gained popularity due to a shorter treatment course compared with isoniazide (4 versus 6-9 months) since this can lead to a higher proportion of treatment completion. An estimated 25% of the global population is latently infected with tuberculosis. Hence, a shift towards rifampicin instead of isoniazide, which has a more narrow antibacterial spectrum, could have a large impact on the prevalence of rifampicin resistance among commensal bacteria with pathogenic potential, such as Staphylococcus aureus (S.aureus).

The investigators will investigate the risk of acquisition of rifampicin resistance in commensal S.aureus during out-patient treatment for latent tuberculosis using 4 months rifampicin versus 6-9 months isoniazide at Skåne University Hospital in Malmö, Sweden.

Swabs will be obtained from the nose, throat, groin and possible wounds for culture and resistance testing before, during and after cessation of treatment for latent tuberculosis. Whole genome sequencing will be used to analyze accumulation of mutations over time and to determine if it is the primarily detected S.aureus that develop resistance or if the individual is colonized by new, rifampicin-resistant S.aureus over the course of treatment. Household contacts to persons with rifampicin-resistant S.aureus will be examined to investigate onward spread of bacteria within a household.

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Sweden
      • Malmö, Sweden, 20502
        • Recruiting
        • Skane University Hospital
        • Contact:
          • Anton Reepalu, MD PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Individuals 16 years or older diagnosed with latent tuberculosis and prescribed prophylactic treatment with rifampicin or isoniazide as part of routine care at the out-patient department of the departments for infectious diseases at Skåne University Hospital in Malmö, Helsingborg and Växjö, Sweden.

Description

Inclusion Criteria:

  • diagnosed with latent tuberculosis
  • prescribed either 4 months rifampicin or 6-9 months isoniazide
  • informed consent

Exclusion Criteria:

  • none

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Persons with latent tuberculosis treated with 4 months rifampicin
Oral rifampicin 10 mg/kg (max 600mg) once daily during 4 months
Other: No intervention is part of the study protocol
No intervention is part of the study protocol. The choice of treatment for latent tuberculosis is is made by the treating physician.
Persons with latent tuberculosis treated with 6-9 months isoniazide
Oral isoniazide 5 mg/kg (max 300mg) once daily in combination with 40mg vitamin B6 (pyridoxin) during 6-9 months
Other: No intervention is part of the study protocol
No intervention is part of the study protocol. The choice of treatment for latent tuberculosis is is made by the treating physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of rifampicin resistant S. aureus in individuals treated with rifampicin versus isoniazide for latent tuberculosis infection
Time Frame: 5 months
The proportion of individuals colonized with rifampicin-resistant S.aureus during and after 4 months treatment with rifampicin for latent tuberculosis will be compared with a control group of individuals treated with isoniazide during a similar time period to determine the relative risk of acquiring rifampicin-resistant S.aureus carriage.
5 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of mutations associated with rifampicin resistance in S.aureus during and after rifampicin treatment for latent tuberculosis infection
Time Frame: 10 months
The frequency of mutations associated with rifampicin resistance will be determined thorugh whole-genome sequencing at pre-specified time points before, during and after 4 months treatment with rifampicin for latent tubeculosis infection.
10 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Region Skane

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2021

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

September 9, 2021

First Submitted That Met QC Criteria

October 11, 2021

First Posted (Actual)

October 12, 2021

Study Record Updates

Last Update Posted (Actual)

July 15, 2024

Last Update Submitted That Met QC Criteria

July 12, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-02312

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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