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

Recruiting

• Conditions: Staphylococcus Aureus; Latent Tuberculosis
• Interventions: Other: No intervention is part of the study protocol

• Registration Number: NCT05073926
• Lead Sponsor: Region Skane

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-09-09
• Study Start: 2021-09-30
• Study First Submitted QC: 2021-10-11
• Study First Posted: 2021-10-12
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-12
• Last Update Posted: 2024-07-15
• Primary Completion: 2026-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

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

Exclusion Criteria

• none

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Persons with latent tuberculosis treated with 4 months rifampicin	No intervention is part of the study protocol	Oral rifampicin 10 mg/kg (max 600mg) once daily during 4 months
Persons with latent tuberculosis treated with 6-9 months isoniazide	No intervention is part of the study protocol	Oral isoniazide 5 mg/kg (max 300mg) once daily in combination with 40mg vitamin B6 (pyridoxin) during 6-9 months

Primary Outcome Measures

Name	Time	Method
Incidence of rifampicin resistant S. aureus in individuals treated with rifampicin versus isoniazide for latent tuberculosis infection	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.

Secondary Outcome Measures

Name	Time	Method
Frequency of mutations associated with rifampicin resistance in S.aureus during and after rifampicin treatment for latent tuberculosis infection	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.

Trial Locations

Locations (1)

Skåne University Hospital; 🇸🇪 Malmö, Sweden