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

Sponsor

Region Skane (Other)

Overall Status

Recruiting

CT.gov ID

NCT05073926

Collaborator

(none)

100

Enrollment

Location

Anticipated Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Latent Tuberculosis Staphylococcus Aureus	Other: No intervention is part of the study protocol

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 Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Sep 30, 2021

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	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.

Arm

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.

Outcome Measures

Primary Outcome Measures

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

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.