Clinical trial NCT05073926: Rifampicin Resistance in S. Aureus During and After Treatment for Latent Tuberculosis
Official title: Acquisition and Persistence of Rifampicin Resistance in Staphylococcus Aureus During and After Treatment for Latent Tuberculosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Latent Tuberculosis
Staphylococcus Aureus
Keywords: rifampicin
isoniazide
staphylococcus aureus
latent tuberculosis
Drug Resistance, Microbial
Lead sponsor: Region Skane
Sponsor class: OTHER
First posted: 2021-10-12
Enrollment: 100
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* none

Primary outcomes:
measure: Incidence of rifampicin resistant S. aureus in individuals treated with rifampicin versus isoniazide for latent tuberculosis infection
timeFrame: 5 months
Secondary outcomes:
measure: Frequency of mutations associated with rifampicin resistance in S.aureus during and after rifampicin treatment for latent tuberculosis infection
timeFrame: 10 months
Other outcomes:
Locations:
city: Malmö
country: Sweden
facility: Skåne University Hospital
Study officials:
References: