16.7 Latent tuberculosis infection and multidrug-resistant tuberculosis

Due to limited evidence, routine LTBI treatment for all household contacts of patients with multidrug-resistant TB (MDR-TB) cannot be recommended at this time.

However, treatment of LTBI should be considered in certain high-risk household contacts based on an individual risk-benefit assessment.
Individual assessment includes:

• Risk of progression to active TB: this risk is high in children under 5 years and people with HIV infection or on immunosuppressive therapy.
• Resistance pattern of the source case: the LTBI treatment regimen must be individually tailored as contacts of MDR-TB patients are often infected with the same strain [1] Citation 1. Verver S et al. Proportion of tuberculosis transmission that takes place in households in a high-incidence area. Lancet, 2004, 363(9404):212.
  https://doi.org/10.1016/S0140-6736(03)15332-9 .
• Intensity of exposure.
• Contra-indication or risk of adverse effects.

A TST or IGRA should be performed prior to LTBI treatment. If not feasible, LTBI treatment may be considered, weighing benefits and risks.

16.7.1 Household contacts of multidrug-resistant tuberculosis cases eligible for treatment

Evidence is lacking on the choice of treatment to prevent disease in MDR-TB contacts. Few observational studies, primarily using a fluoroquinolone (FQ) for 6 months, reported promising results [2] Citation 2. Trieu L, Proops DC, Ahuja SD. Moxifloxacin Prophylaxis against MDR TB. New York, USA. Emerg Infect Dis. 2015;21(3):500–3. 
https://doi.org/10.3201/eid2103.141313 [3] Citation 3. Bamrah S, Brostrom R, Dorina F, Setik L, Song R, Kawamura LM, et al. Treatment for LTBI in contacts of MDR-TB patients, Federated States of Micronesia, 2009–2012. Int J Tuberc Lung Dis. 2014;18(8):912–8.
https://doi.org/10.5588/ijtld.13.0028 . Randomized clinical trials are ongoing [4] Citation 4. Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients (PHOENIx MDR-TB).
https://clinicaltrials.gov/ct2/show/NCT03568383 [5] Citation 5. Tuberculosis child multidrug-resistant preventive therapy: TB CHAMP trial.
 https://doi.org/10.1186/ISRCTN92634082 .

For contacts of patients with FQ-susceptible MDR-TB, levofloxacin PO for 6 months can be proposed at the following doses:

If active TB develops during LTBI treatment, DST should be performed due to the potential risk associated with use of FQs in monotherapy (development of resistance to FQs in patients with undiagnosed active TB).
In addition to LTBI treatment, monitor these patients for 2 years for the development of active TB.

16.7.2 Household contacts of multidrug-resistant tuberculosis cases not eligible for treatment

If the contact is not eligible for LTBI treatment, closely monitor for signs and symptoms of active TB every 3 months for the next 2 years.

If active TB develops, start TB treatment promptly with a regimen based on the DST results or on the resistance profile of the source case if a DST is not feasible.