10.4 Special situations

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    10.4.1 Women (pregnant or breastfeeding or of childbearing age) 

    Pregnant women

    Early treatment initiation after diagnosis is recommended. For choosing or building a regimen, see Appendix 11.  

    Pregnancy outcome and any congenital anomalies in the neonate should be documented.

    Breastfeeding women

    Use of infant formula is recommended as many second-line drugs should be avoided in breastfeeding women (Appendix 11). Mothers must be informed of its benefits and risks and provided with infant formula, clean water, fuel for boiling water and a heating device (stove, saucepan and bottles). They must also receive training on how to prepare and use the formula. When infant formula cannot be used safely, infants must be breastfed.

     

    If the mother is smear-positive, mother-infant contact should be maintained, but kept to a minimum. Appropriate infection prevention and control measures should be taken during contact. Care of the infant should be largely entrusted to family members until the mother becomes smear-negative.

    Women of childbearing age

    A pregnancy test should be performed before starting treatment and, if necessary, repeated during treatment. A highly effective contraception method (e.g. intra-uterine device or implantable hormonal contraceptive) should be offered prior to starting treatment.

    10.4.2 Children and adolescents

    Given the severity of MDR/RR-TB, no TB drugs are contra-indicated (except pretomanid while waiting data on appropriate dosing) [1] Citation 1. World Health Organization. WHO consolidated guidelines on tuberculosis. Module 5: management of tuberculosis in children and adolescents. Geneva: World Health Organization; 2022.
    https://apps.who.int/iris/rest/bitstreams/1414329/retrieve         . Children and adolescents generally tolerate second-line TB drugs well. They should be treated without delay based on the index case resistance profile when DST is not available (e.g. clinically diagnosed TB, EPTB).

     

    Children and adolescents should receive an STR when eligible, however BPaLM and BPaL regimens are not recommended in patients under 14 years.

     

    Children with non-severe TB receiving an LTR can usually be treated for less than 18 months [1] Citation 1. World Health Organization. WHO consolidated guidelines on tuberculosis. Module 5: management of tuberculosis in children and adolescents. Geneva: World Health Organization; 2022.
    https://apps.who.int/iris/rest/bitstreams/1414329/retrieve         . Some experts suggest that even severe TB could be treated for less than 18 months [2] Citation 2. The Sentinel Project for Pediatric Drug-Resistant Tuberculosis. Management of Drug-Resistant Tuberculosis in Children: A Field Guide. Boston, USA. November 2021, Fifth edition.
    http://sentinel-project.org/wp-content/uploads/2022/04/DRTB-Field-Guide-2021_v5.1.pdf         .

    10.4.3 Patients with malnutrition or risk of malnutrition

    See Chapter 9.

    10.4.4 Extrapulmonary tuberculosis

    Patients with some forms of EPTB are not eligible for STRs (Section 10.2.1) and should be treated with an LTR as described in Section 10.2.2.

     

    For patients with TB of the CNS, drug penetration into the CNS should be taken into account.

     

    Table 10.5 – Choice of TB drugs for TB of the CNS [3] Citation 3. World Health Organization. WHO operational handbook on tuberculosis. Module 4: treatment - drug-resistant tuberculosis treatment, 2022 update.
    https://www.who.int/publications/i/item/9789240065116         [4] Citation 4. Sun F, Ruan Q, Wang J, Chen S, Jin J, Shao L, et al. Linezolid manifests a rapid and dramatic therapeutic effect for patients with life-threatening tuberculous meningitis. Antimicrob Agents Chemother. 2014;58(10):6297–301.
    https://doi.org/10.1128/AAC.02784-14         [5] Citation 5. Thwaites GE, Bhavnani SM, Chau TTH, Hammel JP, Torok ME, Van Wart SA, et al. Randomized pharmacokinetic and pharmacodynamic comparison of fluoroquinolones for tuberculous meningitis. Antimicrob Agents Chemother. 2011;55(7):3244–53.
    https://doi.org/10.1128/AAC.00064-11

     

    Drugs

    CNS penetration

    Group A

    Fluoroquinolones and linezolid: good CNS penetration.

    Bedaquiline: limited data; can be used, but not counted.

    Group B

    Cycloserine: good CNS penetration.

    Clofazimine: limited data; can be used, but not counted.

    Group C

    Pyrazinamide, carbapenems, thionamides and isoniazid high dose: good CNS penetration.

    Delamanid: limited data; can be used, but not counted.

    Ethambutol and PAS: poor CNS penetration.

    Aminoglycosides: better CNS penetration if meningeal inflammation.

    Other

    Pretomanid: no data.

     

    If the regimen contains a carbapenem, use preferably meropenem in patients with TB meningitis (less risk of seizures than with imipenem/cilastatin).

    10.4.5 Diabetes

    TB can impair glycaemic control in patients with diabetes [6] Citation 6. World Health Organization & International Union against Tuberculosis and Lung Disease. (‎2011)‎. Collaborative framework for care and control of tuberculosis and diabetes. World Health Organization. 
    https://iris.who.int/bitstream/handle/10665/44698/9789241502252_eng.pdf?sequence=1         . It is therefore necessary to increase blood glucose monitoring in these patients.

     

    TB drugs may exacerbate complications of diabetes (e.g. peripheral neuropathy). Avoid prescribing ethambutol or linezolid for patients with pre-existing diabetic retinopathy.

     

    If diabetes is diagnosed, treat and monitor according to standard protocols. At the end of TB treatment, it is recommended to schedule a specialist consultation for a complete evaluation and, if necessary, adjustment of antidiabetic treatment.

    10.4.6 Renal insufficiency

    In patients with renal insufficiency, creatinine clearance should be calculated. If it is less than 30 ml/minute, doses of certain TB drugs should be adjusted.

    For the formula to estimate creatinine clearance and dose adjustments in renal insufficiency, see Appendix 12.

     

    References
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