10.9 Special situations

10.9.1 Pregnant women

Pregnant women should be carefully evaluated, such that the risks and benefits of treatment considered according to gestational age and severity of disease.
– The primary goal is culture conversion to protect the health of the mother and child, both before and after birth.
– If the patient is very stable with minimum disease, treatment may be delayed and started in the second trimester with 3 or 4 drugs known to be safe in pregnancy and active on the infecting strain. In most cases of moderate to severe disease the treatment should be started right away with the risks and benefits explained to the mother.
– Aminoglycosides are contraindicated. If an injectable agent is required, capreomycin is the only option as there are case reports of safe use in pregnancy.
– Ethionamide and prothiomanide should be avoided due to data suggesting teratogenicity in animals.
– Fluoroquinolones are considered acceptable to use despite limited data.
– Moxifloxacin, para-aminosalicylic acid, cycloserine and amoxicillin/clavulanic acid is an appropriate initial regimen with a consideration of capreomycin in cases of advanced disease (extensive parenchymal damage or life-threatening condition).
– If some drugs were withheld because of the pregnancy, they can be added back postpartum if needed to make a more complete regimen.

The child should receive BCG at birth.

10.9.2 Breastfeeding women

Most anti-TB drugs will be found in the breast milk in concentrations that would equal only a small fraction of the therapeutic dose used in an infant. Effects on infants of such exposure during the full course of DR-TB treatment have not been established. Therefore, when resources and training are available, it is recommended to provide infant formula as an alternative to breastfeeding. If infant formula is used, the infant formula, clean water, fuel for boiling water and the apparatus (stove, heating pans and bottles) must be provided to the mother, as well as training on how to prepare and use the infant formula. If infant formula cannot be provided regularly and used safely, the child should be breastfed and the risks/benefits explained to the mother.

Treatment administered timely and properly is the best way to prevent transmission of tubercle bacilli to the breastfed infant.

If a mother is smear-positive and there is a possibility the mother is failing treatment, the care of the infant should be entrusted to family members until she becomes smearnegative, if feasible. Otherwise, nursing mothers with DR-TB should not be separated from their infants.

10.9.3 Women of child-bearing age

A pregnancy test should be performed before starting anti-TB therapy (to be repeated if indicated).

Women of child-bearing age should be provided contraception in addition to MDR-TB treatment.

Patients should be advised to take their oral contraceptives at times well away from when they may experience vomiting caused by the anti-TB drugs. Patients who vomit within the first two hours of taking the contraceptive tablet should use a barrier method of contraception for the duration of symptoms and for seven days after recovery.

Note: for patients with mono- and poly-drug resistant TB susceptible to rifampicin (Chapter 11), rifampicin interacts with hormonal contraceptives and decreases their efficacy. Patients may choose between these options, throughout the course of anti-TB treatment: medroxyprogesterone IM or barrier methods (diaphragm, condom, UID) or, as a last resort, oral contraceptive containing a high dose of estrogen (50 micrograms/tablet).

10.9.4 Children

Children with DR-TB generally have primary resistance transmitted from an adult contact with DR-TB.

Culture and DST, if available, should be used to guide therapy. In other cases, the child should be treated empirically, guided by the DST pattern of the index case. However, every effort should be made to obtain a sample from the child for culture and DST.

Given the severity of DR-TB, there are no drugs that are absolutely contraindicated in children.

Children generally tolerate well second-line anti-TB drugs.

The administration of second-line drugs can be problematic due to the lack of commercially available paediatric formulations.

10.9.5 Extrapulmonary drug-resistant TB

Regimen construction and duration for extrapulmonary DR-TB is the same as for pulmonary DR-TB.

If a patient with DR-TB has symptoms suggestive of central nervous system involvement, the regimen should include drugs with good cerebrospinal fluid (CSF) penetration31,32:
– Ethionamide or prothionamide and cycloserine have good penetration into the CSF.
– Kanamycin, amikacin, and capreomycin do so only in the presence of meningeal inflammation.
– Para-aminosalicylic acid and ethambutol have little or no penetration.
– Fluoroquinolones have variable CSF penetration, with better penetration seen in the higher generations.

10.9.6 Renal insufficiency

Renal insufficiency may be due an injectable anti-TB drug or other aetiologies including longstanding TB infection.

In patients with renal insufficiency, the creatinine clearance should be calculated. If less < 30 ml/min, anti-TB drugs should be adjusted. The formula to estimate the creatinine clearance, and the dose of anti-TB drugs in renal insufficiency are presented in Appendix 12.