Maternal and Infant Outcomes Among Pregnant Women Treated for Multidrug/Rifampicin-Resistant Tuberculosis in South Africa.

BACKGROUND: Data on safety and efficacy of second-line tuberculosis drugs in pregnant women and their infants are severely limited due to exclusion from clinical trials and expanded access programs. METHODS: Pregnant women starting treatment for multidrug/rifampicin-resistant (MDR/RR)-tuberculosis at King Dinuzulu Hospital in KwaZulu-Natal, South Africa, from 1 January 2013 to 31 December 2017, were included. We conducted a record review to describe maternal treatment and pregnancy outcomes, and a clinical assessment to describe infant outcomes. RESULTS: Of 108 pregnant women treated for MDR/RR-tuberculosis, 88 (81%) were living with human immunodeficiency virus.. Favorable MDR/RR-tuberculosis treatment outcomes were reported in 72 (67%) women. Ninety-nine (91%) of the 109 babies were born alive, but overall, 52 (48%) women had unfavorable pregnancy outcomes. Fifty-eight (54%) women received bedaquiline, and 49 (45%) babies were exposed to bedaquiline in utero. Low birth weight was reported in more babies exposed to bedaquiline compared to babies not exposed (45% vs 26%; P = .034). In multivariate analyses, bedaquiline and levofloxacin, drugs often used in combination, were both independently associated with increased risk of low birth weight. Of the 86 children evaluated at 12 months, 72 (84%) had favorable outcomes; 88% of babies exposed to bedaquiline were thriving and developing normally compared to 82% of the babies not exposed. CONCLUSIONS: MDR/RR-tuberculosis treatment outcomes among pregnant women were comparable to nonpregnant women. Although more babies exposed to bedaquiline were of low birth weight, over 80% had gained weight and were developing normally at 1 year.

Dilemma of managing asymptomatic children referred with 'culture-confirmed' drug-resistant tuberculosis.

BACKGROUND: The diagnosis of drug-resistant tuberculosis (DR-TB) in children is challenging and treatment is associated with many adverse effects. OBJECTIVE: We aimed to assess if careful observation, without initiation of second-line treatment, is safe in asymptomatic children referred with 'culture-confirmed' DR-TB. SETTING: KwaZulu-Natal, South Africa-an area with high burdens of HIV, TB and DR-TB. DESIGN, INTERVENTION AND MAIN OUTCOME MEASURES: We performed an outcome review of children with 'culture-confirmed' DR-TB who were not initiated on second-line TB treatment, as they were asymptomatic with normal chest radiographs on examination at our specialist referral hospital. Children were followed up every other month for the first year, with a final outcome assessment at the end of the study. RESULTS: In total, 43 asymptomatic children with normal chest radiographs were reviewed. The median length of follow-up until final evaluation was 549 days (IQR 259-722 days); most (34; 83%) children were HIV uninfected. Resistance patterns included 9 (21%) monoresistant and 34 (79%) multidrug-resistant (MDR) strains. Fifteen children (35%) had been treated with first-line TB treatment, prior to presentation at our referral hospital. At the final evaluation, 34 (80%) children were well, 7 (16%) were lost to follow-up, 1 (2%) received MDR-TB treatment and 1 (2%) died of unknown causes. The child who received MDR-TB treatment developed new symptoms at the 12-month review and responded well to second-line treatment. CONCLUSIONS: Bacteriological evaluation should not be performed in the absence of any clinical indication. If drug-resistant Mycobacterium tuberculosis is detected in an asymptomatic child with a normal chest radiograph, close observation may be an appropriate strategy, especially in settings where potential laboratory error and poor record keeping are constant challenges.