Tuberculosis Disease during Pregnancy and Treatment Outcomes in HIV-Infected and Uninfected Women at a Referral Hospital in Cape Town.

BACKGROUND: Tuberculosis during pregnancy and treatment outcomes are poorly defined in high prevalence tuberculosis and HIV settings. METHODS: A prospective cohort study of pregnant and postpartum women identified to be routinely on antituberculosis treatment was conducted at Tygerberg Hospital, Cape Town, South Africa, from January 2011 through December 2011. Maternal tuberculosis disease spectrum and tuberculosis-exposed newborns were characterized by maternal HIV status. Maternal tuberculosis treatment outcomes were documented and a multivariable regression model identified predictors of unfavourable tuberculosis treatment outcomes. Infant outcomes were also described. RESULTS: Seventy-four women with tuberculosis, 53 (72%) HIV-infected, were consecutively enrolled; 35 (47%) were diagnosed at delivery or postpartum and 22 (30%) of women reported previous antituberculosis treatment. HIV-infected women were 5.67 times more likely to have extrapulmonary tuberculosis (95% CI 1.18-27.25, p = 0.03). All 5 maternal deaths were amongst HIV-infected women. Birth outcomes were available for 75 newborns (2 sets of twins, missing data for 1 stillbirth). Of the 75 newborns, 49 (65%) were premature and 44 (59%) were low birth weight (LBW; <2500 grams). All 6 infants who died and the 4 stillbirths were born to HIV-infected women. Unfavourable tuberculosis treatment outcomes were documented in 33/74 (45%) women. Unfavourable maternal tuberculosis outcome was associated with delivery of LBW infants (OR 3.83; 95% CI 1.40-10.53, p = 0.009). CONCLUSIONS: A large number of pregnant women with tuberculosis presented at a provincial referral hospital. All maternal and infant deaths occurred in HIV-infected women and their newborns. Maternal tuberculosis treatment outcomes were poor.

Dose regimen of para-aminosalicylic acid gastro-resistant formulation (PAS-GR) in multidrug-resistant tuberculosis.

BACKGROUND AND OBJECTIVES: Resurgence of multidrug-resistant tuberculosis (MDR-TB) has raised a renewed interest in para-aminosalicylic acid (PAS) and other efficacious drugs. A gastro-resistant granule formulation (PAS-GR) was designed to be better tolerated than earlier forms of PAS, with fewer adverse effects from reduced production of meta-aminophenol. PAS release from PAS-GR granules is slower than with earlier formulations. Pharmacokinetic data are, however, limited and only a few studies have assisted in defining the best PAS-GR dose regimen. Interest in refining the latter continues and recent data contributed in better defining the optimal PAS-GR dose regimen in adults and children. The present paper draws on these recent studies, synthesizes pharmacokinetic results from different population groups, and draws comparisons with in vitro data and the results of earlier pharmacokinetic studies in order to discuss the most appropriate dosing regimen for PAS-GR. METHODS: A comparative in vitro dissolution study was carried out with a 1 g acid PAS equivalent of various formulations of PAS and PAS-GR and in vitro-in vivo correlations. Retrospective comparisons between recent and earlier clinical studies were also gathered to clarify the dose regimen of PAS-GR in adults and children. RESULTS: Exposure after a 4 g twice- or three times daily dose regimen in adult MDR-TB patients confirmed that both dose regimens can be used. The twice-daily dose regimen does not, however, confer any safety margin over the potentiality of "too" high plasma concentrations after a three times daily dose regimen and may lead to under-dosage when a dose is missed, as compliance often decreases over time. CONCLUSIONS: Based on available data and practical considerations, a 4 g three times daily dose regimen of PAS-GR should be the preferred dose in hospital settings, where it remains the best regimen to cover the around-the-clock suppression of mycobacteria based on the minimal inhibitory concentration for PAS. In MDR-TB adults and in hospital settings, there is no safety advantage in administering a regimen of 4 g twice daily. As compliance is critical to the effectiveness of the treatment, a 4 g three times daily dose regimen may be more forgiving if the patient misses a dose.

Isoniazid preventive therapy in HIV-infected and -uninfected children (0 - 14 years).

Isoniazid preventive therapy (IPT) prevents tuberculosis (TB) in immunocompetent children <5 years of age after exposure to an infectious TB source case. Routine IPT has been advocated in all HIV-infected children without TB, but has been controversial. Antiretroviral therapy markedly reduces the risk for TB in HIV-infected children, especially when started early in infancy. In HIV-infected children, as in HIV- uninfected children, we recommend post-exposure IPT after each TB exposure episode; but in HIV-infected children, this should be given irrespective of age or antiretroviral therapy. However, evidence for routine IPT without known exposure to TB in HIV-infected children is not convincing and is therefore not recommended. 

Resistant Mycobacterium bovis Bacillus Calmette-Guérin disease: implications for management of Bacillus Calmette-Guérin Disease in human immunodeficiency virus-infected children.

Guidelines for the diagnosis and management of Bacillus Calmette-Guérin (BCG) disease in children are lacking, and there are limited data on drug resistance of Mycobacterium bovis BCG. A 6-month-old HIV-infected infant presented with right axillary adenitis ipsilateral to the site of BCG immunization. M. tuberculosis complex was cultured from axillary lymph nodes and gastric aspirates, and M. bovis BCG was isolated. Susceptibility testing before initiation of therapy demonstrated inherent resistance to isoniazid. The organism acquired rifampin resistance during therapy. This was confirmed by the presence of a mutation in codon 531 (Ser531Tyr) of the rpoB gene. Treatment guidelines for BCG disease with consideration of inherent and possible acquired drug resistance should be established in settings with high rates of vertical HIV transmission and routine BCG vaccination.