Treatment outcomes in patients with drug-resistant TB-HIV co-infection treated with bedaquiline and linezolid.

BACKGROUND: Bedaquiline (BDQ) has not been extensively studied among patients co-infected with HIV drug-resistant tuberculosis (DR-TB). We compared treatment outcomes in DR-TB patients treated with BDQ- and linezolid (LZD) containing regimens to historic controls treated with second-line injectable-containing regimens.METHODS: Retrospective cohort study of consecutive DR-TB patients initiated on BDQ- and LZD-containing regimens at a TB referral hospital in KwaZulu-Natal, South Africa. Participants were prospectively followed through 24 months for treatment outcome and adverse events. Outcomes were compared to a historic control cohort of DR-TB HIV patients enrolled at the same facility prior to BDQ introduction.RESULTS: Adult DR-TB patients initiating BDQ between January 2014 and November 2015 were enrolled (n = 151). The majority of patients were female (52%), HIV co-infected (77%) and on antiretroviral therapy (100%). End of treatment outcomes included cure (63%), TB culture conversion (83%), completion (0.7%), loss to follow-up (15%), treatment failure (5%), and death (17%). Compared to historic controls (n = 105), patients treated with BDQ experienced significantly higher TB culture conversion and cure, with significantly lower mortality. Adverse effects were common (92%), and most frequently attributed to LZD (24.1%). QT segment prolongation was common but without clinical sequelae.CONCLUSION: Treatment with BDQ- and LZD-containing regimens was associated with improved treatment outcomes and survival in DR-TB HIV patients.

Drug-resistant tuberculosis in patients with minimal symptoms: favourable outcomes in the absence of treatment.

SETTING: Referral hospital for drug-resistant tuberculosis (DR-TB) in KwaZulu-Natal Province, South Africa. OBJECTIVE: To review the clinical outcomes of patients (age  14 years) with a laboratory-confirmed diagnosis of DR-TB who had minimal symptoms and/or did not have chest radiographic evidence of active disease at referral. These patients were not started on treatment, but were enrolled in an observation programme with follow-up at 2, 6 and 12 months. RESULTS: Of 3345 referred patients diagnosed with DR-TB, 192 (6%) were enrolled in the observation programme. The median duration from initial sputum collection in primary care to examination at our hospital was 92 days (IQR 64-124). After 12 months, 120 (62%) patients were well, 36 (19%) were lost to follow-up, 30 (16%) had deteriorated and were started on second-line anti-tuberculosis treatment and 6 (3%) had died. Bilateral disease (OR 4.25, 95%CI 1.14-15.77, P = 0.030) and previous TB (OR 2.14, 95%CI 1.10-4.19, P = 0.026) were independent predictors of an unfavourable end result in a multivariate model. CONCLUSION: In our high-burden setting, most patients diagnosed with DR-TB who had minimal symptoms at referral remained well without treatment. Longitudinal observation, coupled with symptom checking and chest radiograph, is a viable strategy.

Case series of the long-term psychosocial impact of drug-resistant tuberculosis in HIV-negative medical doctors.

BACKGROUND: Health care workers (HCWs) are at greater risk for tuberculosis (TB), including multidrug-resistant TB (MDR-TB), compared to the general population. The psychosocial impact of nosocomial TB on HCWs has received little attention in the literature. METHODS: A retrospective medical record review from 1999 to 2003 found 15 HCWs who were treated for drug-resistant TB at a specialist hospital in South Africa. Five human immunodeficiency virus (HIV) negative doctors with no predisposing factors for drug resistance are included in this case series. We collectively present their clinical case histories based on medical records from 2000 to 2005, and explore the long-term psychosocial impact of TB from interviews conducted in 2009. RESULTS: Four doctors had primary MDR-TB and one had primary resistance to multiple first-line drugs. Time from symptom onset to commencement of effective treatment ranged from 8 to 39 weeks. Time for bacteriological confirmation of drug-resistant TB ranged from 6 to 24 weeks. All were cured within 3 years of initial presentation. Content analysis of follow-up interviews revealed five main themes: 1) prolonged morbidity, 2) psychological impact, 3) poor infection control, 4) weak support structures and 5) attrition from the field. CONCLUSION: Themes emergent from this case series encourage prioritisation of TB infection control education and practice to minimise HCW morbidity and prevent HCW attrition from high-burden resource-constrained settings.

Pregnancies complicated by multidrug-resistant tuberculosis and HIV co-infection in Durban, South Africa.

SETTING: Tertiary hospitals in KwaZulu Natal, South Africa. OBJECTIVE: To study the impact of multidrug-resistant tuberculosis (MDR-TB) and human immunodeficiency virus-1 (HIV-1) co-infection during pregnancy on maternal and perinatal outcome. DESIGN: Prospective study performed between 1996 and 2001. Symptomatic pregnant women were investigated for TB. Those with confirmed MDR-TB were reported on. RESULTS: Three of five pregnant women with MDR-TB were HIV-1 co-infected. One woman decided to terminate the pregnancy and one experienced pre-term labour. Two neonates had features of growth restriction. CONCLUSION: Management of pregnant women with MDR-TB in an HIV-endemic area is possible in developing countries.

Vertical transmission of Mycobacterium tuberculosis in KwaZulu Natal: impact of HIV-1 co-infection.

BACKGROUND: Increases in perinatal TB have paralleled the exacerbation of the TB epidemic in KwaZulu Natal. The exact risks for vertical transfer of Mycobacterium tuberculosis (VTRTB) to the baby are unknown, as is the impact of HIV-1 co-infection, which frequently accompanies maternal TB disease in the region. DESIGN: Prospective case series study of 82 HIV-1-infected and 25 non-infected pregnant mothers, King Edward VIII Hospital, KwaZulu Natal, South Africa. RESULTS: Perinatal mortality in HIV-1/TB diseased mothers was 85/1000 and associated with maternal anaemia (P = 0.02); 46% of newborns were premature, 66% low birth weight and 49% intrauterine growth restricted. These were significantly higher than overall hospital rates (P < 0.01, OR 4.8, 95%CI 3.2-7.0). Sites of detection of maternal TB, distribution of bacteriologically-proven TB, obstetric comorbidity and perinatal morbidity were similar in HIV-1-infected and non-infected mothers. VTRTB was detected in 16 newborns (16%), occurring similarly in bacteriologically-proven and suspected maternal TB disease, with no difference between HIV-1-infected and non-infected mothers. Eleven newborns with VTRTB were HIV-1 exposed; 64% acquired HIV-1 and died from rapidly progressive disease by 10 months of age. HIV-1-infected mothers and their exposed newborns had significantly lower CD4 counts. No association between perinatal maternal viral load, CD4 count or VTRTB was detected. CONCLUSION: Mothers with TB disease in pregnancy are at risk for significant perinatal morbidity, mortality and VTRTB.

Do steroids prevent reintubation in children with laryngotracheobronchitis?

BACKGROUND: Classic laryngotrachoebronchitis (LTB) is an inflammatory process, with oedema and secretions that involve the entire laryngotracheobronchial tree. The severity of lower airway disease in African children with LTB has previously been documented. The aim of the present study was to determine whether steroids prevent reintubation in African children with classic LTB. METHOD AND RESULTS: The study was a retrospective analysis from January 1993 to December 1996. Eighty-two black children with LTB were mechanically ventilated in the intensive care unit (ICU). By univariate regression, the estimated B coefficients for variables such as age, pneumonia, days of intubation, arterial partial oxygen tension (PaO2) : fractional inspired oxygen (FIO2) ratio, atelectasis and antibiotic use were not statistically significant (P > 0.05) as predictors for reintubation. Using multiple regression (all independent variables in combination), none of the variables acted as predictors of reintubation (P = 0.25). Steroids were shown to have no effect alone or in association with other variables in altering reintubation rates. An increase in the days of intubation showed a tendency towards reintubation (P = 0.06) in the univariate analysis (odds ratio 1.00-1.14), but showed no statistically significant difference in multivariate analysis. Of the variables used as predictors of reintubation, none acted either as a preventive factor or as a risk factor. CONCLUSION: The present results suggest that steroids should not be recommended at any stage in treatment of intubated patients with classic LTB. Prospective studies should evaluate the major risk factors for reintubation: duration of intubation, trauma to the airway at intubation and during ICU stay, and dose and timing of steroids. They should also evaluate whether upper airway disease is present alone or in association with lower airway disease.