Background The utility of heated and humidified high-flow nasal oxygen (HFNO) for severe COVID-19-related hypoxaemic respiratory failure (HRF), particularly in s``ettings with limited access to intensive care unit (ICU) resources, remains unclear, and predictors of outcome have been poorly studied. Methods We included consecutive patients with COVID-19-related HRF treated with HFNO at two tertiary hospitals in Cape Town, South Africa. The primary outcome was the proportion of patients who were successfully weaned from HFNO, whilst failure comprised intubation or death on HFNO. Findings The median (IQR) arterial oxygen partial pressure to fraction inspired oxygen ratio (P a O2/FiO 2 ) was 68 (54–92) in 293 enroled patients. Of these, 137/293 (47%) of patients [P a O2/FiO 2 76 (63–93)] were successfully weaned from HFNO. The median duration of HFNO was 6 (3–9) in those successfully treated versus 2 (1–5) days in those who failed ( p <0.001). A higher ratio of oxygen saturation/FiO2 to respiratory rate within 6 h (ROX-6 score) after HFNO commencement was associated with HFNO success (ROX-6; AHR 0.43, 0.31–0.60), as was use of steroids (AHR 0.35, 95%CI 0.19–0.64). A ROX-6 score of ≥3.7 was 80% predictive of successful weaning whilst ROX-6 ≤ 2.2 was 74% predictive of failure. In total, 139 patents (52%) survived to hospital discharge, whilst mortality amongst HFNO failures with outcomes was 129/140 (92%). Interpretation In a resource-constrained setting, HFNO for severe COVID-19 HRF is feasible and more almost half of those who receive it can be successfully weaned without the need for mechanical ventilation.

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Optimal treatment regimens for patients with extensively drug-resistant tuberculosis (XDR-TB) remain unclear. Long-term prospective outcome data comparing XDR-TB regimens with and without bedaquiline from an endemic setting are lacking.We prospectively followed-up 272 South African patients (49.3% HIV-infected; median CD4 count 169 cells·µL) with newly diagnosed XDR-TB between 2008 and 2017. Outcomes were compared between those who had not received bedaquiline (pre-2013; n=204) and those who had (post-2013; n=68; 80.9% received linezolid in addition).The 24-month favourable outcome rate was substantially better in the bedaquiline the non-bedaquiline group (66.2% (45 out of 68) 13.2% (27 out of 204); p<0.001). In addition, the bedaquiline group exhibited reduced 24-month rates of treatment failure (5.9% 26.0%; p<0.001) and default (1.5% 15.2%; p<0.001). However, linezolid was withdrawn in 32.7% (18 out of 55) of patients in the bedaquiline group because of adverse events. Admission weight >50 kg, an increasing number of anti-TB drugs and bedaquiline were independent predictors of survival (the bedaquiline survival effect remained significant in HIV-infected persons, irrespective of CD4 count).XDR-TB patients receiving a backbone of bedaquiline and linezolid had substantially better favourable outcomes compared to those not using these drugs. These data inform the selection of XDR-TB treatment regimens and roll-out of newer drugs in TB-endemic countries.

Rationale The accuracy and impact of new tuberculosis (TB) tests, such as Xpert MTB/RIF, when performed on bronchoalveolar lavage fluid (BALF) obtained from patients with sputum-scarce or smear-negative TB is unclear. Methods South African patients with suspected pulmonary TB (n=160) who were sputum-scarce or smear-negative underwent bronchoscopy. MTB/RIF was performed on uncentrifuged BALF (1 ml) and/or a resuspended pellet of centrifuged BALF (~10 ml). Time to TB detection and anti-TB treatment initiation were compared between phase one, when MTB/RIF was performed as a research tool, and phase two, when it was used for patient management. Results 27 of 154 patients with complete data had culture-confirmed TB. Of these, a significantly lower proportion were detected by smear microscopy compared with MTB/RIF (58%, 95% CI 39% to 75% versus 93%, 77% to 98%; p<0.001). Of the 127 patients who were culture negative, 96% (91% to 98%) were MTB/RIF negative. When phase two was compared with phase one, MTB/RIF reduced the median days to TB detection (29 (18–41) to 0 (0–0); p<0.001). However, more patients initiated empirical therapy (absence of a positive test in those commencing treatment) in phase one versus phase two (79% (11/14) versus 28% (10/25); p=0.026). Consequently, there was no detectable difference in the overall proportion of patients initiating treatment (26% (17/67; 17% to 37%) versus 36% (26/73; 26% to 47%); p=0.196) or the days to treatment initiation (10 (1–49) versus 7 (0–21); p=0.330). BALF centrifugation, HIV coinfection and a second MTB/RIF did not result in detectable changes in accuracy. Conclusions MTB/RIF detected TB cases more accurately and more rapidly than smear microscopy and significantly reduced the rate of empirical treatment.

Background: The utility of heated and humidified high-flow nasal oxygen (HFNO) for severe COVID-19related hypoxaemic respiratory failure (HRF), particularly in settings with limited access to intensive care unit (ICU) resources, remains unclear, and predictors of outcome have been poorly studied. Methods: We included consecutive patients with COVID-19-related HRF treated with HFNO at two tertiary hospitals in Cape Town, South Africa. The primary outcome was the proportion of patients who were successfully weaned from HFNO, whilst failure comprised intubation or death on HFNO. Findings: The median (IQR) arterial oxygen partial pressure to fraction inspired oxygen ratio (P a O2/FiO 2 ) was 68 (54À92) in 293 enroled patients. Of these, 137/293 (47%) of patients [P a O2/FiO 2 76 (63À93)] were successfully weaned from HFNO. The median duration of HFNO was 6 (3À9) in those successfully treated versus 2 (1À5) days in those who failed (p<0.001). A higher ratio of oxygen saturation/FiO2 to respiratory rate within 6 h (ROX-6 score) after HFNO commencement was associated with HFNO success (ROX-6; AHR 0.43, 0.31À0.60), as was use of steroids (AHR 0.35, 95%CI 0.19À0.64). A ROX-6 score of 3.7 was 80% predictive of successful weaning whilst ROX-6 2.2 was 74% predictive of failure. In total, 139 patents (52%) survived to hospital discharge, whilst mortality amongst HFNO failures with outcomes was 129/140 (92%). Interpretation: In a resource-constrained setting, HFNO for severe COVID-19 HRF is feasible and more almost half of those who receive it can be successfully weaned without the need for mechanical ventilation.