An outbreak of multi-drug resistant (MDR) tuberculosis (TB) has been reported on Daru Island, Papua New Guinea. Mycobacterium tuberculosis strains driving this outbreak and the temporal accrual of drug resistance mutations have not been described. Whole genome sequencing of 100 of 165 clinical isolates referred from Daru General Hospital to the Supranational reference laboratory, Brisbane, during 2012–2015 revealed that 95 belonged to a single modern Beijing sub-lineage strain. Molecular dating suggested acquisition of streptomycin and isoniazid resistance in the 1960s, with potentially enhanced virulence mediated by an mycP1 mutation. The Beijing sub-lineage strain demonstrated a high degree of co-resistance between isoniazid and ethionamide (80/95; 84.2 %) attributed to an inhA promoter mutation combined with inhA and ndh coding mutations. Multi-drug resistance, observed in 78/95 samples, emerged with the acquisition of a typical rpoB mutation together with a compensatory rpoC mutation in the 1980s. There was independent acquisition of fluoroquinolone and aminoglycoside resistance, and evidence of local transmission of extensively drug resistant (XDR) strains from 2009. These findings underline the importance of whole genome sequencing in informing an effective public health response to MDR/XDR TB.

Setting: Bedaquiline (BDQ) was introduced in the multidrug-resistant tuberculosis (MDR-TB) programme in Daru in remote Papua New Guinea in 2015, along with a core package of active drug-safety monitoring (aDSM). Objective: To assess interim results and safety of BDQ for the treatment of MDR-TB from 1 July 2015 to 31 December 2017. Design: A retrospective cohort analysis of routine programme data. Results: Of 277 MDR-TB patients, 77 (39%) received BDQ with a total of 8 serious adverse events including 5 (6.5%) deaths, of which 1 (1.3% QTcF prolongation, grade 3) was attributable to BDQ. Of 200 (61%) patients who did not receive BDQ, there were 17 (9%) deaths. Completeness of monitoring for the BDQ group was 90% for 5 electrocardiograms and 79% for 2 cultures. In the interim result indicator analysis at month 6 in the BDQ and non-BDQ groups, there were respectively 0% and 1% lost to follow-up; 6.5% and 8.5% who died; 94% and 91% in care; and 92% and 96% with negative culture among those monitored. Conclusion:Early experience in Daru shows BDQ is safe and feasible to implement with aDSM with good interim effectiveness supporting the rapid adoption and scale-up of the 2019 WHO MDR-TB treatment guidelines in the programme and in similar remote settings. * Among eligible patients who had 2 valid culture tests sent 30 days apart (see Figure 2 for full definitions). MDR-TB = multidrug-resistant tuberculosis; BDQ = bedaquiline.

20An outbreak of multi-drug resistant tuberculosis has been reported on Daru Island, Papua New 21Guinea. The Mycobacterium tuberculosis strains driving this outbreak and the temporal accrual 22 of drug resistance mutations have not been described. We analyzed 100 isolates using whole