Pulmonary extensively drug-resistant tuberculosis in Melbourne: local control of a global health challenge

Clinical record

A 21-year-old HIV-negative man presented with haemoptysis preceded by 2 weeks of cough and 1 month of constitutional symptoms. He had migrated from Nepal 11 months earlier and reported childhood contact with tuberculosis (TB). He was febrile (38.2°C); otherwise vital signs and examination were normal. A chest x-ray showed bilateral mid-zone infiltrates. From smear-negative sputum, Xpert MTB/RIF (Cepheid) assay was positive for Mycobacterium tuberculosis and a rifampicin-resistant mutation within the rpoB gene was indicated. Consequently, amikacin, moxifloxacin and prothionamide were added to first line TB therapy of isoniazid, rifampicin, ethambutol and pyrazinamide.

The Victorian Mycobacterium Reference Laboratory confirmed the identification of M. tuberculosis from sputum cultured in mycobacteria growth indicator tube broth. Box 1 summarises phenotypic susceptibility results and mutations associated with resistance identified from sequencing target genes. After 6 weeks of treatment, M. tuberculosis culture of sputum collected on the day of laboratory notification of extensively drug-resistant TB (XDR-TB) was negative. Remaining cough was minimal and the patient gained 4 kg in weight. Therapy was intensified (Box 2) and included bedaquiline, which had just completed phase 2 trials. Radiologically, bilateral cavities had evolved (Box 3). De-bulking surgery was considered but later deemed unnecessary given early culture conversion and radiological resolution over 6 months.

In the early months of treatment, psychological distress from isolation was a major issue. As shown in Box 2, side effects increased during treatment, which led to dose alterations, treatment interruptions and ultimately cessation of several agents. Treatment was completed in June 2016 after 112 weeks of TB therapy at an estimated cost of about $400 000. Monitoring for recurrence is planned for at least 5 years. At 12-month follow-up there were no signs of recurrent TB. Persistent medication side effects included right shoulder pain and headaches with associated nausea and impaired concentration.

Four adult family members were identified as household contacts; all had normal chest x-rays and were negative by either tuberculin skin test or QuantiFERON-TB Gold (Qiagen) at baseline and 3 months.

The patient identified through social media that three friends that he shared a dormitory with at boarding school in Nepal had subsequently been treated for multidrug-resistant TB (MDR-TB) or XDR-TB: one for XDR-TB in the United States and two for MDR-TB in Nepal. One of these was reportedly unwell for 2–3 months with cough while attending the boarding school. One patient treated in Nepal has since relocated internationally. Relevant jurisdictional TB programs were contacted to allow appropriate follow-up of cases and potential contacts.

Lessons from practice

• Health care professionals need to maintain awareness of the symptoms and signs of TB.

• Rapid molecular diagnosis of rifampicin resistance should be undertaken at the time of diagnosis for all patients with TB and, if detected, a rapid molecular drug-resistance profile should be used to guide timely administration of effective therapy.

• Patient engagement and social support, rather than relying on enforcing treatment, is essential in delivering highly toxic XDR-TB treatment.

• Public health investigations for MDR/XDR-TB should consider international jurisdictions, as a cluster of MDR/XDR-TB in one country may spread globally.