Late Breaking Abstract - Therapeutic drug monitoring in a patient with very advanced XDR-TB

Therapeutic drug monitoring (TDM) has been suggested to improve treatment responses in multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB), but evidence is still scarce. We share our experience with TDM in anti-tuberculosis therapy in a patient with very advanced XDR-TB. A 34-year-old male from Ukraine was admitted to our hospital in November 2018 for the treatment of tuberculosis. He had been diagnosed in December 2008 and had since received 8 treatment episodes in Ukraine with relapses and failing therapies. On admission, time to positivity for Mycobacterium tuberculosis in liquid sputum culture was 7 days. Phenotypic drug susceptibility testing revealed drug-resistance to all 1st- and 2nd-line anti-tuberculosis drugs apart from terizidone, delamanid, and pretomanid. Under treatment with 800 mg moxifloxacin and standard doses of bedaquiline, terizidone, delamanid, and meropenem/amoxiclav, no sustainable culture conversion could be achieved over five months. In contrast, a TDM-controlled high-dose treatment, including i.a. 1600 mg moxifloxacin, bedaquiline 300 mg thrice/week, and 1000 mg terizidone, induced culture negativity that was stable over 15 months. However, a subsequent attempt to stop therapy resulted in a microbiological relapse and necessitated a therapy re-start, now under even further intensified treatment including i.a. bedaquiline 400 mg thrice/week, 9.6 g meropenem, and 7.2 g amoxiclav per day. This regimen quickly led to culture conversion again. There were no serious adverse events or acquired drug resistances observed. In summary, TDM-guided therapy can help to overcome low-intermediate level resistance in M/XDR-TB. However, extended treatment duration might be needed to achieve cure.