The treatment of drug-resistant Mycobacterium tuberculosis relies on complex antibiotic therapy. Inadequate antibiotic exposure can lead to treatment failure, acquired drug resistance, and an increased risk of adverse events. Therapeutic drug monitoring (TDM) can be used to optimize the antibiotic exposure. Therefore, we aimed to develop a single-run multiplex assay using high-performance liquid chromatography–mass spectrometry (HPLC–MS) for TDM of patients with multidrug-resistant, pre-extensively drug-resistant and extensively drug-resistant tuberculosis. A target profile for sufficient performance, based on the intended clinical application, was established and the assay was developed accordingly. Antibiotics were analyzed on a zwitterionic hydrophilic interaction liquid chromatography column and a triple quadrupole mass spectrometer using stable isotope-labeled internal standards. The assay was sufficiently sensitive to monitor drug concentrations over five half-lives for rifampicin, rifabutin, levofloxacin, moxifloxacin, bedaquiline, linezolid, clofazimine, terizidone/cycloserine, ethambutol, delamanid, pyrazinamide, meropenem, prothionamide, and para-amino salicylic acid (PAS). Accuracy and precision were sufficient to support clinical decision making (≤±15% in clinical samples and ±20–25% in spiked samples, with 80% of future measured concentrations predicted to fall within ±40% of nominal concentrations). The method was applied in the TDM of two patients with complex drug-resistant tuberculosis. All relevant antibiotics from their regimens could be quantified and high-dose therapy was initiated, followed by microbiological conversion. In conclusion, we developed a multiplex assay that enables TDM of the relevant first- and second-line anti-tuberculosis medicines in a single run and was able to show its applicability in TDM of two drug-resistant tuberculosis patients.

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.

Objectives To investigate the safety profiles and clinical outcomes in a continuous cohort of tuberculosis (TB) patients from a clinical referral centre in Germany receiving self-administered outpatient parenteral antimicrobial therapy (sOPAT). Methods We conducted a retrospective observational cohort study of patients receiving sOPAT after discharge from the Research Center Borstel in Germany between January 2015 and December 2020. Data were extracted from medical records. Results In the observation period, 150 patients received parenteral antibiotics at the Research Center Borstel. Of these, 89 received sOPAT via a port catheter and were further analysed. The majority were male (n = 59, 66.3%), with a median age of 33.6 years (interquartile range—IQR 26.2–42.8). Most patients had multidrug-resistant (MDR)-TB (n = 56, 62.9%) or pre-extensively drug resistant (pre-XDR)-TB (n = 21; 23.6%). Fifty-eight (65.2%) patients received one and 24 patients (27.0%) received two parenteral drugs, most commonly capreomycin (n = 53, 59.6%) and meropenem (n = 44, 49.4%). The median duration of sOPAT was 7.4 months (IQR 5.2–17.2). In total, 71,128 intravenous drug administrations were recorded. One patient died of TB while another patient was lost to follow-up. Sixty-two (69.7%) patients completed the sOPAT regimen, the most common reason for premature discontinuation was adverse drug events (n = 12, 13.5%). There were eight (9.0%) port-related complications requiring port explantation (bloodstream infections: n = 6, local infection: n = 1, port thrombosis: n = 1). Conclusions In selected patients requiring long-term intravenous anti-TB therapy, sOPAT is a feasible treatment option with a low risk of complications when adequate infrastructure and training are in place.

Die Tuberkulose ist eine bakterielle Infektionskrankheit durch Mycobacterium tuberculosis und wird in der Regel als Tröpfcheninfektion durch Personen übertragen, die von einer Lungentuberkulose betroffen sind, der häufigsten Manifestation dieser Erkrankung. Mit 1,25 Millionen Todesfällen pro Jahr ist die Tuberkulose die häufigste Todesursache durch eine erregerspezifische Infektionskrankheit weltweit. Tuberculosis remains the leading cause of death from a single infectious pathogen. Despite global health initiatives and the WHO’s “End TB” Strategy, progress toward TB elimination has been slow, particularly in low- and middle-income countries. The standard treatment for drug-susceptible tuberculosis involves a 6-month combination of rifampicin, isoniazid, pyrazinamide, and ethambutol. However, results from recent clinical trials suggest that with novel treatment regimens standard tuberculosis treatment can be shortened substantially in the majority of affected patients. In the field of drug-resistant tuberculosis, innovations include 6–9-month all-oral regimens with improved efficacy and tolerability. An integrated management approach includes patient support, culturally sensitive education, management of adverse drug reactions, and close clinical monitoring. Novel diagnostic tools and biomarkers may enhance treatment monitoring in the future. Additionally, 20 new drug candidates are currently in clinical development and may offer shorter, safer, and more effective therapies. Article published online: 29 September 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany