Pneumologie 2020; 74(S 01): 110
DOI: 10.1055/s-0039-3403305
Posterbegehung (PO21) – Sektion Infektiologie und Tuberkulose
Pneumologische Infektiologie
Georg Thieme Verlag KG Stuttgart · New York

Therapeutic drug monitoring in the treatment of M/XDR RB

N Köhler
1   Research Center Borstel, Clinical Infectious Diseases, Borstel; German Center for Infection Research (Dzif) Tuberculosis Unit, Borstel, Germany; International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany
,
F Waldow
2   Research Center Borstel, Bioanalytical Chemistry, Borstel, Germany; German Center for Infection Research (Dzif) Tuberculosis Unit, Borstel, Germany
,
HP Grobbel
1   Research Center Borstel, Clinical Infectious Diseases, Borstel; German Center for Infection Research (Dzif) Tuberculosis Unit, Borstel, Germany; International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany
,
H Karaköse
2   Research Center Borstel, Bioanalytical Chemistry, Borstel, Germany; German Center for Infection Research (Dzif) Tuberculosis Unit, Borstel, Germany
,
C Lange
1   Research Center Borstel, Clinical Infectious Diseases, Borstel; German Center for Infection Research (Dzif) Tuberculosis Unit, Borstel, Germany; International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany
,
H Hoffmann
3   Institute of Microbiology and Laboratory Medicine, WHO Supranational Reference Laboratory of Tb, Gauting, Bavaria; Institute of Microbiology and Laboratory Medicine, Synlab Mvz Gauting, Bavaria, Germany
,
PM Sachez Carballo
1   Research Center Borstel, Clinical Infectious Diseases, Borstel; German Center for Infection Research (Dzif) Tuberculosis Unit, Borstel, Germany; International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany
,
D Schwudke
2   Research Center Borstel, Bioanalytical Chemistry, Borstel, Germany; German Center for Infection Research (Dzif) Tuberculosis Unit, Borstel, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
28 February 2020 (online)

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Introduction: With more than 1.6 million deaths in 2017, tuberculosis (TB) is currently the leading cause of death by a single pathogen. The WHOʼs plans to drastically reduce TB incidence and mortality by 2035 is hampered by emerging drug resistance: The management of patients with multidrug-resistant TB (MDR-TB) and especially extensively drug-resistant TB (XDR-TB) it is costly and the drug regimens often lead to adverse drug events. Acquired drug resistance (ADR) on inadequate treatment regimens is regularly observed. Therapeutic drug monitoring (TDM) can individually optimise the dosages of drugs thus reducing the risk for ADR and adverse events. We present the effect of individualised drug dosages based on TDM for a patient with advanced XDR-TB.

Methods: In a 34 y/o male patient from Ukraine with phenotypic resistance against all 2nd-line anti-TB drugs (SLDs) except for delamanid, we evaluated minimal inhibitory concentrations (MIC) of the causative M. tuberculosis strain against all SLDs by TREK plate analysis and SLD-plasma-blood-levels by HPLC-MS². Drug levels were adjusted according to the results of the analysis.

Results: We identified intermediate level resistance against bedaquiline, moxifloxacin and cycloserine based on the MIC determination. Following the analysis of plasma concentrations of 2nd-line anti-TB agents by HPLC-MS², drug dosages were adjusted to bedaquiline 300 mg once daily 3 ×/week, moxifloxacin 1.6 g once daily, meropenem/amoxicillin/clavulanate 2 g/875 mg/125 mg trice daily, PAS13 g once daily, delamanid 100 mg twice daily, ethambutol 2.5 g once daily and terizidone 1 g once daily under careful clinical monitoring for adverse drug events. Time to culture positivity increased from 25 days to > 40 days on modified anti-TB treatment within 24 weeks.

Conclusion: Therapeutic drug monitoring could become a useful clinical tool to individualise treatment regimens for patients with M/XDR-TB where therapeutic options are limited.