Multi-drug resistant tuberculosis in the Netherlands: Personalised treatment and outcome

Tuberculosis (TB) caused by bacilli that are resistant to the two major drugs, rifampicin and isoniazid is defined as Multi-Drug Resistant TB or MDRTB. MDRTB kills around 50% of people affected around the world. In contrast, treatment results of MDR-TB in the Netherlands (1985-2013) have consistently shown a high success rate (86%). This is comparable with worldwide WHO-targets for drug TB that is susceptible to 1st line TB drugs. Treatment of MDRTB was based on drug susceptibility testing (DST) and fast molecular genetic tests, while dosage was adjusted by pharmacokinetic measurements, by measuring drug concentrations in blood samples over time to estimate the total exposure of the drug and modeled these measurements to optimize dosing by maintaining efficacy while at the same time minimizing dose-dependent toxicity. We advocate a search for other antibiotics, not only new ones like bedaquiline and delamanid, but also antibiotics registered for other infections that may help treat TB. As such we describe ertapenem, not included in the WHO list of MDR-TB drugs. We argue that ertapenem is a promising drug for TB, with reasonable efficacy and limited side effects. Using aminoglycosides for MDR-TB, we applied individualized dosing based on the peak concentration divided by the minimal inhibitory concentration; we reduced the number of blood samples taken by comparing a limited sampling strategy with standard multiple blood sampling. The median dose was in our patients 400 mg, more than two-fold lower than the dose recommended by WHO, while outcome in our patients was favourable without failures or relapses. Concluding remarks. Molecular sensitivity testing combined with pharmacokinetic/pharmacodynamics may be an important weapon in the global fight against MDR-TB.In regard to aminoglycosides prospective PK/PD studies are necessary to confirm the efficacy of the lower dosage.Likewise, ertapenem needs further investigations as is seems to be a highly promising drug for the treatment of MDR-TB, parameters being efficacy and safety.