With rising antibiotic resistance and limited novel antibiotic armamentarium, infections caused by multidrug-resistant bacterial infections are increasingly challenging to treat. In such dire situations, clinicians may need to resort to currently available antimicrobials but the dosing regimens may have to exceed conventional dosing recommendations to ensure adequate antimicrobial exposures for efficacy. This narrows the therapeutic windows for several antimicrobials, such as beta-lactams, which originally did not require therapeutic drug therapeutic monitoring (TDM) due to their excellent safety profile. In addition, patients often have complex pharmacokinetics and conventional dosing recommendations derived from healthy volunteers may be irrelevant and potentially inadequate. Conversely, subtherapeutic antimicrobial exposures due to inadequate dosing may encourage further resistance development. Hence, antimicrobial TDM becomes a valuable tool to individualise dosing regimens to ensure maximal efficacy and minimal toxicity. In this session, Nathalie shares her experience in utilising TDM as a form of precision medicine in infectious diseases to help prevent resistance development and manage multidrug resistant infections.

The exposure to toxic plants or mushrooms whether by accident, misuse, or intention can lead to serious health risks or even death. The assessment of suspected poisoning remains a major challenge in clinical toxicology due to the considerable variety of toxic plants and mushrooms, containing different harmful constituents. Depending on the ingested toxin, clinical diagnosis can be difficult as first symptoms are often unspecific and occur with a delayed onset. Treatment must often be symptomatic and supportive as a specific antidote is not always available. Currently, straightforward sample preparation procedures combined with liquid chromatography mass spectrometry (LC-MS)-based analysis may allow for fast, sensitive, and unambiguous toxin detection and/or quantification in plasma and urine. The analysis spectrum should cover non-peptide toxins such as aconitine (Aconitum napellus), atropine (Atropa belladonna), colchicine (Colchicum autumnale), cytisine (Laburnum anagyroides), digoxin and digitoxin (Digitalis purpurea/lanata), muscarin and muscimol (Amanita muscaria), nicotine (Nicotiana tabacum), or yew constituents (Taxus baccata) but also peptide toxins such as ricin (Ricinus communis), abrin (Abrus precatorius), and amanitin (Amanita phalloides, death cap). Extraction can be performed either by conventional techniques including protein precipitation, liquid-liquid extraction, and solid-phase extraction or via antibody-based enrichment using magnetic beads. The talk will give an overview of plant and mushroom toxins relevant in clinical toxicology with a focus on current LC-MS-based approaches that are used to assess suspected poisoning.

Anaplastic lymphoma kinase (ALK) inhibitors are the first-line treatment for ALK mutation-positive non-small cell lung cancer. The second-generation ALK inhibitors, which overcome crizotinib-resistance and are effective for lung cancer with brain metastases, are widely used in clinic. However, the hepatotoxic mechanism of ALK inhibitors remains unclear. Reactive metabolite (RM) is one of the risk factors for drug-induced liver injury. This lecture will provide the metabolic characteristics of three of the second-generation ALK inhibitors both in vitro and in vivo, to show that chemically reactive metabolites were formed and oxidative stress occurred. This lecture may provide new insights into the mechanism of hepatotoxic adverse reactions of ALK inhibitors from drug metabolism perspectives.