oa Editorial [Hot Topic: Tuberculosis; Opportunities for Treatment Optimization (Executive Guest Editor: Jan-Willem C. Alffenaar)]

Treatment options for Tuberculosis (TB) have increased and knowledge has greatly increased in the past decades. To reduce the burden of TB, it's the intention to expand and enhance DOTS, to tackle TB/HIV and MDR -TB, empower health care systems, create political commitment and inspire health care providers and investigators. Yet new efforts are required to fight the new challenges and threats of multidrug-resistant and extensively drug-resistant TB. Two different approaches are necessary. First, the development and further testing of novel compounds and shorter treatment regimens; and second the optimization of treatment with currently available drugs. Early diagnosis, drug susceptibility testing and choosing the appropriate drugs are likely to contribute to the reduction and spread of TB. In this issue of the Journal we have selected several important aspects of the treatment of TB with an emphasis on optimization of currently available antimicrobial treatment. Van Altena and co-authors provide an update on the current concepts of local and systemic immune response to Mycobacterium tuberculosis, and focus on potentially modifiable factors - i.e., the micro-nutrients iron, and vitamin D. Along with drug treatment optimizing these may have a beneficial effect on the outcome of TB treatment. As emphasized by the WHO drug susceptibility testing is important to select the appropriate drug and appropriate dosage. New rapid testing can distinguish between drug susceptible and drug resistant TB and therefore guide the initial treatment. Simons and van Soolingen discuss the advantages of the recently developed methods - notably, molecular techniques, but also address important points like bio-safety, reproducibility and quality control. Finally they place drug sensitivity testing in a broader perspective of pharmacokinetics and pharmacodynamics of TB drugs and its potential use to tailor TB treatment and have an impact on global TB treatment strategies. Although the potential role of FDG PET in the routine diagnosis of tuberculosis is limited, Kosterink showed that especially FDG PET, as diagnostic tool, could be a noninvasive method that gives additional information about the disease status. These data can be of use to improve TB treatment. Besides, PET imaging could be useful in the evaluation of antimicrobial drugs for the treatment of TB as its enables to study bio-distribution and, tissue or TB lesions penetration or targeting. In vitro and in vivo modeling of TB drugs has increased our knowledge on how to optimize the use of TB drugs considerably. Integrating both pharmacokinetics and pharmacodynamics in in vitro and in vivo models made it possible to detect the correlation between drug exposure and killing of the TB bacteria. Srivastava and Gumbo discuss studies using static and dynamic models and their use to design and optimize dosage regimens. More importantly, they also discuss the translation of these optimized regimens into clinical practice. Population pharmacokinetics has been used to identify and explain variability among patients. As TB patients fail on current treatment regimens important parameters may be identified that can be related to the safety and efficacy of TB drugs. Egelund and colleagues give a clear introduction on population pharmacokinetics and compartmental modelling. They discuss the different studies that support the hypothesis that the current dosage of several TB drugs may be too low. While these studies investigated only mono therapy, the authors emphasize that combination regimens are used in daily practice and new studies are urgently needed to investigate the effect of combined antimicrobial treatment. Finally, the new dosage regimens based on population pharmacokinetics and simulations have to be evaluated in prospective clinical studies to assess their added value and superiority over the current treatment.....