Preserving old antibiotics for the future : assessment of clinical efficacy by a pharmacokinetic/pharmacodynamic approach to optimize effectiveness and reduce resistance for off-patent antibiotics (AIDA)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Netherlands,Israel,Sweden,Denmark,Switzerland,Greece,United Kingdom,France,Poland,Italy,United Kingdom,Italy,Netherlands,Serbia,Austria,United Kingdom
Call:  (FP7-HEALTH-2011-two-stage, 2011)
Start date: 2011-12-01
End date: 2017-11-30
Duration (months): 72.0
Total project cost (EUR): 7768103.93
EU funding (EUR): 5999860.0
Participants: 19
Project status: CLOSED

The AIDA project aims to answer the question of clinical effectiveness and optimal dosing of 5 off-patent antibiotics for infections caused by multiple drug resistant (MDR) bacteria in three randomized controlled clinical trials. In an era of increasing emergence of drug resistance (EDR) and lack of new antibiotics, old off- patent antibiotics are increasingly being prescribed to patients. However, many of these were developed in an age before the advent of a structured process for drug assessment and approval, and the establishment of clinical efficacy and effectiveness in randomized controlled trials in particular. In a multidisciplinary approach the exposure response relationships for each antibiotic will be elucidated by including pharmacokinetic (PK), pharmacodynamic (PD) and microbiological studies, including emergence of drug resistance (EDR). The project addresses the optimization of treatment of infections caused by MDR pathogens that impose a major burden of disease in Europe and the rest of the world by selecting 5 off-patent-antibiotics that are increasingly being used without clear evidence with respect to their effectiveness, duration of therapy and issues of EDR. In the first trial the efficacy of colistin alone is compared to colistin plus imipenem for severe infections caused by carbapenem-resistant bacteria. The second trial compares fosfomycin vs. nitrofurantoin for the treatment of lower urinary tract infection in women at high risk of antibiotic-resistant pathogens. In the third trial antimicrobial oral treatment with minocycline plus rifampicin is compared with oral treatment with linezolid for complicated skin and soft tissue infections (cSSTI) due to MRSA. Exposure – response relationships, PK/PD and EDR issues will be addressed in a separate project component and is an essential element of the research project that will interrelate synergistically with the clinical studies. The results thereof will be used to refine exposure response relationships but also to study effects of exposure that are not readily observed in the trials. This will aid to delineate optimal exposures and drug dosing. This project addresses an urgent medical need that is critical both for individual patients and for society. An effective dissemination strategy is essential to effectively communicate project results to the target groups therefore supporting the project goal of preserving and strengthening the public health benefits of the studied off-patent antibiotics. The dissemination of project results to professional groups and the public in general, communication to policymakers, and implementation of results in national formularies is an important aspect.

Keywords: off-patent antibiotics,colistin,nitrofurantoin,minocyclin,rifampicin,fosfomycin,rct,trial,pharmacokinetics,pharmacodynamics,emergence multi-drug resistance,esbl,kpc,gram-negatives,mrsa