• F Trémolières, R Garraffo, and O Lortholary.
• Service de médecine interne, hôpital François-Quesnay, 78200 Mantes-la-Jolie, France. ftremo@noos.fr
• Med Mal Infect. 2005 Aug 1; 35 Suppl 3: S229-35.

AbstractThe golden age of antibacterial antibiotics extend from year 1941 to the 1990s decade. At that time, something like an earth quake occurred: from the thirty molecules or so whose development was being achieved or was already marketed, only three were put on the French market, and faced the greatest difficulties to be prescribed by practicians, because: the knights of good practice want a strict limitation of their use to precise indications; the pharmaceutical companies find that the return on investment is almost impossible; the prescribers are stunned by the inconsistency between the MAs, the advances in science and the health economic authorities advices which claim that these products are not very interesting; the research for new antibiotics is stalling; thus, for the first time in 60 years, an iconoclastic question arises: do we need new antibiotics? However, while the debate is raging, many of us think "yes we do", as it is a duty to anticipate today the consequences of tomorrow's bacterial resistances. This paper presents three types of propositions to optimise the development of future molecules: sharpening of the data concerning preclinical security for a better predicting of both the activity and the toxicity; improvement in performances and organization of clinical trials, which implicates to reconsider some of the present methodological rules; inclusion in the evaluation data of some relevant and new features measuring the anti-bacterial activity while taking into account the present and future bacterial resistances. The development of new concepts to develop new drugs which would be active against tomorrow's bacteria compels us to manage in a new fashion today's systems, which have reached their own limits.

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