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Since the discovery of penicillin in 1928 and it's production in 1938 and Prontosil and related sulfa drugs after 1932, antibiotic resistance has been on the rise. This is currently threatening many gains in infectious diseases which have been made over all those decades. The first penicillin-resistant bacteria where already identified before penicillin came on the market in the 1940s, methicillin-resistance was documented in the 1980s and vancomycin-resistance in the 1990s. It is estimated that more than 50% of the world production of antibiotics is for use in the agricultural sector, not so much to cure sick animals by veterinarians but veterinarians, but for food additives. New threats include multi-resistance in a multitude of pathogens including Plasmodium falciparum, Mycobacterium tuberculosis, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci and the appearance of Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-beta-lactamase (NDM-1) in several Gram-negatives in the first decade of the 21st Century. Since (1) Gram-negative bacteria easily share resistance genes across species, (2) less  fewer new antibiotics are discovered due to several reasons, (3) and the increase in world travel "-both numbers of people and speed of travel"-, the conditions for a perfect storm ("total resistance") are in the making, threatening to bring us back to conditions similar to where we were during World War One. The bottom line in pharmaceutical industries is financial gain. The development of new classes of drugs to treat multi-resistant bacteria is rather challenging. Even if successful, the drugs will probably be used for a short period of time before resistance arrives, and therefore are not considered to be worth the great expense of research and development time. Better incentives (e.g. longer patent protection) are needed. Maybe formal agreements such as were used during polio vaccine development are needed to protect companies against financial disaster. Basic as well as applied research needs to be boosted. Let's hope that we won't need a Manhattan-type of project if things seriously get out of hand. In our direct workplaces as doctors and nurses, meticulous disinfection of hands and surfaces will need to be instituted to limit spread and outbreaks.