BACTERIAL-RESISTANCE TO ANTIBIOTICS

50 years ago, the introduction of penicillin, followed by many other a ntibacterial agents, represented an often underestimated medical revol ution. Indeed, until that time, bacterial infections were the prime ca use of mortality, especially in children and elderly patients. The dis covery of numerous new substances and their development on an industri al scale gave us the illusion that bacterial infections were all but v anquished. However, the widespread and sometimes uncontrolled use of t hese agents has led to the selection of bacteria resistant to practica lly all available antibiotics. Bacteria utilize three main resistance strategies: (1) modification of their permeability, (2) modification o f target, and (3) modification of the antibiotic. Bacteria modify thei r permeability either by becoming impermeable to antibiotics, or by ac tively excreting the drug accumulated in the cell. As an alternative, they can modify the structure of the antibiotic's molecular target usu ally an essential metabolic enzyme of the bacterium - and thus escape the drug's toxic effect. Lastly, they can produce enzymes capable of m odifying and directly inactivating antibiotics. In addition, bacteria have evolved extremely efficient genetic transfer systems capable of e xchanging and accumulating resistance genes. Some pathogens, such as m ethicillin-resistant Staphylococcus aureus and multiresistant Mycobact erium tuberculosis, have become resistant to almost all available anti biotics and there are only one or two substances still active against such organisms. Antibiotics are very precious drugs which must be admi nistered to patients who need them. On the other hand, the development of resistance must be kept under control by a better comprehension of its mechanisms and modes of transmission and by abiding by the fundam ental rules of anti-infectious chemotherapy, i.e.: (1) choose the most efficient antibiotic according to clinical and local epidemiological data, (2) target the bacteria according to the microbiological data at hand, and (3) administer the antibiotic in an adequate dose which wil l leave the pathogen no chance to develop resistance.