[Epidemiology and mechanisms of resistance: clinical and environmental impact]

The increasing spread of multi-resistant strains of bacteria, particularly in the hospital setting, is currently one of the major challenges that antibiotic therapy must face. Initial, inappropriate antibiotic treatment that does not provide sufficient activity against multi-resistant pathogens is often responsible for increased mortality. The micro-organisms causing infections that are particularly problematic to treat include the Gram-negative bacilli, in particular Pseudomonas aeruginosa, and the Gram-positive cocci, such as methicillin-resistant Staphylococcus aureus (MRSA) or enterococci. The most appropriate empirical therapy should include broad-spectrum antibiotics with the ability to reach therapeutic concentrations in the site of the infection in order to limit the emergence of resistant strains. The use of combinations of antibiotics that have synergistic effects on certain bacterial species can contribute substantially to achieving this goal. A large body of published data shows that the efficacy and induction of resistance vary markedly when different antibiotics are used, alone or in combination, and when different concentrations of the antibiotics are reached in the various sites of infection. In vitro studies have shown that, compared to monotherapy with a single antibiotic, synergistic combinations of antibiotics lead to significantly less selection of resistant strains of both P. aeruginosa and MRSA.