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Infections with organisms that are resistant to various anti-microbial agents pose a serious challenge to effective management of infections. Resistance to antimicrobial agents, which may be intrinsic or acquired, has been noted in a wide variety of microorganisms causing human infections. These include resistance to antiviral agents in HIV, HBV, CMV and influenza virus, anti-parasitic agents in Plasmodium falciparum, anti-fungal agents in certain Candida species and MDR (multidrug-resistant) tuberculosis. It is however, the problem of multidrug-resistant bacterial infections (caused by MRSA, VRE, ESBL/AmpC/metallo-β lactamase producers and colistin-resistant Gram-negative bacilli) that has become a cause of major concern in clinical settings. Infections with these organisms can increase morbidity, mortality, increase the cost of therapy and increase the duration of hospitalization. The objective of this article is to review the question how early diagnosis of these infections, affects the overall management of infected or colonized patients, with regard to antimicrobial therapy.