Despite of the widespread antibiotic use, the hospital acquired infections are still a great problem. Several factors influence the changing spectrum of etiological agents: an increased level of drug resistance, a possible bacterial synergism in more frequent polymicrobial infections, some environmental risk factors, and a higher number of compromised hosts. For these reasons a lot of opportunists such as the enterobacteria, the Gram positive resurgent cocci and the new ones (nonfermenting Gram negative bacilli, anaerobes, Legionellas, atypical mycobacteria and fungi) still emerge creating a significant therapeutic challenge.