When and how to cover for resistant gram-negative bacilli in severe sepsis and septic shock

In the 80s and 90s, increasing antibiotic resistance was met by the introduction of new effective agents with broader antibacterial spectra for the empirical treatment of severe infections. In recent years, however, few novel antimicrobials have been developed, and this has critically weakened our strength in the fight against resistant bacteria, especially Gram-negative bacilli. It has been well proven that mortality increases if initial empirical antibiotic treatment for severe infection is inappropriate due to resistance of the pathogen. Physicians are already faced with the increasing challenge of untreatable or almost untreatable Gram-negative infections due to antibiotic resistance. Empirical treatment with broader spectra and high antibiotic pressure both in- and outside hospital is the driving force behind resistance. Since new efficient drugs against Gram-negative bacilli will not be available for some time, the best we can do to stop infections caused by multidrug-resistant bacteria is to improve infection control and choice of antibiotics, which should be based on surveillance of local antibiotic consumption and resistance. We must learn more about the revived antibacterial agents colistin and fosfomycin, and the few next generation Gram-negative antibiotics that have been developed. The aim of this review is to give an update on present therapeutic options in the fight against multidrug-resistant Gram-negative bacteria.