Multidrug-resistant Gram-negative bacterial infections: are you ready for the challenge?

Paralleling the developments in Gram-positive bacteria, infections caused by multidrug-resistant (MDR) Gramnegative bacilli have become a growing challenge. The most important resistance problems are encountered in Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp., with increasing trends observed for all major anti- Gram-negative agents (beta-lactams, fluoroquinolones and aminoglycosides). A matter of major concern is the emergence of new beta-lactamases capable of degrading the expanded-spectrum cephalosporins and/or carbapenems, such as the extended-spectrum beta-lactamases (ESBLs) and the carbapenemases (ie. KPC, NDM and other metallo-β; -lactamases). This paper reviews the evidence in the published literature of the pharmacokinetic/pharmacodynamic profile, clinical efficacy of new antimicrobial agents, against MDR- Gram-negative pathogens, such us: i-new carbapenems (doripenem, biapenem, panipenem, tonopenem, FSI-1686); ii-new cephalosporins (ceftaroline, ceftobiprole); iii-tigecycline; and iv- β- lactamases inhibitors (BLI-489, Ro 48-1220, ME 1071, aviactam [NXL104]).