IntroductionIn the last decade, we have witnessed a dramatic increase worldwide in the number of multidrug resistant Gram-negative (MDRGN) bacterial pathogens, with Enterobacteriacae (mostly Klebsiella pneumoniae), Pseudomonas aeruginosa and Acinetobacter baumannii being the major threats in clinical practice. Due to the resistance to the most common antibiotics prescribed as empiric regimens, MDRGN bugs have been associated with delays in an adequate treatment, leading to significant increases in morbidity and mortality.1 In addition, the spread of MDRGN pathogens resulted over last years in a vicious circle of an indiscriminate prescription of broad-spectrum antimicrobials and further resistance selection.
2The aim of this review is to describe the mechanism of resistance, epidemiology, risk factors, clinical issues, and therapeutic options of MDRGN pathogens.
Mechanism of resistance of Gram-negative bacteriaMGRGN bacteria are defined as pathogens carrying resistance to one or more antimicrobials from at least three different classes. The most common mechanism of resistance is represented by intrinsic and acquired production of b-lactamases, which can be chromosomal or plasmid mediated. b-lactamases are hydrolytic enzymes able to disrupt the b-lactam ring, thus inactivating different classes of b-lactams.3,4 The most common enzymes in clinical practice are the extended-spectrum-b-lactamases (ESBLs), which are mostly expressed by Enterobacteriaceae. A novel type of class C b-lactamases also showing activity against cefepime and denominated extended spectrum AmpC b-lactamases has been described. 4 The consequent abuse of carbapenems, representing the first choice for ESBL infections, led to a progressive increase in carbapenem resistance, mainly due to the production of carbapenem-hydrolyzing b-lactamases, or carbapenemases, that usually confer clinical resistance to most b-lactams.5,6 K. pneumoniae carbapenemases (KPCs) are the most relevant enzymes among Enterobacteriaceae, and confer resistance to all the blactams, including b-lactam/b-lactamase inhibitors combinations. Class B enzymes, named metallo-b-lactamases are expressed by both enterics and P. aeruginosa and confer resistance to all b-lactams with the exception of aztreonam. Oxacillinases belong to the class D b-lactamases, and are mostly expressed in P.
Multidrug-resistant Gram-negative bacteria-resistant infections: epidemiology, clinical issues and therapeutic optionsMatteo Bassetti, Davide Pecori, Maddalena Peghin Infectious Diseases Clinic, Santa Maria Misericordia University Hospital, Udine, Italy
ABSTRACTIn the last decade, we have witnessed a dramatic increase in the number of multidrug resistant Gram-negative (MDRGN) bacterial pathogens, both in Italy and worldwide, with Enterobacteriacae (mostly Klebsiella pneumoniae), Pseudomonas aeruginosa and Acinetobacter baumannii being the major threats in clinical practice. Inadequate empirical antimicrobial therapy of severe infections caused by MDR Enterobacteriacae has been associated with an increa...