Emerging antimicrobial resistance mechanisms in Gram-negative bacteria: focus on the Italian epidemiology

ABSTRACT The phenomenon of antibiotic resistance in clinical bacterial isolates is a serious worldwide health problem. The clinical efficacy of certain antibiotic molecules, such as carbapenems, considered antimicrobial drugs of last resort for the treatment of severe infections sustained by Enterobacteriaceae, is now little bit uncertain because of the diffusion of microorganisms able to resist to these molecules. At least two mechanisms can be responsible for acquired carbapenem resistance in Enterobacteriaceae: (i) reduced outer membrane permeability by porin loss in combination with the production of an extended-spectrum β-lactamase (ESBL) or of AmpC-type β-lactamase; and (ii) production of β-lactamases capable of hydrolysing carbapenems (carbapenemases). The latter is the most important from a clinical point of view for its diffusion and efficacy. In Italy Carbapenem-resistant Enterobacteriaceae (CRE) are diffused throughout all territory. Particularly in recent years there has been a significant and rapid increase of Klebsiella pneumoniae resistant to carbapenems. KPC producing K. pneumoniae were described in Italy for the first time in 2009 and now account for 29% of overall K. pneumoniae from invasive infections. The problem is a matter of concern due to the few therapeutic options available and to the high mortality rate associated to such infections. Most of this PhD study was focused on the detection of emerging resistance determinants in gram negative bacteria, with particular attention on carbapenemase producing Enterobacteriaceae. In this work are reported the results of a nationwide survey promoted by the ISS (Istituto Superiore di Sanità) for the project AR-ISS to investigate the rate of resistance to carbapenem of carbapenemase in Italy and to characterize the most prevalent resistance mechanism and their dissemination patterns, confirming that CREs are showing an endemic diffusion across the Italian territory. Moreover, are reported others works describing the identification of new carbapenemase variants have been performed, in collaboration with other Italian hospitals. Surveillance and efficient infection control practices are of paramount importance to limit the spread of these multi-drug resistant microorganism within health-care structure, and national infection control program is urgent and needed.