Pseudomonas aeruginosa and Acinetobacter baumannii are important nosocomial pathogens in health care settings. Treatment of serious nosocomial infections caused by these microorganisms is complicated by multi-drug resistance. Increasing of P. aeruginosa and A. baumannii resistance to carbapenems mediated by Metallo-beta-Lactamases (MBLs), by acquired OXA-23, OXA-40 or OXA-58-like carbapenemases and other mechanisms, is a cause for concern.
Resistance in P. aeruginosa may be mediated via several distinct mechanisms. TEM, SHV and CTX-M Extended-Spectrum-beta-Lactamases (ESBLs) all have been reported in P. aeruginosa, but are uncommon. The presence of multiple efflux pumps, outer membrane changes and acquisition of MBLs, remain significant resistance problems in this species as well as in other non-fermenters. In MDR isolates, the relative contributions of different molecular mechanisms toward phenotypic multidrug resistance are not well established. It is commonly believed that in MDR P. aeruginosa isolates, reduced virulence may result due to decreased biofitness. However, recent data suggest otherwise, and MDR P. aeruginosa may remain fully pathogenic. Molecular virulence factors characterization and clonality studies could be therefore essential in demonstrating the whole pathogen potential, the bacterial environmental persistence and ability to cause outbreaks.
This analysis could be also important for documenting the start of chronic colonisation in patients for whom eradication treatment following the first isolation of P. aeruginosa has failed, for demonstrating cross-colonisations between patients, or for identifying hyper-transmissible clones.
A. baumannii, infections tend to occur mostly in Intensive Care Units (ICUs).
The pathogenic determinants that have been reported for A. baumannii include a novel pilus assembly system involved in biofilm formation, an outer membrane protein (Omp38) that causes apoptosis and a conserved polycistronic siderophore-mediated iron-acquisition system.
Exopolysaccharide production by pathogenic bacteria is a major virulence factor. Quorum-sensing might be a central mechanism for auto-induction of multiple virulence factors in an opportunistic pathogen such as Acinetobacter and this process should be studied for its clinical implications. Many parameters, including host factors, bacterial burden and virulence of individual strains, may play important roles in causing infection in colonised patients. The aim of this study will be to investigate the relationships among antibiotic resistance, pathogenicity of P. aeruginosa and A. baumannii post-surgical invasive strains and host factors predisposing to infection.
The research plan will lead to completely characterize antibiotic-resistance, survival and persistence mechanisms of the highly successful gram-negative non-fermenter strains spread in Italian settings. A. baumannii clones will be evaluated for the association with major European clonal lineages.
The results will be instrumental for the development of novel strategies to counteract the persistence of A. baumannii and P. aeruginosa invasive clones, for the design of novel specific inhibitors/or antimicrobials and to circumvent multidrug-resistance of these bacteria.
Recently Klebsiella pneumoniae producing class A carbapenemase of KPC type, characterized by multidrug- or pandrug- resistance has emerged as a new important nosocomial pathogen and the dissemination of KPC-producing K. pneumoniae is of great concern to public health services worldwide. In KPC-producing K. pneumoniae infections, antibiotic options are dramatically restricted. The study will investigate phenotypic/molecular features and clonal relatedness of carbapenem-resistant K. pneumoniae isolates from different Italian settings. Improved detection of new resistant strains especially by using practical and affordable screening methods and by evaluating mechanisms of resistance is a priority to implement infection control measures and limit the spread of these worrisome strains.