Antimicrobial Drug Resistance in Enterobacterales and the Impact of Biofilm on Staphylococcus aureus Infections Outcomes

Antimicrobial resistance is one of the greatest challenges of the 21st century. Both Gram-negative, particularly Enterobacterales, and Gram-positive bacteria, such as Staphylococcus aureus, are commonly involved in Healthcare-Associated Infections (HCAIs) and Community-Acquired Infections (CAIs). Due to the excessive use and/or misuse of antibiotics, bacteria have evolved resistance mechanisms to almost all currently available classes. The focus of the thesis was to characterize the most important antibiotic-resistance mechanisms expressed by bacterial species representing a high threat to human health, according to the reports released by World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC). Among these Multi-Drug Resistant (MDR) pathogens, we studied and identified ESβLs and carbapenemases-producing Gram-negative bacteria involved in hospital outbreaks or causing serious infection in humans and/or animals. Antibiotic resistance is furthermore enhanced by bacterial biofilm production, which renders bacterial cells tolerant/ highly resistant to antimicrobial drugs and more difficult to eradicate. Thesis work is divided into two parts (Fig. 1). Part one includes two projects discussing the resistance mechanisms associated with carbapenem-resistant isolates belonging to the Order of Enterobacterales: KPC-2/3-producing Klebsiella pneumoniae, and NDM-5-producing Escherichia coli. Part two involves two projects. The first one includes (i) five-year retrospective analysis of bacterial species involved in ocular infections and (ii) an assessment of antibacterial and anti-biofilm activity of four currently used antibiotics against ophthalmic clinical S. aureus isolates. The second project discusses the antimicrobial activity of two compounds commonly used in ophthalmic solutions as antimicrobial preservatives, benzalkonium chloride, and zinc sulfate when they are used singly and in combination.