Klebsiella pneumoniae is a Gram-negative opportunistic pathogen responsible for a variety of community and hospital infections. Infections caused by carbapenem-resistant K. pneumoniae (CRKP) constitute a major threat for public health and are strongly associated with high rates of mortality, especially in immunocompromised and critically ill patients. Adhesive fimbriae, capsule, lipopolysaccharide (LPS), and siderophores or iron carriers constitute the main virulence factors which contribute to the pathogenicity of K. pneumoniae. Colistin and tigecycline constitute some of the last resorts for the treatment of CRKP infections. Carbapenemase production, especially K. pneumoniae carbapenemase (KPC) and metallo-β-lactamase (MBL), constitutes the basic molecular mechanism of CRKP emergence. Knowledge of the mechanism of CRKP appearance is crucial, as it can determine the selection of the most suitable antimicrobial agent among those most recently launched. Plazomicin, eravacycline, cefiderocol, temocillin, ceftolozane–tazobactam, imipenem–cilastatin/relebactam, meropenem–vaborbactam, ceftazidime–avibactam and aztreonam–avibactam constitute potent alternatives for treating CRKP infections. The aim of the current review is to highlight the virulence factors and molecular pathogenesis of CRKP and provide recent updates on the molecular epidemiology and antimicrobial treatment options.

Acinetobacter baumannii is a Gram-negative pathogen responsible for a variety of community- and hospital-acquired infections. It is recognized as a life-threatening pathogen among hospitalized individuals and, in particular, immunocompromised patients in many countries. A. baumannii, as a member of the ESKAPE group, encompasses high genomic plasticity and simultaneously is predisposed to receive and exchange the mobile genetic elements (MGEs) through horizontal genetic transfer (HGT). Indeed, A. baumannii is a treasure trove that contains a high number of virulence factors. In accordance with these unique pathogenic characteristics of A. baumannii, the authors aim to discuss the natural treasure trove of pan-genome and virulence factors pertaining to this bacterial monster and try to highlight the reasons why this bacterium is a great concern in the global public health system.

Pseudomonas aeruginosa, a Gram-negative, motile bacterium, may cause significant infections in both community and hospital settings, leading to substantial morbidity and mortality. This opportunistic pathogen can thrive in various environments, making it a public health concern worldwide. P. aeruginosa’s genomic pool is highly dynamic and diverse, with a pan-genome size ranging from 5.5 to 7.76 Mbp. This versatility arises from its ability to acquire genes through horizontal gene transfer (HGT) via different genetic elements (GEs), such as mobile genetic elements (MGEs). These MGEs, collectively known as the mobilome, facilitate the spread of genes encoding resistance to antimicrobials (ARGs), resistance to heavy metals (HMRGs), virulence (VGs), and metabolic functions (MGs). Of particular concern are the acquired carbapenemase genes (ACGs) and other β-lactamase genes, such as classes A, B [metallo-β-lactamases (MBLs)], and D carbapenemases, which can lead to increased antimicrobial resistance. This review emphasizes the importance of the mobilome in understanding antimicrobial resistance in P. aeruginosa.

Changes in hospitals’ daily practice due to COVID-19 pandemic may have an impact on antimicrobial resistance (AMR). We aimed to assess this possible impact as captured by the Greek Electronic System for the Surveillance of Antimicrobial Resistance (WHONET-Greece). Routine susceptibility data of 17,837 Gram-negative and Gram-positive bacterial isolates from blood and respiratory specimens of hospitalized patients in nine COVID-19 tertiary hospitals were used in order to identify potential differences in AMR trends in the last three years, divided into two periods, January 2018–March 2020 and April 2020–March 2021. Interrupted time-series analysis was used to evaluate differences in the trends of non-susceptibility before and after the changes due to COVID-19. We found significant differences in the slope of non-susceptibility trends of Acinetobacter baumannii blood and respiratory isolates to amikacin, tigecycline and colistin; of Klebsiella pneumoniae blood and respiratory isolates to meropenem and tigecycline; and of Pseudomonas aeruginosa respiratory isolates to imipenem, meropenem and levofloxacin. Additionally, we found significant differences in the slope of non-susceptibility trends of Staphylococcus aureus isolates to oxacillin and of Enterococcus faecium isolates to glycopeptides. Assessing in this early stage, through surveillance of routine laboratory data, the way a new global threat like COVID-19 could affect an already ongoing pandemic like AMR provides useful information for prompt action.

Clostridioides difficile infection (CDI) is the leading cause of nosocomial antibiotic-associated diarrhea, and colitis, with increasing incidence and healthcare costs. Its pathogenesis is primarily driven by toxins produced by the bacterium C. difficile, Toxin A (TcdA) and Toxin B (TcdB). Certain strains produce an additional toxin, the C. difficile transferase (CDT), which further enhances the virulence and pathogenicity of C. difficile. These toxins disrupt colonic epithelial barrier integrity, and induce inflammation and cellular damage, leading to CDI symptoms. Significant progress has been made in the past decade in elucidating the molecular mechanisms of TcdA, TcdB, and CDT, which provide insights into the management of CDI and the future development of novel treatment strategies based on anti-toxin therapies. While antibiotics are common treatments, high recurrence rates necessitate alternative therapies. Bezlotoxumab, targeting TcdB, is the only available anti-toxin, yet limitations persist, prompting ongoing research. This review highlights the current knowledge of the structure and mechanism of action of C. difficile toxins and their role in disease. By comprehensively describing the toxin-mediated mechanisms, this review provides insights for the future development of novel treatment strategies and the management of CDI.