Phenotypic and genotypic characterization of Klebsiella pneumoniae isolates recovered from colonized patients

• Grant number: 25/11181-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Ana Cristina Gales
• Grantee: Beatriz Borges Gentil
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 21/10599-3 - The Antimicrobial Resistance Institute of São Paulo (The Aries Project), AP.CEPID

Abstract

Klebsiella pneumoniae (KPN) is a major pathogen in healthcare-associated infections (HAIs). In 2023, it was the second most frequently reported pathogen (n=4063) in bloodstream infections in adult ICUs across Brazil, with 60.5% of isolates showing resistance to carbapenems7. Carbapenem-resistant K. pneumoniae (CR-KPN) is classified by the WHO as a critical priority pathogen for antibiotic development and is among the most clinically relevant microorganisms worldwide. Globally, K. pneumoniae was responsible for over 150,000 deaths in 2019, with 55,700 deaths attributed to its carbapenem-resistant form-approximately 15% of these occurred in Latin America and the Caribbean.Carbapenem resistance in KPN is usually mediated by carbapenemases, enzymes that hydrolyze carbapenems. These resistance genes are often plasmid-borne, enabling horizontal transfer across and within species. Until 2020, KPC (K. pneumoniae carbapenemase) was the most commonly detected carbapenemase in Brazil. However, during the COVID-19 pandemic, there was a notable rise in the detection of NDM (New Delhi metallo-¿-lactamase) and the co-production of KPC and NDM within the same bacterial strain9.This shift is concerning, as newer antimicrobials such as ceftazidime-avibactam are ineffective against metallo-¿-lactamase-producing strains.K. pneumoniae can colonize mucosal surfaces, especially the gastrointestinal tract, and may translocate to the bloodstream, leading to bacteremia, pneumonia, liver abscesses, and urinary tract infections, often resulting in poor clinical outcomes6. Colonization by CR-KPN is a significant risk factor for subsequent invasive infections. Studies have shown bloodstream infection rates ranging from 4.5% to 7.9% in colonized patients5 In high-risk groups, such as those evaluated by Cano et al., 47% of KPC-colonized patients developed infections, with a 90-day mortality rate of 41.6% compared to 18% in non-colonized individuals2. Temkin et al. also identified KPC and NDM as the most common carbapenemases in colonized patients who progressed to bloodstream infections.These findings underscore the increased susceptibility of CR-KPN-colonized patients to invasive disease. However, important knowledge gaps remain regarding the microbial mechanisms driving this progression. Recent studies have identified molecular features in K. pneumoniae, such as the expression of the type VI secretion system (T6SS), that may enhance colonization and facilitate bloodstream invasion. (AU)