Molecular characterization and descriptive analysis of carbapenemase-producing Gram-negative rod infections in Bogota, Colombia
Authors: Ibáñez-Prada Elsa D. , Bustos Ingrid G. , Gamboa-Silva Enrique , Josa Diego F. , Mendez Lina , Fuentes Yuli V. , Serrano-Mayorga Cristian C. , Baron Oscar , Ruiz-Cuartas Alejandra , Silva Edwin , Judd Louise M. , Harshegyi Taylor , Africano Hector F. , Urrego-Reyes Juan , Beltran Claudia C. , Medina Sebastian , Leal Rafael , Stewardson Andrew J. , Wyres Kelly L. , Hawkey Jane , Reyes Luis Felipe 
Published: April 2024

In this study, the genetic differences and clinical impact of the carbapenemase-encoding genes among the community and healthcare-acquired infections were assessed. This retrospective, multicenter cohort study was conducted in Colombia and included patients infected with carbapenem-resistant Gram-negative rods between 2017 and 2021. Carbapenem resistance was identified by Vitek, and carbapenemase-encoding genes were identified by whole-genome sequencing (WGS) to classify the alleles and sequence types (STs). Descriptive statistics were used to determine the association of any pathogen or gene with clinical outcomes. A total of 248 patients were included, of which only 0.8% (2/248) had community-acquired infections. Regarding the identified bacteria, the most prevalent pathogens were
Pseudomonas aeruginosa
and
Klebsiella pneumoniae
. In the WGS analysis, 228 isolates passed all the quality criteria and were analyzed. The principal carbapenemase-encoding gene was
bla
KPC, specifically
bla
KPC-2 [38.6% (88/228)] and
bla
KPC-3 [36.4% (83/228)]. These were frequently detected in co-concurrence with
bla
VIM-2 and
bla
NDM-1 in healthcare-acquired infections. Notably, the only identified allele among community-acquired infections was
bla
KPC-3 [50.0% (1/2)]. In reference to the STs, 78 were identified, of which
Pseudomonas aeruginosa
ST111 was mainly related to blaKPC-3.
Klebsiella pneumoniae
ST512, ST258, ST14, and ST1082 were exclusively associated with
bla
KPC-3. Finally, no particular carbapenemase-encoding gene was associated with worse clinical outcomes. The most identified genes in carbapenemase-producing Gram-negative rods were
bla
KPC-2 and
bla
KPC-3, both related to gene co-occurrence and diverse STs in the healthcare environment. Patients had several systemic complications and poor clinical outcomes that were not associated with a particular gene.

IMPORTANCE

Antimicrobial resistance is a pandemic and a worldwide public health problem, especially carbapenem resistance in low- and middle-income countries. Limited data regarding the molecular characteristics and clinical outcomes of patients infected with these bacteria are available. Thus, our study described the carbapenemase-encoding genes among community- and healthcare-acquired infections. Notably, the co-occurrence of carbapenemase-encoding genes was frequently identified. We also found 78 distinct sequence types, of which two were novel
Pseudomonas aeruginosa
, which could represent challenges in treating these infections. Our study shows that in low and middle-income countries, such as Colombia, the burden of carbapenem resistance in Gram-negative rods is a concern for public health, and regardless of the allele, these infections are associated with poor clinical outcomes. Thus, studies assessing local epidemiology, prevention strategies (including trials), and underpinning genetic mechanisms are urgently needed, especially in low and middle-income countries.