RESUMEN
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 blaKPC, specifically blaKPC-2 [38.6% (88/228)] and blaKPC-3 [36.4% (83/228)]. These were frequently detected in co-concurrence with blaVIM-2 and blaNDM-1 in healthcare-acquired infections. Notably, the only identified allele among community-acquired infections was blaKPC-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 blaKPC-3. Finally, no particular carbapenemase-encoding gene was associated with worse clinical outcomes. The most identified genes in carbapenemase-producing Gram-negative rods were blaKPC-2 and blaKPC-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.IMPORTANCEAntimicrobial 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.
Asunto(s)
Antibacterianos , Proteínas Bacterianas , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas , Pseudomonas aeruginosa , beta-Lactamasas , Humanos , Colombia/epidemiología , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Estudios Retrospectivos , Masculino , Femenino , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/epidemiología , Persona de Mediana Edad , Bacterias Gramnegativas/genética , Bacterias Gramnegativas/enzimología , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/clasificación , Antibacterianos/farmacología , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/enzimología , Adulto , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/enzimología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Anciano , Infección Hospitalaria/microbiología , Infección Hospitalaria/epidemiología , Carbapenémicos/farmacología , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/epidemiología , Secuenciación Completa del Genoma , Adolescente , Adulto JovenRESUMEN
BACKGROUND: Up to 30% of patients admitted to hospitals with invasive pneumococcal disease (IPD) experience major adverse cardiovascular event (MACE) including new/worsening heart failure, new/worsening arrhythmia, and/or myocardial infarction. Streptococcus pneumoniae (Spn) is the most frequently isolated bacterial pathogen among community-acquired pneumonia (CAP) patients and the only etiological agent linked independently to MACE. Nevertheless, no clinical data exist identifying which serotypes of Spn are principally responsible for MACE. METHODS: This was an observational multicenter retrospective study conducted through the Public Health Secretary of Bogotá, Colombia. We included patients with a confirmed clinical diagnosis of IPD with record of pneumococcal serotyping and clinical information between 2012 and 2019. Spn were serotyped using the quellung method by the National Center of Microbiology. MACE were determined by a retrospective chart review. RESULTS: The prevalence of MACE was 23% (71/310) in IPD patients and 28% (53/181) in patients admitted for CAP. The most prevalent S. pneumoniae serotype identified in our study was the 19A, responsible for the 13% (42/310) of IPD in our cohort, of which 21% (9/42) presented MACE. Serotypes independently associated with MACE in IPD patients were serotype 3 (odds ratio [OR] 1, 48; 95% confidence interval [CI] [1.21-2.27]; P = .013) and serotype 9n (OR 1.29; 95% CI [1.08-2.24]; P = .020). Bacteremia occurred in 87% of patients with MACE. Moreover, serum concentrations of C-reactive protein were elevated in patients with MACE versus in non-MACE patients (mean [standard deviation], 138 [145] vs 73 [106], P = .01). CONCLUSIONS: MACE are common during IPD with serotype 3 and 9n independently of frequency.