Infecções relacionadas à assistência à saúde em unidades de terapia intensiva de adultos no Brasil: Uma abordagem multicêntrica

Abstract

Healthcare-associated infections (HAIs) remain one of the major global health challenges, particularly in low- and middle-income countries such as Brazil, where the clinical and economic impact is exacerbated by the high prevalence of multidrug-resistant microorganisms. This thesis, composed of three interrelated articles, integrates different aspects of the epidemiology and dissemination of Klebsiella pneumoniae and Acinetobacter baumannii resistant to carbapenems, as well as a discussion of the clinical impact of HAIs in Brazilian intensive care units (ICUs). The first article aimed to determine the point prevalence of HAIs and identify factors associated with microbiologically confirmed infections in adult ICUs across Brazil. This multicenter study, conducted in 57 ICUs from different regions of the country, included 664 patients, of whom 47.7% had HAIs, with 68.1% acquired in the ICU. Only 47.2% of these infections were microbiologically confirmed. Mechanical ventilation and the use of polymyxins were identified as independent risk factors. The etiology of pneumonia, urinary tract infections, and bloodstream infections (BSIs) was predominantly associated with Pseudomonas aeruginosa and Acinetobacter baumannii; Candida spp.; and coagulase-negative Staphylococcus, respectively. The second article investigated the dissemination of resistance genes (by polymerase chain reaction – PCR) and pulsotypes (by pulsed-field gel electrophoresis – PFGE) in Klebsiella pneumoniae carbapenemase- producing (KPC) and Acinetobacter baumannii oxacillinase-producing (OXA-23) isolates from hospitals located in the North, Northeast, Southeast, and Central-West regions of Brazil. The blaOXA-23 and blaKPC genes were detected in 88.1% and 83.3% of A. baumannii and K. pneumoniae isolates, respectively, and all displayed multidrug- resistant profiles. Eleven distinct genotypes of A. baumannii were identified, with clone E detected in the Southeast (2016) and Central-West (2019) regions. No inter-regional dissemination of identical K. pneumoniae pulsotypes was observed. The third article, presented as a letter complementing a previous international study, expanded the discussion on the clinical impact of carbapenem-resistant Klebsiella pneumoniae infections. As part of this thesis, a letter was written discussing the study by Shao et al. (2024), which analyzed bloodstream infections in pediatric intensive care units in China. Our contribution compared those findings with data from our multicenter cohort of adult ICU patients with multidrug-resistant K. pneumoniae infections, emphasizing the high mortality associated with carbapenem-resistant strains. The letter highlighted

similarities between pediatric and adult populations regarding risk factors and clinical outcomes, particularly in severe infections such as BSIs and pneumonia, and reinforced the urgent need for targeted strategies to combat antimicrobial resistance in both patient groups. Taken together, the three studies provide a comprehensive overview of HAIs in Brazilian ICUs, revealing their high prevalence, regional dissemination, and clinical impact, particularly regarding infections caused by multidrug-resistant K. pneumoniae. The findings underscore the importance of strengthening epidemiological surveillance policies, microbiological diagnosis, and rational antimicrobial use, as well as promoting the integration of national and international data to address the global challenge of bacterial resistance.