World Health Organization priority antimicrobial resistance in Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecium healthcare-associated bloodstream infections in Brazil (ASCENSION): a prospective, multicentre, observational study

Abstract

Background: Carbapenem-resistant Enterobacterales (CRE), Acinetobacter baumannii (CRAB), Pseudomonas aeruginosa (CRPA), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) are listed by World Health Organization (WHO) as priority antimicrobial-resistant bacteria. Data on WHO Priority Antimicrobial resistance Phenotype (WPAP) bacteria from low- and middle-income countries are scarce. In this study, we investigated the occurrence of WPAP in healthcare-associated bloodstream infections (BSI) in Brazil, an upper-middle-income country in South America.

Methods: ASCENSION was a prospective, multicentre, observational study conducted in 14 hospitals from four of five Brazilian regions. Enterobacterales, A. baumannii, P. aeruginosa, S. aureus and E. faecium BSIs in hospitalised patients were analysed. The primary outcome was the frequency of WPAP among all bacteria of interest. Secondary outcomes were incidence-density of bacteria isolates in hospitalised patients, WPAP proportions within bacterial species, and 28-day mortality. PCR for carbapenemase genes was performed in carbapenem-resistant Gram-negative bacteria.

Findings: Between August 15, 2022, and August 14, 2023, 1350 isolates (1220 BSI episodes) were included. WPAP accounted for 38.8% (n = 524; 95% Confidence Interval 32.0-46.1) of all isolates, with CRE (19.3%) as the most frequent, followed by CRAB (9.6%), MRSA (4.9%), VRE (2.7%), and CRPA (2.4%). Incidence-density of all and WPAP isolates were 1.91 and 0.77/1000 patients-day, respectively. Carbapenem-resistant Klebsiella pneumoniae (CRKP) was the most common CRE, corresponding to 14.2% of all BSIs. A. baumannii isolates presented the highest proportion of WPAP (87.8%). Mortality rates were higher in patients with BSIs by WPAP than non-WPAP isolates. KPC (64.4%) was the predominant carbapenemase in CRE, followed by NDM (28.4%) and KPC + NDM co-production (7.1%). OXA-23 was the most frequent in CRAB.

Interpretation: A high frequency of WPAP bacteria, particularly CRKP and CRAB, were found in healthcare-associated BSIs in Brazil, posing them as a major public health problem in this country.

Funding: National Council for Scientific and Technological Development, Brazil.

Keywords: Acinetobacter baumannii; Antimicrobial resistance; Bloodstream infections; Carbapenem resistance; Enterobacterales; Enterococcus faecium; Epidemiology; Healthcare-associated infections; Klebsiella pneumoniae; Methicillin resistance; Pseudomonas aeruginosa; Staphylococcus aureus; Vancomycin resistance.

Fig. 1

Flowchart of the study. WPAP, World Health Organization priority antimicrobial resistance profile; BSI, bloodstream infection. Of the 72 patients with >1 BSI episode, only the first episode was considered, except if the second or any following episode was by a WPAP isolate, when the later was considered.

Fig. 2

Incidence-density of all bacteria of interest and WHO priority antimicrobial resistance phenotype (WPAP) bacteria in bloodstream infections in hospitalised patients. Incidence-densities per 1000 patients-day (95% Confidence Interval) of all bacteria of interest in the entire hospital (EH), intensive care unit (ICU) and non-ICU patients are 1.91 (1.81–2.02), 5.80 (5.27–6.37) and 1.38 (1.29–1.48), respectively; all WPAP in EH, ICU and non-ICU = 0.77 (0.70–0.84), 3.11 (2.72–3.53) and 0.45 (0.39–0.51), respectively. Incidence-densities, including those of carbapenem-resistant Klebsiella pneumoniae separately, are shown in Supplementary Material, p10.

Fig. 3

Proportion of WHO priority antimicrobial resistance phenotype within each bacteria of interest. Proportion (95% Confidence Interval [CI]) of carbapenem-resistant Enterobacterales: Total = 34.1 (95% CI 26.1–42.5), Intensive Care Unit (ICU) isolates = 45.5 (31.4–60.4), non-ICU = 27.6 (22.2–33.7); carbapenem-resistant A. baumannii: Total = 87.8 (79.3–93.1), ICU = 94.4 (83.9–98.2), non-ICU = 81.3 (71.9–88.1); carbapenem-resistant P. aeruginosa: Total = 26.7 (18.4–36.9), ICU = 30.6 (18.0–47.1), non-ICU = 23.9 (14.3–37.3); methicillin-resistant S. aureus: Total = 25.9 (17.9–35.8), ICU = 35.6 (21.8–52.3), non-ICU = 23.0 (15.7–32.3); vancomycin-resistant E. faecium: Total = 56.9 (44.8–68.3), ICU = 52.6 (42.7–62.4), non-ICU = 63.0 (43.3–79.1). The proportions of carbapenem-resistant Klebsiella pneumoniae are shown in Supplementary Material, p11.

Fig. 4

Kaplan–Meier curve of 28-day mortality of unique patients with monomicrobial WHO priority antimicrobial resistance phenotype (WPAP) and non-WPAP bloodstream infections. Of 1001 unique patients with monomicrobial bloodstream infections (BSIs), 331 (33.1) died within 28 days: 154 (40.5%) of 380 and 177 (28.5%) of 621 with BSI by WPAP and non-WPAP isolates, respectively; hazard ratio 1.36 (95% Confidence Interval 1.09–1.69), p = 0.007. Hazard ratio and p value were determined using a Cox proportional hazards model adjusted for hospital of origin. Shadow areas are 95% Confidence Intervals.