A global view on carbapenem-resistant Acinetobacter baumannii

Abstract

Carbapenem-resistant Acinetobacter baumannii are of increasing public health importance, as they are resistant to last-line antibiotics. International clones with well-characterized resistance genes dominate globally; however, locally, other lineages with different properties may be of importance to consider. This study investigated isolates from a broad geographic origin from 114 hospitals in 47 countries and from five world regions ensuring the greatest possible diversity in an organism known for its propensity for clonal epidemic spread and reflecting the current global epidemiology of carbapenem-resistant A. baumannii. In Latin America, a lineage different from other geographic regions circulates, with a different resistance gene profile. This knowledge is important to adjust local infection prevention measures. In a global world with migration and increasing use of antimicrobials, multidrug-resistant bacteria will continue to adapt and challenge our healthcare systems worldwide.

Keywords: Acinetobacter baumannii; carbapenem resistance; carbapenemase; genome analysis; international clone; molecular epidemiology.

Fig 1

(A) Global phylogeny of A. baumannii with distribution of isolates and international clones. Midpoint-rooted phylogeny of collected isolates. Global clones are highlighted by colored branches as well as the innermost circular ring. Regions are colored, as are countries with more than five isolates within these regions. Graded gray color scheme for year of sample collection. (B) Geographical distribution of ICs of the 313 carbapenem-resistant A. baumannii isolates, number of isolates, and contributing centers.

Fig 2

Phylogeny of IC2 with associated carbapenemases and regions of recombination. Colored strips next to the phylogeny show region and country of isolation and presence of various carbapenemases (intrinsic and acquired). Recombination blocks (red) along the chromosome coordinates (top) are highlighted. The capsule K locus (blue) is under recombination, as is the pilus/fimbrial operon (gray), whereas phage loci (pink) are not. Two isolates of ST636 at the base of the tree show larger regions of recombination, corresponding to the fact that this ST shares alleles both with ST1 (three alleles) and ST2 (four alleles).

Fig 3

Distribution of carbapenemases across international clones and regions. Top boxplot shows the number of isolates per IC and carbapenemase; note the broken y-axis for non-distortion by overrepresentation of IC2. Jitterplot: visual representation of isolates per IC and region. Tilted boxplot shows the number of isolates per region and carbapenemase. The color scheme is the same across all plots and given in the top right corner.

Fig 4

View of IC5. Whole genome maximum likelihood phylogeny of Latin American IC5 based on 44 isolates from this study and 145 genomes from public databases. The innermost circle shows ST, followed by region and country, then study and year to show whether isolates may be part of particular outbreak investigations, and lastly acquired carbapenemases. Several distinct clades with geographic restrictions are visible. A predominance of Latin American isolates is evident, with single exportation events, although a large proportion of isolates are also linked to North America.

Fig 5

View of IC9. Whole genome maximum likelihood phylogenetic representation after recombination removal of the novel international clone 9 (IC9), based on six isolates from this study and 25 additional genomes from publicly available databases. The global scale of the isolates is visible; carbapenemases like OXA-23 and NDM-1 are widespread.