Emergence and spread of carbapenem-resistant Acinetobacter baumannii international clones II and III in Lima, Peru

Abstract

Carbapenem-resistant Acinetobacter baumannii is the top-ranked pathogen in the World Health Organization priority list of antibiotic-resistant bacteria. It emerged as a global pathogen due to the successful expansion of a few epidemic lineages, or international clones (ICs), producing acquired class D carbapenemases (OXA-type). During the past decade, however, reports regarding IC-I isolates in Latin America are scarce and are non-existent for IC-II and IC-III isolates. This study evaluates the molecular mechanisms of carbapenem resistance and the epidemiology of 80 non-duplicate clinical samples of A. baumannii collected from February 2014 through April 2016 at two tertiary care hospitals in Lima. Almost all isolates were carbapenem-resistant (97.5%), and susceptibility only remained high for colistin (95%). Pulsed-field gel electrophoresis showed two main clusters spread between both hospitals: cluster D containing 51 isolates (63.8%) associated with sequence type 2 (ST2) and carrying OXA-72, and cluster F containing 13 isolates (16.3%) associated with ST79 and also carrying OXA-72. ST2 and ST79 were endemic in at least one of the hospitals. ST1 and ST3 OXA-23-producing isolates were also identified. They accounted for sporadic hospital isolates. Interestingly, two isolates carried the novel OXA-253 variant of OXA-143 together with an upstream novel insertion sequence (ISAba47). While the predominant A. baumannii lineages in Latin America are linked to ST79, ST25, ST15, and ST1 producing OXA-23 enzymes, we report the emergence of highly resistant ST2 (IC-II) isolates in Peru producing OXA-72 and the first identification of ST3 isolates (IC-III) in Latin America, both considered a serious threat to public health worldwide.

Fig. 1. PFGE dendrogram of A. baumannii isolates from two tertiary hospitals in Lima showing carriage of intrinsic (iOXA) and acquired bla_OXA variants (aOXA); susceptibility (S) or resistance (R) to carbapenems (Carb); categorization as MDR, XDR, or PDR (RStatus); pulsotype (PT); and sequence type (ST).

Isolates in red were selected as representative of each clonal group. Braces indicate classification to the corresponding international clones I–V (IC). Isolates were included in the same pulsotype if their Dice similarity index was ≥85%. Colored squares indicate production of distinct families of acquired OXA-type enzymes: blue: OXA-23; green: OXA-24; black: OXA-143; magenta: none. INEN Instituto Nacional de Enfermedades Neoplásicas, HNAL Hospital Nacional Arzobispo Loayza, MDR multidrug-resistant, XDR extensively drug-resistant, PDR; pan-drug-resistant

Fig. 2. Temporal and spatial distribution of A. baumannii isolates recovered from patients at two tertiary hospitals in Lima, Peru.

Stacked columns show the number of isolates from each pulsotype/sequence type (PT/ST) recovered at each institute over a 3-month period. INEN Instituto Nacional de Enfermedades Neoplásicas, HNAL Hospital Nacional Arzobispo Loayza

Fig. 3. Partial snapshot of the population structure of A. baumannii according to MLST and using goeBURST (PHYLOViZ).

Blue links show SLVs. Founder STs are highlighted in yellow. Reddish circles indicate isolates grouped into a particular international clone (IC). The black arrow points at ST108 and its SLV, ST112