Molecular and clinical epidemiology of carbapenem resistant ST2 in Oceania: a multicountry cohort study.

Background: Carbapenem resistant (CR) is categorised by the World Health Organization (WHO) as a pathogen of critical concern. However, little is known about CR transmission within the Oceania region. This study addresses this knowledge gap by using molecular epidemiology to characterise the phylogenetic relationships of CR isolated in hospitals in Fiji, Samoa, and other countries within the Oceania region including Australia and New Zealand, and India from South Asia.

Methods: In this multicountry cohort study, we analysed clinical isolates of CR collected from the Colonial War Memorial Hospital (CWMH) in Fiji from January through December 2019 (n = 64) and Tupua Tamasese Mea'ole Hospital (TTMH) in Samoa from November 2017 through June 2021 (n = 32). All isolates were characterised using mass spectrometry, antimicrobial susceptibility testing, and whole-genome sequencing. For CWMH, data were collected on clinical and demographic characteristics of patients with CR, duration of hospital stay, mortality and assessing the appropriateness of meropenem use from the treated patients who had CR infections. To provide a broader geographical context, CR strains from Fiji and Samoa were compared with CR sequences from Australia collected in 2016-2018 (n = 22), New Zealand in 2018-2021 (n = 13), and India in 2019 (n = 58), a country which has close medical links with Fiji. Phylogenetic relationships of all these CR isolates were determined using differences in core genome SNPs.

Findings: Of CR isolates, 49 (77%) of 64 from Fiji and all 32 (100%) from Samoa belonged to CR sequence type 2 (ST2). All ST2 isolates from both countries harboured , and genes, mediating resistance to β-lactam antimicrobials, including cephalosporins and carbapenems. The gene was associated with two copies of IS insertion element, forming the composite transposon Tn on the chromosome. Two distinct clusters (group 1 and group 2) of CR ST2 were detected in Fiji. The first group shared common ancestral linkage to all CR ST2 collected from Fiji's historic outbreak in 2016/2017, Samoa, Australia and 54% of total New Zealand isolates; they formed a single cluster with a median (range) SNP difference of 13 (0-102). The second group shared common ancestral linkage to 3% of the total CR ST2 isolated from India. Fifty eight of the 64 patients with CR infections at the CWMH had their first positive CR sample collected 72 h or more following admission. Meropenem use was deemed inappropriate in 15 (48%) of the 31 patients that received treatment with meropenem in Fiji. Other strains of CR ST1, ST25, ST107, and ST1112 were also detected in Fiji.

Interpretation: We identified unrecognised outbreaks of CR ST2 in Fiji and Samoa that linked to strains in other parts of Oceania and South Asia. The existence of Tn, containing the and IS insertion element, within CR ST2 from Fiji and Samoa indicates the potential for high mobility and dissemination. This raises concerns about unmitigated prolonged outbreaks of CR ST2 in the two major hospitals in Fiji and Samoa. Given the magnitude of this problem, there is a need to re-evaluate the current strategies used for infection prevention and control, antimicrobial stewardship, and public health measures locally and internationally. Moreover, a collaborative approach to AMR surveillance within the Oceania region with technical, management and budgetary support systems is required to prevent introduction and control transmission of these highly problematic strains within the island nation health systems.

Funding: This project was funded by an Otago Global Health Institute seed grant and Maurice Wilkins Centre of Research Excellence (CoREs) grant (SC0000169653, RO0000002300).