Genomic surveillance, characterization and intervention of a polymicrobial multidrug-resistant outbreak in critical care

Abstract

Background. Infections caused by carbapenem-resistant Acinetobacter baumannii (CR-Ab) have become increasingly prevalent in clinical settings and often result in significant morbidity and mortality due to their multidrug resistance (MDR). Here we present an integrated whole-genome sequencing (WGS) response to a persistent CR-Ab outbreak in a Brisbane hospital between 2016–2018. Methods. A. baumannii, Klebsiella pneumoniae, Serratia marcescens and Pseudomonas aeruginosa isolates were sequenced using the Illumina platform primarily to establish isolate relationships based on core-genome SNPs, MLST and antimicrobial resistance gene profiles. Representative isolates were selected for PacBio sequencing. Environmental metagenomic sequencing with Illumina was used to detect persistence of the outbreak strain in the hospital. Results. In response to a suspected polymicrobial outbreak between May to August of 2016, 28 CR-Ab (and 21 other MDR Gram-negative bacilli) were collected from Intensive Care Unit and Burns Unit patients and sent for WGS with a 7 day turn-around time in clinical reporting. All CR-Ab were sequence type (ST)1050 (Pasteur ST2) and within 10 SNPs apart, indicative of an ongoing outbreak, and distinct from historical CR-Ab isolates from the same hospital. Possible transmission routes between patients were identified on the basis of CR-Ab and K. pneumoniae SNP profiles. Continued WGS surveillance between 2016 to 2018 enabled suspected outbreak cases to be refuted, but a resurgence of the outbreak CR-Ab mid-2018 in the Burns Unit prompted additional screening. Environmental metagenomic sequencing identified the hospital plumbing as a potential source. Replacement of the plumbing and routine drain maintenance resulted in rapid resolution of the secondary outbreak and significant risk reduction with no discernable transmission in the Burns Unit since. Conclusion. We implemented a comprehensive WGS and metagenomics investigation that resolved a persistent CR-Ab outbreak in a critical care setting.

Rescuing Tetracycline Class Antibiotics for the Treatment of Multidrug-Resistant Acinetobacter baumannii Pulmonary Infection

“…Unfortunately, resistance to these antibiotics is now being reported, which significantly reduces patient treatment options ( 26 , 27 ). To address this challenge, in accordance with the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines ( 28 , 29 ), the combination of PBT2 ± zinc to disrupt resistance to tetracycline class antibiotics in the clinical MDR A. baumannii strains MS14413 ( 30 ), AB5075 ( 31 ), and PGC-204089 (clinical isolate from the Royal Brisbane Women’s Hospital) and the XDR A. baumannii strain AB0057 ( 32 ) was investigated. All A. baumannii strains demonstrated resistance to either tetracycline, doxycycline, or tigecycline ( Table 1 ).…”

“… A. baumannii strains MS14413 ( 30 ) AB0057 ( 32 ), AB5075 ( 31 ), and PGC-204089 (kindly provided by David L. Paterson) were grown in cation-adjusted Mueller-Hinton broth (CA-MHB) (cat. no.…”

Queensland Genomics: an adaptive approach for integrating genomics into a public healthcare system

“…In the Strategy and Legacy Rounds, 11 Clinical projects were funded. These projects were organised into three clinical portfolio areas; Cancer, Whole-of-Life, and Infectious Diseases (Table 1) [23][24][25][26] . Structuring projects into portfolios enabled sharing of resources, processes and learning, enabling sustainable implementation.…”

Cost-effectiveness analysis of whole-genome sequencing during an outbreak of carbapenem-resistantAcinetobacter baumannii

“…1). 16 Monthly WGS reporting starting in June 2016 identified environmental contamination as the likely source of the ongoing outbreak. Environmental metagenomics was introduced in November 2017 but had reduced sensitivity due to low DNA yields from sampling.…”

“…Immediate reporting of WGS results were available when the CRAB outbreak resurfaced in May 2018. Additional details about the outbreak, implementation of metagenomics, environmental swabbing, and sequencing outcomes are discussed in the Supplementary Materials and by Roberts et al 16…”