Genomic Epidemiology of a Protracted Hospital Outbreak caused by Multi-Drug-Resistant Acinetobacter baumannii

BACKGROUND Multi-drug-resistant Acinetobacter baumannii commonly causes hospital outbreaks. However, within any given outbreak, it can be difficult to identify the precise mechanisms and sources of infection rapidly and accurately enough to inform infection control teams how best to terminate an outbreak. Here we describe a protracted hospital outbreak of multidrug-resistant A. baumannii, in which whole-genome sequencing (WGS) was used to obtain a high-resolution view of the relationships between isolates, allowing us to reconstruct chains of transmission, confirm or refute epidemiological hypotheses and to provide the infection control team with useful insights into the sources and routes of infection during this outbreak. METHODS 117 putative Acinetobacter isolates obtained from 59 patients and 10 environmental swabs were genome-sequenced on the Illumina MiSeq. Genomes were mapped against a reference sequence for the outbreak strain to identify single-nucleotide polymorphisms (SNPs). A combination of SNP genotype and conventional epidemiologic analysis was used to reconstruct a parsimonious set of transmission events. RESULTS The outbreak strain was found to be distinct from other genome-sequenced strains. We identified 31 SNPs among isolates from the outbreak and defined six major SNP-based genotypic clusters within the outbreak, together with one additional genotype defined by loss of a plasmid. We were able to rule seventeen isolates out of the outbreak. We documented within-host diversity in several patients, including mixtures of unrelated Acinetobacter strains and within-strain clouds of SNP diversity. Using genome sequence data and conventional epidemiology, we were able to reconstruct 67 transmission events that linked all but seven of the patients. We were also able to link patient-derived isolates directly to environmental isolates. These efforts focused our attention on a contaminated bed and a burns operating theatre as sources of transmission, which led to improvements in decontamination protocols. CONCLUSIONS With falling costs and higher throughput, WGS is now poised to make a decisive impact on hospital infection prevention and control, delivering cost-effective identification of routes of infection within a clinically relevant timeframe and allowing infection control teams to track, and even prevent, the spread of multi-drug-resistant hospital pathogens.