Biochemistry and Pharmacology - Theses
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ItemPopulation structure and carriage-infection dynamics of Klebsiella pneumoniae( 2018)Klebsiella pneumoniae is an opportunistic pathogen and global cause of hospital-associated (HA) infections. K. pneumoniae is also part of the healthy human microbiome, providing a potential reservoir for infection. However, the frequency of colonisation and its contribution to infections are not well characterised. A prospective, hospital-wide surveillance of all infections attributed to K. pneumoniae – across the Alfred Health network, Melbourne, Australia – was conducted over a one-year period in 2013. Concurrently, patients in the intensive care unit (Alfred Hospital; AH) and geriatric care wards (Caulfield Hospital; CH) were screened for asymptomatic colonisation. Isolates were characterised using whole genome sequencing and antimicrobial susceptibility profiling. This study aimed to address several objectives: i) To investigate the frequency of colonisation in intensive care unit (ICU) patients and whether colonising strains are a source of infection; ii) To investigate the frequency and source of antimicrobial-resistant colonisation or infection in geriatric patients; iii) To characterise the population structure and genetic diversity of K. pneumoniae causing infections in hospital patients. This study estimated community-associated (CA) asymptomatic gastrointestinal carriage among ICU patients was at 6%, rising significantly to 19% among HA individuals, the latter including all identified multi-drug resistant carriage isolates. Many patients had their own unique colonising and infecting strains, often matching within a patient, though there were instances suggestive of transmission. The combination of genomic and epidemiological data supported five clusters of recent patient-to-patient transmission, frequently involving carriage. Among the CH geriatric patients screened, GI carriage rates were 10.8% and 1.7% of patients had extended-spectrum beta-lactamase (ESBL) producing carriage strains. There were three variably MDR lineages observed among multiple patients, and though there was no direct transmission within the CH, there was evidence supporting transmission at the AH prior to CH admission. The major MDR plasmids were identified; all had regions of clustered AMR genes on transposons and/or integrons. Two of the lineages shared variants of the same plasmid indicating transmission of AMR mobile elements between strains. Across all Klebsiella infections extensive diversity was observed including multiple species, lineages, capsule types, and O-antigen types. Most patients had their own unique carriage and infection strains but there were a small number of transmission chains detected. In most transmission cases, the lineages responsible were ESBL, MDR, or carbapenemase producers. Therefore, patients with antimicrobial-resistant strains pose a greater threat to those around them, as these strains were most strongly associated with transmission. This study showed that the majority of hospital Klebsiella infections arise from the host microbiome, though there is also a smaller burden of infection due to transmission of typically antimicrobial-resistant strains. This has important implications for infection prevention and control: people who are not colonised with Klebsiella have low risk of subsequent infection, except for when infections arise from acquisition of other patients’ antimicrobial-resistant strains. This work revealed that screening for colonisation can elucidate; i) which patients are at risk from infection through self-contamination, and ii) the AMR status of patients’ strains and therefore which individuals pose a risk to other patients through potential transmission.