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Burden of antibiotic resistance in neonates from developing societies: The role of Klebsiella pneumoniae in neonatal sepsis

Ferreira, Ana 2021. Burden of antibiotic resistance in neonates from developing societies: The role of Klebsiella pneumoniae in neonatal sepsis. PhD Thesis, Cardiff University.
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The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) study was a multi-site international study in 12 sites across seven different low- and middle-income countries (LMICs) in Africa and South Asia. The primary aim of BARNARDS was to assess the burden of antibiotic resistance in neonates looking at neonatal morbidity and mortality. In BARNARDS, K. pneumoniae was the leading Gram-negative bacterial cause of neonatal sepsis and was frequently isolated from rectal samples from mothers (MR), neonates (BR) and samples from the clinical environment (ENV). I found that K. pneumoniae was a particularly dominant species recovered from samples in Ethiopia and Pakistan, and for different reasons. Firstly, multiple outbreaks, or epidemiological clusters (that are still being investigated with the local clinical sites) of isolates recovered from blood cultures were isolated over a period of 12 months (2016-2017) from Addis Ababa, Ethiopia. Secondly, in Islamabad Pakistan, the rectal carriage of carbapenemase positive Gram-negative bacteria (GNB) was high, particularly in neonates, and the most frequently identified species was K. pneumoniae. In sampling the clinical environment to ascertain the frequency of carbapenemase colonisation within the wards and surrounding hospital environment, I also found that K. pneumoniae was often recovered in multiple countries. With this in mind this PhD study characterised BB, MR, BR and ENV K. pneumoniae from Pakistan and Ethiopia. The population structure and phylogeny of K. pneumoniae was studied with focus on their resistome and virulome to characterise the genomic traits, and antibiotic susceptibility testing for a phenotypic characterisation. The results showed that K. pneumoniae were resistant to many antibiotics used in treatment including carbapenems and cephalosporins and harboured high numbers of ARG belonging to different classes, including those encoding carbapenemases and extended-spectrum β-lactamases. Furthermore, the K. pneumoniae population in Ethiopia and Pakistan varied, for example, in Pakistan the most common ST was ST15 whereas in Ethiopia ST35 and ST37 were the most common. Additionally, carbapenemase ARG were frequently found among isolates from Pakistan, with ST15 isolates carrying blaNDM-1 and blaOXA-181, but carbapenemase ARG were not frequently found among isolates from Ethiopia. Patterns of virulence determinants also varied, for example, Ethiopian K. pneumoniae showed capsule loci ii KL15, as the most common whereas Pakistani isolates displayed KL112, also, ybt was the most common siderophore loci among both PP and ES isolates but iuc and iro loci were rare in Pakistani isolates. Lastly, K. pneumoniae belonging to the same were found among different sample types indicating the possible transmission of bacteria capable of causing sepsis between mother, neonate and the environment. Of note, this thesis detected cases whereby transmission of the same of K. pneumoniae strain between the mother, neonate and clinical environment is likely to have occurred.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 4 November 2021
Last Modified: 04 Nov 2021 16:06

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