Assessment of antibiotic resistance in pathogens causing neonatal sepsis, associated mortality and recommended treatment options in low- and middle- income countries.

Thomson, Kathryn 2022. Assessment of antibiotic resistance in pathogens causing neonatal sepsis, associated mortality and recommended treatment options in low- and middle- income countries. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Sepsis is a leading cause of neonatal mortality, particularly in low- and middleincome countries (LMICs). Current studies evidence alarming rates of antimicrobial resistance (AMR) in bacterial pathogens causing neonatal sepsis, however, these are often single site studies, limiting the extrapolation of data to inform policy change. BARNARDS was undertaken in 12 sites across Africa and South Asia. Mothers attending clinical sites in labour or presenting neonates with suspected sepsis were enrolled and data regarding mother socio-demographics and birth of the neonate was collected. Associated antibiotic use was collated retrospectively, and neonates followed up for 60 days. Isolates grown from positive blood cultures were sent to the UK for further analyses, including minimum inhibition concentrations, whole genome sequencing, frequency of resistance and pathogenicity indexing. Over 30 bacterial species were identified from blood cultures across BARNARDS sites with Klebsiella spp., E. coli and Staphylococcus aureus most identified discounting outbreaks, which were prominently caused by Klebsiella spp. and Serratia marcescens. High rates of AMR were seen against multiple antibiotics, with 71.5% of Gram-negative bacteria resistant to ampicillin and/or gentamicin, recommended first-line treatment. Furthermore, 83% resistance was found against recommended second-line treatments cefotaxime and 80% against ceftriaxone, slightly reduced for ceftazidime (60%). Sites often veered from ampicillin and gentamicin due to known resistance and varied antibiotics were prescribed by sites, including piperacillin-tazobactam and amikacin, amoxicillin-clavulanate and amikacin, ceftazidime and amikacin in addition to ampicillin and gentamicin. Amikacin and ceftazidime could act as potential empirical therapy alternatives for neonatal sepsis due to lower prevalence of resistance, reported survival, current usage, cost, and availability. However, antibiotic usage was uneven between countries, which could not be accounted for regarding iii reported survival with usage of a specific antibiotic. Availability, price and whether costs were deferred to patients varied between sites and needs to be considered when deliberating alternative treatments. Empirical therapy for neonatal sepsis urgently needs to be re-evaluated in LMICs.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Medicine
Date of First Compliant Deposit:	3 May 2023
Last Modified:	02 May 2024 01:30
URI:	https://orca.cardiff.ac.uk/id/eprint/159120

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