Genomic study of Klebsiella pnuemoniae from neonatal invasive, neonatal and maternal carriage at Kawempe National Referral Hospital, Uganda

Abstract

Neonatal infections particularly bloodstream infections (BSI) pose a significant health risk, necessitating a comprehensive understanding of the genetic characteristics of causative strains for effective treatment and epidemiological insights. This study aimed to investigate the genetic diversity and antimicrobial resistance (AMR) profiles of Klebsiella pneumoniae strains responsible for neonatal bloodstream infections in the Kampala region. Whole genome sequencing (Illumina) was performed on K. pneumoniae isolates from newborns with invasive disease, neonatal and maternal colonization in Kampala Uganda between 2019-2021. Draft genomes were assembled (Shovill). Then Multilocus sequence typing (MLST), AMR, K-antigen, and O-antigen profiles were extracted using Kaptive, Kleborate, Pasteur MLST, Pathogenwatch and Microreact whereas analysis and visualization was done in R. The study identified 19 distinct K. pneumoniae Sequence Types (STs) in invasive disease. Remarkably, 4 previously unreported STs were reported, accounting for 21% of cases. ST14 emerged as the most prevalent, followed by ST17 and ST6671. Notably, all neonates infected with a same ST shared a common ancestral lineage. Additionally, the strains displayed a diverse range of capsular polysaccharides (K) and lipopolysaccharides (O) combinations, highlighting the complex nature of K. pneumoniae strains in this study. The STs displayed high resistance to aminoglycosides, sulfonamides, and third-generation cephalosporins with the dominance of CTX-M-15 and CTX-M-3 in addition to carbapenem resistance of 13%. Vertical transmission of K. pneumoniae from mothers to neonates, with shared genetic characteristics, was identified in 50% of maternal-neonatal pairs. This suggests a potential route for targeted vaccinations in mothers to protect neonates. However, some neonates harboured strains different from those isolated in maternal samples, emphasizing the need for robust infection prevention measures. These findings highlight the high genetic diversity of K. pneumoniae strains causing neonatal bloodstream infections. Several STs identified in our study have been previously documented in different regions, suggesting potential interstate transmission or global dissemination of particular strains. The observed diversity in K:O combinations have implications for vaccine development and targeted prevention strategies. The results also have implications for treatment guidelines, as a substantial proportion of neonatal blood isolates exhibited resistance to recommended treatments. The dominance of Beta-lactamases genes CTX-M-15 and CTX-M-3 aligns with findings in other setting while isolation of Carbapenem resistant strains reveal the complicated nature of BSI in neonates in Uganda. Overall, this study highlights the urgent need for enhanced diagnostics, revised treatment guidelines for neonatal sepsis, rigorous infection prevention practices, and novel therapies to combat antimicrobial-resistant K. pneumoniae infections. Additionally, it underscores the importance of understanding the genetic diversity of K. pneumoniae for vaccine development and global surveillance efforts. Despite some limitations, including a small sample size this study provides valuable insights into the complex dynamics of K. pneumoniae infections in neonates and mothers in Kampala, Uganda.