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Clinical predictors of bacteraemia in neonates with suspected early-onset sepsis in Malawi: a prospective cohort study
  1. Tessa de Baat1,2,
  2. Rebecca Lester1,3,
  3. Lugano Ghambi1,4,
  4. Hussein H Twabi1,5,
  5. Maryke Nielsen1,6,
  6. Stephen B Gordon1,3,
  7. Mirjam M van Weissenbruch2,
  8. Nicholas A Feasey1,3,
  9. Queen Dube4,5,7,
  10. Kondwani Kawaza4,5,
  11. Pui-Ying Iroh Tam1,3,4,5
  1. 1Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
  2. 2Department of Neonatology, Emma Children’s Hospital, Amsterdam University Medical Centers, Amsterdam, Netherlands
  3. 3Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK
  4. 4Department of Paediatrics, Queen Elizabeth Central Hospital, Blantyre, Malawi
  5. 5Department of Paediatrics and Child Health, Kamuzu University of Health Sciences, Blantyre, Malawi
  6. 6Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
  7. 7Malawi Ministry of Health, Lilongwe, Malawi
  1. Correspondence to Tessa de Baat, Department of Neonatology, Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam, Netherlands; t.debaat{at}amsterdamumc.nl

Abstract

Objectives We studied neonates with suspected early-onset sepsis (EOS, sepsis developing in the first 72 hours after delivery) in Malawi to (1) describe clinical characteristics and microbiological findings, (2) identify which patient characteristics may be associated with pathogen positivity on blood culture, and (3) describe mortality and its potential determinants.

Design Prospective observational study (May 2018–June 2019).

Setting Neonatal ward in Queen Elizabeth Central Hospital, the largest government hospital in Malawi.

Patients All neonates with suspected EOS in whom a blood culture was obtained.

Results Out of 4308 neonatal admissions, 1244 (28.9%) had suspected EOS. We included 1149 neonates, of which 109 blood cultures had significant growth (9.5%). The most commonly isolated pathogens were Staphylococcus aureus, Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli and Acinetobacter baumanii. Many of the Gram negatives were extended-spectrum beta lactamase-producing Enterobacteriaceae, and these were 40–100% resistant to first-line and second-line antimicrobials. Gestational age (GA) of <32 weeks was associated with pathogen-positive blood cultures (<28 weeks: adjusted OR (AOR) 2.72, 95% CI 1.04 to 7.13; 28–32 weeks: AOR 2.26, 95% CI 1.21 to 4.21; p=0.005). Mortality was 17.6% (202/1149) and associated with low birth weight (<1000 g: AOR 47.57, 95% CI 12.59 to 179.81; 1000–1500 g: AOR 11.31, 95% CI 6.97 to 18.36; 1500–2500 g: AOR 2.20, 95% CI 1.42 to 3.39; p<0.001), low Apgar scores at 5 min (0–3: AOR 18.60, 95% CI 8.81 to 39.27; 4–6: AOR 4.41, 95% CI 2.81 to 6.93; p<0.001), positive maternal venereal disease research laboratory status (AOR 2.53, 95% CI 1.25 to 5.12; p=0.001) and congenital anomalies (AOR 7.37, 95% CI 3.61 to 15.05; p<0.001). Prolonged rupture of membranes was inversely associated with mortality (AOR 0.43, 95% CI 0.19 to 0.98; p 0.007).

Conclusion In Malawi, EOS was suspected in nearly a third of neonatal admissions and had a high mortality. Ten per cent were culture-confirmed and predicted by low GA. To reduce the impact of suspected neonatal sepsis in least developed countries, improved maternal and antenatal care and development of rapid point of care methods to more accurately guide antimicrobial use could simultaneously improve outcome and reduce antimicrobial resistance.

  • Neonatology
  • Sepsis
  • Mortality

Data availability statement

Data are available upon reasonable request. Data are available upon reasonable request to the corresponding author.

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Data availability statement

Data are available upon reasonable request. Data are available upon reasonable request to the corresponding author.

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Footnotes

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  • Contributors TdB and P-YIT contributed to the concept and design of the work. RL, MN, SBG and NAF contributed to the concept. KK and QD oversaw the running of the ward. TdB and LG were involved in data acquisition. HHT and TdB were involved in data analysis and interpretation. TdB wrote the first draft, and P-YIT and MMvW critically reviewed and revised the manuscript. All authors reviewed and approved the manuscript. P-YIT was the guarantor of this study.

  • Funding This work was supported by a Wellcome Trust Programme Grant (grant number 091909/Z/10/Z) and the Malawi-Liverpool-Wellcome Programme Core Award (grant number 206454) from the Wellcome Trust. RL and MN was supported by the Wellcome Trust Clinical PhD Fellowship (University of Liverpool block award (grant number 203919/Z/16/Z). HHT is currently supported by Helse Nord Tuberculosis Initiative.

  • Competing interests PI has received investigator-initiated research grant support from Bill & Melinda Gates Foundation. MN has received grant support from Roche. The remaining authors declare that they have no competing interests.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.