Early onset neonatal bloodstream infections in South African hospitals

doi:10.1186/s12879-024-10406-z

. 2025 Jan 20;25(1):85.

doi: 10.1186/s12879-024-10406-z.

Early onset neonatal bloodstream infections in South African hospitals

Genevieve Theron¹, Adrie Bekker¹, Larisse Bolton², Andrew Whitelaw³, Arnoldus Engelbrecht⁴, Louisa Erasmus¹, Aaqilah Fataar¹, Chandre Geldenhuys⁵, Marlize Kunneke⁴, Dave Le Roux⁶, Natasha O'Connell⁷, Kessendri Reddy³, Natasha Rhoda⁸, Lloyd Tooke^{9

10}, Mark Wates¹¹, Thandi Wessels¹, Angela Dramowski¹²

Affiliations

¹ Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa.
² South African Centre for Epidemiological Modelling and Analysis (SACEMA), School for Data Science and Computational Thinking, Stellenbosch University, Cape Town, South Africa.
³ Division of Medical Microbiology and Immunology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
⁴ Department of Paediatrics, Worcester Provincial Hospital, Worcester, South Africa.
⁵ Department of Paediatrics, Paarl Hospital, Paarl, South Africa.
⁶ Department of Paediatrics, New Somerset Hospital, Cape Town, South Africa.
⁷ Department of Paediatrics, Khayelitsha District Hospital, Cape Town, South Africa.
⁸ Department of Neonatology, Cape Town, School of Child and Adolescent Health, Faculty of Health Sciences, Mowbray Maternity Hospital, University of Cape Town, Cape Town, South Africa.
⁹ Department of Neonatology, Groote Schuur Hospital, Cape Town, South Africa.
¹⁰ School of Child and Adolescent Health, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
¹¹ Department of Paediatrics, Karl Bremer Hospital, Cape Town, South Africa.
¹² Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa. dramowski@sun.ac.za.

PMID: 39833703
PMCID: PMC11744941
DOI: 10.1186/s12879-024-10406-z

Early onset neonatal bloodstream infections in South African hospitals

Genevieve Theron et al. BMC Infect Dis. 2025.

. 2025 Jan 20;25(1):85.

doi: 10.1186/s12879-024-10406-z.

Authors

Affiliations

¹ Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa.
² South African Centre for Epidemiological Modelling and Analysis (SACEMA), School for Data Science and Computational Thinking, Stellenbosch University, Cape Town, South Africa.
³ Division of Medical Microbiology and Immunology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
⁴ Department of Paediatrics, Worcester Provincial Hospital, Worcester, South Africa.
⁵ Department of Paediatrics, Paarl Hospital, Paarl, South Africa.
⁶ Department of Paediatrics, New Somerset Hospital, Cape Town, South Africa.
⁷ Department of Paediatrics, Khayelitsha District Hospital, Cape Town, South Africa.
⁸ Department of Neonatology, Cape Town, School of Child and Adolescent Health, Faculty of Health Sciences, Mowbray Maternity Hospital, University of Cape Town, Cape Town, South Africa.
⁹ Department of Neonatology, Groote Schuur Hospital, Cape Town, South Africa.
¹⁰ School of Child and Adolescent Health, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
¹¹ Department of Paediatrics, Karl Bremer Hospital, Cape Town, South Africa.
¹² Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa. dramowski@sun.ac.za.

PMID: 39833703
PMCID: PMC11744941
DOI: 10.1186/s12879-024-10406-z

Abstract

Background: Neonatal sepsis is a leading cause of death in low- and middle- income countries (LMIC). Increasing antibiotic resistance in early onset (< 72 h of life) bloodstream infection (EO-BSI) pathogens in LMIC has reduced the effectiveness of the recommended empiric antibiotic regimen (ampicillin plus gentamicin).

Methods: We retrospectively analysed blood culture-confirmed EO-BSI episodes at nine neonatal units from three central and six peripheral hospitals in the Western Cape Province, South Africa between 1 January 2017 and 31 December 2018. Clinical and electronic laboratory records were reviewed to determine pathogen profile, empiric antibiotic coverage rates and factors associated with EO-BSI attributable mortality, stratified by hospital type.

Results: Of the 8252 blood culture specimens submitted for the investigation of suspected EO-BSI, 136 EO-BSI episodes yielding 141 pathogens were identified with an EO-BSI rate of 1.3 and 0.5 episodes/1000 live births at central and peripheral hospitals respectively. Preterm (93/136; 68.3%) and low birth weight (84/136; 61.8%) neonates were most affected. The predominant pathogens were Streptococcus agalactiae (46/136; 34%), Klebsiella pneumoniae (17/136; 13%), Listeria monocytogenes (11/136; 8%), Acinetobacter baumannii (11/136; 8%) and Escherichia coli (11/136; 8%). The empiric antibiotic (ampicillin plus gentamicin) coverage rate was 64% (95% CI 51-74) at central hospitals and 84% (95% CI 74-94) at peripheral hospitals. Neonates with Gram-negative EO-BSI and discordant empiric antibiotic therapy had almost four-fold and three-fold higher odds of death respectively.

Conclusion: Preterm and low birth weight neonates are most vulnerable to EO-BSI and have higher odds of death with Gram-negative pathogens and discordant empiric antibiotic therapy.

Keywords: Antimicrobial resistance; Early onset bloodstream infection; Empiric antibiotic; Neonate; Sepsis.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no conflicts of interest to declare. Ethical approval: A waiver of individual informed consent was granted for this study. The Stellenbosch University Health Research Ethics Committee and the Tygerberg Hospital management reviewed and approved the study protocol SU HREC approvals N18/07/068, N20/07/070, in accordance with the Declaration of Helsinki. Funding: A.D. was supported by a NIH Fogarty Emerging Global Leader Award K43 TW010682. The WISCA analysis was supported by a grant to AD from the Science for Africa Foundation through a Data Science for Maternal Neonatal and Child Health Gates Grand Challenges grant. LB: This work is based on research supported by the South African National Research Foundation (NRF). Any opinion, finding, and conclusion or recommendation expressed in this material is that of the authors and the NRF does not accept any liability in this regard.

Figures

**Fig. 1**
Determination of the study population

**Fig. 2**
Spectrum of early onset BSI pathogens at nine neonatal units in the Western Cape Province, South Africa EO-BSI: early onset blood stream infection Other: *Enterobacter cloacae (1)*, *Aeromonas hydrophila (1)*, *Neisseria elongata (1)*, *Citrobacter species (1)*, *Enterococcus faecium (2)*, *Acinetobacter ursingii (1)*, *Burkholderia gladioli (1)*, *Sphingomonas paucimobilis (2)*, *Pseudomonas orizihabitans (1)*, *Proteus mirabilis (1)*

**Fig. 3**
Empiric antibiotic coverage rate for early onset BSI Empiric antibiotic (ampicillin + gentamicin) coverage point estimate (with 95% credible interval) for early onset bloodstream infection pathogens calculated by weighted-incidence syndromic antibiogram (WISCA) for nine Western Cape hospital neonatal units, stratified by site (central versus peripheral hospital). The WISCA was derived using 117 of the 141 (83%) pathogens isolated for EO-BSI. In calculating the coverage estimates, the model assumes that neonates with suspected EO-BSI received the World Health Organization recommended empiric therapy (ampicillin plus gentamicin)

See this image and copyright information in PMC

References

1. Fleischmann C, Reichert F, Cassini A, Horner R, Harder T, Markwart R, et al. Global incidence and mortality of neonatal sepsis: a systematic review and meta-analysis. Arch Dis Child. 2021;106(8):745–52. - PMC - PubMed
1. Dramowski A, Velaphi S, Reubenson G, Bekker A, Perovic O, Finlayson H, et al. National neonatal Sepsis Task Force launch: supporting infection prevention and surveillance, outbreak investigation and antimicrobial stewardship in neonatal units in South Africa. South Afr Med J. 2020;110(5):360–3. - PubMed
1. Zingg W, Hopkins S, Gayet-Ageron A, Holmes A, Sharland M, Suetens C, et al. Health care-associated infections in neonates, children, and adolescents: an analysis of paediatric data from the European Centre for Disease Prevention and Control point prevalence survey. Lancet Infect Dis. 2017;17(4):381–9. - PubMed
1. Arowosegbe AO, Ojo DA, Dedeke IO, Shittu OB, Akingbade OA. Neonatal sepsis in a Nigerian Tertiary Hospital: clinical features, clinical outcome, aetiology and antibiotic susceptibility pattern. S Afr J Infect Dis. 2017;32:127–31.
1. Kim SJ, Kim GE, Park JH, Lee SL, Kim CS. Clinical features and prognostic factors of early-onset sepsis: a 7.5-year experience in one neonatal intensive care unit. Korean J Pediatr. 2019;62(1):36–41. - PMC - PubMed

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[1] Fleischmann C, Reichert F, Cassini A, Horner R, Harder T, Markwart R, et al. Global incidence and mortality of neonatal sepsis: a systematic review and meta-analysis. Arch Dis Child. 2021;106(8):745–52. - PMC - PubMed

[2] Fleischmann C, Reichert F, Cassini A, Horner R, Harder T, Markwart R, et al. Global incidence and mortality of neonatal sepsis: a systematic review and meta-analysis. Arch Dis Child. 2021;106(8):745–52. - PMC - PubMed

[3] Dramowski A, Velaphi S, Reubenson G, Bekker A, Perovic O, Finlayson H, et al. National neonatal Sepsis Task Force launch: supporting infection prevention and surveillance, outbreak investigation and antimicrobial stewardship in neonatal units in South Africa. South Afr Med J. 2020;110(5):360–3. - PubMed

[4] Dramowski A, Velaphi S, Reubenson G, Bekker A, Perovic O, Finlayson H, et al. National neonatal Sepsis Task Force launch: supporting infection prevention and surveillance, outbreak investigation and antimicrobial stewardship in neonatal units in South Africa. South Afr Med J. 2020;110(5):360–3. - PubMed

[5] Zingg W, Hopkins S, Gayet-Ageron A, Holmes A, Sharland M, Suetens C, et al. Health care-associated infections in neonates, children, and adolescents: an analysis of paediatric data from the European Centre for Disease Prevention and Control point prevalence survey. Lancet Infect Dis. 2017;17(4):381–9. - PubMed

[6] Zingg W, Hopkins S, Gayet-Ageron A, Holmes A, Sharland M, Suetens C, et al. Health care-associated infections in neonates, children, and adolescents: an analysis of paediatric data from the European Centre for Disease Prevention and Control point prevalence survey. Lancet Infect Dis. 2017;17(4):381–9. - PubMed

[7] Arowosegbe AO, Ojo DA, Dedeke IO, Shittu OB, Akingbade OA. Neonatal sepsis in a Nigerian Tertiary Hospital: clinical features, clinical outcome, aetiology and antibiotic susceptibility pattern. S Afr J Infect Dis. 2017;32:127–31.

[8] Arowosegbe AO, Ojo DA, Dedeke IO, Shittu OB, Akingbade OA. Neonatal sepsis in a Nigerian Tertiary Hospital: clinical features, clinical outcome, aetiology and antibiotic susceptibility pattern. S Afr J Infect Dis. 2017;32:127–31.

[9] Kim SJ, Kim GE, Park JH, Lee SL, Kim CS. Clinical features and prognostic factors of early-onset sepsis: a 7.5-year experience in one neonatal intensive care unit. Korean J Pediatr. 2019;62(1):36–41. - PMC - PubMed

[10] Kim SJ, Kim GE, Park JH, Lee SL, Kim CS. Clinical features and prognostic factors of early-onset sepsis: a 7.5-year experience in one neonatal intensive care unit. Korean J Pediatr. 2019;62(1):36–41. - PMC - PubMed

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Early onset neonatal bloodstream infections in South African hospitals

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Early onset neonatal bloodstream infections in South African hospitals

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