Antimicrobial resistance in Enterobacterales infections among children in sub-Saharan Africa: a systematic review and meta-analysis

Morgane Kowalski; Basilice Minka Obama; Gaud Catho; Juan Emmanuel Dewez; Arnaud Merglen; Micaela Ruef; Diego O Andrey; Nasreen Hassoun-Kheir; Marlieke E A de Kraker; Christophe Combescure; Stephane Emonet; Annick Galetto-Lacour; Noémie Wagner

doi:10.1016/j.eclinm.2024.102512

Antimicrobial resistance in Enterobacterales infections among children in sub-Saharan Africa: a systematic review and meta-analysis

EClinicalMedicine. 2024 Mar 8:70:102512. doi: 10.1016/j.eclinm.2024.102512. eCollection 2024 Apr.

Authors

Morgane Kowalski¹, Basilice Minka Obama^{2

3}, Gaud Catho^{4

5}, Juan Emmanuel Dewez⁶, Arnaud Merglen⁷, Micaela Ruef¹, Diego O Andrey^{8

9}, Nasreen Hassoun-Kheir¹⁰, Marlieke E A de Kraker¹⁰, Christophe Combescure¹¹, Stephane Emonet^{4

8}, Annick Galetto-Lacour¹², Noémie Wagner^{2

6}

Affiliations

¹ Children's Hospital, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
² Paediatric Infectious Diseases Unit, Children's Hospital, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
³ Regional Hospital Centre for Ebolowa, Ebolowa, Cameroon.
⁴ Division of Infectious Diseases, Central Institute, Hospital of Valais, Switzerland.
⁵ Infection Control Division, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
⁶ Medical Department, Médecins Sans Frontières, Operational Centre Geneva, Geneva, Switzerland.
⁷ Division of General Paediatrics, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
⁸ Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
⁹ Division of Laboratory Medicine, Department of Diagnostics, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
¹⁰ Infection Control Programme, Geneva University Hospitals and Faculty of Medicine, WHO Collaborating Centre, Geneva, Switzerland.
¹¹ Centre for Clinical Research, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
¹² Division of Paediatric Emergency Medicine, Children's Hospital, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.

Abstract

Background: The burden of antimicrobial resistance (AMR) has been estimated to be the highest in sub-Saharan Africa (SSA). The current study estimated the proportion of drug-resistant Enterobacterales causing infections in SSA children.

Methods: We searched MEDLINE/PubMed, Embase and the Cochrane Library to identify retrospective and prospective studies published from 01/01/2005 to 01/06/2022 reporting AMR of Enterobacterales causing infections in sub-Saharan children (0-18 years old). Studies were excluded if they had unclear documentation of antimicrobial susceptibility testing methods or fewer than ten observations per bacteria. Data extraction and quality appraisal were conducted by two authors independently. The primary outcome was the proportion of Enterobacterales resistant to antibiotics commonly used in paediatrics. Proportions were combined across studies using mixed-effects logistic regression models per bacteria and per antibiotic. Between-study heterogeneity was assessed using the I² statistic. The protocol was registered with PROSPERO (CRD42021260157).

Findings: After screening 1111 records, 122 relevant studies were included, providing data on more than 30,000 blood, urine and stool isolates. Escherichia coli and Klebsiella spp. were the predominant species, both presenting high proportions of resistance to third-generation cephalosporins, especially in blood cultures: 40.6% (95% CI: 27.7%-55%; I²: 85.7%, number of isolates (n): 1032) and 84.9% (72.8%-92.2%; I²: 94.1%, n: 2067), respectively. High proportions of resistance to other commonly used antibiotics were also observed. E. coli had high proportions of resistance, especially for ampicillin (92.5%; 95% CI: 76.4%-97.9%; I²: 89.8%, n: 888) and gentamicin (42.7%; 95% CI: 30%-56.5%; I²: 71.9%, n: 968). Gentamicin-resistant Klebsiella spp. were also frequently reported (77.6%; 95% CI: 65.5%-86.3%; I²: 91.6%, n: 1886).

Interpretation: High proportions of resistance to antibiotics commonly used for empirical treatment of infectious syndromes were found for Enterobacterales in sub-Saharan children. There is a critical need to better identify local patterns of AMR to inform and update clinical guidelines for better treatment outcomes.

Funding: No funding was received.

Keywords: Africa; Antimicrobial resistance; Children; E coli; Enterobacterales; Klebsiella; Neonates.