Abstract

In low and middle income countries (LMICs), where the burden of neonatal sepsis is the highest, the spread of extended spectrum beta-lactamase-producing enterobacteriaceae (ESBL-PE) in the community, potentially contributing to the neonatal mortality, is a public health concern. Data regarding the acquisition of ESBL-PE during the neonatal period are scarce. The routes of transmission are not well defined and particularly the possible key role played by pregnant women. This study aimed to understand the neonatal acquisition of ESBL-PE in the community in Madagascar. The study was conducted in urban and semi-rural areas. Newborns were included at birth and followed-up during their first month of life. Maternal stool samples at delivery and six stool samples in each infant were collected to screen for ESBL-PE. A Cox proportional hazards model was performed to identify factors associated with the first ESBL-PE acquisition. The incidence rate of ESBL-PE acquisition was 10.4 cases/1000 newborn-days [95% CI: 8.0–13.4 cases per 1000 newborn-days]. Of the 83 ESBL-PE isolates identified, Escherichia coli was the most frequent species (n = 28, 34.1%), followed by Klebsiella pneumoniae (n = 20, 24.4%). Cox multivariate analysis showed that independent risk factors for ESBL-PE acquisition were low birth weight (adjusted Hazard-ratio (aHR) = 2.7, 95% CI [1.2; 5.9]), cesarean-section, (aHR = 3.4, 95% CI [1.7; 7.1]) and maternal use of antibiotics at delivery (aHR = 2.2, 95% CI [1.1; 4.5]). Our results confirm that mothers play a significant role in the neonatal acquisition of ESBL-PE. In LMICs, public health interventions during pregnancy should be reinforced to avoid unnecessary caesarean section, unnecessary antibiotic use at delivery and low birth weight newborns.

Highlights

  • Since 2000, the number of neonatal deaths has decreased from 3.9 million to 2.7 million [1]

  • In low or middle-income countries (LMICs), neonatal infections are mainly caused by Enterobacteriaceae, Escherichia coli and Klebsiella pneumoniae [6,7]

  • We provide the first community-based estimate of the incidence of extended-spectrum beta-lactamase-producing enterobacteriaceae (ESBL-PE) acquisition in newborn in LMICs

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Summary

Introduction

Since 2000, the number of neonatal deaths has decreased from 3.9 million to 2.7 million [1]. This decline has been slower than the post-neonatal under-five mortality [2] and significant improvements in neonatal health still have to be achieved. Bacterial infections are a leading cause of neonatal deaths in countries with very high under five mortality rate [3,4]. One important driver of unfavorable outcome in infections caused by these bacteria is multidrug resistance which challenges appropriate therapy [8]. The extended-spectrum beta-lactamase-producing enterobacteriaceae (ESBL-PE), are the most frequently isolated multidrug resistant bacteria [6,9,10,11]. Carbapenems remain the last resort to treat pediatric ESBL-PE infections which is onerous and often unavailable in LMICs [14,15,16]

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