# Antimicrobial Resistance and Infant Mortality in Sri Lanka: A Retrospective Cohort Study

## TL;DR

This study shows that antibiotic-resistant gram-negative bacteria cause severe sepsis in infants in Sri Lanka, leading to high mortality and highlighting the need for new treatments.

## Contribution

The study provides detailed data on antimicrobial resistance in neonatal sepsis in Sri Lanka, revealing gaps in current treatment guidelines.

## Key findings

- Gram-negative bacteria caused 66% of culture-positive infections in neonates and young infants.
- 86% of infants who died had gram-negative infections resistant to recommended antibiotics.
- Hospital-acquired bacteria are causing severe infections in the early neonatal period.

## Abstract

Sepsis is a major cause of mortality among children, with the highest burden evident in neonates and young infants, particularly, in resource‐constrained healthcare settings. Despite this burden, there are insufficient published data to delineate the epidemiology of neonatal sepsis from many of these settings. We aimed to address this research gap by evaluating the epidemiology of sepsis in neonates and young infants in Sri Lanka, a populous country in Southeast Asia, and to evaluate the efficacy of currently‐recommended empiric antibiotic regimens to treat these infections in the context of evolving antimicrobial resistance.

We evaluated the pathogens (including susceptibility profiles) responsible for infections in neonates and young infants over a 7‐year period alongside clinical outcomes (2015–2021).

A 1100 bed urban tertiary hospital in Colombo, Sri Lanka.

Neonates and young infants (aged 0 to ≤ 180 days).

Blood culture‐positive pathogen profiles, antibiotic susceptibility against empiric antibiotic regimens and mortality.

We identified 231 neonates and young infants with clinically significant blood cultures incorporating 251 pathogens over the study period, of whom 22 died. Where gestational data were available, most babies with culture‐positive sepsis were premature (71%, 65/91), born at a median gestational age of 32 weeks (interquartile range [IQR] 27–38 weeks). Gram‐negative bacteria predominated as a cause of culture‐positive infections (66%, 166/251), including in 86% of neonates and young infants who died (19/22). There were high rates of non‐susceptibility to first‐ and second‐line antibiotics currently recommended to treat neonatal sepsis.

There is a high burden of antibiotic‐resistant gram‐negative infections in neonates and young infants in Sri Lanka, highlighting an urgent need to prioritise the development of new antimicrobial regimens to treat neonatal infections.

What is already known on this topic○Neonatal sepsis is highly prevalent in resource‐constrained healthcare settings and is responsible for a rising public health challenge in the context of increasing antimicrobial resistance (AMR) globally.○Asia is one of the regions with the highest burden of AMR, yet granular data from many resource‐constrained healthcare settings across the region that identify the microbiology and clinical outcomes of culture‐positive infections in neonates and young infants are lacking.
What this study adds○Our study describes the significant burden of gram‐negative bacterial infections causative of sepsis in neonates and young infants in an urban tertiary hospital in Sri Lanka. Many of these infections are resistant to antibiotics currently recommended to treat these infections.○Our data also revealed bacteria traditionally considered as ‘hospital‐acquired’ infections are causing severe, invasive infections in the early neonatal period.
How this study might affect research, practice or policy○Our findings align with other recent observational studies that reveal increasingly high rates of AMR in gram‐negative bacterial infections in neonates and young infants.○Many of the pathogens identified in our study question the traditional definitions (and presumed pathogens responsible for) ‘early’ and ‘late’ onset neonatal sepsis that currently recommended empirical antibiotic regimens propose to cover.○New antibiotic regimens that provide improved coverage in treating the contemporaneous causes of sepsis in neonates and young infants are urgently needed to reduce the current morbidity and mortality burden due to AMR in this population.

What is already known on this topic○Neonatal sepsis is highly prevalent in resource‐constrained healthcare settings and is responsible for a rising public health challenge in the context of increasing antimicrobial resistance (AMR) globally.○Asia is one of the regions with the highest burden of AMR, yet granular data from many resource‐constrained healthcare settings across the region that identify the microbiology and clinical outcomes of culture‐positive infections in neonates and young infants are lacking.

Neonatal sepsis is highly prevalent in resource‐constrained healthcare settings and is responsible for a rising public health challenge in the context of increasing antimicrobial resistance (AMR) globally.

Asia is one of the regions with the highest burden of AMR, yet granular data from many resource‐constrained healthcare settings across the region that identify the microbiology and clinical outcomes of culture‐positive infections in neonates and young infants are lacking.

What this study adds○Our study describes the significant burden of gram‐negative bacterial infections causative of sepsis in neonates and young infants in an urban tertiary hospital in Sri Lanka. Many of these infections are resistant to antibiotics currently recommended to treat these infections.○Our data also revealed bacteria traditionally considered as ‘hospital‐acquired’ infections are causing severe, invasive infections in the early neonatal period.

Our study describes the significant burden of gram‐negative bacterial infections causative of sepsis in neonates and young infants in an urban tertiary hospital in Sri Lanka. Many of these infections are resistant to antibiotics currently recommended to treat these infections.

Our data also revealed bacteria traditionally considered as ‘hospital‐acquired’ infections are causing severe, invasive infections in the early neonatal period.

How this study might affect research, practice or policy○Our findings align with other recent observational studies that reveal increasingly high rates of AMR in gram‐negative bacterial infections in neonates and young infants.○Many of the pathogens identified in our study question the traditional definitions (and presumed pathogens responsible for) ‘early’ and ‘late’ onset neonatal sepsis that currently recommended empirical antibiotic regimens propose to cover.○New antibiotic regimens that provide improved coverage in treating the contemporaneous causes of sepsis in neonates and young infants are urgently needed to reduce the current morbidity and mortality burden due to AMR in this population.

Our findings align with other recent observational studies that reveal increasingly high rates of AMR in gram‐negative bacterial infections in neonates and young infants.

Many of the pathogens identified in our study question the traditional definitions (and presumed pathogens responsible for) ‘early’ and ‘late’ onset neonatal sepsis that currently recommended empirical antibiotic regimens propose to cover.

New antibiotic regimens that provide improved coverage in treating the contemporaneous causes of sepsis in neonates and young infants are urgently needed to reduce the current morbidity and mortality burden due to AMR in this population.