A systematic review and meta-analysis found a that a “substantial” proportion of infants younger than 3 months in low-resource countries were colonized with antimicrobial-resistant bacteria, researchers reported today in JAMA Network Open.
Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus are leading causes of bacterial infections in newborns in LMICs and have been identified as the three main pathogens responsible for deaths attributable to antimicrobial resistance (AMR).
But data on resistant infections in low- and middle-income countries (LMICs) is scarce because of limited access to healthcare and microbiologic testing, and even less is known about resistant infections in newborns because of sample-collection challenges and low positivity rates of blood cultures.
To better understand the problem, a team of French researchers analyzed literature on bacterial colonization, reasoning that colonization with resistant bacteria is less dependent on access to healthcare, samples are easier to collect, and colonization often precedes subsequent infection.
“Therefore, colonization data can fill existing knowledge gaps and enhance understanding of AMR spread,” the study authors wrote.
Healthcare and antibiotic exposure are risk factors
For the study, they reviewed and analyzed papers published from 2000 through July 29, 2024, that reported on the prevalence of or risk factors for third-generation cephalosporin-resistant Enterobacterales (3GCRE), carbapenem-resistant Enterobacterales (CRE), and methicillin-resistant S aureus (MRSA) colonization in infants up to 3 months of age in LMICs. They then used a random-effects model to compute pooled prevalence rates.
The review yielded 67 studies involving 17,152 infants, with 51 evaluating 3GCRE and CRE colonization and 16 evaluating MRSA colonization. The meta-analysis found that the pooled prevalence of 3GCRE colonization was 30.2% (95% confidence interval [CI], 21.4% to 40.7%), varying from 18.2% in non-hospitalized infants to 48.2% in hospitalized infants. The prevalence of CRE and MRSA colonization was 2.6% (95% CI, 0.7% to 8.8%) and 2.7% (95% CI, 1.0% to 6.7%), respectively.
Among the 19 studies that reported risk factor analysis, 11 reported risk factors for 3GCRE colonization. Analysis of those studies found that increased risk of 3GCRE colonization was associated with hospital birth (odds ratio [OR], 1.87; 95% CI, 1.33 to 2.64), neonatal antibiotic use (OR, 2.96; 95% CI, 1.43 to 6.11), and prolonged rupture of membranes (OR, 3.86; 95% CI, 2.19 to 6.84).
“Health care settings and neonatal antibiotic administration appear to be important factors in the acquisition of antibiotic-resistant bacteria, highlighting the importance of strengthening infection control and antimicrobial stewardship in maternity and neonatal units in LMICs,” the authors wrote.
The authors say the high prevalence of resistant pathogens found in newborns can be explained in part by conceptualizing the neonatal microbiome as “an empty biological niche.” At birth, microbial diversity in the microbiome is low, and it doesn’t reach adult levels until the age of 3. As a result, even limited exposure to resistant pathogens that live in hospitals in LMICs can lead to colonization.
“This limited diversity may facilitate the establishment of antibiotic-resistant pathogens in neonates even after brief exposure,” they wrote. “Additionally, it may lead to faster bacterial selection following antibiotic administration, potentially increasing the effect of antibiotic administration on the acquisition of antibiotic-resistant pathogens in neonates compared with adults or children.”
The authors note that high heterogeneity among the studies suggests that the results should be interpreted with caution. Nonetheless, they say the findings may provide a basis for future research and design of interventions aimed at preventing neonatal colonization with resistant bacteria.
Health care settings and neonatal antibiotic administration appear to be important factors in the acquisition of antibiotic-resistant bacteria, highlighting the importance of strengthening infection control and antimicrobial stewardship in maternity and neonatal units in LMICs.
