Antibiotic Resistance Threatens Children’s Health in Low-Income Countries

Antimicrobial resistance (AMR) stands as a formidable 21st-century threat to global human health. Children and neonates, in particular, bear the brunt of this crisis, facing an alarming surge in resistance to commonly prescribed antibiotics. Neonates, those precious newborns, suffer from an estimated three million cases of sepsis each year, with up to 570,000 of these cases resulting in sepsis-related deaths, many of which are attributable to the resistance of commonly recommended antibiotics. 

The burden of these infections falls disproportionately on low- and middle-income countries (LMICs), where most young children’s deaths occur. Recent systematic reviews have unveiled a disturbingly high level of bacterial resistance to the World Health Organization (WHO)-recommended empirical treatments for bloodstream infections in children in LMICs.

The vulnerability of the Asian region to avoidable neonatal and child mortality is evident. However, a glaring gap exists in published data to comprehensively understand the epidemiology and non-susceptibility rates for severe bacterial infections in this region, especially concerning the dominance of gram-negative bacteria causing invasive infections in Asian countries. 

Southeast Asia and the Pacific face significant concerns regarding AMR. Limited healthcare resources and constrained access to newer agents for treating multidrug-resistant pathogens compound the challenges in this region. To evaluate the effectiveness of commonly prescribed empiric antibiotic regimens for children in Southeast Asia and the Pacific, a Weighted Incidence Syndromic Combination Antibiogram (WISCA) was developed.

This approach was parameterized using data from a systematic review of published literature encompassing WHO-defined SEARO and WPRO regions, drawing from sources like Ovid MEDLINE, EMBASE, Global Health, and PubMed. The susceptibility data of bacterial pathogens were extracted to estimate coverage for specific antibiotics, including aminopenicillins, gentamicin, third generation cephalosporins, and carbapenems, on a regional basis.

A Bayesian WISCA model incorporated 6,648 bacterial isolates from 11 countries across 86 research papers, effectively weighing bacterial incidence and antimicrobial susceptibility. The results are disconcerting. Coverage provided by aminopenicillins for neonatal sepsis/meningitis stood at a mere 26%, with an 80% credible interval ranging from 16% to 49%. Gentamicin offered slightly better coverage at 45%, with a range of 29% to 62%.

Third-generation cephalosporin coverage was shockingly low at 29% for neonatal sepsis/meningitis, 51% for paediatric sepsis, and 65% for paediatric meningitis. Carbapenems, the last line of defence, were estimated to provide the highest coverage: 81% for neonatal sepsis/meningitis, 83% for paediatric sepsis, and 79% for paediatric meningitis. 

These findings expose alarmingly high rates of resistance to commonly prescribed empirical therapies for neonatal and paediatric sepsis and meningitis in the Asia-Pacific region. The data encompassed susceptibility information for 3,423 isolates in neonatal sepsis/meningitis, 9,866 in paediatric sepsis, and 984 in paediatric meningitis.

Notably, some pathogens were overrepresented in specific countries; for instance, 32% of all E. coli isolates were reported in research conducted in China, while 33% of Klebsiella spp. Isolates originated from research in India. This comprehensive analysis employed a modeling approach to provide susceptibility estimates, excluding pre-specified intrinsically resistant combinations.

While susceptibility testing did not necessarily cover the same antibiotics in all studies, it frequently relied on inference, such as using oxacillin/cefoxitin results to deduce susceptibility to β-lactams in Staphylococcus aureus, following standardized microbiological procedures. The pervasive and growing threat of AMR, particularly in neonates and children, highlights a dire need for urgent and concerted efforts to combat this crisis.

The alarming rates of resistance to commonly prescribed antibiotics in the Asia-Pacific region call for immediate attention and action to preserve the effectiveness of antibiotics for future generations. Healthcare systems and governments must work together to address this critical issue and ensure the availability of effective treatments for bacterial infections in the most vulnerable populations. 

Journal Reference  

Coverage gaps in empiric antibiotic regimens used to treat serious bacterial infections in neonates and children in Southeast Asia and the Pacific, The Lancet Regional Health—Southeast Asia (2023). DOI: 10.1016/j.lansea.2023.100291.