Severe acute malnutrition (SAM) affects over 14 million children under the age of five worldwide and is a leading cause of mortality in low-resource settings with infections being the major drivers. With a lack of rigorous studies, the World Health Organization (WHO) has recommended broad-spectrum antibiotics for infections in this population since 2012. Since then, there have been dramatic increases in antimicrobial resistance (AMR), especially in settings like Malawi.
A prospective observational study led by Bryan Vonasek, MD, UJMT Fogarty Fellow (2022-2023) in pediatric infectious diseases, and Tisungane Mvalo, MD, associate professor of pediatrics and in-country director of pediatrics at UNC Project-Malawi, with support from Emily Ciccone, MD, MHS, assistant professor of infectious diseases, describes the current burden of bacterial infections and drug resistance in children <5 years hospitalized with SAM in a new report published in the Journal of the Pediatric Infectious Diseases Society. The study, conducted at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi, fills an important evidence gap for a population with unacceptably high mortality.
Dr. Vonasek, who is now a pediatric infectious disease physician scientist at Michigan State University says AMR has been a growing problem, anecdotally, at KCH. He says the team leveraged strong relationships with the KCH Peds Department and the micro lab at UNC Project-Malawi to conduct the study, quantifying serious bacterial infections and AMR in a highly vulnerable population, children with SAM.
“In 2018, I was encouraged by my mentors—Dr. Msandeni Chiume-Kayuni and the late Dr. Peter Kazembe—to start working with the department’s team that manages children hospitalized with SAM,” Vonasek said. “We started designing this study way back then, and we now have evidence to help answer a persistently difficult question in low- and middle-income countries: How should empiric antibiotics be used to reduce the unacceptably high mortality faced by children with SAM? I am grateful for the opportunity to conduct this research as a UJMT Fogarty Fellow under the strong mentorship of Dr. Mvalo and so many others.”
From February 2023 to January 2024, the team enrolled eligible participants who were identified during routine screening at KCH’s Department of Pediatrics, led by Dr. Mvalo, the in-country director of UNC Project-Malawi. Eligible children had blood and urine collected for culture, as well as cerebrospinal fluid (if symptoms suggested a central nervous system infection was present). Broad-spectrum antibiotics were initiated according to WHO and national guidelines. Microbiologic testing was conducted at UNC Project-Malawi’s internationally accredited microbiology research laboratory adjacent to KCH.
Results
Urinary tract infection was diagnosed in 20% of participants, and bacteremia in 10%. Resistance to first- and second-line antibiotics occurred in >1/3 of the bacteria isolated. In-hospital mortality was 11%, similar to previous studies at KCH, and other reports from low-income countries.
Given the association of bacteremia and meningitis with mortality, these findings suggest treatable infections are likely to be major drivers of mortality in this population.
The high rates of AMR to first- and second-line intravenous antibiotics suggest alternative antibiotics could be used empirically instead of the currently recommended regimen of penicillin or ampicillin with gentamicin. Globally, Dr. Mvalo says SAM in children continues to be a direct or indirect cause of poor health and mortality.
“Infections have been previously known as a cause of illness and death in this population, this study further adds evidence to this with high rates of urinary tract infections and blood stream infections,” said Dr. Mvalo. “Additionally, here, resistance to the standard of care antibiotics has been shown to be unacceptably high in this population already at risk of poor health. This warrants further multi-site research and consideration for alternative empirical antibiotics to improve the outcomes of children with complicated malnutrition.”
Clinicians urgently need improved tools, including access to basic microbiology, to practice antibiotic stewardship and identify patients in need of broad-spectrum antibiotics. Children hospitalized with severe acute malnutrition are a key group on which these efforts should be focused.