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May 3, 2010

Antibiotic Use and Environmental Exposure Are Key Factors Affecting Antibiotic Resistant E. Coli Carriage in Children in Peru

Antimicrobial resistance has emerged as a global health problem and is a major impediment in managing childhood infectious diseases. Direct and indirect exposure of young children to antibiotics through medical and agricultural usage can increase their risk for carriage of resistant E. coli, according to a new study published in the May issue of the American Journal of Tropical Medicine and Hygiene.

It is estimated that E. coli causes disease in hundreds of thousands of people around the world each year, including approximately 70,000 Americans. E. coli can be transmitted from animals and humans through several sources, the most common being contaminated food andwater. While most E. coli are harmless, and are carried as a normal part of the human intestinal fauna, such commensal bacteria might serve as an important reservoir of resistance that can be transmitted to disease-causing E. coli and other bacterial species.

The study, conducted by the Johns Hopkins Bloomberg School of Public Health faculty members Henry D. Kalter, MD, MPH, Robert H. Gilman, MD, and Lawrence H. Moulton, PhD, MS, together with colleagues in Peru, revealed several factors affecting antibiotic-resistant E. coli carriage in young children in Peru. By analyzing E. coli samples from more than 500 children, the researchers were able to identify individual, household and community factors influencing carriage of the resistant bacteria.

"This study is unique in having evaluated a number of risk factors at multiple levels in very young children for carrying antibiotic-resistant E. coli bacteria. By examining all these factors, we were able to reach a more comprehensive understanding of how resistant E. coli is transmitted in the developing world," said Kalter, lead study investigator and an associate in the Department of International Health at the Bloomberg School of Public Health. "In analyzing the study results, we learned that children’s use of antibiotics, as well as their family members’ use, increased their risk for carrying resistant E. coli, and that residing in an area where a greater proportion of households served home-raised chickens protected against resistance. This protective effect can be understood in light of the fact that the home-raised chickens carried significantly lower levels of resistant E. coli than did the market chickens, which in Peru are intensively raised with antibiotics. The strength of this community level variable suggests that this is where the transmission of resistance resulting from agricultural antibiotics use was taking place."

In poor communities in developing countries (such as Peru), with inadequate protection of excreta and water, contamination of the environment with antibiotic-resistant bacteria appeared to play at least as great a role in children’s carriage of resistant E. coli as did the children’s own antibiotics use.

"This study is important in a number of respects," said Edward T. Ryan, M.D., president of the American Society of Tropical Medicine and Hygiene (ASTMH). "It improves our understanding of the growing global public health threat of antibiotic resistant organisms, and underscores the critical role that antibiotic use in animals plays in contributing to this threat. The vast majority of the tons and tons of antibiotics ingested each year on this planet are administered to livestock and animals. This study clearly shows that such use comes with a very real cost to human health."

About the Study

The study was conducted in 16 purposively selected zones in four regions in Peru, including peri-urban slums in Lima and towns and villages in Cajamarca in the Sierra Mountains, Iquitos in the Amazon rain forest, and Chincha on the coast.

Few studies have examined the influence of individual, household, and community-scale risk factors on carriage of resistant commensal bacteria. This study determined children’s medical, agricultural, and environmental exposures by household, pharmacy, and health facility surveys and Escherichia coli cultures of children, mothers’ hands, household animals, and market chickens in Peru.

Among 522 children with a positive stool culture, by log-binominal regression, using “any antibiotic” and 1-4 (versus 0) sulfa doses in the past 3 months increased children’s risk, respectively, for ampicillin and sulfamethoxazole-resistant E. coli carriage (P = 0.01 – 0.02). Each household member taking “any antibiotic” increased children’s risk for sulfamethoxazole and multidrug resistant E. coli carriage (P<0.0001). Residence in a zone where a larger proportion of households served home-raised chicken (as contrasted with intensively antibiotic-raised market chicken) protected against carrying E. coli resistant to all drugs (P = 0.0004 – 0.04). Environmental contamination with drug-resistant bacteria appeared to significantly contribute to children’s carriage of antibiotic-resistant E. coli.

About the Participants

A minimum of 25 households with one or more children 3 months to 3 years of age was sought in each of the 16 zones. A sweep census was conducted in the selected villages and town areas until the desired minimum sample of 25 households was achieved. This entailed sampling all households in villages where the population was below the sample size but only one or two streets in urban areas.

Households where the youngest child had taken any antibiotic within 7 days of the original visit were revisited to take all cultures and conduct the interview at least 7 days after the child completed his/her antibiotics course. At each house, a rectal and hands-dip broth swab was obtained from the youngest child and his/her mother and cultured for E. coli; and a rectal swab for E. coli culture was taken from a convenience sample of one of each animal type.

Using a standardized questionnaire, the mother was asked about a number of potential risk and confounding factors at the individual and household levels, including the child’s age and breastfeeding, her own education, the household head’s employment, home ownership, number of rooms, type of flooring and cooking fuel, the child’s and all other household members’ use of antibiotics in the last three months, the presence of household animals and their consumption of antibiotics, the child’s food and water consumption, the household’s serving of home-raised and market-purchased chicken, and the household’s protection of water and excreta. Community level variables that were examined included E. coli cultures of market chicken viscera, antibiotics sales and prescribing practices, and the proportions of community households exhibiting various risk and protective factors.

Media contact for the American Journal of Tropical Medicine and Hygiene: Christina Witz at 646-509-9379 or cwitz@mww.com.

Media contact for JHSPH: Tim Parsons at 410-955-7619 or tmparson@jhsph.edu.