Antimicrobial resistance (AMR) is a major global public health challenge, and childhood diarrhea represents one of the key contexts for antibiotic overuse. Rotavirus (RV) is the leading cause of acute diarrhea among children under five years of age. Although most infections are self-limiting and do not require antimicrobial treatment, the lack of diagnostic capacity often results in inappropriate antibiotic prescriptions in clinical practice, thereby accelerating the emergence and spread of resistance^1,2. The WHO Immunization Agenda 2030 (IA2030) also explicitly emphasizes that countries which have not yet introduced rotavirus vaccines (RVVs) should do so and aim to achieve ≥90% coverage to reduce antibiotic use and lower the risk of AMR transmission³.

Association between Rotavirus, Diarrhea, and Antibiotic Use

RV is one of the most important pathogens causing childhood diarrhea worldwide. Before the introduction of vaccines, it caused over 200 million diarrheal cases and approximately 450,000 deaths each year⁴. The burden of RV-related hospitalizations and deaths is particularly significant in low- and middle-income countries (LMICs)⁵. Although RV infection is a self-limiting viral disease that does not require antibiotic treatment, empirical antibiotic prescriptions for childhood diarrhea are still common in clinical practice. Unnecessary antibiotic use not only increases the burden on families and health systems, but also directly accelerates the selection and spread of resistant bacterial strains⁶. In some LMICs, even though most diarrhea cases are of viral origin, 40–60% of childhood diarrhea episodes are still treated with antibiotics⁷. Rogawski et al. reported that in eight LMICs, 45.8% of diarrheal episodes among children under two years of age involved antibiotic treatment⁸. The main contributing factors include limited diagnostic capacity, physicians’ empirical prescribing habits, limited access to rapid diagnostics and stewardship support, and insufficient regulatory oversight of rational drug use within health systems^9-11. Even in high-income countries, inappropriate antibiotic use for diarrhea remains prevalent¹².

Studies have shown that RV-associated diarrhea makes a particularly significant contribution to antibiotic use among children. The Global Enteric Multicenter Study (GEMS) reported that among children in LMICs, diarrhea-related antibiotic use accounted for a substantial proportion of total antibiotic consumption¹³. Specifically, RV alone accounted for 29.2% (24.5–35.2%) of antibiotic-treated diarrheal cases, with the highest proportion observed during the first two years of life¹³.

Evidence of RVVs in Reducing Antibiotic Use

The introduction of RVVs has significantly altered the global epidemiological landscape of childhood diarrheal diseases. As of 2024, more than 129 countries have introduced RVVs into their national immunization programs (NIPs)¹⁴. Global surveillance data indicate that in countries where RVVs have been introduced, hospitalizations for RV-related acute gastroenteritis have declined by 40%¹⁵. An increasing number of studies demonstrate that RVV uptake can reduce unnecessary antibiotic prescriptions, thereby playing an indirect but important role in mitigating AMR. According to a technical assessment by WHO, approximately 46 million antibiotic prescriptions worldwide were associated with rotavirus infections in 2019, of which about 15 million could have been averted through vaccination (Table 1).

Table 1. Rotavirus-Associated Antibiotic Use and Vaccine-Avertable Prescriptions by WHO Region, 2019

WHO Region	Antibiotic Use (DDD,95%UI)	Vaccine-Avertable Antibiotic Use(DDD,95%UI)
African Region (AFR)	15 (8.4-22) million	4.6 (2.6–7) million
European Region (EUR)	2.4 (1.7-5.8) million	1.1 (0.48–2.1) million
Eastern Mediterranean Region (EMR)	3.4 (1.7-5.8) million	4.4 (2.3–7) million
South-East Asia Region (SEAR)	3.4 (1.7-5.8) million	2.8 (1.7–3.9) million
Region of the Americas (AMR)	3.4 (1.7-5.8) million	0.48 (0.24–0.82) million
Western Pacific Region (WPR)	3.7 (2.2-6) million	2 (1.2–3.2) million
Global	46 (30-63) million	15 (10–21) million

In a modeling analysis leveraging large-scale household surveys from LMICs, Lewnard et al. estimated that under current vaccine coverage levels, RVVs can directly prevent approximately 13.6 million diarrheal episodes among children aged 0-23 months that would otherwise have received antibiotic treatment⁹. This accounts for 31.0% (95% CI: 17.7–35.2%) of all RV-related antibiotic-treated cases⁹. If universal vaccine coverage were achieved, an additional 18.3 million antibiotic-treated diarrheal cases could be directly prevented in this age group — equivalent to a 42.1% reduction (95% CI: 14.6–50.7%) in rotavirus-associated antibiotic use. Another dynamic modeling study focusing on India found that nationwide RVVs introduction led to a 33.7% reduction in rotavirus prevalence among children under five, accompanied by a 21.8% decrease inappropriate antibiotic use and a 38.3% decline in mortality. The study further projected that if vaccine coverage increased to 68.1%, the prevalence of rotavirus infection and the proportion of inappropriate antibiotic use among under-five children would both decline substantially¹⁵.

Real-world evidence indicates that RVVs are strongly associated with a reduction in antibiotic prescriptions. In the United States (2007–2018), fully vaccinated children had a significantly lower five-year cumulative incidence of antibiotic prescribing after a confirmed acute gastroenteritis diagnosis (HR = 0.793, 95% CI: 0.761–0.827), where less likely to switch antibiotics, and nationwide estimates  approximately 67,045 antibiotic prescriptions were averted¹². Similar findings have been noted in hospital surveillance data from Libya⁷.

It is important to note that current studies may still underestimate the full effect of rotavirus vaccination on reducing antibiotic use. Beyond its direct protective effect for vaccinated individuals, RVV also contributes to herd immunity by reducing viral transmission within the population. This indirect protection has been demonstrated to benefit unvaccinated children and adults, lowering their risk of rotavirus gastroenteritis and associated antibiotic prescriptions^16,17. However, most existing studies have not systematically evaluated these indirect effects and thus may underestimate the overall population-level impact of the vaccination.

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Content Editor: Xinyue Zhou

Proofreading: Ziqi Liu

Page Editor: Ziqi Liu

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References

1. Rappuoli, R., Pizza, M., Del Giudice, G., & De Gregorio, E. (2014). Vaccines, new opportunities for a new society. Proceedings of the National Academy of Sciences of the United States of America, 111(34), 12288–12293. https://doi.org/10.1073/pnas.1402981111

2. Jansen, K. U., Gruber, W. C., Simon, R., Wassil, J., & Anderson, A. S. (2021). The impact of human vaccines on bacterial antimicrobial resistance. A review. Environmental chemistry letters, 19(6), 4031–4062. https://doi.org/10.1007/s10311-021-01274-z

3. World Health Organization. (2021). Implementing the Immunization Agenda 2030. Geneva: WHO. https://www.who.int/publications/m/item/implementing-the-immunization-agenda-2030

4. Tate, J. E., Burton, A. H., Boschi-Pinto, C., Steele, A. D., Duque, J., Parashar, U. D., & GRSN Team. (2012). 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: A systematic review and meta-analysis. The Lancet Infectious Diseases, 12(2), 136–141. https://doi.org/10.1016/S1473-3099(11)70253-5

5. Tate, J. E., Burton, A. H., Boschi-Pinto, C., Parashar, U. D., & World Health Organization–Coordinated Global Rotavirus Surveillance Network (2016). Global, Regional, and National Estimates of Rotavirus Mortality in Children <5 Years of Age, 2000-2013. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 62 Suppl 2(Suppl 2), S96–S105. https://doi.org/10.1093/cid/civ1013

6. World Health Organization. (2015). Global Action Plan on Antimicrobial Resistance. Geneva: WHO. https://www.who.int/publications/i/item/9789241509763

7. Alkoshi, S. I., Ernst, K. C., & Dahlui, M. B. (2017). Antibiotic usage for rotaviral diarrhea among children in Libya. International Journal Of Community Medicine And Public Health, 3(1), 37–41. https://doi.org/10.18203/2394-6040.ijcmph20151545

8. Rogawski, E. T., Platts-Mills, J. A., Seidman, J. C., John, S., Mahfuz, M., Ulak, M., Shrestha, S. K., Soofi, S. B., Yori, P. P., Mduma, E., Svensen, E., Ahmed, T., Lima, A. A., Bhutta, Z. A., Kosek, M. N., Lang, D. R., Gottlieb, M., Zaidi, A. K., Kang, G., Bessong, P. O., … Guerrant, R. L. (2017). Use of antibiotics in children younger than two years in eight countries: a prospective cohort study. Bulletin of the World Health Organization, 95(1), 49–61. https://doi.org/10.2471/BLT.16.176123

9. Lewnard, J. A., Lo, N. C., Arinaminpathy, N., Frost, I., & Laxminarayan, R. (2020). Childhood vaccines and antibiotic use in low- and middle-income countries. Nature, 581(7806), 94–99. https://doi.org/10.1038/s41586-020-2238-4

10. Fink, G., D’Acremont, V., Leslie, H. H., & Cohen, J. (2020). Antibiotic exposure among children younger than 5 years in low-income and middle-income countries: a cross-sectional study of nationally representative facility-based and household-based surveys. The Lancet. Infectious diseases, 20(2), 179–187. https://doi.org/10.1016/S1473-3099(19)30572-9

11.  Holloway, K. A., Ivanovska, V., Wagner, A. K., Vialle-Valentin, C., & Ross-Degnan, D. (2013). Have we improved use of medicines in developing and transitional countries and do we know how to? Two decades of evidence. Tropical medicine & international health : TM & IH, 18(6), 656–664. https://doi.org/10.1111/tmi.12123

12. Hall, E. W., Tippett, A., Fridkin, S., Anderson, E. J., Lopman, B., Benkeser, D., & Baker, J. M. (2022). Association between rotavirus vaccination and antibiotic prescribing among commercially insured US children, 2007–2018. Open Forum Infectious Diseases, 9(7), ofac276. https://doi.org/10.1093/ofid/ofac276

13. Lewnard, J. A., Rogawski McQuade, E. T., Platts-Mills, J. A., Kotloff, K. L., & Laxminarayan, R. (2020). Incidence and etiology of clinically-attended, antibiotic-treated diarrhea among children under five years of age in low- and middle-income countries: Evidence from the Global Enteric Multicenter Study. PLoS neglected tropical diseases, 14(8), e0008520. https://doi.org/10.1371/journal.pntd.0008520

14. World Health Organization. (n.d.). Introduction of rotavirus vaccine. Immunization data. Retrieved September 24, 2025, from https://immunizationdata.who.int/global/wiise-detail-page/introduction-of-rotavirus-vaccine?ISO_3_CODE=&YEAR=

15. Gleason, A., Kumar, C. K., Klein, E., Laxminarayan, R., & Nandi, A. (2024). Effect of rotavirus vaccination on the burden of rotavirus disease and associated antibiotic use in India: A dynamic agent-based simulation analysis. Vaccine, 42(22), 126211. https://doi.org/10.1016/j.vaccine.2024.126211

16. Pindyck, T., Tate, J. E., & Parashar, U. D. (2018). A decade of experience with rotavirus vaccination in the United States – vaccine uptake, effectiveness, and impact. Expert review of vaccines, 17(7), 593–606. https://doi.org/10.1080/14760584.2018.1489724

17. Patel, M. M., Glass, R., Desai, R., Tate, J. E., & Parashar, U. D. (2012). Fulfilling the promise of rotavirus vaccines: how far have we come since licensure?. The Lancet. Infectious diseases, 12(7), 561–570. https://doi.org/10.1016/S1473-3099(12)70029-4