Keenan et al. recently showed that the mass distribution of broad-spectrum antibiotics to preschool children significantly reduced mortality in Niger (18.1%) (1). This is an exciting result, however, the disadvantages of an approach that involves the mass administration of antibiotics must not be downplayed. The potential negative consequences are two-fold.

The first serious concern is that an increase in antibiotic usage will cause resistance to more rapidly emerge. The antibiotic used in the study, azithromycin, is commonly used to treat gonorrhoea, and without it this disease would become even more difficult to combat. Randomized controlled trials looking for the effect of azithromycin on the emergence of resistance have had mixed results. In one study, azithromycinselected for resistance in the oral Streptococci of volunteers (2), however, in Nepal, a single dose of azithromycin to the eye decreased the total bacteria present but did not affect the relative abundance of resistant strains (3). Two studies specifically looking at the effect of the mass distribution of antibiotics for the prevention of trachoma found increased resistance in Escherichia coli (4) and Streptococcus pneumoniae (5). The mass distribution of antimalarials, pyrimethamine in the 1950s and subsequently chloroquine in the 1960s, in each case led to the emergence of resistance and the loss of an effective treatment (6). The authors of the current study (1) have acknowledged that resistance is a potential issue and have expressed their intention to measure the effect of this intervention on resistance in future trials. The World Health Organization is intending to give its own recommendation on the mass administration of antibiotics by the end of 2019 (7).

The second negative consequence is less well understood, however, increasingly, research suggests that the microbial communities growing on and within us have a role in our overall health. Variations in the microbiome have been linked to a variety of diseases including obesity, inflammatory bowel disease, autism, and arthritis (8), and antibiotic-induced disruption of the intestinal flora in the early months of life has been associated with an increased risk of obesity (9,10). It is important to consider the potential impact that administering antibiotics to infants may have later in their lives, especially in Africa where non-communicable diseases are increasingly taking more lives (11).

Intriguingly, the impact of mass antibiotic administration had four times the impact in Niger compared to Tanzania. Furthermore, the data from Niger distort the overall findings; in Malawi and Tanzania, which were both also included in the study, the reductions in mortality attributed to this intervention were not statistically significant. The situational differences between these countries are likely to be large in terms of profile of disease, availability of drugs, availability of health workers, and other factors. This makes it difficult to meaningfully combine the data from these diverse areas, as is done in this publication to reach the figure of a 13.5% overall reduction in mortality (1). In addition, azithromycin had the greatest impact in the one- to five-month old age group, yet this group only received a single antibiotic dose. It will be interesting to see whether the follow-up studies, which have been planned, reproduce these results and are able to explain these findings.

The authors of this study suggest many of the deaths that were prevented were due to dysentery, diarrhoea, malaria, or pneumonia (1). Improvements to sanitation, nutrition and healthcare have long provided the same benefits in the developed world. In areas of Mali, where proactive community case management (ProCCM) was launched, rates of under-five mortality were lower than in any other country in sub-Saharan Africa (12). ProCCM included active case detection, doorstep care, the elimination of user fees, and improvements to primary care infrastructure and staff capacity building. Such studies show the gains that can be made when policymakers focus on the development of comprehensive primary care programs that feature preventative medicine coverage such as immunization, diagnosis, and appropriate care.

Almost 8% of children die before their fifth birthday in sub-Saharan Africa (13). The study by Keenan et al. presents an appealing solution; a cheap and simple intervention that can save many lives. Yet, while this short-term measure may increase access to antibiotics and prevent deaths in this population, it fails to capture the long-term view that access to these life-saving drugs will be diminished if resistance spreads and antibiotics are no longer effective. Such consequential resistance stands to affect, not only this generation, both in Niger and farther afield, but the generations to come.


  1. J. D. Keenan et al., Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa. N. Engl. J. Med. 378, 1583–1592 (2018).
  2. S. Malhotra-Kumar, C. Lammens, S. Coenen, K. Van Herck, H. Goossens, Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study. Lancet. 369, 482–90 (2007).
  3. K. C. Chern et al., Alterations in the conjunctival bacterial flora following a single dose of azithromycin in a trachoma endemic area Alterations in the conjunctival bacterial flora following a single dose of azithromycin in a trachoma endemic area, 1332–1335 (1999).
  4. J. C. Seidman et al., Longitudinal comparison of antibiotic resistance in diarrheagenic and non-pathogenic escherichia coli from young tanzanian children. Front. Microbiol. 7, 1–8 (2016).
  5. D. K. H. Ho, C. Sawicki, N. Grassly, Antibiotic Resistance in Streptococcus pneumoniae after Azithromycin Distribution for Trachoma. J. Trop. Med. 2015 (2015), doi:10.1155/2015/917370.
  6. A. Maxmen, Malaria: A race against resistance. Nature. 501 (2013), pp. 186–188.
  7. A. Maxmen, Giving at-risk children pre-emptive antibiotics reduces deaths. Nature. 557 (2018), pp. 14–15.
  8. J. A. Gilbert et al., Current understanding of the human microbiome. Nat. Med. 24, 392–400 (2018).
  9. L. C. Bailey et al., Association of antibiotics in infancy with early childhood obesity. JAMA Pediatr. 168, 1063–1069 (2014).
  10. L. Trasande et al., Infant antibiotic exposures and early-life body mass. Int. J. Obes. 37, 16–23 (2013).
  11. The Economist, The epidemiological transition is now spreading to the emerging world (2018), (available at
  12. A. D. Johnson et al., Proactive community case management and child survival in periurban Mali. BMJ Glob. Heal. 3, e000634 (2018).
  13. G. Gallagher, Mass antibiotic dosing reduces child mortality in sub-Saharan Africa. Infect. Dis. News (2018), (available at