Mass drug administration of antibacterials: weighing the evidence regarding benefits and risks

Abstract

Background Mass drug administration (MDA) is a strategy to improve health at the population level through widespread delivery of medicine in a community. We surveyed the literature to summarize the benefits and potential risks associated with MDA of antibacterials, focusing predominantly on azithromycin as it has the greatest evidence base. Main body High-quality evidence from randomized controlled trials (RCTs) indicate that MDA-azithromycin is effective in reducing the prevalence of infection due to yaws and trachoma. In addition, RCTs suggest that MDA-azithromycin reduces under-five mortality in certain low-resource settings that have high childhood mortality rates at baseline. This reduction in mortality appears to be sustained over time with twice-yearly MDA-azithromycin, with the greatest effect observed in children < 1 year of age. In addition, observational data suggest that infections such as skin and soft tissue infections, rheumatic heart disease, acute respiratory illness, diarrheal illness, and malaria may all be treated by azithromycin and thus incidentally impacted by MDA-azithromycin. However, the mechanism by which MDA-azithromycin reduces childhood mortality remains unclear. Verbal autopsies performed in MDA-azithromycin childhood mortality studies have produced conflicting data and are underpowered to answer this question. In addition to benefits, there are several important risks associated with MDA-azithromycin. Direct adverse effects potentially resulting from MDA-azithromycin include gastrointestinal side effects, idiopathic hypertrophic pyloric stenosis, cardiovascular side effects, and increase in chronic diseases such as asthma and obesity. Antibacterial resistance is also a risk associated with MDA-azithromycin and has been reported for both gram-positive and enteric organisms. Further, there is the risk for cross-resistance with other antibacterial agents, especially clindamycin. Conclusions Evidence shows that MDA-azithromycin programs may be beneficial for reducing trachoma, yaws, and mortality in children < 5 years of age in certain under-resourced settings. However, there are significant potential risks that need to be considered when deciding how, when, and where to implement these programs. Robust systems to monitor benefits as well as adverse effects and antibacterial resistance are warranted in communities where MDA-azithromycin programs are implemented. Graphical Abstract

Retracted: Prevalence of active trachoma infection and associated factors post‐war resettled population in raya kobo districts, North East Ethiopia: A community‐based cross‐sectional study in 2022

“…41 In this report, there was an 8.9(AOR = 8.9:95%; 12 months of treatment as compared with control groups supporting the use of MDA-azithromycin in trachoma control as being highly acceptable. 42,43 Unlike previous studies, finding in central Ethiopia, 44 Southern Ethiopia, 45 and Tanzania 46 demonstrated that our study had no evidence of distance to drinking water sources, distance to health facilities, and many families and no significant association with acquiring to develop active trachoma infection. Individuals who lived near water sources had higher hygiene standards, more personal cleanses, and a lower risk of trachoma infection from flies, which is directly related to the likelihood of developing Trachoma.…”

“…In this report, there was an 8.9(AOR = 8.9:95%; 2.36‐‐33.6, p = 0.01) time increase for active trachoma infection if mass drug administration of Azitromza as part of chemoprophylaxis for prevention. A recent Cochrane review of four cluster randomized trials (RCTs) that compared community‐level treatment with MDA‐azithromycin showed a reduction of 40–60% active trachoma within 12 months of treatment as compared with control groups supporting the use of MDA‐azithromycin in trachoma control as being highly acceptable 42,43 …”

“…A recent Cochrane review of four cluster randomized trials (RCTs) that compared community‐level treatment with MDA‐azithromycin showed a reduction of 40–60% active trachoma within 12 months of treatment as compared with control groups supporting the use of MDA‐azithromycin in trachoma control as being highly acceptable. 42 , 43 …”

Mass Azithromycin Distribution to Prevent Child Mortality in Burkina Faso

“…Mass periodic distribution of azithromycin clearly selects for macrolide-resistant bacteria. 22 Increased resistance in Streptococcus pneumoniae and Escherichia coli has been well documented following mass azithromycin distribution for trachoma. 23 The prevalence of macrolide resistance appears to decline after mass distributions are discontinued.…”

Pre-vaccination carriage prevalence ofStreptococcus pneumoniaeserotypes among internally displaced people in Somaliland

“…The ermB gene was found in 9% of pneumococci, and is associated with macrolide resistance (40). Future improved understanding of antimicrobial resistance in pneumococci would be useful to better understand the impact of more clinically-relevant antibiotics for standard care as well as the potential impact of mass-drug administration campaigns, a potential alternative intervention to reduce the pneumococcal disease burden proposed for crisis settings (41).…”