Antibiotic Selection Pressure and Macrolide Resistance in Nasopharyngeal Streptococcus pneumoniae: A Cluster-Randomized Clinical Trial

Abstract

Jeremy Keenan and colleagues report that during a cluster-randomized clinical trial in Ethiopia, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to receive azithromycin compared with untreated control communities.

Epidemiological Interpretation of Studies Examining the Effect of Antibiotic Usage on Resistance

“…For instance, Skalet et al randomly assigned 24 communities in Ethiopia to receive either immediate (at months 0, 3, 6, and 9) or delayed (after month 12) mass azithromycin treatment of children for trachoma control (162). They compared the prevalence of macrolide resistance in nasopharyngeal S. pneumoniae isolates in the immediate-treatment group (pre-and posttreatment) with that in the delayed-treatment group (pretreatment).…”

“…Accordingly, many RCTs in the field of antibiotic resistance use cluster randomization. Units of random- ization may vary, including, for example, patient care units (164,165) and communities (162). One drawback of performing cluster randomization is the reduced statistical efficiency, which mandates recruitment of more participants in order to obtain the same statistical power as individual randomization.…”

Coinfection dynamics of two diseases in a single host population

“…However, simultaneous colonization or infection may occur even when there appears to be little or no interaction between the two agents, as in the case of infection by ocular strains of chlamydia and nasopharyngeal colonization by pneumococcus [24]. The dynamics of coinfection is important in this case, because antimicrobials used to treat one infection may affect the other (e.g., [51, 24]).…”

Mass administration of azithromycin andStreptococcus pneumoniaecarriage: cross-sectional surveys in the Gambia

“…Although currently there is no evidence that repeated MDA increases the prevalence of azithromycinresistant C. trachomatis, 9 there is epidemiological evidence suggesting that pharyngeal carriage of macrolide-resistant Streptococcus pneumoniae increases following repeated MDA for trachoma control. 10,11 Because S. pneumoniae is a leading cause of childhood mortality, especially in Africa, and because asymptomatic nasopharyngeal carriage is the initial step in the pathogenesis of pneumococcal disease, increased carriage of macrolide-resistant strains is a public health concern.…”