Mass distribution of Azithromycin for strep pneumonia not linked to long-term antibiotic resistance

USA: Macrolide and β-lactam resistance in Streptococcus Pneumoniae following single-dose azithromycin is short-term with no prevalence at six months after treatment, according to a study published in The Pediatric Infectious Disease Journal.

The study's findings are in line with the previous observational studies, with similar phenomena occurring in mass azithromycin distribution at the community and individual levels.

In sub-Saharan Africa, biannual mass distribution of azithromycin reduces the burden of all-cause childhood mortality, thereby necessitating the monitoring of antibiotic resistance. An increase in selection for macrolide resistance occurs following mass azithromycin distribution for trachoma control, but the resistance prevalence declines following cessation of antibiotic distribution.

The present trial evaluated antibiotic resistance selection in an individually randomized trial of single-dose azithromycin versus placebo over six months in S. pneumoniae isolates from children.

The study enrolled 450 children aged between 8 days and 59 months of age and were residents of Nouna Town, Burkina Faso. 230 children were randomized to azithromycin and 220 to a placebo. Participants received a 20 mg/kg single dose of azithromycin orally or an equivalent volume of matching placebo. The nasopharyngeal swabs were collected at baseline and 14 days and six months after treatment. Antibiotic susceptibility included testing for erythromycin, oxacillin, tetracycline, clindamycin, and trimethoprim-sulfamethoxazole.

Boubacar Coulibaly, the first author, commented, " We compared the proportion of isolates with pneumococcal carriage and, for isolates which grew pneumococcus, resistant to each antibiotic at each follow-up time point separately." The researchers calculated binomial 95 % confidence intervals for the prevalence of carriage and resistance to each antibiotic at each time point.

The conclusive study points are:

• At the baseline, the prevalence for pneumococcal carriage and placebo was 44 % and 47 %, respectively.

• The pneumococcal carriage was lower in children receiving azithromycin (27 %) at 14 days after treatment, compared to 47 % of placebo. False discovery rate (FDR) adjusted P value was < 0.001.

• Among the positive isolates, 55 % in the azithromycin arm were resistant to erythromycin compared to 13 % in the placebo.

• Oxacillin and clindamycin resistance was common in the azithromycin group compared with placebo. (oxacillin:azithromycin 73 %, with placebo 43 % and clindamycin:azithromycin 33 % with placebo 9 %).

• Mostly 83 % of erythromycin-resistant isolates were also resistant to oxacillin.

• At six months after treatment, there was no significant difference in pneumococcal carriage between children receiving azithromycin 44 % compared to placebo (51 %)

The researcher commented. "Coselection for resistance to multiple antibiotic classes is possible. This finding is well explained in the study as coresistance was observed between erythromycin-resistant and oxacillin isolates.

The study has promising results in explaining antibiotic resistance where no difference exists between two arms at six months, concluding the short-term selection getting normalized over time.

Reference:

Coulibaly, Boubacar PhD; Kiemde, Dramane MS; Zonou, Guillaume MS; Sié, Ali MD, PhD; Dah, Clarisse MD; Bountogo, Mamadou MD; Brogdon, Jessica MPH; Hu, Huiyu MS; Lebas, Elodie RN; Porco, Travis C. PhD, MPH; Doan, Thuy MD, PhD; Lietman, Thomas M. MD; Oldenburg, Catherine E. ScD, MPH. Effect of Single-dose Azithromycin on Pneumococcal Carriage and Resistance: A Randomized Controlled Trial. The Pediatric Infectious Disease Journal: September 2022 - Volume 41 - Issue 9 - p 728-730