TY - JOUR
T1 - Antibiotic selection pressure and macrolide resistance in Nasopharyngeal Streptococcus pneumoniae
T2 - A cluster-randomized clinical trial
AU - Skalet, Alison H.
AU - Cevallos, Vicky
AU - Ayele, Berhan
AU - Gebre, Teshome
AU - Zhou, Zhaoxia
AU - Jorgensen, James H.
AU - Zerihun, Mulat
AU - Habte, Dereje
AU - Assefa, Yared
AU - Emerson, Paul M.
AU - Gaynor, Bruce D.
AU - Porco, Travis C.
AU - Lietman, Thomas M.
AU - Keenan, Jeremy D.
N1 - Funding Information:
We thank the International Trachoma Initiative for their generous donation of azithromycin; the project officer for the study, Donald Everett (National Eye Institute, Bethesda, Maryland, United States); the data safety and monitoring committee including William Barlow (University of Washington, Washington, DC, United States; Chair), Donald Everett (National Eye Institute, Bethesda, Maryland, United States), Larry Schwab (International Eye Foundation, Kensington, Maryland, United States), Arthur Reingold (University of California, Berkeley, California, United States), and Serge Resnikoff (WHO, Geneva, Switzerland), who were generous with their time and advice and met before, during, and after this 12-month study; Amy Markowitz, for assistance revising the manuscript; the head of the Goncha woreda health office, Tadege Alemayehu; the head of the Amhara regional health bureau, Asrat Genet Amnie; the Ethiopian Ministry of Health; and the nurses and health workers who helped collect samples for the study, including Tesfaye Belay, Azmeraw Adgo, Melese Temesgen, Gebeyehu Sibhatu, Manahlosh Berihun, Temesgen Demile, Melkam Andualem, Mitselal Abrhale, Banchu Gedamu, Tessema Eneyew, and Muluken Gobezie. The trachoma control program in Amhara is supported by the Amhara Regional Health Bureau, the Lions-Carter Center SightFirst Initiative, and many individual donors.
PY - 2010/12
Y1 - 2010/12
N2 - Background: It is widely thought that widespread antibiotic use selects for community antibiotic resistance, though this has been difficult to prove in the setting of a community-randomized clinical trial. In this study, we used a randomized clinical trial design to assess whether macrolide resistance was higher in communities treated with mass azithromycin for trachoma, compared to untreated control communities. Methods and Findings: In a cluster-randomized trial for trachoma control in Ethiopia, 12 communities were randomized to receive mass azithromycin treatment of children aged 1-10 years at months 0, 3, 6, and 9. Twelve control communities were randomized to receive no antibiotic treatments until the conclusion of the study. Nasopharyngeal swabs were collected from randomly selected children in the treated group at baseline and month 12, and in the control group at month 12. Antibiotic susceptibility testing was performed on Streptococcus pneumoniae isolated from the swabs using Etest strips. In the treated group, the mean prevalence of azithromycin resistance among all monitored children increased from 3.6% (95% confidence interval [CI] 0.8%-8.9%) at baseline, to 46.9% (37.5%-57.5%) at month 12 (p =0.003). In control communities, azithromycin resistance was 9.2% (95% CI 6.7%-13.3%) at month 12, significantly lower than the treated group (p,0.0001). Penicillin resistance was identified in 0.8% (95% CI 0%-4.2%) of isolates in the control group at 1 year, and in no isolates in the children-treated group at baseline or 1 year. Conclusions: This cluster-randomized clinical trial demonstrated that compared to untreated control communities, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to intensive azithromycin treatment. Mass azithromycin distributions were given more frequently than currently recommended by the World Health Organization's trachoma program. Azithromycin use in this setting did not select for resistance to penicillins, which remain the drug of choice for pneumococcal infections.
AB - Background: It is widely thought that widespread antibiotic use selects for community antibiotic resistance, though this has been difficult to prove in the setting of a community-randomized clinical trial. In this study, we used a randomized clinical trial design to assess whether macrolide resistance was higher in communities treated with mass azithromycin for trachoma, compared to untreated control communities. Methods and Findings: In a cluster-randomized trial for trachoma control in Ethiopia, 12 communities were randomized to receive mass azithromycin treatment of children aged 1-10 years at months 0, 3, 6, and 9. Twelve control communities were randomized to receive no antibiotic treatments until the conclusion of the study. Nasopharyngeal swabs were collected from randomly selected children in the treated group at baseline and month 12, and in the control group at month 12. Antibiotic susceptibility testing was performed on Streptococcus pneumoniae isolated from the swabs using Etest strips. In the treated group, the mean prevalence of azithromycin resistance among all monitored children increased from 3.6% (95% confidence interval [CI] 0.8%-8.9%) at baseline, to 46.9% (37.5%-57.5%) at month 12 (p =0.003). In control communities, azithromycin resistance was 9.2% (95% CI 6.7%-13.3%) at month 12, significantly lower than the treated group (p,0.0001). Penicillin resistance was identified in 0.8% (95% CI 0%-4.2%) of isolates in the control group at 1 year, and in no isolates in the children-treated group at baseline or 1 year. Conclusions: This cluster-randomized clinical trial demonstrated that compared to untreated control communities, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to intensive azithromycin treatment. Mass azithromycin distributions were given more frequently than currently recommended by the World Health Organization's trachoma program. Azithromycin use in this setting did not select for resistance to penicillins, which remain the drug of choice for pneumococcal infections.
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U2 - 10.1371/journal.pmed.1000377
DO - 10.1371/journal.pmed.1000377
M3 - Article
C2 - 21179434
AN - SCOPUS:78650425412
SN - 1549-1277
VL - 7
JO - PLoS Medicine
JF - PLoS Medicine
IS - 12
M1 - e1000377
ER -