Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus-Exposed, Uninfected Infants
| Autor: | Anna Coutsoudis, Gautam Dantas, Indi Trehan, Tejas Kelkar, Brodie Daniels, Bin Wang, Alaric W. D’Souza, Xiaoqing Sun, Bertram M. Berla, Eshia Moodley-Govender |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Microbiology (medical) medicine.medical_specialty medicine.drug_class Antibiotics Human immunodeficiency virus (HIV) HIV Infections medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Antibiotic resistance Pregnancy Internal medicine Trimethoprim Sulfamethoxazole Drug Combination Prevalence Medicine Humans 030212 general & internal medicine Microbiome Antibiotic prophylaxis Gene business.industry HIV Infant Guideline Confidence interval Gastrointestinal Microbiome Major Articles and Commentaries 030104 developmental biology Infectious Diseases Female business |
| Zdroj: | Clin Infect Dis |
| ISSN: | 1537-6591 |
| Popis: | Background Prophylactic cotrimoxazole treatment is recommended in human immunodeficiency virus (HIV)–exposed, uninfected (HEU) infants, but the effects of this treatment on developing HEU infant gut microbiotas and resistomes are largely undefined. Methods We analyzed whole-metagenome sequencing data from 163 longitudinally collected stool samples from 63 HEU infants randomized to receive (n = 34; CTX-T) or to not receive (n = 29; CTX-N) prophylactic cotrimoxazole treatment. We generated taxonomic, functional pathway, and resistance gene profiles for each sample and compared microbiome signatures between the CTX-T and CTX-N infants. Results Metagenomic analysis did not reveal significant differences in taxonomic or functional pathway α-diversity between CTX-T and CTX-N infants. In contrast, resistance gene prevalence (P = .00719) and α-diversity (P = .0045) increased in CTX-T infants. These differences increased over time for both resistance gene prevalence measured by log-normalized abundance (4-month mean, 0.71 [95% confidence interval {CI}, .2–1.2] and 6-month mean, 0.85 [95% CI, .1–1.7]) and α-diversity (P = .0045). Unlike α-diversity, interindividual gut microbiome taxonomic (mean, −0.11 [95% CI, −.15 to −.077]), functional taxonomic (mean, −0.050 [95% CI, −.084 to −.017]), and resistance gene (mean, −0.13 [95% CI, −.17 to −.099]) β-diversity decreased in CTX-T infants compared with CTX-N infants. These results are consistent with persistent antibiotic selection pressure. Conclusions Cotrimoxazole prophylaxis in HEU infants decreased gut microbiome β-diversity and increased antibiotic resistance gene α-diversity and prevalence. Antibiotic resistance is a growing threat, especially in low- and middle-income countries where the higher perinatal HIV exposure rates result in cotrimoxazole prophylaxis. Understanding effects from current HEU infant antibiotic prophylaxis guidelines will inform guideline revisions and efforts to reduce increasing antibiotic resistance. |
| Databáze: | OpenAIRE |
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