title: The co-selection of fluoroquinolone resistance genes in the gut flora of Vietnamese children.
abstract: Antimicrobial consumption is one of the major contributing factors facilitating the development and maintenance of bacteria exhibiting antimicrobial resistance. Plasmid-mediated quinolone resistance (PMQR) genes, such as the qnr family, can be horizontally transferred and contribute to reduced susceptibility to fluoroquinolones. We performed an observational study, investigating the copy number of PMQR after antimicrobial therapy. We enrolled 300 children resident in Ho Chi Minh City receiving antimicrobial therapy for acute respiratory tract infections (ARIs). Rectal swabs were taken on enrollment and seven days subsequently, counts for Enterobacteriaceae were performed and qnrA, qnrB and qnrS were quantified by using real-time PCR on metagenomic stool DNA. On enrollment, we found no association between age, gender or location of the participants and the prevalence of qnrA, qnrB or qnrS. Yet, all three loci demonstrated a proportional increase in the number of samples testing positive between day 0 and day 7. Furthermore, qnrB demonstrated a significant increase in copy number between paired samples (p<0.001; Wilcoxon rank-sum), associated with non-fluoroquinolone combination antimicrobial therapy. To our knowledge, this is the first study describing an association between the use of non-fluoroquinolone antimicrobials and the increasing relative prevalence and quantity of qnr genes. Our work outlines a potential mechanism for the selection and maintenance of PMQR genes and predicts a strong effect of co-selection of these resistance determinants through the use of unrelated and potentially unnecessary antimicrobial regimes.
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
authors.forename: Le Thi Minh
authors.initials: le TM
authors.lastname: Vien
authors.forename: Ngo Ngoc Quang
authors.initials: NN
authors.lastname: Minh
authors.forename: Tang Chi
authors.initials: TC
authors.lastname: Thuong
authors.forename: Huynh Duy
authors.initials: HD
authors.lastname: Khuong
authors.forename: Tran Vu Thieu
authors.initials: TV
authors.lastname: Nga
authors.forename: Corinne
authors.initials: C
authors.lastname: Thompson
authors.forename: James I
authors.initials: JI
authors.lastname: Campbell
authors.forename: Menno
authors.initials: M
authors.lastname: de Jong
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Farrar
authors.forename: Constance
authors.initials: C
authors.lastname: Schultsz
authors.forename: H Rogier
authors.initials: HR
authors.lastname: van Doorn
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002675:Child, Preschool; D002954:Citrobacter / Q000187:drug effects / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000276:immunology; D004755:Enterobacteriaceae / Q000187:drug effects / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D007223:Infant; D007709:Klebsiella / Q000187:drug effects / Q000235:genetics; D008297:Male; D008826:Microbial Sensitivity Tests; D020636:Pantoea / Q000187:drug effects / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011511:Proteus / Q000187:drug effects / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012760:Shigella / Q000187:drug effects / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones