title: Rapid evolution of fluoroquinolone-resistant Escherichia coli in Nigeria is temporally associated with fluoroquinolone use.
abstract: BACKGROUND
  Antibiotic resistance has necessitated fluoroquinolone use but little is known about the selective forces and resistance trajectory in malaria-endemic settings, where selection from the antimalarial chloroquine for fluoroquinolone-resistant bacteria has been proposed.
  
  
  METHODS
  Antimicrobial resistance was studied in fecal Escherichia coli isolates in a Nigerian community. Quinolone-resistance determining regions of gyrA and parC were sequenced in nalidixic acid resistant strains and horizontally-transmitted quinolone-resistance genes were sought by PCR. Antimicrobial prescription practices were compared with antimicrobial resistance rates over a period spanning three decades.
  
  
  RESULTS
  Before 2005, quinolone resistance was limited to low-level nalixidic acid resistance in fewer than 4% of E. coli isolates. In 2005, the proportion of isolates demonstrating low-level quinolone resistance due to elevated efflux increased and high-level quinolone resistance and resistance to the fluoroquinolones appeared. Fluoroquinolone resistance was attributable to single nucleotide polymorphisms in quinolone target genes gyrA and/or parC. By 2009, 35 (34.5%) of isolates were quinolone non-susceptible with nine carrying gyrA and parC SNPs and six bearing identical qnrS1 alleles. The antimalarial chloroquine was heavily used throughout the entire period but E. coli with quinolone-specific resistance mechanisms were only detected in the final half decade, immediately following the introduction of the fluoroquinolone antibacterial ciprofloxacin.
  
  
  CONCLUSIONS
  Fluoroquinolones, and not chloroquine, appear to be the selective force for fluoroquinolone-resistant fecal E. coli in this setting. Rapid evolution to resistance following fluoroquinolone introduction points the need to implement resistant containment strategies when new antibacterials are introduced into resource-poor settings with high infectious disease burdens.
authors: Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.
authors: Adebayo
authors: A
authors: Lamikanra
authors: Jennifer L
authors: JL
authors: Crowe
authors: Rebeccah S
authors: RS
authors: Lijek
authors: Babatunde W
authors: BW
authors: Odetoyin
authors: John
authors: J
authors: Wain
authors: A Oladipo
authors: AO
authors: Aboderin
authors: Iruka N
authors: IN
authors: Okeke
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial; D004363:Drug Utilization; D004926:Escherichia coli / Q000187:drug effects* / Q000302:isolation & purification; D005243:Feces / Q000382:microbiology*; D024841:Fluoroquinolones / Q000494:pharmacology*; D022761:Gene Transfer, Horizontal; D006805:Human Experimentation; D006801:Humans; D009549:Nigeria; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase