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.

Figure 1

Antibacterial and Antimalarial prescription at the University Health Center. Daily defined doses (DDDs) of antimalarials (A) and antibacterials (B) dispensed from the Health center pharmacy in the 1980s, 1990s and 2000s.

Figure 2

Proportion of Escherichia coli isolates from students in Ile-Ife, Nigeria that were quinolone resistant (1986-2009, right axis) with grey portions of the bars indicating strains resistant to nalidixic acid alone and black shading representing strains resistant to nalixic acid and the fluoroquinolone ciprofloxacin. Daily defined doses of chloroquine (diamonds) and ciprofloxacin (circles) dispensed from the University Health center pharmacy in 1984-86, 1994-96 and 2004-06 are plotted from the left axis.