Abstract
BackgroundQuinolones are potent broad-spectrum bactericidal agents increasingly employed also in resource-limited countries. Resistance to quinolones is an increasing problem, known to be strongly associated with quinolone exposure. We report on the emergence of quinolone resistance in a very remote community in the Amazon forest, where quinolones have never been used and quinolone resistance was absent in 2002.MethodsThe community exhibited a considerable level of geographical isolation, limited contact with the exterior and minimal antibiotic use (not including quinolones). In December 2009, fecal carriage of antibiotic resistant Escherichia coli was investigated in 120 of the 140 inhabitants, and in 48 animals reared in the community. All fluoroquinolone-resistant isolates were genotyped and characterized for the mechanisms of plasmid- and chromosomal-mediated quinolone resistance.Principal FindingsDespite the characteristics of the community remained substantially unchanged during the period 2002–2009, carriage of quinolone-resistant E. coli was found to be common in 2009 both in humans (45% nalidixic acid, 14% ciprofloxacin) and animals (54% nalidixic acid, 23% ciprofloxacin). Ciprofloxacin-resistant isolates of human and animal origin showed multidrug resistance phenotypes, a high level of genetic heterogeneity, and a combination of GyrA (Ser83Leu and Asp87Asn) and ParC (Ser80Ile) substitutions commonly observed in fluoroquinolone-resistant clinical isolates of E. coli.ConclusionsRemoteness and absence of antibiotic selective pressure did not protect the community from the remarkable emergence of quinolone resistance in E. coli. Introduction of the resistant strains from antibiotic-exposed settings is the most likely source, while persistence and dissemination in the absence of quinolone exposure is likely mostly related with poor sanitation. Interventions aimed at reducing the spreading of resistant isolates (by improving sanitation and water/food safety) are urgently needed to preserve the efficacy of quinolones in resource-limited countries, as control strategies based only on antibiotic restriction policies are unlikely to succeed in those settings.
Highlights
Quinolones are broad-spectrum antimicrobial agents with rapid bactericidal activity, overall low toxicity, and the possibility of being administered either orally or parenterally
Remoteness and absence of antibiotic selective pressure did not protect the community from the remarkable emergence of quinolone resistance in E. coli
Introduction of the resistant strains from antibiotic-exposed settings is the most likely source, while persistence and dissemination in the absence of quinolone exposure is likely mostly related with poor sanitation
Summary
Quinolones are broad-spectrum antimicrobial agents with rapid bactericidal activity, overall low toxicity, and the possibility of being administered either orally or parenterally. Quinolones are broad-spectrum antibiotics which bind to type II topoisomerases (DNA gyrase and topoisomerase IV) and inhibit DNA re-ligation after enzyme cut, exerting a rapid bactericidal activity They are widely used for the treatment of several community- and hospital-acquired infections and have become increasingly important in resource-limited countries, following the availability of generics (which have drastically reduced drug costs) and the remarkable increase of resistance to the oldest and cheapest antibiotic classes. This study describes the dissemination of quinolone resistant E. coli in a very remote community in the Amazon forest, with a high level isolation and minimal antibiotic use, not including quinolones These findings demonstrate that intervention strategies based only on quinolone restriction are unlikely to succeed in resource-limited countries, unless accompanied by measures for reducing dissemination of resistant isolates by improving sanitation. We report on the emergence of quinolone resistance in a very remote community in the Amazon forest, where quinolones have never been used and quinolone resistance was absent in 2002
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