It is possible that the presence of small AMN107 concentrations of chloroquine in the drinking water may have provided an ongoing selective advantage to ciprofloxacin resistant E. coli within patient��s intestines, prolonging carriage. Some local residents may have acquired quinolone resistant E. coli from exposure to contaminated drinking water. Nevertheless, the identification of 24 distinct isolates of quinolone resistant E. coli in this population, suggests that a single point source of water contamination would not be able to explain the multiple circulating strains. Rather generation of resistant strains is likely occurring in many different patients�� intestines, with some horizontal transmission within the community via drinking water contamination. The potential exposure to both quinolone resistant organisms and chloroquine itself from human waste contaminated river water may explain the failure to identify an association between individual reported use of chloroquine and carriage of quinolone resistant E. coli. Furthermore the reliability of individual reports of chloroquine exposure is unknown. Nevertheless the fact that increased total community chloroquine use was significantly associated with prevalence of resistance, is strong ecological evidence of the association of quinoline use with the development of quinolone resistance in the community. This situation is analogous to that seen with AP24534 antibacterial antibiotics, where there are very few reports of individual use being associated with the development of resistance, but the evidence of total community use leading to increased resistance is more compelling. Indeed, this may be one circumstance in which ecological data are more useful than individual-level data. Although no clinical outcomes were impacted in this area by quinolone resistance,, we believe the same phenomenon is likely also occurring in other malarious communities, and may be leading to a lack of clinical efficacy of quinolones. This site was particularly interesting to study, because the lack of the confounding presence of quinolones in the community allowed us to identify the relationship between community wide quinoline use for malaria and quinolone resistance in bacteria. One limitation of this study is that we failed to rule out the possibility that other quinoline antimalarials, particularly primaquine, which together with chloroquine is the standard treatment regimen in Guyana for cases of P. vivax, may also be selecting for ciprofloxacin resistance. Other quinoline and quinoline-like compounds include quinine, mefloquine, quinidine, halofantrine, lumefantrine, piperaquine, pyronaridine, and amodiaquine. Other study limitations include a limited number and timing of water samples, and failure to ask about chloroquine exposure in the first year. This study is the first to identify human carriage of quinolone resistant organisms in communities that lack any quinolone exposure. It is also the first to identify antimalarial therapy as a factor in the development of carriage of quinolone resistant bacteria. We have reported the selection of E. coli resistance by chloroquine in this study.