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closeWhere did the putative selection take place?
Posted by NJWhite on 16 Jul 2008 at 15:54 GMT
The concentrations of chloroquine required to inhibit E.coli are orders of magnitude higher than in bodily fluids, and although faecal excretion of unchanged chloroquine in humans has not been well characterised, given the oral bioavailability, elimination profile, and urinary excretion it seems unlikely that concentrations close to those inhibitory to E.coli would occur in faeces in the gut. Concentration in sewage is a possibility. If the hypothesis is correct the epidemiological pattern of fluoroquinolone resistance in enteric bacteria (before the introduc tion of inexpensive fluoroquinolones) should have mirrored that of chloroquine use, with high levels in parts of Africa and Asia.
RE: Where did the putative selection take place?
Michael_Silverman replied to NJWhite on 17 Jul 2008 at 17:48 GMT
We believe that the antibacterial selection pressure is occuring in the gut with a gradation of concentrations between the upper small bowel and the colon. Treatment of malaria involves ingestion of 1gram of chloroquine and then either 3 more doses of 500mg or 2 more 1 gram doses. Therefore concentrations above those of MIC [625micrograms/ml] would be present in the duodenum (which normally is colonized with E.coli) and a gradient of descending concentrations down the small bowel and colon. This would therefore be an ideal setting in which to select for resistance.
To our knowledge this is the first study to screen for quinolone resistant E.coli carriage in a region with no quinolone exposure, and yet with extensive antimalarial use. We are unaware of this having been done in the recent or remote past. In most highly malarious areas of Africa and Asia widespread availability of culture and sensitivity testing was not available, and empiric therapy was generally the rule.
RE: RE: Where did the putative selection take place?
Michael_Silverman replied to Michael_Silverman on 17 Jul 2008 at 19:31 GMT
Please also note that prior to the availability of quinolone antibiotics, even laboratories that could perform culture and sensitivity testing, would not have tested for quinolone resistance in clinical isolates. Once quinolones became available, this testing would have begun, but then resistance at that time would have been attributed to the availability of quinolones.