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During a recent clinical trial of ciprofloxacin in the therapy of acute diarrhea, two subjects infected with Campylobacter jejuni who received ciprofloxacin failed microbiologically and one also failed clinically. Although both pretreatment isolates were susceptible to ciprofloxacin, the posttreatment isolates were resistant to ciprofloxacin (MIC = 32 micrograms/ml) and to other quinolones. The posttreatment isolates remained susceptible to nonquinolone antimicrobials. DNA gyrase holoenzyme was isolated from one of the resistant posttreatment isolates and was 8- to 16-fold less sensitive to inhibition by ciprofloxacin than was the gyrase from the paired pretreatment susceptible isolate. Ciprofloxacin accumulation was diminished in the two resistant posttreatment isolates. These results show that mutation in C. jejuni can occur in vivo and is associated with clinically significant resistance to the newer quinolones.

In vitro studies on primaquine have been carried out to examine its ability to stimulate the oxidative pathway of glucose metabolism in human erythrocytes and in vivo studies were carried out after ingestion of the drug to determine plasma levels and to investigate the formation of metabolites and the effects of the drug on human erythrocytes. These investigations showed that:1) Two mechanisms are involved in the stimulation of the oxidative pathway. This was demonstrated by comparing the effects of methylene blue, ascorbic acid, primaquine, and other drugs on normal, glutathione-reductase-deficient, and G6PD-deficient erythrocytes. A start was made towards classifying drugs according to the mechanism by which they stimulate CO(2) production.2) Following oral ingestion of primaquine, three as yet unidentified metabolites were present, two in the plasma and one in the urine. The rapid disappearance of primaquine from the plasma (within 24 hours) was confirmed.3) Two factors that stimulate glucose oxidation in human erythrocytes were found in plasma; one occurred only in fresh plasma, when EDTA was present, and the other occurred in all plasma and serum samples studied.4) The erythrocytes of blood drawn 24 hours after the ingestion of primaquine (after primaquine had disappeared from the plasma) showed increased ability to oxidize glucose.It is not yet known whether serum or plasma prepared from blood drawn 24 hours after ingestion of primaquine has the ability to increase the oxidation of glucose.