The effect of gavage or intravenous (i.v.) administration of sodium chlorate salts on the fecal shedding of generic Escherichia coli in wether lambs was studied. To this end, 9 lambs (27 ± 2.5 kg) were administered 150 mg NaClO3/kg BW by gavage or i.v. infusion in a crossover design with saline-dosed controls. The crossover design allowed each animal to receive each treatment during 1 of 3 trial periods, resulting in 9 observations for each treatment. Immediately before and subsequent to dosing, jugular blood and rectal fecal samples were collected at 4, 8, 16, 24, and 36 h. Endpoints measured were fecal generic E. coli concentrations, blood packed cell volume (PCV), blood methemoglobin concentration, and serum and fecal sodium chlorate concentrations. Sodium chlorate had no effects (P > 0.05) on blood PVC or methemoglobin. Fecal generic E. coli concentrations were decreased (P < 0.05) approximately 2 log units (99%) relative to controls 16 and 24 h after sodium chlorate infusion and 24 h after sodium chlorate gavage. Within and across time and treatment, fecal chlorate concentrations were highly variable for both gavage and i.v. lambs. Average fecal sodium chlorate concentrations never exceeded 100 µg/g and were typically less than 60 µg/g from 4 to 24 h after dosing. Times of maximal average fecal sodium chlorate concentration did not correspond with times of lowered average generic E. coli concentrations. Within route of administration, serum sodium chlorate concentrations were greatest (P < 0.01) 4 h after dosing; at the same time point, serum chlorate was greater (P< 0.01) in i.v.-dosed lambs than gavaged lambs but not at 16 or 24 h (P > 0.05). At 8 h, serum chlorate concentrations of gavaged lambs were greater (P < 0.05) than in i.v.-dosed lambs. Serum chlorate data are consistent with earlier studies indicating very rapid transfer of orally dosed chlorate to systemic circulation, and fecal chlorate data are consistent with earlier data showing the excretion of low to marginal concentrations of sodium chlorate in orally dosed animals. Efficacy of sodium chlorate at reducing fecal E. coli concentrations after i.v. infusion suggests that low concentrations of chlorate in gastrointestinal contents, delivered by biliary excretion, intestinal cell sloughing, or simple diffusion, are effective at reducing fecal E. coli levels. Alternatively, chlorate could be eliciting systemic effects that influence fecal E. coli populations.
It has been reported that the inhibitory action of streptomycin on bacteria can be counteracted by culture medium components, pH, salts, etc. (1-4). In many instances, however, these results were obtained by seeding a small inoculum of organisms into media containing varying concentrations of the antibiotic and the material tested, and determining the occurrence of growth after a period of incubation of approximately 24 hours. Little cognizance was taken of the metabolic activity of the organisms surviving the antibiotic treatment, although this may differ markedly from that of the parent organisms. Growth may have resulted from (1) selection of a few resistant organisms, (2) adaptation of the majority of cells in the original inoculum to alternate metabolic pathways, or (3) a general stimulatory effect of the added test compound which would increase growth of normal cells as well as that of cells exposed to streptomycin.To demonstrate the true reversal of the antibiotic action of streptomycin it should be shown that (I) almost all the org~tni.~ms present (at least 99.9 per cent) are injured after a short exposure to the antibiotic, (2) in the presence of the reversing agent, the viable count of the streptomycin-treated culture returns to approximately that of the control, and (3) the duration of exposure to the reversing agent is short enough to preclude the possibility of selection of resistant organisms or the adaptation of the culture to the new conditions.To fulfill these requirements it would appear desirable to utilize a culture in the logarithmic growth phase, carried in a chemically defined medium. The presence of an inhibitor, therefore, would interfere with the normal activities of actively metabolizing cells, and the organisms would be injured in such a manner that death would follow quickly unless some interruption of the process were introduced. Reversal of this pathological condition could be accomplished by the removal of the toxic agent and the addition of substances which could be
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