No abstract

The effect of daily administration of trimethoprim (TMP), trimethoprim--sulfamethoxazole (TMP--SMX), or placebo on aerobically grown fecal gram-negative bacteria was monitored in 136 students from the United States during a two-week diarrhea-prevention study in Mexico. Unlike patients in other studies with these agents, who had urinary-tract infection or granulocytopenia, most persons in this study had no change in total fecal Enterobacteriaceae and had high-level TMP and SMX resistance in virtually all these strains. Escherichia coli was the predominant TMP-resistant organism isolated; 96 per cent of 165 TMP-resistant Esch. coli isolates were resistant to at least four antimicrobial agents, and 25 per cent were resistant to seven. TMP resistance was transferable in 40 ot 100 strains tested. Despite the lack of TMP resistance in other studies of prophylaxis, our results clearly demonstrate the remarkable capacity for emergence and dissemination of resistance to this agent.

No abstract

Forty-one of 100 trimethoprim-resistant fecal isolates of Escherichia coli isolated during a diarrhea prophylaxis study transferred trimethoprim resistance to an E. coli K12 derivative at frequencies ranging from 1 x 10(-7) to 2 x 10(-2). Analysis of these transconjugants, after attempting to select those that had received only one plasmid, revealed that 34 (83%) were resistant to trimethoprim plus only one or two of seven other antimicrobial agents tested, most often ampicillin and/or streptomycin. In contrast, 91% of the donor strains were resistant to four or more antimicrobial agents. Plasmid analysis demonstrated that a 35-megadalton plasmid was present in 35 transconjugants and was usually associated with resistance to trimethoprim, streptomycin, and ampicillin; 19 transconjugants had only a 35-megadalton plasmid and were resistant to only these three antimicrobial agents, raising the possibility that a common plasmid was present in many strains. Although resistance to multiple antimicrobial agents could be transferred to the K12 recipient, resistance to more than three agents was seldom mediated by a single plasmid. The high degree of transferability of trimethoprim resistance from these fecal isolates of E. coli emphasizes the potential for the dissemination of genes carrying trimethoprim resistance.

The comparative bioavailability of chloramphenicol from intravenous succinate, oral palmitate, and oral base preparations was studied in a crossover manner in 12 adult patients. Chloramphenicol was administered at a dose of 1 Gm every 6 hours, and blood samples were collected at steady state. For the succinate study, total urine output was also collected. The bioavailability of active chloramphenicol from the succinate preparation averaged 85.8 +/- 42.3 and 78.8 +/- 50.1 per cent of the free base and palmitate forms, respectively. This lower availability appeared to be due to variable excretion of unchanged succinate in the urine, averaging 27 +/- 11 per cent of the dose. Regardless of dosage form or route of administration, plasma chloramphenicol concentrations remained in the therapeutic range (5 to 25 mg/liter) for the entire dosage interval, implying that no change needs to be made when changing dosage form or route of administration. The interpatient variability, however, supports the need for monitoring of plasma chloramphenicol concentrations, especially in newborn infants, persons with liver disease, or those receiving other medications that alter chloramphenicol metabolism.