No abstract

Strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger were tested for in vitro susceptibility to amphotericin B alone and in combination with fixed concentrations of tetracycline, doxycycline, or minocycline, using buffered minimal essential medium in microtiter plates. Enhanced inhibitory activity was seen, especially with combinations of amphotericin B and minocycline. Synergistic activity between amphotericin B and minocycline was observed in each of five isolates of each species when tested in a checkerboard dilution scheme. Time-kill curves demonstrated killing an A. fumigatus isolated at concentrations of amphotericin B that were four-or eightfold lower in the presence of 5 or 15 ,ug of minocycline per ml than with amphotericin B alone. Of the tetracycline analogs tested, minocycline has the greatest activity against A. fumigatus, A. flavus, and A. niger conidia when potentiated by amphotericin B.

The development of bacterial resistance to chloramphenicol was observed during a study of patients who were being treated with this drug for infections of the urinary tract (1). Nine of 33 strains of gram-negative bacilli isolated from the urine of 24 patients prior to therapy demonstrated during treatment a decrease in susceptibility to chloramphenicol. The development of resistance to the drug by some of these organisms was associated with therapeutic failures in five of these subjects. Similar observations had not been reported. Because of the potential clinical importance of these findings the results of a bacteriologic study of the strains which developed fastness to chloramphenicol in vivo, and quantitative observations on the origin of this phenomenon made in vitro are presented. METHODSThe strains of organisms that were studied were recovered from the urine of patients before, during, and after treatment with chloramphenicol. A description of cases and the schedules of treatment used in the clinical study have been noted elsewhere (1). Specimens of urine were obtained from females by catheterization and from males by careful local preparation prior to voiding. Ten cc. samples of urine were centrifuged and the sediment was stained for bacteria and cultured on MacConkey agar and on tryptose phosphate agar containing 5 per cent human blood. The various organisms that appeared were isolated in pure culture and were stored on tryptose phosphate agar slants at -200 C. In several instances agar pour plates of 10-fold dilutions of urine were made to determine the numbers of bacteria present. All strains of bacteria recovered from a single patient during all periods of observation were compared at the same time as regards their morphology, cultural and biochemical