Effects of antifungal pretreatment on the susceptibility of Candida albicans to human leukocytes.

The aim of this work was to measure the susceptibility of Candida albicans pretreated for 2 or 6 h with fluconazole (Flu), ketoconazole (Ktz), amphotericin B (AmB) and 5-fluorocytosine (5-Fc) to the fungicidal action of human polymorphic leukocytes. The influence of pretreatment was measured by comparing the delay (in hours) and reduction (log10) in growth of pretreated cultures in the presence of leukocytes and serum with that of non-pretreated control cultures. Six-hour pretreatments with Flu, Ktz, AmB and 5-Fc led to growth delays of 1, 3, 3 and 3 h, respectively. No significant differences were found when pretreatment lasted only 2 h. With respect to a reduction in growth, this was larger when the preincubation was 6 h, mainly for 5-Fc and AmB. 5-Fc was seen to be the most effective, followed by Ktz, AmB and finally Flu. It may be concluded that antifungal pretreatment renders this yeast more susceptible to the action of leukocytes. The degree of susceptibility achieved is dependent on the antifungal agent employed.

In vivo postantibiotic effect of isepamicin and other aminoglycosides in a thigh infection model in neutropenic mice.

The object of this work is to study in neutropenic mice the in vivo postantibiotic effect (PAE) of isepamicin, a new aminoglycoside, gentamicin and netilmicin on Staphylococcus aureus and Escherichia coli and in vivo killing kinetics using two different schedules (A and B) of isepamicin and gentamicin administration against S. aureus: (A) at time zero and every hour up to the 7th or 9th hour and (B) two doses only, at time zero and at the end of the PAE. The PAE of the three aminoglycosides was long (3-5 h), showing that of isepamicin to be the largest, especially on S. aureus. Both A and B treatment models show the same effectiveness for the two tested drugs. These results support the idea that the major significance of the PAE is in its application to dosing regimens.