IN-VITRO BRODIMOPRIM ACTIVITY ON NOSOCOMIAL BACTERIAL STRAINS

The activity of brodimoprim, a new diaminopyrimidine, against 385 recent clinical isolates of Gram positive cocci and Gram-negative bacilli was in vitro tested by the disk sensitivity test (DST) of Bauer et al. with disk concentration of 2.5 mu g and by the agar dilution method. The postantibiotic effect (PAE) and the postantibiotic leukocyte killing enhancement (PALE) were determined on selected pathogens. The MICs were determined with Muller Hinton II agar (BD) and a multipoint inoculator (Denley A 400); thymidine phosphorylase (0.08 U/ml) was added to the test agar. Brodimoprim was very active against S. pyogenes (27), Salmonella sp. (30), methicillin susceptible S. aureus (36) and E. faecalis (34). The geometric means (GM) of MICs ranged from 0.08 to 0.63 and % of resistance from 0.0 to 14.7. Higher MICs (GM from 1.02 to 2.67) were shown against Citrobacter sp. (32), Klebsiella sp. (27), E. coli (36), methicillin-resistant S. aureus (33), Enterobacter sp. (32), Proteus sp. (31) and methicillin-susceptible coagulase negative staphylococci (34); resistant strains ranged from 18.7 to 41.2%. The in vitro activity against methicillin-resistant coagulase-negative staphylococci (33) (72.7% of resistance to brodimoprim) was very low. Regression analysis, obtained correlating the results of MICs with those of agar diffusion, shows that the resistant strains have a diameter less than 11 mm, the intermediate ones a diameter of 11-13 mm and susceptible strains a diameter greater than 13 mm. The PAE was determined using the Abbott AVANTAGE system. Strains were exposed to brodimoprim (1/4 x MIC - 4 x MIC range) for 2 or 6 h. The PAE ranged from 1.2 to 9.0 h on Gram-positive cocci and from 1.9 to 10.6 h on Gramnegative bacilli. PALE was determined by treating the different strains with 4 X MIC for 2 h. Exposure to brodimoprim increased phagocytic killing by approximately 2- to 5- fold for Gram positive and -negative bacteria respectively.