[Development of resistance to difuracil (PAP-49) in bacteria and its activity in combination with other antibacterial drugs].

Possible increasing of resistance to difuracil or N-(5-nitrofurfuryliden)-5-nitrofuran-2-(N'-acetyl) carboxamidohydrazon (PAP-49) in Staphylococcus sp., Streptococcus sp. and Escherichia coli was studied and the level of the resistance increasing was determined by the method of 30-fold passage of the cultures in subbacteriostatic concentrations of the drug. It was shown in vitro that the increase of the resistance to the new nitrofuran was insignificant. The most intensive adaptation was observed during the first 10 passages. During the following 10-15 passages the susceptibility level remained unchanged (E.coli) or was even somewhat higher (S. aureus and Streptococcus sp.). After that a new increase of the resistance was observed. The most marked changes in the susceptibility were detected in Streptococcus sp. and the least marked in Staphylococcus sp. and E.coli. Combinations of difuracil in subbacteriostatic concentrations with various antibacterial drugs provided both additive and synergistic effects with respect to S.epidermidis, S. pneumonase, E.coli and P.mirabilis. The most active combinations were those of difuracil with aminoglycoside antibiotics, penicillins or chloramphenicol.