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Polymer complexons, such as copolymers of vinylpyrrolidone with vinyliminodiacetic acid and metacryloilacetone changed the permeability of the bacterial cell wall due to chelating of the metalic ions contained in the cell wall. An increase in the bacterial sensitivity to chloretracycline, methicillin, ampicillin and methicillin was observed in the presence of the above complexons.

The antimicrobial effect of cationic surface-active substances, such as cetylpyridinyi chloride, alkylmethylbenzylammonium chloride ("roccal" and "catamine AB") and chlorhexidine was studied in vitro. The above compounds had a high bactericidal activity against poly-resistant staphylococcal strains. In non-bactericidal concentrations they significantly increased the efficacy of antibiotcs with different modes of action, i.e. penicillins, tetracyclines, amino-glycosides, macrolides. The effect of the cationic surface-active substances increasing the antibiotic activity against staphylococci did not depend on the resistance type, i.e. chromosomal or extrachromosomal. This was mainly associated with impairement of the function of the bacterial cytoplasmic membrane by these compounds. The cationic surface-active compounds were poor inhibitors of the specific enzyme of Bac. licheninformis 749/C, i.e. penicillinase. A marked inhibition of the enzyme was observed only at concentrations above the bactericidal ones and those damaging the cell membrane of staphylococci.

The kinetics of inhibition of penicillinase of Bac. licheniformis 749/c by various alkyl-sulphates (with a long hydrocarbon chain from C8 to C16), n-toluolsulphoacid and alkylbenzol-sulphonate (R-C12--C16) was studied. The inhibition rate increased with elongation of the alkyl radical and rising of the inhibitor concentraiton. This means that the determining factor in inhibition process was hydrophobic interaction of the alkyl chains and not the electrostatic interaction with the enzyme. In-vitro experiments with penicillinase-producing strains of staphylococcus showed that non-bactericidal concentrations of the alkylsulphates and alkylben zolsulphonates increased the effect of benzylpenicillin, ampicillin and methicillin. The highest increase in the antibiotic activity, as well as in the enzyme inhibition was observed with respect to the compound with the hydrocarbon chain fron C12 to C16. The increase in the activity of methicillin against the staphylococcal strains resistant simultaneously to benzylpenicillin, ampicillin and methicillin was indicative of possible using of the above surface active substances as inhibitors of the realization process of various mechanisms of penicillin resistance.

Competing inhibition of Bacillus licheniformis 749/C penicillinase by alkylsulfates CnH2n+ 1OSO3N1 where n was 8--16 was studied. The values of the inhibition constants Ki of individual homologues were estimated. It was shown that stability of complex "enzyme-inhibitor" increased with lengthening of the hydrocarbon radical which was probably due to increased hydrophobic interaction of the alkyl radical with the lipophilic areas of the penicillinase active center. Inhibition in the presence of sopolymers of vinylpirrolidone with N-alkylvinylamine was studied with the aim of modeling the process of penicillinase inhibitions by alkylsulfates in the presence of the blood serum. It was shown that polyelectrolytes posessing hydrophobic substituents had an ability of reducing the activity of inhibited penicillinase, cooperative transfer of alkylsulfate molecules from the enzyme to polyelectrolyte being observed. The maximum effect was registered in the polyelectrolytes with substituents C12H25 and C16H33 which was confirmed in the experiments with the penicillinase-producing strains of staphylococci.

The study of the effect of synthetic polyelectrolites of the cationic type on benzylpenicillin resistant staphylococci showed that the cation polyelectrolites induced changes in the cell membrane permeability and increased penicillin absorption by the cells thus increasing sensitivity of the penicillin-resistant staphylococci to the antibiotic. Low inhibitory effect of the polyelectrolites with respect to penicillinase and hyaluronidase was shown. Changes in the membrane apparatus of staphylococcus cells due to the effect of polyelectrolites were found.