Commensal strains of the human intestine Escherichia coli K12 and of the human skin Staphylococcus epi-dermidis are often found in the same atypical biotopes, where they can act as infectious agents. The metabo-lism of bacteria changes in polymicrobial associations and in the presence of increased osmotic pressure in biotopes, associated with a number of pathological conditions that may affect their sensitivity to antibacterial factors of various nature. In this regard, the aim of the work was to study the effectiveness of chlorampheni-col, ceftriaxone, polyvalent pyobacteriophage and chlorhexidine on single and mixed cultures of opportunistic microorganisms E. coli K12 and S. epidermidis at a background of 2% NaCl. It was shown that the effect of ceftriaxone, a broad-spectrum antibiotic, and chloramphenicol, with antibacterial properties only against E. coli, were leveled under conditions of increased osmotic pressure at concentrations of 12-200 mg/l in a mixed culture. For E. coli K12, a decrease in the effectiveness of the bacteriophage at high osmotic pressure was noted, which is the opposite in effect towards S. epidermidis. As for chlorhexidine, its effect on E. coli K12 and S. epidermidis was enhanced in single and mixed cultures under conditions of 2% NaCl. In general, in most cases, an increase in the osmotic pressure of the medium acted as a synergist for inhibiting bacterial growth with antibiotics and bacteriostatic.