Synergism has been demonstrated between selected pairs of β-lactam antibiotics against four representative strains of β-lactamase-producing Gramnegative bacteria ( and an R-factor-bearing strain). A pour-plate double-diffusion technique with subinhibitory concentrations of antibiotics was used. Synergism has been proven by demonstrating a bactericidal effect, and by the isobologram technique. Seven out of 14 highly resistant strains of Gram-negative bacteria proved to be more sensitive to certain combinations of β-lactam antibiotics than to any of these antibiotics alone, tested at 1 mg per ml (a concentration attainable in the urine during therapy). Some aspects of the possible clinical use of combined therapy with two β-lactam antibiotics are discussed.


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