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Abstract
Tube sensitivity tests show that, of twelve penicillins, ampicillin, benzylpenicillin and 6-aminopenicillanic acid were the most active when tested against medium-sized inocula (106 organisms) of twelve strains of penicillinase-producing Klebsiella (11 Klebsiella aerogenes and 1 K. ozaenae), which had been isolated from clinical material and were resistant to both ampicillin and tetracycline. An inoculum size effect was consistently noted when ampicillin and benzylpenicillin were tested against different inocula; the effect was significantly greater with ampicillin. The following parameters were measured for the strains, using both benzylpenicillin and ampicillin: magnitude of the inoculum size effect; inherent sensitivity (sensitivity of a small inoculum); rate of penicillin destruction; ability of penicillins to pass bacterial permeability barriers. From considerations of the relationships between these values, it has been concluded that penicillinase is primarily responsible for the observed resistance of only two of the twelve strains; although penicillinase and the lack of ability of penicillins to obtain free access into the bacterial cells add to the over-all penicillin resistance of the other ten strains, the primary reason for their penicillin resistance is neither their possession of penicillinase nor their permeability barrier: such resistance presumably reflects an innate lack of sensitivity of the cell wall synthesizing complex to inhibition by penicillins.
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