The Nature of the Insensitivity of Gram-Negative Bacteria towards Penicillins

Abstract

SUMMARY: The insensitivity of Gram-negative bacteria towards different penicillins has been correlated with the inactivation of these compounds by the penicillinases produced by these bacteria. Penicillins such as phenethicillin, propicillin, methicillin, and cloxacillin were relatively inactive against Gram-negative bacteria, but resistance was not accompanied by inactivation of these compounds. With ampicillin and benzylpenicillin, however, bacterial resistance was associated with destruction of the penicillins. Ampicillin was more stable to the penicillinases produced by certain Gram-negative bacteria than was benzylpenicillin and was correspondingly more active against these organisms. Gram-negative bacteria which produced little or no penicillinase were two to four times more sensitive to ampicillin than to benzylpenicillin, but ampicillin was at least ten times more active than benzylpenicillin against several penicillinase-producing coliform organisms. All strains of bacteria which were resistant to both ampicillin and benzylpenicillin were capable of inactivating both compounds, but the insensitivity of these bacteria was not necessarily due solely to penicillinase production. Strains of Pseudomonas aeruginosa and certain strains of Escherichia coli and Proteus mirabilis were able to grow in high concentrations of these antibiotics, whereas with the strains of Aerobacter aerogenes, Proteus morganii and Proteus vulgaris examined, the resistance appeared to be due solely to inactivation of the penicillins.