Activity of Aminoglycoside Antibiotics against Pseudomonas aeruginosa: Specificity and Site of Calcium and Magnesium Antagonism

Four aminoglycoside antibiotics were tested against five species of gram-negative bacilli in defined media with various concentrations of calcium and magnesium. A species-specific antagonism of antimicrobial action against Pseudomonas aeruginosa was observed. Antibiotics were not inactivated, but the bacilli became unsusceptible. Even after a long incubation in a bactericidal concentration of gentamicin, the addition of calcium stabilized P. aeruginosa and permitted bacterial replication in the presence of an otherwise lethal concentration of drug. Calcium and magnesium exerted their inhibitory effect only if the bacterial cell wall was intact. Also, the action of gentamicin on carbenicillin-induced spheroplasts of P. aeruginosa was not antagonized by calcium. It was concluded that the interaction of magnesium or calcium with P. aeruginosa, which results in its resistance to amino glycoside antibiotics, is at a locus exterior to the bacterial membrane, probably in the cell wall or a linkage between the cell wall and membrane. Of five common species of gram-negative bacilli tested, the effect is species-specific for P. aeruginosa and is similar for all of the aminoglycoside antibiotics.