Comparison of the effects of mecillinam and 6-aminopenicillanic acid on Proteus mirabilis, Escherichia coli, and Staphylococcus aureus.

Single strains of Proteus mirabilis, Escherichia coli, and Staphylococcus aureus were grown on filter membranes placed on agar containing concentration series of mecillinam (FL 1060), 6-aminopenicillanic acid (6-APA), or ampicillin. P. mirabilis and E. coli were also exposed to combinations of mecillinam or 6-APA with ampicillin. Colony-forming units were counted, and cells were examined by interference phase-contrast and transmission electron microscopy. Mecillinam and 6-APA were very effective in reducing the viability of the two gram-negative species, but they were less effective against S. aureus. Combinations of mecillinam and 6-APA with ampicillin acted synergistically against the gram-negative bacilli. When the antibiotics were presented consecutively, their effects on viability were usually no greater than the effects of the individual antibiotics acting alone. When P. mirabilis and E. coli were exposed to mecillinam alone or in combination with ampicillin, the cells became rounded. 6-APA alone or in combination with ampicillin produced elongated polymorphic cells in these species. The most unusual morphological effects were ultrastructural. Mecillinam and, to a lesser extent, 6-APA produced inward growth of numerous pairs of trilamellar membranous structures within the cells. It is possible that these membranes represent the growth initiation of aberrant cross walls. Both mecillinam and 6-APA produced multiple, thick cross walls in S. aureus.