Plasmid loss from gram-negative bacteria exposed to subinhibitory concentrations of beta-lactam drugs and azithromycin.

The stability of F'lac, pW101 and pHSG298 in Escherichia coli K12 exposed to subinhibitory concentrations of beta-lactam antibiotics, amikacin and tetracycline was studied. High molecular weight low copy plasmids (F'lac and pW101) were eliminated from bacteria treated with PBP-3 binding molecules, while a low molecular weight high copy extrachromosomal element (pHSG298) was not. None of the carbapenem antibiotics, mecillinam, amikacin or tetracycline promoted high rate plasmid loss from their hosts. Under the same conditions, plasmid-mediated ampicillin-resistance due to beta-lactamase production was also lost from F'lacTn1-carrying bacteria. In contrast, the high copy R6K plasmid was stably inherited in their hosts with the exception of those organisms treated with cefixime. When the same experiments were performed with a Klebsiella pneumoniae strain induced to form filaments by azithromycin at sub-MICs, F'lacTn1 and pW101 loss was detected, while pHSG298 was stably inherited. These results confirm previous observations that plasmid stability is correlated with cell shape and that recovery is more easily achieved when bacteria undergo an unbalanced division resulting in cell filamentation.