Microcalorimetric, Turbidimetric, Phase-Contrast Microscopic, and Electron Microscopic Investigations of the Actions of Amoxicillin, Clavulanic Acid and Augmentin on Amoxicillin-Sensitive and Amoxicillin-Resistant Strains of Escherichia coli

Abstract

The actions of amoxicillin (AMX), clavulanic acid (CA) and Augmentin (AUG) on one ampicillin (AMP)-sensitive and two ampicillin-resistant strains of Escherichia coli were investigated by microcalorimetry, turbidimetry, phase-contrast microscopy and electron microscopy in such a way as to allow correlation of the results obtained by the four techniques. CA alone had no microcalorimetrically or turbidimetrically detectable effect on the AMP-sensitive or AMP-resistant strains at the concentrations used. AMX had a marked turbidimetric and microcalorimetric effect on the AMP-sensitive strain of E. coli but little or no effect on the AMP-resistant strains. Treatment of the AMP-resistant strains with AMX in the presence of CA produced turbidimetric and microcalorimetric patterns which were similar or identical to those of the AMP-sensitive strain treated with AMX. On exposure of the AMP-sensitive strain to a combination of AMX and CA at concentrations which on their own had no effect there was turbidimetrically and microcalorimetrically evident lysis and inhibition of heat production. Phase-contrast microscopy and electron microscopy showed that the morphological changes undergone by the AMP-resistant strains in the presence of a combination of AMX and CA were qualitatively similar to those produced in the AMP-sensitive strain by AMX alone. It is concluded that in the presence of CA an AMP-resistant strain of E. coli reacts microcalorimetrically, turbidimetrically and morphologically to AMX in a qualitatively similar manner to an AMP-sensitive strain. This effect of CA can be ascribed to its β-Lactamase inhibitory activity. There was microcalorimetric and turbidimetric evidence of synergism of AMX and CA against an AMX-sensitive strain. The later phenomenon cannot be explained by the β-lactamase inhibitory effect of the CA and requires further investigation.