Transformation reactions of erythromycin in superheated water and their implications for microbial resistance.

Abstract

The documented presence of antibiotics in the environment continues to prompt debate over the potential human health implications of these organic micropollutants. Clinical and agricultural exploitation of these compounds has created a breeding ground for resistant strains of bacteria. The stringent treatment of point discharges of antibiotic wastes holds promise as an approach to curtailing growing trends of microbial resistance. This thesis serves as a framework for evaluation of superheated water as a medium for degradation of the target antibiotic erythromycin. Batch and flow reactor studies were used to examine the effect of the system variables temperature, pressure, pH, and concentration on conversion. Secondary to the investigation of parent compound conversion were experiments aimed at describing the transformations occurring in the reactor. In particular, these studies attempted to link parent compound degradation to the desired elimination of antibiotic function. Reactor studies in both the batch and flow-through modes confirmed that conversion of erythromycin does take place in the constructed superheated water reactor. Although inadequate mixing at early reaction times impaired reactor performance, greater than 85% apparent conversion was achieved in the batch system at all of the temperatures within the range tested. The observed decomposition of erythromycin was described by a pseudo-first order rate expression. The structures of major reaction products were investigated using Infrared Spectroscopy. Functional group analysis of sample effluents indicated that the C9-carbonyl carried by erythromycin was lost during reaction and ether bonds formed. These findings were confirmed by Liquid Chromatography/Mass Spectrometry (LC/MS) data, which suggested that dehydration is the first step in erythromycin decomposition. LC/MS analysis of effluents from pH-adjusted reactions also indicated that further hydrolysis leads to cleavage of the sugar cladinose. The goal of disrupting the mechanism of action of these drugs required a final evaluation of the impact of treatment on target microorganisms. Commonly used in the antibiotic susceptibility literature, agar dilution tests were an important microbiological tool. Growth trends observed in this data indicated that transformation of erythromycin in superheated water results in a loss of antibiotic activity.