Effect of Triethylenetetramine Dihydrochloride on the Antibiotic Susceptibility of Pseudomonas aeruginosa

Abstract

Recently, Pseudomonas aeruginosa has become a major problem for both patients and clinicians. Its increased prevalence in morbidity and mortality has been greatly complicated by its resistance to several antibiotic agents. Investigators have searched for both intrinsic and extrinsic factors which may be responsible for this antibiotic resistance (3,4,10,12,16). Many strains of P. aeruginosa may possess a cell wall which acts as a permeability barrier for antibiotic penetration (13). Studies have shown that the chelating agent, ethylenediaminetetraacetic acid (EDTA), increases the susceptibility of P. aeruginosa to various antibiotics in vitro (1, 17). EDTA has been shown to increase cell wall permeability by removal of calcium, which is involved in essential cross-linkages and cell wall integrity (5,(7)(8)(9)14). However, due to the toxic properties of EDTA, its use in systemic therapy of P. aeruginosa infections has been limited (2). In contrast to EDTA, triethylenetetramine dihydrochloride (TRIEN dihydrochloride) has been shown to be a chelating agent of low toxicity (6). In addition, the compound has been noted to enhance the activity of carbenicillin against P. aeruginosa (15). The purpose of this study was to determine the efficacy of TRIEN dihydrochloride in enhancing the susceptibility of P. aeruginosa to carbenicillin and gentamicin. In a similar manner this experiment was performed in TSB containing 50% serum (vol/vol), which was designated TSB-50S. The concentration of TRIEN dihydrochloride was increased to 0.0100 M in these experiments because at lower concentrations when serum was added to the growth medium, there was no effect on the MIC of the antibiotic. This higher con-