Ciprofloxacin-metal complexes -stability and toxicity tests in the presence of humic substances

Abstract

The co-contamination of ciprofloxacin (CIP) with metal ions results in alteration of CIP mobility, antimicrobial activity and distribution/development of the antibiotic-resistance genes. In this study, the stability of five CIP-Me complexes [Me = Al(III), Co(II), Cu(II), Fe(III), Mg] was investigated in the presence of humic substances (HS) at two temperatures 18 ± 2 °C and 4 ± 1 °C for seven days period. The most stable complexes were CIP-Al, CIP-Cu, and CIP-Co with the stability constants (K) at 18 °C 35.5 ± 1.4 11.5 ± 1.5 and 11.7 ± 1.5 respectively. At lower temperature (4 °C), the stability constants decreased: 1-fold for CIP-Al, 14-fold for CIP-Co and 2-fold for CIP-Cu. The presence of humic substances decreased the stability of complexes. The chemical reactions of Fe³⁺ in water at circumneutral pH resulted in stability alteration. The formation of CIP-Mg complexes at lower temperatures and in the presence of HS was limited. In ultrapure water, CIP-Me complexes exhibit higher toxicity towards Gram-negative Enterobacter aeruginosa (ranged between 0.125 and 0.5 μg/ml). However, the presence of HS reduced the antimicrobial activity of CIP-Me complexes by at least 2-fold. Gram-positive representative, Bacillus subtilis was not affected by the presence of metal ions and/or HS. The toxicity toward B. subtilis for the complexes was equal to toxicity of CIP alone (MIC = 0.25 μg/ml). This suggested the different susceptibility to CIP and its complexes.

Keywords: Ciprofloxacin; Complexation; Metal ion; Stability; Toxicity; Water.