CEPHALOSPORINS ARE SCAVENGERS OF HYPOCHLOROUS ACID

Potential scavenging properties of cephalosporins (i.e. cefamandole, cefotaxime and ceftriaxone) towards hypochlorous acid (HOCl) as well as the antibacterial activity of control and HOCl-reacted antibiotics were investigated. We found that these drugs, at therapeutically relevant concentrations, are indeed scavengers of HOCl, with ceftriaxone showing the highest anti-HOCl capacity. However, the efficiency of cephalosporins in protecting biological molecules is also related to the chemical identity of such molecules. Indeed, the polyenoic compound beta-carotene is much better protected than the thiol compound GSH against HOCl attack. Moreover, the drugs do not appear to form chloramine derivatives as a result of their reaction with HOCl, and they inhibit taurine-chloramine formation. After HOCl challenge, the antibacterial activity of cefamandole, cefotaxime and ceftriaxone (tested against the standard strain Escherichia coli ATCC 25922) is approx. 8-, 5- and ii-fold lower, respectively, than that of the HOCl-unreacted antibiotics. The depression of the antibacterial activity of cephalosporins appears inversely related to their HOCl scavenging capacity, suggesting that the drug antioxidant groups may protect the beta-lactam ring against HOCl attack. In conclusion, physiological biomolecules are protected by cephalosporins against HOCl-driven oxidative injury with varying efficiency, this antioxidant defence being a consequence of a direct drug scavenging capacity towards HOCl. The interaction of cephalosporins with HOCl, however, results in a depression of their antibacterial activity.