Reduction in the antibacterial effect of oxy-tetracycline in sea water by complex formation with magnesium and calcium

Abstract

Oxytetracycline (OT) is used extensively in the treatment of bacterial diseases in marine f~sh . The standard dose recommended for treatment of fish is 5 to 10 times higher than doses commonly used in medical practice, indicating that OT is poorly absorbed. This is especially true for fish held in sea water, where the intestinal uptake is substantially reduced as compared to fish in fresh water. OT forms complexes with magnesium and calc~um We have determined the con~plex constants and calculated that when therapeutic concentrations of OT are present in sea water, only about 5 O/O of the OT exists in the free form. Of the bound OT, the 1:l OT-magnesium complex predominates. The complex formation in sea water results in a strong reduction in the antibacterial effect of OT This has been demonstrated in vitro. The poor intestinal uptake and reduced antibacterial effect of complex-bound OT is caused by an alteration of the molecular charge that diminishes its ability to cross lipid-rich biological membranes. A major portion of the OT administered to farmed salmonids inevitably ends up in the environment, especially in the sediments under aquaculture facilities. No mechanism is known for biodegradation of OT and thus it can remain in the sediments long enough to affect the indigenous bacterial flora and induce resistance. For these reasons the use of OT in marine environments should be questioned.