Pivotal Dose-titration Studies to Evaluate the Efficacy of Oxytetracycline-HCL Bath Immersion  
to Control Mortality Associated with External Flavobacter Infections on Cool- and Warmwater 
Fish Cultured at Hatcheries

      External bacterial infections (bacterial gill disease and columnaris) have caused 
major problems in the culture of finfish.  All known agents are gram-negative bacteria 
including flavobacteria, aeromanads, and pseudomonads.  If flavobacteria diseases are 
not diagnosed and treated early, significant mortality may occur within a 24-h period.  
Mortality is the result of damage caused by massive bacterial infection on the gill or 
epitheal tissue.  Stressing factors associated with intensive culture such as crowding 
and low concentrations of dissolved oxygen, not only predispose fish to infection, but 
also increase mortality.  Therapeutic agents are needed to maintain healthy stocks of 
fish in the intensive culture systems of federal, state, and private hatcheries.
      Preliminary research indicates that oxytetrcycline-hydrochloride (OTC-HCL) 
applied in a bath may be effective in controlling external flavobacter infections.  
Immersion therapy with OTC-HCL may be an effective means of treating certain 
external fish diseases, especially with small fish reared on feed that cannot be 
medicated or fish that go off feed during a disease outbreak.  One criterion to gain a 
New Animal Drug Application (NADA) for OTC-HCL immersion therapy is pivotal 
efficacy data.  An efficacy report that summarizes call-in data for OTC-HCL immersion 
therapy with cool and warm water fish has been submitted to the Center for Veterinary 
Medicine (CVM).  The successful use of OTC immersion therapy will depend on 
attainment of adequate concentrations of OTC-HCL.  The draft label claim for OTC-
HCL, based on the results of the data call-in, proposed that the daily treatment dose for 
OTC-HCL immersion therapy be from 10 to 20 mg/L as an immersion bath for a period 
of 1 to 4 hours with the treatment period lasting from 1 to 10 consecutive days. 
      Definitive data on the effective concentrations of OTC-HCL to control mortalities 
resulting from external flavobacter infections is limited.  Data on the efficacy of OTC-HCL to 
control mortalities associated with flavobacter infections on fish is difficult to obtain without 
methods to induce the disease state in the laboratory.  One alternative is to determine efficacy in 
situ by treatment of disease outbreaks at hatcheries under experimental conditions of use.  There 
is a need to conduct scientifically sound studies to verify these initial results so that these data 
may be used to support a NADA.  These studies will be conducted using guidelines 
recommended by CVM for protocol development and the conduct of efficacy studies.
      The objective of this study was to conduct pivotal dose-titration studies to determine the 
efficacy of OTC-HCL bath immersion to control mortality associated with external bacterial 
infections (flavobacters) on cool- and warmwater fish cultured at state or federal hatcheries.