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POTENTIATED SULFONAMIDES
(SDZ & TMP @ 5:1)

Characteristics:

The sulfonamides are a large range of chemically related synthetic compounds, which are derivatives of sulfanilamide. They are usually formulated as their sodium salts. The sulfonamides have a broad spectrum of activity against many bacterial fish pathogens, especially when used in synergistic combination with pyrimidine potentiators. The potentiated sulfonamides show combined antibacterial potency which is greater than the sum of the potencies of the two separate drugs, the sulfonamide and the pyrimidine potentiator. This is because they act as competitive inhibitors of two successive steps in the synthetic pathway of folinic acid in bacteria, which is necessary for the synthesis of the bacterial DNA.

Synthetic pathway of folinic acid:
Step 1: p-amino-benzoic acid (PABA) converted to folic acid (inhibited by sulfonamides)
Step 2: folic acid to folinic acid (inhibited by diamino-pyrimidines).

The combination delays, although it does not entirely prevent, the development of bacterial resistance, because the bacteria have to produce resistance factors for both drugs simultaneously. In particular, sulfadiazine (SDZ) combined with the pyrimidine potentiator, trimethoprim (TMP) at the ratio 5:1 produce a potent wide spectrum bactericidal synergistic effect with very slow development of bacterial resistance.

Compound composition (SDZ+TMP @ 5:1):

Commercially available 40% premixes for compounding with fish feed contain 6.7g of trimethoprim (TMP) and 33.3g sulfadiazine (SDZ) in every 100g of powdered premix.

Commercially available oral suspensions contain 80mg trimethoprim (TMP) and 400mg sulfadiazine (SDZ) in every 1ml of liquid suspension. (Oral suspensions are useful for incorporation in fry feed.)

Indications:

Orally administered potentiated sulfonamides are effective for the treatment of systemic infections of fish caused by Gram negative and Gram positive pathogenic bacteria, such as Aeromonas spp., Vibrio spp., Photobacterium spp., Yersinia spp., Staphylococcus spp. and many others.

Always investigate the sensitivity/resistance of bacteria (antibiogramme) prior to administration.

Precautions:

Toxicity of potentiated sulfonamides is minimal. In rare cases, immunosupression and renal damage may occur subsequent to prolonged therapy with high doses.

Administration alongside quinolones and tetracyclines should be avoided. As with other drugs, do not administer to fish for more than 10 consecutive days without a break.

Administration and dosage:

40% premixes are orally administered via compounding with the fish feed. They may be mixed with fish oil, which is then top-dressed onto pre-pelleted diets.

48% oral suspensions are also orally administered after mixing with the feed (soaking). After the feed dries in air, some fish oil may be used for top coating.

Daily feeding rate

Fish biomass fed 25kg of feed

Premix 40% powder /25kg feed

0.5%

5,000 kg

875 g

1.0%

2,500 kg

438 g

1.5%

1,670 kg

298 g

2.0%

1,250 kg

219 g

Withdrawal period:

400 degree-days (22 days after the last administration at water temperature no less than 18° C).

Storage and packing:

The 40% premixes are available in 5kg plastic containers/tubs and in 20kg reinforced sacks. May be stored for up to 36 months in a dry, dark and cool (up to 25°C) environment.

The 48% oral suspensions are distributed in 200ml vials and may be stored for 48 months in a dry, dark and cool place (up to 25°C).

Close containers or vials firmly after use.

 

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