# Consequences of Improper Dosage and Treatment Time



## seanyuki (Apr 22, 2010)

Just sharing......

Consequences of Improper Dosage and Treatment Time

If the dose is too high or treatment times are too long, there is a danger of toxicity to the fish, frequently causing liver, kidney, or other organ damage that may or may not be reversible.

On the other hand, if the dose of antibiotic is too low or treatment time is too short, the bacteria will not be killed or weakened enough for the immune system of the fish to remove them, and this greatly increases the risk of the bacteria developing resistance to the antibiotic. When bacteria become resistant to a specific antibiotic, even high concentrations of that drug will not be effective.

Antibiotic resistance can also occur when antibiotics are used improperly, such as the 'shot-gunning' method. 'Shot-gunning' involves administering one antibiotic after another to a population of fish, frequently at improper dosages, for shortened treatment times, and without the aid of proper diagnosis (i.e., without culture and sensitivity tests). If shot-gunning is used frequently at a facility, resistance is almost certain to occur. In some cases, the problem may not be due to bacteria, but rather poor water quality or other management issues that have not been properly investigated.

While shot-gunning may work occasionally, over time, it introduces too great a risk of producing populations of bacteria that are resistant to multiple antibiotics, which can result in the very real possibility of a 'superinfection,' where the bacteria cannot be controlled with antibiotics. Once a system has a superinfection, it is usually necessary to sacrifice the entire affected population, completely break down and disinfect the affected system, and start over. This is obviously not a desirable outcome. The importance of using antibiotics wisely (running culture and sensitivity tests, using proper dosages and adhering to proper treatment times) cannot be overstressed.
Combining Antibiotics

Combining different antibiotics is generally not recommended. Antibiotics work at many different sites on and in the targeted bacterial cell. Using more than one antibiotic can result in interference between them and, as a worst case scenario, the antibiotics can essentially 'cancel each other out.' Most bacterial infections can be treated effectively with a single antibiotic.
Proper Handling of Antibiotics

When preparing or administering any type of medication, it is always a good idea to wear gloves in order to avoid unnecessary exposure to the user.

It is important to use antibiotics that are as fresh as possible and that have been stored properly. Antibiotics used after their expiration date or after being stored in hot and humid conditions will have greatly reduced efficacy at best and, at worst, they may be toxic.
Notes on Specific Antibiotics

The following are some notes on specific antibiotics used in the ornamental fish trade. Many of them are strictly forbidden for use by food fish producers or are otherwise of concern to the Food and Drug Administration (FDA). The FDA has elected to use regulatory discretion to keep products intended for the treatment of aquarium fish available. Officially there are no FDA-approved antibiotics for treating ornamental fish. Therefore, should you have any questions regarding the legalities of using any antibiotics, consult a fish health specialist. For information on antibiotic use in channel catfish, including specifics on use of oxytetracycline (Terramycin®) and Romet B®, see UF/IFAS Fact Sheet VM-70 Use of Medicated Feed in Channel Catfish.

Erythromycin is most effective against gram-positive bacteria, such as Streptococcus species. The vast majority of bacteria that cause disease in fish are gram-negative, so erythromycin should only be used after culture and sensitivity test results confirm it will be effective. Also, erythromycin is not very effective in a bath treatment, and it should only be administered by injection or in feed. Erythromycin is not FDA-approved for use with food fish.

The penicillins, including penicillin, amoxicillin, and ampicillin, are most effective against gram-positive bacteria such as Streptococcus species; therefore, for the same reasons as those given above, these antibiotics are not a good first choice for most bacterial infections in fish. None of the penicillins are FDA-approved for use in food fish.

Oxytetracycline and related antibiotics are considered broad-spectrum antibiotics (effective against a wide variety of bacteria), and they work well when mixed with food. (See UF/IFAS Fact Sheet VM-70 Use of Medicated Feed in Channel Catfish.) However, bath treatments may not be as effective for all species. One study (Nusbaum and Shotts, 1981) demonstrated that channel catfish absorbed approximately 15-17% of the oxytetracycline added to water with hardness of 20 mg/L and pH of 6.7. However, at least two freshwater fish species (yellow perch and hybrid tilapia) did not have the expected levels of this antibiotic in their blood when exposed experimentally to oxytetracycline as a bath treatment for up to 8 hours (K. Hughes, unpublished data; S.A. Smith, Virginia Tech, pers. comm. 2002; and R.P.E. Yanong, University of Florida, unpublished data). In addition, calcium and magnesium bind to tetracycline and oxytetracycline rendering them inactive. This means that with increasing water hardness (i.e., increases in calcium and magnesium levels), it is necessary to increase the dosages of these drugs in bath treatments. Tetracyclines are ineffective when used as a bath treatment for saltwater fish.

Tetracyclines are light sensitive, and they turn brown when decomposing. This contributes to poor water quality and may be harmful to the fish. Water should be changed immediately after the bath treatment period is concluded. Due to years of misuse, several bacteria in many different facilities are now resistant to tetracyclines. Oxytetracycline still works adequately against most cases of Flavobacterium columnare (columnaris disease).

Terramycin ® is a brand of oxytetracycline manufactured by Pfizer that is FDA approved for use in the production of salmonids, channel catfish and lobsters (See UF/IFAS Fact Sheet VM-70 Use of Medicated Feed in Channel Catfish).

The aminoglycosides, including gentamicin, neomycin, kanamycin, and amikacin, are very effective against gram-negative bacteria infections when administered by injection. Unfortunately, this group has also been shown to cause kidney damage in fish when administered by this technique.

As a group, these antibiotics are not considered effective when used in oral or bath treatments. A couple of exceptions may be kanamycin and neomycin, both of which may be effective against external infections if used in bath treatments. In addition, kanamycin is also believed to be effective when mixed with feed to treat gastrointestinal bacterial infections (Gilmartin, Camp and Lewis, 1976).

None of the aminoglycosides are approved by the FDA for use with food fish.

The quinolones, including nalidixic acid and oxolinic acid are considered broad-spectrum antibiotics, like the tetracyclines, and they work against a wide variety of bacteria. These antibiotics work best at acidic pHs of 6.9 or less, and they are inhibited by hard water. Although they appear to work well in both bath and oral treatments, some fish may sink to the bottom and appear lethargic after bath treatments.

These antibiotics have been shown to damage the nervous system of other animals and none are approved by the FDA for use with fish. Quinolones are closely related to a category of antibacterials known as 'fluoroquinolones,' which are categorized as 'of high regulatory concern' by the FDA. Use of fluoroquinolones or quinolones to treat any food animal is illegal and completely irresponsible.

The nitrofurans, including nitrofurantoin, nitrofurazone, furanace, and furazolidone, are commonly used in the ornamental fish trade, but the FDA strictly forbids their use by producers of food fish. Nitrofurazone is specifically categorized as 'of high regulatory concern' by the FDA and should not be present at any facility where food species are raised.

Although nitrofurans are commonly used in bath treatments, they are probably most effective against superficial infections and, in at least one study, nitrofurazone was not readily absorbed into the body of either gilthead sea bream (Sparus aurata) or tilapia (Oreochromis mossambicus) in experimental trials (Colorni and Paperna, 1983). Within the group, furanace appears to be the most effective for use in bath treatments.

To achieve the most effective result when using a nitrofuran in a bath treatment, either some sort of cover or a darkened treatment location should be considered, as the nitrofurans can be inactivated by light. Nitrofurans as oral treatments may not be as effective as previously believed, although the proper pharmacokinetic research needs to be performed to verify this conclusion.

The sulfa drugs, including Romet®, are also considered to be broad-spectrum antibiotics. There are many different types of sulfa drugs. The more common sulfas are not as effective as they once were, due to their misuse or overuse resulting in the creation of many bacteria that are now resistant to them. On the other hand, the potentiated sulfas, including Romet®, are still very effective.

Romet® works well when mixed with feed, but it does not work well as a bath treatment. It is FDA-approved for use with channel catfish and salmonids.

*Summary

Many bacterial infections in ornamental fish are avoidable with proper management. However, if a population does become infected, it is important to eliminate or reduce all contributing stresses. A fish health specialist should be consulted to assist with proper diagnosis, to run culture and sensitivity tests, and to provide the best information regarding dosages and treatment intervals.

Misuse of any antibiotic can lead to the creation of resistant bacteria in a facility. In an attempt to avoid this, some farms will rotate the antibiotics they use every few months or every year. However, the best solution is to positively identify the bacteria by running culture and sensitivity tests, and thereby avoid unnecessary, costly and potentially harmful treatments.

The most extreme cases of misuse and 'shot-gunning' can result in 'superinfections' in fish. These infections are caused by bacteria that are resistant to most of the commonly used antibiotics. Obviously, this situation is not desirable, and it is completely avoidable in most cases. Once it occurs, however, little can be done to reverse the situation, and the farmer is left with no treatment options other than depopulation of the fish followed by sterilization of the culture system and equipment or scrupulously good management.*


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## Morainy (Apr 21, 2010)

This is very helpful information. Thank you for posting it. 
I wish there were a way to take cultures at home, for example to stick a swab into the tank water and then mail it in somewhere for a diagnosis. Maybe we have a member here at BCA who would like to diagnose our fish?


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## seanyuki (Apr 22, 2010)

I have brought some discus to The Animal Health Centre and have them checked out for min fee.

quote
Our mandate is to diagnose, monitor, and assist in controlling and preventing animal disease in British Columbia. We provide a full range of fee-for-service diagnostic testing, including Pathology, Bacteriology, Virology, and Toxicology. In addition, laboratory staff is frequently involved in the development of new diagnostic tests and the initiation of investigative projects to address emerging disease problems in production animals, poultry, and fish.

http://www.agf.gov.bc.ca/ahc/

unquote



Morainy said:


> This is very helpful information. Thank you for posting it.
> I wish there were a way to take cultures at home, for example to stick a swab into the tank water and then mail it in somewhere for a diagnosis. Maybe we have a member here at BCA who would like to diagnose our fish?


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