Antibiotics and bacterial diseases

Bacteria are minute organisms invisible to the naked eye. There are many different types of bacteria and they are probably the most diverse group of organisms on the planet – each like a little chemical factory. Very few species are pathogenic (disease-causing). Those that are harmful can be divided into two basic types; Gram-negative and Gram-positive. This simple grouping is based on a staining technique in which Gram-negative bacteria stain red, while the Gram-positives stain blue because of differences in the cell-wall structure.

Bacteria stained using Gram differential staining method
	Stained Gram-positive bacteria viewed at high magnification
	Stained Gram-negative bacteria viewed at high magnification

Most bacterial fish pathogens, such as Aeromonas, Pseudomonas, Vibrio, Flavobacterium and Cytophaga are Gram-negative bacteria. These are the bacteria that are usually involved with bacterial disease such as ulcers, fin rot, acute septicaemia and bacterial gill disease. Less common pathogens are Mycobacterium and Norcardia sp. which cause chronic granulomas (or abscesses).

How do bacteria cause disease?

Although they are incredible small most pathogenic bacteria have tremendous reproductive potential. They simple divide in two and once each half has re-grown sufficiently they divide again. Under ideal conditions the reproductive cycle can be as little as 20 - 30 minutes, which means that just one bacterium can multiple to several million within 24-hours or so!

As I have said, bacteria are like little chemical factories. Some bacteria produce toxins that are excreted into the blood and tissues of the host. Other bacteria, particularly the Gram-negatives do not secrete a soluble toxin but make an endotoxin that is liberated when the cell dies and disintegrates. These endotoxins are usually lipopolysaccharide structural components of the bacterial cell-wall (specifically the lipid A portion). In addition to toxins the virulence of many bacteria is partly due to the production of extracellular enzymes, which attack healthy fish cells.

So although tiny, the net effect of millions of bacteria can quickly overwhelm the defences of the fish host – which is why early treatment is so vital if the fish is to survive.

How do antibiotics work?

Antibiotics are chemical substances produced by microorganisms that either destroy (bactericidal) or inhibit the growth of other microorganisms (bacteriostatic). Antibiotics can be either broad spectrum, which means that they are active against a wide range of microorganisms – both good and bad. Narrow spectrum drugs target a specific group of microorganisms and are able to interfere with a metabolic process specific to those organisms. In general antibiotics work by;

	Preventing the synthesis of bacterial cell-wall components – typically penicillin
	Damaging the bacterial cytoplasmic membrane
	Interfering with protein or nucleic acid synthesis – typically tetracyclines

However, the microorganisms under attack don’t take all this sitting down. Many are able to produce enzymes that neutralise antimicrobial compounds. Others can acquire resistance to weak, short-term or repeated exposure to antibiotics. For example there are now high levels of resistance to oxolinic acid and oxytetracycline because of overuse and misuse.

What antibiotics are available?

Every country has its own regulations on the control of antibiotics and therefore availability will vary. The range of drugs available or licensed for use with fish is generally small. In the UK all antibiotics are classed as POMs (Prescription only Medicines) and are only available under veterinary supervision. Among the antibiotics in common use are;

Broad-spectrum penicillins that include amoxycillin and ampicillin. These are bactericidal in action and are effective against Gram-positive and Gram-negative bacteria, but not very effective against Pseudomonas.

Chloramphenicol is a broad spectrum antibiotic, but again it is not usually effective against Pseudomonas. Because it is used in human medicine it is illegal for use in food animals in most countries. Some people are sensitive to the drug so rubber gloves should be worn when it is handled.

There are several potentiated sulphonamide drugs in which a sulphurdrug is combined with trimethoprim. They are broad spectrum and mainly bacteriostatic. They are well absorbed from the gut when used with medicated food but poorly absorbed from water. They can sometimes form crystals in urine and should not be used where there is already kidney damage. They should not be used at the same time as organophosphates. Co-trimazine is a combination of trimethoprim and sulphadiazine and Borgal is a combination of trimethoprim and sulfadoxine. They are effective against Aeromonas and other Gram-negatives, but not particularly effective against Pseudomonas.

Gentamicin is a broad spectrum antibiotic with a bactericidal effect. It is useful against all Gram-negatives including Pseudomonas but can be toxic to kidneys. There is concern that bacteria may acquire rapid resistance, so it would not be the drug of first choice but does have a use when other drugs do not work.

Nitrofurans are a group of synthetic antimicrobials. Both nifurpirinol and nitrofurazone are effective against many fish pathogens. They are well absorbed through the skin, making them ideal for bath treatments. However, they are carcinogenic and mutagenic and their use with food fish is illegal in most countries.

Oxytetracycline is bacteriostatic drug with a broad spectrum of activity. However, there is widespread resistance and it has little effect on Pseudomonas. The long-acting injectable formulation has caused sterile cysts at the injection site. When used for bath treatments it readily chelates calcium and magnesium ions found in hard water, significantly reducing its effectiveness. It is also light-sensitive when used as a bath treatment, turning brown as it decomposes. The degraded form can be toxic to both fish and humans. Some studies show that oxytetracycline is immunosuppressive in some fish species.

The quinolones are narrow spectrum range of drugs acting mainly against Gram-negatives such as Pseudomonas and Aeromonas. The first generation quinolones include oxolinic acid to which there is now widespread resistance. Newer quinolones include enrofloxacin and sarafloxacin. These are effective against Pseudomonas and Aeromonas and as yet there is little resistance. All quinolones are chelated in hard water, so they are not practical for bath treatments. They are well absorbed through the gut, making them useful for medicated food.

Antibiotic sensitivity

Bacterial resistance is an issue that needs to be considered when choosing an appropriate antibiotic. While it may be necessary to start a course of treatment based on personal experience, it is also prudent to have bacterial identification and antibiotic sensitivity tests carried out at the same time. At worse this simply confirms the treatment choice, while possible saving valuable time and money if the initial course of action is ineffective.

A sterile swab is used to take a bacterial sample from either the posterior kidney or other organ of a newly dead fish, or alternatively from a body ulcer. When taking a swab of a body ulcer it should be sampled from the infected rim of the ulcer only.

The swab is then sent to a specialist laboratory for analysis and testing. Your local veterinarian can arrange this. The results from a body ulcer can be difficult to interpret because of the problem of secondary pathogens. It is quite common for samples from body lesions to show a mixed growth of several bacterial species and takes some experience to determine the relevance of the results.