Medications for Treating Infections in Koi

by Keith Tom from Canada Koi Club of British Columbia, Canada <ktom@cw.bc.ca>

This article provides information on some drugs and their compatibility in a syringe for the treatment of infectious diseases in Koi.  Injecting Koi with medications should be the last resort for treating sick fish since the administration process or intervention may exacerbate symptoms or cause premature death. 

What are the common pathogens found in diseased Koi?

Veterinarian Erik Johnson cited four groups of bacteria that may be responsible for many morbid lesions among Koi.  Empirical sensitivity of these bacteria to conventional drugs is listed below.  Super-infections involving fungal and viral pathogens may also complicate infectious diseases in Koi. 

Aeromonas Hydrophila are a common group of bacteria that can cause a life-threatening infection among Koi.  These bacteria thrive in filthy water that carries a heavy fecal load resulting from inadequate filtration and over-crowding.  Parasites such as flukes  that flourish in dirty water often initiate the invasion process.  These bacteria produce hydrogen sulfide, which emits a smell like rotten eggs or sulphur, and they cause bloody lesions.   Another group of bacteria commonly responsible for Koi death is Pseudomonas fluorescens, which cause bacterial tail rot, characterised by fin or tail deterioration.  Lesions secondary to Pseudomonas strains are not hemorrhagic contrary to those associated with Aeromonas strains.  They do not produce hydrogen sulfide.  Nonetheless, Pseudomonas strains can be equally pathogenic as those responsible for Aeromonas infections.   Death is imminent when the Koi is unable to fight the infection. Prompt medical attention with the appropriate parenteral anti-microbial treatment can improve its chances of survival.

Sensitivity of pathogens in Koi Pathology

What are these drugs?

Aminoglycosides  (Amikacin, Gentamicin, Tobramycin) are a group of drugs that are usually effective against gram-negative bacteria, including Aeromonas and Pseudomonas strains.  The difference between therapeutic and lethal doses of these agents is small, so the weight of the fish determines the dose.  Adverse effects affecting their central nervous system and renal impairment often make it difficult to treat sick Koi with aminoglycoside  injections.   You can use the dosing regimen shown below every 24 hours.  To minimise the occurrence of toxicity, you can dose the Koi every 48 to 72 hours.  Improvement of symptoms should be evident after 3 days, and recovery  should occur after 3 injections.   Drugs related to penicillin (including cephalosporins) could weaken or eliminate the anti-bactericidal effects of aminoglycosides.   Ideally, they should be spaced apart by 2-3 days, or avoided completely.  Amikacin should be reserved for strains that are resistant to gentamicin and tobramycin, such as those related to Mycobacterium (tuberculosis).   Gentamicin and tobramycin can be used  for Pseudomonas infections.  However, they  impair the Koi’s kidney function  and brain function and lead to premature death.  Careful clinical assessment is necessary  prior to giving subsequent injections.  Aminoglycosides should be used sparingly in view of their inherent toxicity profile.  Dosing  based on the body length of the Koi is a major risk factor in using this group of drugs.

Beta-lactam or penicillin (Piperacillin, Piperacillin-Tazobactam, Ampicillin) is another group of antibiotics that are useful in combating infections in Koi.  Piperacillin with or without tazobactam are the Canadian version of Azactam^Ò (azetronam) commonly used in USA.  It is often referred to as the “silver bullet” when it is given concurrently with amikacin.  This combination provides a broad coverage of bacteria.  However, they are not effective against fungal infections and other non-sensitive strains of bacteria.

Third Generation Cephalosporins such as cefotaxime, and ceftriaxone are efficacious towards Aeromonas, Streptococcus, and Psuedomonas species.  Since this group of drugs may complicate  bleeding disorder in Koi that have already been inflicted with bacterial hemorrhagic septicemia, they have not been used as often as they should.   For example, giving cefotaxime alone to a sick Koi may lead to premature death.  Because of this, they are not perceived as a useful agent in combating infections among Koi.  However, adding dexamethasone to cefotaxime in a same syringe may nullify this negative effect.   Mono-therapy by using a single agent of either cefotaxime or ceftriaxone provides a convenient regimen of therapy.  Like  the penicillin group, third generation cephalosporins may attenuate the effects of aminoglycosides, so co-administration of these drugs should be avoided.

Fluroquinolones (enrofloxacin /Baytril^Ò, ciprofloxacin) have been extensively used in treating lesions on Koi since they cover both the Aeromonas and Pseudomonas strains.  Single agent therapy appears to be the treatment of choice among Koi keepers.  However, emergence of resistant strains or presence of other microbes demands a combination therapy with other agents or a higher dosing regimen.  Concurrent use of aminoglycoside, anti-psuedomonal penicillin, or third-generation cephalosporins may augment bactericidal effects towards resistant strains.  Fluroquinolones are easy for hobbyists to handle.  Current trends of using higher doses and longer intervals have shown to be equally therapeutic in comparison to conventional frequent dosing intervals with smaller doses.

Anti-fungal agents such as fluconazole and amphotericin B are useful to treat fungal infections that are often over-looked in the Koi-keeping community.  Compared to amphotericin B, fluconazole is easier to use.  You should give it  along with an anti-bacterial agent to provide a complete coverage if fungal involvement is suspected at the onset of the illness.  Koi that live in an exygen-deprived environment can develop a fungal infection.  Compared to amphotericin B with respect to their safety profile, fluconazole is the drug of choice in treating Koi with fungal infections.   Amphotericin B is neither practical nor cost-effective to use in this hobby.

 Miscellaneous Agents

Clindamycin that is effective against some anaerobes, staphylococcus, and streptococcus species may prevent deadly toxin from forming in Koi that are dying from dropsy or hemorrhagic septicaemia.  It must be combined with another drug to be effective.   Clindamycin cannot be used as a single agent to treat Koi at the onset.  Its versatile compatibility with other agents allows combination of medications in a same syringe.  Clindaymcin can be easily replaced with  dexamethasone  since the latter provides a safer outcome.

Dexamethasone is a corticosteroid that replenishes the  “hormone” that is essential to life.  Dying Koi often have diminishing steroid.   Dexamethasone can be dosed at 0.2 to 4 mg/kg and injected intra-peritoneally along with other drugs.   Beneficial effects of this steroid include immediate control of inflammation associated with ulcer formation, stimulation of appetite, and restoration of previous energy level of a sick Koi.  Empiric combination of dexamethasone and cefotaxime will control sepsis as a result of Koi suffering from “dropsy”—a premorbid condition characterised by raising scales, bloating body, and protruding eyes.    Dexamethasone can be mixed with the following drugs in a same syringe:  amikacin, gentamicin, tobramycin, aztreonam, fluconazole, piperacillin +/- tazobactam, and cefotaxime.  Dexamethasone-induced suppressant effects on the immune system are not significant. 

Metronidazole is the only agent that can eradicate Heximita protozoa present  in water and Koi.  It may require another antibiotic agent to be efficacious against systemic infections in Koi.  It may play a role in treating schistosomiasis associated with Hexamita parasites.   Drugs that can be mixed with metronidazole in a same syringe include amikacin, gentamicin, tobramycin, ampicillin, cefotaxime, ceftriaxone, ciprofloxacin, enrofloxacin, piperacillin +/- tazobactam, and fluconazole.  The drawback in administering metronidazole to sick Koi is that  a  large volume of injection is required.

Erythromycin is a macrolide, which is effective against water-borne bacteria including Mycoplasma.  It is irritating to tissue and should therefore be administered intra-peritoneally.  This drug has not been tested or used to any meaningful extent in our setting.

Co-trimoxazole (Trimethoprim/Sulfamethoxazole) is a sulfonamide that remains to be effective against Aeromonas infection despite its long history of existence.   It is cost-effective when compared to other agents used to treat similar lesions.   Septra^Ò or Bactrim^Ò needs to be diluted in dextrose solution to be stable.   When it is  given along with gentamicin, the combination becomes an economical choice in treating an infection involving both Aeromonas and Pseudomonas strains.  Nonetheless, another option that provides a safer outcome is by using a combination of piperacillin and co-trimoxazole.

Furosemide is a diuretic, which promotes urine formation and removal of excess fluid in a body.  This can symptomatically treat severe bloating in a Koi by eliminating excess fluid from a Koi suffering from kidney impairment.  Since furosemide could impair kidney function, it should not be used  repeatedly to treat Koi with dropsy.

Medication Dosage Guide for Treating Koi Ailments (based on limited clinical trials)

Legend:  DNF= do not freeze, DNR = do not refrigerate, ASL = Avoid exposure to sun light, IM = intra-muscular, IP = intra-peritoneal F Cost of medication listed here is the acquisition cost which does not include mark-up or dispensing fee

Compatibility of drugs being mixed in a same syringe

Empirical Approach for treating  life-threatening infections in Koi:

Since the pattern of pathogens infecting Koi varies widely from region to region, the treatment option must be individualised.  Koi-keepers wishing to initiate treatment for severely sick Koi with multiple lesions may consult their “Koi-certified” veterinarian as health professionals may have access to a local biogram, authority to prescribe drugs, and experience in treating sick Koi.  Aminoglycosides such as gentamicin, tobramycin, and amikacin are associated with a high incidence of injection-related morbidity as well as mortality.  Chloramphenicol and its derivatives are equally toxic to sick Koi.  Fluoroquinolones such as enrofloxacin and ciprofloxacin have become less effective in treating sick Koi due to a rapid emergence of drug resistance to this group of drugs.  Cephalosporins such as cefotaxime and ceftriaxone have a greater margin of safety when compared to aminoglycosides and chlorampheicols.  When used appropriately, cefotaxime and dexamethasone becomes a convenient, feasible, and cost-effective combination to control sepsis or “dropsy” in a dying Koi.  Piperacillin and co-trimoxazole can be seen as the Canadian version of a “magic bullet” used to treat Koi showing “dropsy” symptoms.

Treatment Strategy:

Examine the lesions and  condition of the affected Koi before initiating therapy.  Begin supportive measures such as warm-temperature therapy (indoor temperature), regular water changes, and vigorous aeration at the outset.  Sick Koi with severe mouth rot or extensive body erosion, deep lesions penetrating through the abdomen, weak respiration, loss of equilibrium, uncoordinated swimming, muscular fibrillation, sporadic hyperactivity, distended abdomen with ascites (fluid retention), protruding eyes (exophthalmic), and extensive skin lesions have an extremely poor prognosis.   Depending on clinical findings at the onset of treatment, begin empiric coverage of bacteria, fungi, and parasites.  Therefore, a Koi may tolerate 4-5 drugs at one setting provided they are given appropriately and correctly.   Collecting specimen at the wound site can be useful although it may not reflect the true pathogens present in the blood.  Modifying treatment plan according to a culture and sensitivity test (C & S) may eliminate the guesswork of diagnosing.  Once the infection is under control, the fish should be left to heal naturally.  Medications only can eradicate pathogens in Koi; therefore, the healing process takes its own course that may last for 1-3 months depending on the extent of missing body parts or nature of the infection. 

Stability of Medications after opening or reconstitution (days)

Legends: RT= room temperature, Å unable to maintain sterility although stability remains intact until expiry date stated on vial

Closing Note:

Treating sick fish is not easy.  A veterinarian’s signature is required to obtain medicines.  More importantly, injecting Koi with drugs is not a natural process of raising ornamental fish.  To minimise the inherent stress, Koi with topical lesions should be treated with non-intrusive measures at the outset if clinically appropriate. Stay with aerated salt water (0.3 to 0.6% sodium chloride), or medicated bath with 10-20 PPM tetracycline.  Warm temperature (³25C°) treatment and regular water changes are crucial to healing sick Koi.   Be aware of  “snake oil” or magic potions. Topical application of medications may not reach the site of action.  Systemic infections in Koi often require parenteral administration of drugs.  Extreme caution is necessary in delivering such chemicals into the fish under veterinarian supervision.  A sick Koi is only a symptom of a greater  problem in the aquatic environment, which deserves immediate attention.  Bacteria, viruses, fungi, and protozoa co-exist with Koi in a pond.  These microbes do not become pathogenic unless the immune system of Koi becomes compromised as a result of environmental injuries such as over-crowding, improper handling, poor nutrition, and poor water quality secondary to heavy fecal load.  Humans can control all of these factors.  Nitrogenous by-products, such as nitrites and nitrates, must be converted to nitrogen in a healthy pond.   Emergence of bacterial resistance has been linked to antibiotic usage, and improper use of medication to treat sick Koi can lead to premature death; therefore, veterinarian consultation is necessary prior to any invasive treatment with medications.

Acknowledgement:

Special thanks to Mr. Roger M^cPherson for providing guidance and helpful information on keeping Koi; Ms. Patricia Partida for her excellent linguistic assistance;  and Mr. Jackson Hui for his generous supports in conducting on-going clinical trials in treating severely sick fish.