Penicillins in rabbits - bicillin and all that stuff.....

A few years ago, the idea of treating rabbits with any member of the penicillin drug family would have been met with horror from anyone "in the know"..... rabbit owners and vets alike shied away from these drugs for fear of causing serious (sometimes fatal) digestive upsets.

Then something changed. Reports began to circulate on the internet, tales of rabbits brought back from the brink with penicillin treatment for serious bone infections and abscesses. One particular combination of long-acting penicillins (procaine and benzathine penicillin, usually referred to as "bicillin") started to acquire a reputation as a near-miracle treatment for such bunnies.

The story might end there, but for the fact that bicillin cannot be legally used in the UK without a special licence from the Veterinary Medicines Directorate (VMD). And, without hard evidence that bicillin is more effective and at least as safe as other antibiotics already available in the UK, that situation looks set to continue.

This section of the website aims to:

Penicillins: some myths dispelled

We've all heard of penicillin. In fact, most of us have probably taken it ourselves at some point. The discovery of penicillin by Fleming in the 1940s kicked off the antibiotic era, and today there are many different types of antibiotics grouped into several different "families". Although discovered more than 60 years ago, the penicillins are still very useful drugs in both human and veterinary medicine, although penicillin itself is prescribed less frequently today than related drugs like flucloxacillin, amoxycillin and ampicillin.

Several drugs from the penicillin family - amoxycillin in particular - are regarded with dread by many rabbit owners, and understandably so. This is because rabbits treated with amoxycillin may develop serious (and often fatal) gastrointestinal upsets. This is why vets traditionally shy away from the whole penicillin family of drugs when treating rabbits. But is this degree of caution really justified?

In order to understand the arguments both for and against, we need to look at exactly how antibiotic toxicity occurs in the rabbit.

Why some rabbits react badly to some antibiotics... high risk and low risk drugs

Did you know that your bunny's gut is a sophisticated bag full of bugs? The rabbit digestive system depends upon a healthy population of bacteria to function properly. In normal circumstances, this bacterial flora of "friendly" bacteria will completely overwhelm the small numbers of bacteria capable of causing mischief and keep them safely in check.

Antibiotics have the potential to disturb this crucial balance, by killing off the friendly bacteria, allowing disease-causing species to proliferate and cause problems. The result may just be transient loose droppings, which is common but rarely harmful. Any antibiotic is capable of disrupting the crucial balance of bacteria. However, some are far more likely to do so than others.

Serious or fatal reactions to antibiotics represent a more extreme condition, which is sometimes seen when rabbits are given antibiotics from certain drug "families", especially by the oral route. Certain antibiotics are usually avoided in rabbits for this reason, as they are perceived as very "high risk" choices. Examples would include amoxycillin and ampicillin from the penicillin family, and clindamycin and lincomycin.

In these cases, the disturbance in gut bacteria allows specific bacteria (usually a Clostridium species) to overgrow. Some strains of Clostridia are capable of producing toxins that attack the gut wall, leading to severe diarrhoea. The condition is not confined to rabbits - exactly the same sequence of events can develop in humans taking broad-spectrum antibiotics, and is called pseudomembranous colitis.

If we pause for a moment, we can now understand why not all rabbits are harmed by the "no go" antibiotics (the best-known example to rabbit owners being amoxycillin). These drugs will only cause problems if the rabbit has in its gut a particular toxin producing strain of Clostridium or something similar. If the bunny doesn't possess that type of bacteria in the gut or if the bug present is not a toxin producing strain, then the rabbit may well tolerate supposedly "deadly" antibiotics. The problem is that there is no realistic way to identify which rabbits could be given amoxycillin and other "high risk" antibiotics safely, so such drugs should be avoided in all rabbits except in extreme circumstances.

Theoretically, a situation could arise where a culture & sensitivity test revealed that a rabbit was suffering from a bacterial infection that could only be treated using one of the "high risk" antibiotics, in which case the benefit may outweigh the risk, but this would be unusual and there are nearly always safer alternatives.

If a rabbit is given amoxycillin or one of the other high-risk antibiotics and reacts badly to it, then intensive treatment is likely to be required to try to avert a tragic outcome. Supportive therapy may help, for example, a high fibre diet; fluid therapy if the rabbit has diarrhoea; and replacing the "friendly" bacteria using probiotics.

More specific treatments may also be attempted. For example, a drug called cholestyramine (used in humans to lower cholestrol) can be given to try to mop up the Clostridial toxins; and other antibiotics such as metronidazole can be given orally in an attempt to kill off the Clostridial bacteria in the gut.

So, are penicillins safe in rabbits?

Important note:
This section refers only to the use of parenteral (injectable) penicillins. We are not suggesting in any way that penicillins should ever be given orally to rabbits - doing so may prove fatal.

"Safe" antibiotics are less likely to kill off the "friendly" bacteria and cause the problems described above, although there is a theoretical risk with any antibiotic. But where does the old fashioned, original penicillin fit into the equation?

Injectable penicillin has been used successfully for many years to treat rabbits with vent disease (rabbit syphilis) with no apparent problems. But it's only recently that a possible role in treating stubborn rabbit abscesses has come to light. There are anecdotal reports suggesting that an old-fashioned combination of two long acting penicillins (penicillin G benzathine + penicillin G procaine, referred to as "bicillin" in this article) can halt the advance of abscesses in bone and even lead to resolution of the problem.

In the UK, where bicillin is not available, alternative long-acting penicillins are being used instead.

American rabbit enthusiast and scientist Marcy Moore has been a key figure in raising awareness of the potential role for long-acting injectable penicillins (specifically, bicillin - see her Web page) in treating rabbits with bone infections and abscesses. After being tipped off by researchers caring for laboratory rabbits, Marcy developed a protocol for treating these rabbits and persuaded her vet to use it to treat her own 7 year old bunny Pal when he developed a large abscess on his face that would have been extremely difficult to treat surgically. Mary's account of Pal's treatment describes how he had bicillin injections every two or three days for three months, after which he was declared abscess-free. He went on to live another two and a half years with no further problems - not bad for a bunny whose initial abscess might well have led to his death.

Mary is building a database of cases treated with bicillin, and has placed the information on her Website

Please note that no bicillin preparations are currently licensed for use in the UK, although other injectable penicillins are available. Further information on the legal situation regarding bicillin use in the UK.

Is there a role for injectable long-acting antibiotics in rabbits with abscesses and osteomyelitis?

The rationale behind the use of long-acting injectable penicillins is sound: the drug is released slowly into the blood stream, killing species of bacteria that may not be affected by the antibiotics more commonly used (and licensed) for use in rabbits.

It's already known from years of experience treating rabbits with rabbit syphilis that injectable, long acting penicillins are generally safe and well tolerated. There does not seem to be any great risk of causing diarrhoeal problems, although they are always a possibility and the rabbit's droppings and general condition must be closely observed during treatment.

Abscesses, particularly in the head, are a serious problem for companion rabbits. They are fairly common and are often associated with dental disease. They can be extremely difficult to treat, often requiring repeated surgery and prolonged treatment with a very uncertain final prognosis.

Nobody knows the "best" way to treat bone infections and abscesses in rabbits - there have been no studies to compare different treatment options. Surgical options include draining abscesses; cutting away infected bone; and putting antibiotic-impregnated beads into the wound cavity. If the "medical" treatment option of injectable antibiotics works even in some cases, it will be a very welcome step forward in rabbit medicine.

However, we do already know that long-acting penicillins are not an all-encompassing miracle cure for all rabbits with these problems.... sometimes it works, and sometimes it doesn't. We have heard of plenty of rabbits in the USA that responded to bicillin treatment, and most of these were "last chance" bunnies, who would have had to be put to sleep had the treatment not worked. But the treatment didn't work in every case.

Without a formal trial (or even a registry of treated cases) we may never know the exact role for injectable long-acting penicillins in rabbits. Individual vets are forced to make decisions based upon only their own personal list of cases, or those reported to them informally by other vets. There's also the potential problem of antibiotic resistance. If vets start to use penicillin more regularly to treat rabbits, resistant bacteria may become more of a problem in the future.

The bottom line is that without solid data and reliable evidence, rabbit vets are faced with a dilemma. When treating a bunny suffering from a serious bony infection in the head and neck, they can stick with the conventional treatment strategies based upon surgical prinicpals (endeavouring to find the source of the problem and try to rectify it); or try long-acting penicillins and see what happens. Neither option is guaranteed to work, and at present there is no way of predicting which is the best option for any particular rabbit.

There's no right answer. Individual vets may have strong opinions one way or the other, but at the moment, these can only be opinions. In the absence of hard facts, the best advice we can offer to rabbit owners is that they find a rabbit-friendly vet they trust and stick with his/her recommendations.

Bicillin: the UK position

Basic facts about bicillin

Many rabbit owners seeking background information about the treatment of serious bony infections in rabbits have read about bicillin treatment, mainly on websites based in the USA. This is one topic where the situation between the US and the UK differs!

Your vet's prescribing and the law

Veterinary surgeons in the UK cannot give any drug they fancy to an animal - they're obliged by law to follow the "cascade" system.

The first choice would be to use a drug licensed to treat that problem in that species. The second choice would be to use either a drug licensed to treat the same problem in another species or, a different problem in the same species. Only if these options are not available is a British vet free to choose any drug available in the UK (either for animals or humans) for use in any species. If the desired drug isn't available in the UK, then the vet must obtain permission from the Veterinary Medicines Directorate to import and use the substance.

Bicillin falls into this category - it isn't licensed in the UK at all. It can only be imported and used legally in the UK if the vet treating a particular rabbit has obtained a Special Treatment Authorisation (STA) from the Veterinary Medicines Directorate (VMD). Obtaining an STA is usually relatively straightforward - so long as the treating vet can convince the VMD that there is no safe alternative available in the UK, and that the proposed treatment is both safe and effective. And this is where the bicillin story starts to unravel.

There's no firm scientific evidence that bicillin is an effective treatment for rabbits with abscesses and osteomyelitis. Although rabbit owners and vets have reported successes in individual rabbits - including some "near miracles" - no formal studies or trials have been conducted. And these anecdotal reports are not enough to convince the VMD.

At the end of 2002, the RWA/RWF wrote to the VMD enquiring about their position on bicillin and were informed that every application for an STA to use bicillin in rabbits had (so far) been refused - because nobody had presented them "with data or any convincing evidence that this combination is the only effective treatment for conditions in rabbits....". The VMD went on to add that, "If unequivocal evidence was presented to the VMD then we would reconsider our position."

Realistically, it is unlikely that any such evidence will emerge. Bicillin is an old-fashioned combination of two penicillins that came off patent years ago, so there's no commercial incentive for manufacturers of the drug to run a complex and costly trial to formally study the effectiveness of bicillin in rabbit. Also, many British vets maintain that there is nothing unique about bicillin, and that other penicillin preparations have just as much chance of working just as well.

Do not be tempted to use smuggled bicillin!

Obtaining and using bicillin (or any other drug not available in the UK) without an STA is a very serious criminal offence, and yet some rabbit owners have been so desperate to help their seriously ill rabbits that they have risked a hefty fine and a criminal record by using bicillin smuggled into the UK from abroad.

Some rabbit owners who obtained bicillin for their bunnies via internet contacts were not aware they were breaking the law. Others knew, but didn't realise the scale of the fine they were risking if caught, which can run to thousands of pounds.

One rabbit vet told the RWA in autumn 2002,
"One of my clients turned up with an un-labelled bottle of what he said was bicillin, and asked me to inject his rabbit with it. I refused. Not only would it be grossly negligent of me to inject an unknown substance of unknown quality into an animal, but by doing so I would be committing a criminal offence as well as the client."

Clients turning up with illegal supplies of bicillin in this way are putting their vet in an impossible situation, as Christine Shield (a Council member of the Royal College of Veterinary Surgeons) explains:

"The Medicines Regulations 1994 states that it is an offence to administer; cause; or permit to be administered an unauthorised veterinary medicinal product. So, vets who co-operate in treating rabbits with illegally obtained bicillin - such as by injecting the rabbits, or supplying needles - could be risking their career. On the other hand, vets have a duty to ensure that the welfare of animals in their care is not compromised. They then have to decide between throwing the client off their books, which might place the rabbit at greater risk, or agreeing to monitor the animal's condition."


Bicillin Facts

What's bicillin?

A combination of penicillin G benzathine plus penicillin G procaine. Bicillin is not available in the UK but rabbit vets in other countries (particularly the United States) have gained considerable experience with it.

What's it used for?

Bicillin has been used to treat abscesses and bone infections(osteomyelitis), especially if surgery has failed or is not an option.

Does it work?

The different treatment options for abscesses & osteomyelitis in rabbits have never been compared in a proper trial. So the only "evidence" for bicillin is in the form of case reports.... but the same applies to surgical alternatives.

Devotees of bicillin (usually rabbit owners) claim near-miraculous results. Many vets aren't quite so convinced, but increasingly regard bicillin as a useful addition to their armoury.

Aren't penicillins dangerous to rabbits?

Penicillins can cause serious or fatal diarrhoea in rabbits. But, given by injection, rather than by mouth, bicillin is remarkably well tolerated. Nevertheless, the risks/benefits have to be carefully weighed up by the prescribing vet.

This information is brought to you by the Rabbit Welfare Fund - the charitable wing of the Rabbit Welfare Association. If you love rabbits, please consider supporting the Rabbit Welfare Fund. You can make a donation, or you may like to join the RWA. The £17.50 adult subscription includes a subscription to "Rabbiting On", a fabulous quarterly magazine packed with health, behaviour and care advice to help you build a wonderful relationship with your bunny - whether s/he lives indoors or out.

The original version of this article was written by Dr Linda Dykes MBBS (Hons) MRCSEd A&E and Owen Davies BVSc MRCVS. It appeared in "Rabbit Health Matters", Rabbiting On, Summer 2001.

This completely revised version was prepared by Dr Linda Dykes, Owen Davies, and Judith Brown MRCVS in April 2003.

Copyright © BHRA 1999