Penicillan - Friend or Foe?

Written for Vet2Pet by Dr Linda Dykes MBBS (Hons) MRCSEd A&E and Owen Davies BVSc MRCVS

The houserabbit community on the Internet has been buzzing over the past couple of years with tales of rabbits brought back from the brink with penicillin treatment for serious bone infections and abscesses. And yet rabbit owners are frequently advised that penicillin-type drugs are dangerous for rabbits. What's going on?

In this article we're going to look at the use of penicillins and other antibiotics in rabbits. We've tried to bring you a balanced account of the dangers and the benefits, stripped of the hype.

In a nutshell...

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 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. The problem is that if rabbits are treated with amoxycillin, they may develop a serious and frequently fatal gastrointestinal upset. This is why most vets shy away from the whole penicillin family of drugs when they are 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.

Gut reaction

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 the healthy gut, the vast majority of bugs will be desirable, "friendly" bacteria which completely overwhelm the small numbers of bacteria capable of causing mischief and keep them safely in check.

The problem with antibiotics is that they can 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 - but some are far more likely to do so than others.

Serious or fatal reactions represent a more extreme condition and are classically seen when rabbits are given drugs including amoxycillin, ampicillin, and (even more toxic), clindamycin and lncomycin. In these cases, the disturbance in gut bacteria allow specific bacteria (usually a bug called Clostridium difficile) to overgrow. Some strains of this bacteria are capable of producing toxins which attack the gut wall, leading to severe diarrhoea. The condition is not confined to rabbits - exactly the same sequence of events can occur in humans taking broad spectrum antibiotics, and is called psuedomembranous colitis.

If we pause for a moment, we can now understand why not all rabbits are harmed by amoxycillin...... it will only cause problems if the rabbit has in its gut a particular toxin producing strain of C. difficile 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 "deadly" antibiotics like amoxycillin. The problem is that there is no realistic way to identify which rabbits could be given amoxycillin safely, so the drug should be avoided in all rabbits except in extreme circumstances.

Theoretically, there could be a situation where a rabbit develops an infection that can only be treated by amoxycillin, 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 required to try to avert a tragic outcome. A high fibre diet; fluid therapy if the rabbit has diarrhoea; replacing the "friendly" bacteria using probiotics are all useful. There's a also a treatment available to mop up the toxin, a drug called cholestyramine (Questran) which is used in humans to bind cholesterol.

Bicillin

The "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's now quite a large handful of anecdotal reports suggesting that an old-fashioned combination of two long acting penicillins (penicillin G benzathine plus 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.

American rabbit enthusiast and scientist Marcy Moore has been working hard to publicise the use of bicillin. 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. Marcy'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.

Miracle or false dawn?

The rationale behind the use of bicillin is sound: the drug is released slowly into the blood stream, and kills antibiotic species that are not affected by other antibiotics such as Baytril. Although not the most obvious choice, it's already known from years of experience treating rabbits with 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 as seen with amoxycillin, although it is always a possibility and the rabbit's droppings and general condition must be closely observed.

There is no doubt that abscesses, particularly in the head, are a serious problem for companion rabbits. They are fairly common, and often associated with dental disease. And they are extremely difficult to treat, often requiring repeated surgery and prolonged treatment with a very uncertain prognosis. If bicillin really can clear up some of these abscesses then it will be a major step forward in rabbit medicine.

Of course, it is early days yet and like any other apparent "miracle", Marcy's claims have understandably been met with scepticism both here and in the US. Marcy is aware of more than 15 cases, all of whom have reportedly done well: the bicillin treatment has either halted the progression of the abscess, or improved the situation to a greater or lesser extent. However, here in the UK, the RWA is aware of other cases where bicillin therapy doesn't seem to have helped.

In all cases, these have been "last chance" bunnies. We still have no idea what the role is for bicillin in treating abscesses at a much earlier stage, or what percentage of rabbits might benefit. There's also a question mark over whether resistant bacteria may become more of a problem if vets start to use penicillin more regularly to treat rabbits.

Until then, rabbit vets both in the UK and the US are faced with a dilemma. When treating a bunny suffering from a serious bony infection in the head and neck, should they stick with the conventional (and not always successful) treatment strategies based upon surgical drainage; or try bicillin and see what happens?

An increasing number of rabbit owners and their vets have been convinced enough to try bicillin as a last resort, but it remains to be seen whether we should be regarding this drug as something to use earlier in the treatment process. Once again, rabbit medicine desperately needs clinical research to provide an evidence-based answer. Determining this will take a carefully designed, controlled clinical trial. We will keep RWA members informed via Rabbiting On ands this website as this story develops either way.

Further information

There are no longer any preparations of penicillin G benzathine plus penicillin G procaine available on the UK market. If a UK vet wishes to treat a British rabbit with bicillin, supplies have to be imported from abroad (usually either France or the USA) with the accompanying special licences and red tape. This inevitably takes time, and licences have to be obtained for each animal on a "named patient" basis.