Antibiotic usage has been a growing concern in both human and veterinary medicine in recent years as resistant bacteria appear to be an increasingly widespread problem in all species. Conversely, the development of new antibiotics has slowed, leaving both doctors and veterinarians with a finite number of options for treating microbial infections. Particular challenges surround the use of antibiotics in small mammals, such as species-specific sensitivities to certain drugs and the limited range of licensed products available. This article will outline factors affecting antibiotic selection in small mammals and discuss approaches to common presentations.
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Joanna Hedley qualified from the Royal (Dick) School of Veterinary Studies in 2003 and spent time in mixed, small animal, exotic and wildlife practice before undertaking a residency in exotic animal and wildlife medicine back at the R(D)SVS. She obtained her RCVS Diploma in Zoological Medicine in 2012 and European College of Zoological Medicine specialist status in herpetology in 2014. She is currently working as a lecturer in exotic species and small mammal medicine and surgery at the Royal Veterinary College in Camden, where she is developing the exotics clinical service and student teaching.
Choosing antibiotics for use in small mammals
The limited number of antibiotic products licensed for use in small mammals (Tables 1 and 2) makes the treatment of infections challenging. The fact that the most widely used product on the market is a fluoroquinolone (enrofloxacin) is a particular concern, as fluoroquinolones are classified by the World Health Organization as one of the groups of ‘Highest Priority Critically Important Antimicrobials’ for human medicine. As such, veterinary surgeons have a duty to use them responsibly, not only to minimise the development of resistance in animal patients, but also to reduce the risk of transmission of antimicrobial resistance to humans. Certain countries, such as Denmark and the Netherlands, have already started putting legal restrictions on the use of fluoroquinolones as first-line antibiotics in food-producing animals, unless it has been proven that there are no other treatment options available.
Currently in the UK, when selecting any medication for an animal, guidelines from the Veterinary Medicines Directorate (VMD) state that where an authorised product exists for the treatment of that condition in that species, this should be used first. If there is no authorised product, an alternative medication may be prescribed under the cascade. This would ideally be a product licensed for the same condition in another species or another condition in the same species. If there are no such suitable alternatives, a human medication may be prescribed or a veterinary pro duct licensed in another EU member state.
There is room for veterinarians to apply their clinical judgement in individual cases. For example, if a medication is only available in a tablet formulation, which would not be practical to administer to a small mammal, an alternative oral solution may be selected.
The VMD has also published guidelines for responsible antibiotic use under the cascade which state that’it is justified, on a case-by-case basis, to prescribe an antibiotic on the cascade in the interests of minimising the development of resistance’. Consequently, use of an alternative antibiotic may be justified, rather than first-line use of a licensed fluoroquinolone, if the veterinary surgeon feels that this is appropriate for the individual case.
However, if using an off-licence medication under the cascade it is important to ensure that informed owner consent is always obtained from the outset (this is generally necessary when prescribing most medications for small mammals).
Other factors influencing antibiotic selection include:
Ease of administration – oral suspensions are normally easiest to administer depending on their palatability. However, certain antibiotics are only available in tablet or injectable formulations, so solutions may need to be formulated or another antibiotic selected.
Patient size – some medications may need to be diluted to be administered at acceptable dosages to small patients, while the volume of drug can also be challenging for smaller patients (Fig 1).
Metabolic rate – rabbits and rodents often metabolise many drugs rapidly, so dosages may be higher or more frequently administered than those for other species.
Severity of disease – most small mammals will not show obvious clinical signs of disease until their condition is advanced, at which stage waiting for a culture and sensitivity result before starting treatment may not be practical.
Species-specific reactions to drugs – for example, gerbils appear susceptible to streptomycin toxicity.
Cost – this can be a concern for some small mammal owners, although it is not a valid reason to use off-licence drugs and should not be the main criteria for antibiotic selection.
Under European law rabbits are classed as food-producing animals. Although a number of antibiotics may be licensed for use in rabbits, their formulation as a premix for medicating feeds means that they are not designed to be used in pet rabbits.
A further challenge when treating small herbivores is their reliance on microorganisms within the hindgut to help with digestion. Rabbits, guinea pigs, chinchillas and degus all need to maintain their hindgut flora for effective digestion. Any drugs affecting the microbial balance can lead to proliferation of more pathogenic bacteria such as Clostridium species and rapid death due to the effect of enterotoxins. Hamsters, although omnivorous by nature, also appear particularly sensitive to the effects of certain drugs. Antibiotics that have been associated with this problem when given orally include penicillins, lincosamides, aminoglycosides (possibly), cephalosporins and erythromycin, often remembered as the PLACE rule (Box 1). Some species appear more sensitive to some of these drugs than others, while certain medications actually appear well-tolerated by alternative routes (for example, injectable benzylpenicillin in rabbits).
Antibiotics that may result in serious side effects in small herbivores
The ‘PLACE’ rule
The remaining groups of antibiotics can usually be used without problems in most small herbivores (Box 2), although gastrointestinal side effects are a risk with any antibiotic treatment. Certain species-specific adverse reactions have also been reported anecdotally; for example, metronidazole has been associated with hepatic failure in chinchillas. If in any doubt, especially when using a drug for the first time in a species, an up-to-date exotics formulary such as the BSAVA Small Animal Formulary: Part B: Exotic Pets, or Carpenter’s Exotic Animal Formulary should be consulted to ensure that no species-specific reactions have been reported.
Antibiotics that may be used in small herbivores
’Medications For Treating Small Mammals’
Fluoroquinolones (except pradofloxacin)
Macrolides (most, except for a few notable exceptions such as erythromycin)
Is a bacterial infection present?
Before selecting an antibiotic for a small mammal patient, it is important to establish if possible that a bacterial infection is actually present. In some cases this may be based on external signs; for example, if a purulent ocular or nasal discharge is seen, then bacterial infection is likely to be involved, although fungal infections should also be considered. In other cases, this can be challenging if the patient is showing non-specific signs such as lethargy or inappetence. A detailed history and clinical examination are necessary to try to ascertain the body system(s) involved. Ideally, the type of bacterial infection should then be confirmed by culture and sensitivity testing. However, obtaining an accurate sample or waiting to start treatment may not always be practical for every patient, so common presentations and suggested approaches for empirical treatment are discussed below.
Antibiotics for respiratory infections
The normal respiratory systems of both rabbits and rodents contain a range of bacteria and most common respiratory problems result from an overgrowth of ‘normal’ commensals. For upper respiratory tract infections, a deep nasal swab (to the depth of >1-2 cm) is recommended to maximise the chance of a positive and representative culture (Fig 2). More superficial samples of nasal discharge are often complicated by skin contaminants so results are unreliable. Alternatively, for lower respiratory tract infections, a tracheal wash or bronchoalveolar lavage may be performed. However, even under sedation or anaesthesia, these procedures may not be possible in smaller animals.
Even if sampling is possible, false negatives are common and a positive culture of a bacterium usually found in the respiratory tract (such as Pasteurella in a rabbit) by itself is not a definitive diagnosis of an infectious aetiology. Results can help to guide antibiotic treatment, but should be taken in context with clinical signs and any other pathological findings. Treatment of the animal is therefore often based on empirical antibiotic choice, supportive treatment, including NSAIDs, mucolytics and nebulisation, and correction of any predisposing factors. Poor ventilation, dusty bedding, inadequate hygiene (leading to high ammonia levels which irritate the respiratory epithelium) and overcrowding should all be considered in addition to any other stressors or causes of immunosuppression such as concurrent disease.
In rabbits, the most common bacteria associated with upper respiratory tract infections appear to be Pasteurella multocida (54.8 per cent) and Bordetella bronchiseptica (52.2 per cent) and these are often found concurrently (Rougier and others 2006). Marbofloxacin appears to be the most effective antibiotic against Pasteurella, followed by enrofloxacin. A high percentage of strains are also susceptible to trimethoprim-sulfonamides (TMPS). Marbofloxacin also appears the most effective against Bordetella but TMPS is more effective than enrofloxacin in these cases (Rougier and others 2006).
TMPS is therefore a sensible first-line antibiotic choice for mild cases of upper respiratory tract signs, whereas fluoroquinolones may be considered for non-responsive cases, ideally based on culture and sensitivity results. Other useful antibiotic groups include the tetracyclines and certain macrolides such as azithromycin.
For lower respiratory tract infections, similar bacteria are often involved and for a severe pneumonia fluoroquinolones may be preferred as a first choice, similar to recommendations for dogs and cats.
Treatment should be for a minimum of two weeks for upper respiratory tract problems and usually at least six weeks for lower respiratory tract infections to maximise the chance of success. It is important that owner expectations are realistic; many chronic respiratory infections in rabbits and rodents are managed rather than cured.
In guinea pigs, B bronchiseptica and Streptococcus pneumoniae appear to be the most common respiratory pathogens (Rigby 1976), so again TMPS would be the preferred first-line antibiotic for mild clinical signs or marbofloxacin for more severe cases. Doxycycline and azithromycin can also be useful.
In rats, the main respiratory pathogen appears to be Mycoplasma pulmonis, although other important pathogens include S pneumoniae and Corynebacterium kutscheri, which can often occur concurrently (Gaillard and Clifford 2000). Doxycycline is therefore a sensible first-line antibiotic choice for mild cases of upper respiratory tract signs, whereas azithromycin or fluoroquinolones may be considered for more severe cases where pneumonia is suspected. Combinations of antibiotics may also be helpful for non-responsive cases.
Antibiotics for urinary infections
Urinary tract infections (UTIs) are another common reason for antibiotic prescription in small mammal practice. Guidelines have been published by the International Society for Companion Animal Infectious Diseases to promote prudent use of antibiotics in canine and feline UTIs (Weese and others 2011). Complete urinalysis, including dipstick, specific gravity and sediment examination, in addition to bacteria culture and sensitivity testing, are recommended in every case. Realistically, this may not be possible for every small mammal patient, especially as meaningful samples for urine culture would require collection by cystocentesis, a procedure that carries higher risks in smaller individuals and often requires sedation or anaesthesia. However, free catch urinalysis can still provide helpful information in animals exhibiting any changes in urination; for example, in establishing whether a large number of bacteria are present (interpretation depending on the surface from which the urine was collected), whether there is a strong inflammatory response, and whether there are any other potential urinary problems such as uroliths or neoplastic cells.
Empirical treatment should be based on the most likely bacterial aetiology if culture results are unavailable. In guinea pigs, urinary infections are mostly associated with Staphylococcus species or Escherichia coli so TMPS is a sensible first-line choice (Peng and others 1990). In other rodents and rabbits, primary bacterial cystitis is less common and concurrent disease should be considered. However, E coli again appears to be the predominant bacterium involved so similar treatment principles apply. For ongoing infections, further diagnostics should be performed to try to identify any predisposing cause and anaesthesia for cystocentesis, culture and sensitivity testing and imaging to rule out uroliths is likely to be justified (Fig 3).
Antibiotics for ocular problems
Ocular infections are a common presentation for small mammals in practice, especially conjunctivitis and dacryocystitis (Fig 4). As with other body systems, antibiotic selection should be based on the most likely bacteria involved. Ease of use of different formulations may also be a factor.
For rabbits, there are two licensed topical preparations available, one containing fusidic acid, while the other contains gentamicin. Staphylococcus is the predominant bacterium cultured from conjunctival flora in rabbits and is the most likely to overgrow in cases of conjunctivitis (Cooper and others 2001). Fusidic acid is effective against Gram-positive bacteria and therefore is appropriate for first-line treatment in an uncomplicated case of conjunctivitis, although consideration should be given to any pre-disposing factors.
In guinea pigs and chinchillas, although Staphylococcus is commonly cultured, Streptococcus and, in guinea pigs, Corynebacterium are also common pathogens (Coster and others 2008, Lima and others 2010). Topical chloramphenicol may therefore be preferred for these species.
Dacryocystitis may occur concurrently with conjunctivitis or be associated with ascending upper respiratory tract infections, so systemic antibiotic therapy may be necessary. For ongoing cases, tear duct flushing is recommended in addition to investigation of any underlying dental disease. Cytology can be performed to provide an initial overview of bacteria involved or, ideally, for culture and sensitivity testing.
For cases where the corneal surface is compromised, an antibiotic should be selected with minimal epithelial toxicity. Chloramphenicol drops can be a useful first choice, having a broad spectrum of activity against Gram-positive, Gram-negative and obligate anaerobic bacteria, in addition to Chlamydophila and Mycoplasma, which may sometimes be involved.
Antibiotics for otitis
Otitis externa is commonly encountered in rabbits, especially lop eared varieties, which appear to have a particularly narrowed external ear canal, predisposing to bacterial overgrowth. Potential pathogens include Staphylococcus aureus and Corynebacterium species (Snook and others 2013). Ideally, a swab should be taken from the affected ear and cytology performed to establish if the predominant microflora is composed of yeasts, coc-coid or rod-shaped bacteria or alternatively whether ear mites are present (Fig 5). Malasezzia yeasts are commonly observed in normal rabbit ear cytology, whereas bacteria are rarely detected so their presence is more likely to reflect pathology (Quinton and others 2014).
Based on these results, a topical antimicrobial may be selected for use after initial ear cleaning. There is debate whether topical formulations containing a mixture of antibiotics and steroids are appropriate for rabbits and rodents (particularly guinea pigs and chinchillas) due to their apparent steroid sensitivity. Some practitioners report using them without apparent problems, whereas others have significant concerns about side effects, especially immuno-suppression. If they are used it is advisable to limit treatment to a short course initially before rechecking the animal for potential side effects. It is also important to ensure that the tympanic membrane is intact in these cases.
Alternatively, topical antibiotic formulations designed for ocular use can be applied to the ear canal. However, infection is often linked to underlying otitis media, so if there are any palpable swellings of the ear canal, if infection is ongoing despite treatment, or if any neurological deficits are noted, further investigations are recommended as topical treatment alone will be insufficient.
Antibiotics for wounds and abscesses
Superficial wounds in rabbits and rodents are most likely to be contaminated with skin flora such as S aureus. For small herbivores, TMPS is an appropriate first-line treatment if antibiosis is required. This is, however, ineffective in the presence of necrotic tissue, so should not be used if penetrating wounds and potential underlying abscessation is suspected. Alternatively, in small omnivores such as rats, amoxicillin-clavulanate or cephalexin may be considered.
Abscesses in rabbits and rodents can be a particular challenge compared to those of cats and dogs, due to their encapsulated nature (Fig 6). Antibiotic penetration is often poor and complete surgical resection is usually recommended followed by topical and systemic antibiotic treatment. Culture and sensitivity testing should ideally be performed in every case, as abscesses can often be a chronic problem. A sample of the purulent discharge alone is often sterile, but a piece of abscess capsule can be submitted for culture and sensitivity tests.
Dental abscesses in rabbits have been shown to involve a mix of aerobic and anaerobic bacteria, including Fusobacterium nucleatum, Prevotella heparinolytica, Prevotella species, Peptostreptococcus micros, Streptococcus milleri group, Actinomyces israelii and Arcanobacterium haemolyticum (Tyrrell and others 2002).
Clindamycin has been shown to be the most effective antibiotic for dental abscesses (Tyrrell and others 2002), but cannot be given orally due to its potentially lethal effect on the rabbit’s intestinal microflora. Topical application can be considered, for example, by placing clindamycin powder within the abscess site at the time of surgery. However, care must be taken to ensure that there is no tract into the oral cavity (this is often not possible with dental abscesses) as this could result in ingestion of the powder.
The next most effective choices in the Tyrrell and others study appeared to be penicillin and ceftriaxone. Again these cannot be administered by the oral route, but subcutaneous penicillin injections do appear useful in rabbits, and owners can be taught to give injections at home. Small herbivorous rodents such as guinea pigs and chinchillas unfortunately appear even more sensitive than rabbits to the side effects of penicillins and even injectable formulations carry high risks of serious gastrointestinal side effects. For these species, fluoroquinolones may be preferred, although they will need to be combined with metronidazole to combat any anaerobic bacteria present (Minarikova and others 2016).
Topical treatments may include antibacterials such as F10 Germicidal Barrier Ointment (F10 Products) or manuka honey in addition to regular wound flushing.
Perioperative antibiotic usage
Whenever a surgical procedure is performed, there is a risk of infection at the surgical site. Perioperative antibiotic usage has therefore often been commonplace (Knights and others 2012). Various factors have been shown to increase the risks of surgical site infections, including the degree of initial bacterial contamination, the duration of the procedure and the surgical technique, as well as individual patient factors. Every effort should be made to address these factors; for example, changing the surgical approach for castration in guinea pigs from scrotal to abdominal has been shown to significantly reduce the incidence of postoperative infections without the use of any perioperative antibiotics (Guilmette and others 2015).
In certain surgical procedures, antibiotic use may be indicated, either prophylactically or therapeutically. Examples would be contaminated or dirty surgeries. Alternatively, antibiotics may be considered for certain clean procedures if the surgical time is longer than 90 minutes or for procedures where introduction of infection would be catastrophic (for example, central nervous system surgery).
For maximum efficacy, it is important to ensure that adequate levels of the drug are present in the wound and surrounding tissues at the time of surgery, so antibiotics should be started before the procedure. In dogs and cats, intravenous first-generation cephalosporins are the most widely recommended antibiotics for perioperative use, started 30 minutes before surgery, repeated every two hours intraoperatively to ensure adequate concentrations throughout the procedure, and then discontinued within 24 hours following surgery. However, as previously discussed, significant side effects are potentially possible when using cephalosporins in some of the small mammal species and intravenous access may not always be possible.
Instead, antibiotics may be selected depending where contamination is expected. For most procedures, contamination would be anticipated from the skin microflora (usually Gram-positive cocci), so TMPS would be an appropriate choice for small herbivores, whereas amoxicillin-clavulanate or cephalexin can be used for small omnivores such as rats. These would also be appropriate for urinary tract surgery. Alternatively, if contamination from the caecum or colon is anticipated, the addition of metronidazole may be considered.
Typically, prophylactic antibiotics should not be required for routine clean surgical procedures such as neutering or simple mass removals. An exception may be for rabbits or rodents with known pre-existing respiratory infections where a course of antibiotic treatment, ideally before the anaesthetic, may be helpful to reduce any flare up of respiratory signs which can often occur following anaesthesia.
Antibiotic resistance is an increasing problem and careful consideration should be given to the use of antibiotics in small mammals as for other species. The choice of antibiotics may be somewhat limited compared to those used in dogs and cats, but should always be carefully considered based on knowledge of the most likely pathogen(s) if culture and sensitivity results are not available. Ideally, practice guidelines should be formulated for each species to optimise therapy and minimise inappropriate use of antibiotics. If in any doubt, drug dosages should always be checked carefully, especially when using a drug for the first time in a species due to some species-specific reactions.
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References and further reading
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