The pneumonias of small mammals (Proceedings)

Pneumonia is a common presenting complaint in exotic companion mammals. Although there are some species that present with pneumonia more often than others, there are no reported breed or gender predilections to it. Pneumonia usually occurs in young sick, debilitated, or immunodeficient animals when natural defense mechanisms have been eroded. It can be precipitated by stress such as shipment, overcrowding, or social conflict among cage mates. Improper environment and husbandry has a significant impact on an individual's resistance to pneumonia. Extremes in temperature, humidity, exposure to waste, and poor nutrition all tend to increase one's susceptibility to it. Likewise, the stress of concurrent infection, advanced age, dental disease, or other concurrent illness can lead to breakdown of the immune system and onset of pneumonia.

Clinical signs

Patients with pneumonia may exhibit haunched posture, unkempt appearance, lethargy, unfocussed eyes, disinterest in the surroundings, reduced appetite, weight loss, and/or diarrhea. Other clinical signs might include coughing, wheezing, or rapid respirations. Increased respiratory effort is usually manifested as pronounced abdominal movement when breathing. Discharge from the eyes or nose, and/or diarrhea may be present. A complete physical examination may reveal ocular or nasal discharge (found either on the face or the medial aspect of the front feet) and/or wheezing, and crackles, increased bronchovesicular sounds, or rhales may be ausculted. There may be tachypnea or overt dyspnea, and possibly a fever.

Diagnosis

Diagnosis of pneumonia in small mammals begins with thorough history and careful observation. The clinician should ask about diet, nutritional supplementation, the type of cage, bedding material, how often cage is cleaned, the presence of other animals, and any new animals that may have been introduced. Also ask about the routine and whether or not any changes to the routine (e.g. pet sitter, new diet, death of bonded cage mate) have occurred recently.

Diagnostic workup for pneumonia generally begins with thoracic radiographs. In a normal small mammal the caudal lung lobes are large and well aerated. Evaluation of the cranial lung lobes may difficult because in some species (e.g. guinea pigs) they are small. The classic radiographic appearance of bacterial pneumonia is an alveolar pattern, with air bronchograms in severe cases. Lesions can be diffuse, localized to a general area, or lobar in nature. If solitary masses are identified, differential diagnosis should include abscessation or consolidation of lung due to bacterial infection.

When pneumonia is suspected, culture and sensitivity testing should be done before antimicrobial therapy is started. Since small exotic mammals often present in severe respiratory distress, nasal swabs are often preferred because they can usually be obtained with minimal handling of the patient. However, nasal passages are prone to bacterial contamination from the environment, thus nasal cultures may not accurately represent tracheal and pulmonary flora. A tracheal wash is generally considered to be more accurate than a nasal swab for diagnosing pneumonia because it can provide material for cytologic exam and bacterial culture. Identification of degenerative neutrophils containing bacterial debris in a tracheal wash specimen is highly supportive of the diagnosis of bacterial pneumonia. While not a widespread practice, transthoracic needle aspiration is another way to obtain lung samples for cytology and culture.

Culture and sensitivity should test for both aerobic and anaerobic organisms, and empirical treatment with broad-spectrum antibiotics should start before results are available. In general, light growths of mixed bacterial populations are less important than the heavy growth of a single species in conjunction with a pathogenic response. Caution must be used when interpreting results; some labs will not report normal flora. However, in an immunocompromised individual, infections may result from normal flora that are opportunistic pathogens. In addition, the normal flora of many species still have not been established or are obscure. If culture can't be done because antibiotics have already been started, then PCR should be considered. Bacterial PCR can also be helpful in identifying anaerobes (because these frequently do not survive the transport to the lab) and for getting results from an area where bacteria are likely to be dead (e.g. abscess, caseous pus). Where Chlamydophila is suspected (i.e. guinea pigs), a conjunctival scraping from affected individuals by will contain intracytoplasmic, coccoid, basophilic organisms (i.e. Chlamydia elementary and reticulate bodies), or a PCR test is available for this infection, as well.

Necropsy findings from small mammals with pneumonia will vary by duration and severity of the disease, and by the organism(s) involved. Mild and acute cases will result in lung congestion, atelectasis. More severe and chronic cases develop supperative lesions, fibrin adhesions and fibrosis. Severely affected individuals can develop pulmonary abscesses, granulomas, and consolidation. There may also be other organ involvement: lymphadentitis, myocarditis, peritonitis, meningitis, septicemia, tracheitis, bronchitis, otitis media, etc.

There are a number of non-infections conditions that can cause respiratory distress in exotic companion mammals including heat stress, diaphragmatic hernia, pregnancy toxemia, and gastric torsion. Dyspnea and weakness may also be found with heart failure or pulmonary neoplasia.

Treatment

General

There are no antimicrobials approved by the FDA for use in small exotic mammals, and it is important to inform owners of this. Much of the veterinary literature concerning respiratory disease of exotic mammals is from the area of laboratory animal medicine. Information concerning the treatment of individual animals is scant. As a result, there are no pharmacologic studies to guide practitioners as to dose, frequency or length of drug treatment. Veterinarians must rely largely on empirical data or anecdotal information, however, the general principals of antibiotic selection still apply. The ideal antibiotic treatment plan for pneumonia in small mammals will provide "four-quadrant" coverage, will be bacteriocidal, easy to administer, safe, and not cause gastrointestinal disease. Antibiotics with a post-antibiotic effect (e.g. aminoglycosides, fluoroquinolones) are preferred, so "pulse therapy" can be employed. Post-antibiotic effect permits once a day dosing, which is less stressful to the patient and improves owner compliance. Aminoglycosides are potentially nephrotoxic, however, supplemental fluids are advisable.

As hind gut fermenters, rabbits, guinea pigs, and chinchillas rely on active cecal flora for digestion. If antibiotics with a gram-positive spectrum are given, dysbiosis and the overgrowth of pathogenic bacteria will occur, often resulting in death. For this reason, the antibiotics amoxicillin, ampicillin, clindamycin, and lincomycin are avoided when treating small herbivores. The antibiotics that are least likely to incite gastrointestinal disease in hind gut fermenters include trimethoprim-sulfa, fluoroquinolones, chloramphenicol, aminoglycosides, and metronidazole. Antibiotics that pose an intermediate risk to guinea pigs include oral cephalosporins, tetracyclines, and erythromycins. In small mammals with a simple digestive tract (e.g. ferret), or minimal cecal fermentation (e.g. rat), the risk of antibiotic-associated gastrointestinal disease is minimal or greatly reduced.

The route of drug delivery for pneumonia will depend, in part, on the severity of the illness. For severely affected animals, parenteral administration is used initially, and then usually switched to the oral route as the patient's condition improves. One advantage of the parenteral route in hind gut fermenters is that the antibiotics bypass the digestive tract and avoid potentially disturbing cecal microorganisms. Subcutaneous injections are preferred if long-term parenteral administration is required. Exotic companion mammals have relatively little muscle mass; intramuscular injections are painful, stressful, and potentially dangerous. Intravenous and intraosseous injections are reserved mostly for short-term administration. Most small mammals will not consume tablets, eat medicated food, or drink medicated water. Antibiotics are usually suspended in syrup and/or flavored in some way, and given directly PO with a syringe to be certain that the whole dose is consumed. Antibiotics for bacterial pneumonia are usually continued for at least seven days beyond a clinical cure, or a minimum of three weeks.

Nebulization therapy is an important method of getting moisture and medication into the trachea, bronchi, and small airways. Nebulizers should secrete particles between 0.5 and 3.0 micrometers (a room humidifier will not suffice). Saline nebulization alone is helpful. When patients get dehydrated, the mucociliary escalator (ME) becomes impaired. The ME functions to trap particulates and bacteria and moves them craniad by the movement of cilia, to the oropharynx, where they can be coughed up and swallowed. The mucus layer is made up of two layers—the sol, which is watery, where the cilia move, and the gel lying on top, which traps particles. If the sol layer is depleted through dehydration, the cilia become trapped in the gel layer and movement is impeded, inhibiting the escalator. Systemic fluids and airway nebulization can contribute to the effective action of the mucociliary escalator by allowing the sol layer to perform as required. Nebulization can be used to deliver antibiotics directly to the airway surface, bypassing systemic circulation and minimizing side-effects. Sometimes other agents are added: mucolytics (N-acetylcystein), or bronchodilators.* Use caution, however, when nebulizing products that were not intended for that purpose (i.e. injectable antibiotics), because some animals may respond to the medication with bronchoconstriction.

*Nebulization Mixture Example

5cc 0.9% sterile saline

1cc antibiotic (e.g. amikacin 50mg/ml, gentamicin 50mg/ml, or enrofloxacin 22.7 mg/ml)

0.5cc aminophylline 25 mg/ml

0.25cc acetylcystein 20%

There is a "blood-bronchus-barrier" which limits penetration of drugs into the airway secretions much the same way the "blood-brain-barrier" or the" blood-prostate-barrier" prevent drug penetration into those tissues. Penetration into airway secretions is important, since many bacterial airway infections remain largely on the luminal airway surface. Nebulization therapy bypasses the "blood bronchus barrier" and provides topical treatment to the airway. It is important to remember than the major function of the respiratory defenses is the removal of particulates, so nebulized drugs are efficiently removed, and only a very small portion of the administered medication reaches the lower airways. Therefore, it is also important to choose a systemic antibiotic that can penetrate the barrier, as well. Lipid-soluble compounds are better able to penetrate the barrier and reach adequate concentrations at the airway surface: metronidazole, chloramphenicol, azithromycin, tetracyclines (doxycycline), and flouroquinolones penetrate barrier better than penicillin-based antimicrobials; cephalosporins and aminoglycosides have intermediate penetration. Cough suppressants should be avoided when treating pneumonia, since the goal of treatment is to break up and eliminate airway debris and mucus. Gentle coupage (physiotherapy), frequent turning of patients, short walks, and mild to moderate exercise may help to encourage the clearance of sputum.

There are few specific therapies for viral pneumonia. Most viral diseases of rodents do not cause severe disease, but can do so in very young animals or those carrying potential secondary bacterial pathogens. Polymicrobial infections are common and, as is the case with pneumonia in most other animals, in small mammals it can involve one or more bacteria or viruses. In many instances where bacteria and virus are both isolated, bacteria are secondary invaders. Provide antibiotics to prevent or treat secondary bacterial infection, and provide supportive care measures.

Good supportive care is important to treatment success. Exotic companion mammals often present in an advanced state of disease, and may not tolerate treatment unless initially stabilized with oxygen (if indicated), fluids, warmth, and nutritional support. Oxygen supplementation should be provided when there is detectable tachypnea, dyspnea, cyanosis, open-mouth breathing, or when pulse oximeter readings fall below 94%. Oxygen can be provided in an oxygen cage for small animals. It should be humidified prior to use, and is toxic over time. The maximum inspired oxygen concentration for long term use is 40%; higher levels may be used for two days or less. Rabbits, guinea pigs, and chinchillas are "obligate nasal-breathers"; they have a long soft palate, and they only open their mouths to breathe when in extreme distress. Animals with pneumonia are usually febrile, weak, depressed, and easily become dehydrated. Maintaining normal hydration is an important key to treatment success. Supplemental fluids should be given warmed to restore hydration status and normal body temperature. Warm sterile saline or lactated Ringer's solution should be given at 25-35 ml/kg subcutaneously every 8 hours initially. Anorexia is a non-specific sign, and can be life-threatening in small mammals. If the patient is stable enough to syringe feed, oral fluids such as Rebound OES (Virbac) or Pedialyte (Abbott) at 15-20 ml/kg q 8 hrs should be given until drinking normally. For nutritional support, an appropriate hand feeding formula should be administered (e.g. Critical Care for herbivores; Carnivore Care for ferrets; Emeraid for rats) 20-30 ml/kg PO every 8 hours initially, then tapered as the patient begins to eat on his own.

Many exotic companion mammals are prey animals by nature, and are nervous in captivity. Many small mammals, especially guinea pigs, are creatures of habit and do not handle changes in routine as well as dogs and cats. Small mammals should be hospitalized in a quiet area away from cats, barking dogs, and other loud noises. Provide hide box, towel, or other shelter. Animals that are socialized and well-adapted to their environment tend to have a much better response to hospital care. Bonded pairs may need to be kept in the hospital together in order to reduce stress. Probiotics such as lactobacillus supplements (e.g. Bene Bac) have not been proven to work, but may be of benefit when treating with antibiotics.

Comments on particular species and etiologies

Rabbits

Respiratory disease in rabbits is often caused by bacterial agents: Pasteurella multocida, Bordetella bronchiseptica, Staphylococcus aureus, and many others. Reports of viral pneumonia in pet rabbits are rare. Pasteurella pneumonia can be chronic or acute; chronic disease is likely to take the form of pleuropneumonia or pericarditis, with abscesses developing in or around the lungs. Anorexia, weight loss, depression, and rapid fatigue are nonspecific signs, but in a rabbit should raise suspicion of lower respiratory tract disease. Rabbits often appear relatively normal, even with minimally functioning lungs.

Bordetella is a common inhabitant of the respiratory tract of rabbits. Its prevalence increases with age. Bordetella bronchiseptica infection risk is greatest in young rabbits and in hosts with compromised immune function. Bordetella has local-acting cytotoxic effects that impair host defenses, and may be an important predisposing factor in Pasteurella infections.

Staphlococcus aureus can be isolated from the respiratory tract of both healthy and diseased rabbits. While it is probably a secondary invader of compromised mucosa, S. aureus produces toxins that are able to block a number of host defenses. Like Pasteurella, disseminated infection can cause pneumonia and abscessation of the lungs and heart.

Antibiotics to consider for pneumonia in rabbits include chloramphenicol (30-50 mg/kg PO q 12 hr), azithromycin (15-30 mg/kg PO q 24 hr), enrofloxacin (15 mg/kg SQ [dilute 4:1 in saline], PO q 24 hr), and penicillin G benzathine/penicillin G procaine combination (80,000 IU/kg SQ q 48 hr). Discontinue or change antibiotics if soft stools develop.

Guinea pigs

Pneumonia is considered to be one of the most significant diseases affecting guinea pigs; it is the number one cause of death among guinea pigs in some surveys. Young guinea pigs are particularly at risk. Many of the organisms that cause pneumonia are acquired by guinea pigs as babies while they are still in the breeding colony, protected by maternal antibodies. Those with subclinical infection often continue to carry these pathogens, and only develop clinical disease later, when stress or concurrent illness occurs.

The course of pneumonia can vary from rapidly progressive and fatal, associated with respiratory failure and/or sepsis, or it can be a much milder presentation with lethargy subtle clinical signs. Guinea pigs are by nature very stoic and this combined with their natural tendency to hide disease means pneumonia is often advanced by the time clinical signs are noticed.

Pneumonia in guinea pigs is usually associated with opportunistic microbes. The two most important pathogens are the bacteria Bordetella bronchiseptica and Streptococcus pneumoniae. Other common bacteria include Klebsiella pneumonia, Streptobaccillus moniliformis, Staphylococcus aureus, E. coli, Pasteurella pneumotropica, Pasteurella multocida, Streptococcus zooepidemicus, Streptococcus pyogenes, Citrobacter freundii, Yersinia pseudotuberculosis, and Pseudomonas aerogenosa. Chlamydophila psittaci can also cause pneumonia, however, in guinea pigs it usually causes a mild, self-limiting conjunctivitis.

Guinea pigs may also develop viral pneumonia. Guinea pig adenovirus is can cause severe, necrotizing bronchopneumonia with high mortality. Parainfluinzavirus has also been shown to cause disease. Pneumonia in guinea pigs also can be caused by atypical organisms including Pneumocystis carinii and nematode parasites. Vitamin C should be supplemented, initially by injection 100 mg/kg subcutaneously, and then provided through hand feeding and fresh vitamin-C rich vegetables and fruit. Guinea pigs can be vaccinated against Bordetella with commercially available vaccines.

Antibiotic choices in guinea pigs include chloramphenicol (30-50 mg/kg PO q 12 hr), trimethoprim-sulfa (30-50 mg/kg PO q 12 hr), enrofloxacin (15 mg/kg SQ [dilute 4:1 in saline], PO q 24 hr), and azithromycin (15-30 mg/kg PO q 24 hr). Discontinue or change antibiotics if soft stools develop.

Chinchillas

Pneumonia in chinchillas is relatively uncommon. Affected individuals usually are immunocompromised by age, nutritional status, or husbandry-related stress (overcrowding, high humidity, poor ventilation). Pneumonia in the chinchilla tends to be chronic, resulting in ocular or nasal discharge, lymphadenopathy, dyspnea, anorexia, depression, poor hair coat, and weight loss. Likely pathogens include Pasteurella, Bordetella, Streptococcus, Klebsiella, and Pseudomonas. Viral respiratory disease of chinchillas is not reported. Antibiotic combinations may be indicated. Prevention is by correcting husbandry and reducing stress.

Antibiotic for use in chinchillas include chloramphenicol (30-50 mg/kg PO q 12 hr), trimethoprim-sulfa (30-50 mg/kg PO q 12 hr), enrofloxacin (15 mg/kg SQ [dilute 4:1 in saline], PO q 24 hr), and azithromycin (15-30 mg/kg PO q 24 hr). Discontinue or change antibiotics if soft stools develop.

Ferrets

Pneumonia is uncommon in ferrets. Viral causes in ferrets include canine distemper virus and influenza virus. Bacterial pneumonia in ferrets is typically suppurative, affecting the bronchial airways, the lung lobes, or both. Reported primary bacterial that cause pneumonia in ferrets are Streptococcus zooepidemicus, S. pneumoniae, and groups C and G streptococci. Gram negative bacterial pneumonia has been documented with Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bordetella bronchiseptica and Listeria monocytogenes. The unicellular fungal organism Pneumocystis carinii is also known to infect the lung of ferrets, however pulmonary mycoses such as blastomycosis and coccidiomycosis are uncommon in pet ferrets.

Antibiotic therapy options for use in ferrets include amoxicillin (20 mg/kg PO q 12 hr), amoxicillin/clavulanate (20 mg/kg PO q 12 hr), enrofloxacin (15 mg/kg SQ [dilute 4:1 in saline], PO q 24 hr), chloramphenicol (30-50 mg/kg PO q 12 hr), and trimethoprim-sulfa (30 mg/kg PO q 12 hr).

Rats

Respiratory disease caused by infectious agents is the most common health problem in rats. Three major respiratory pathogens cause overt clinical disease: Mycoplasma pulmonis, Streptococcus pneumoniae, and Corynebacterium kutscheri. Two additional bacteria, cilia-associated respiratory (CAR) bacillus and Haemophilus spp, and three viruses, Sendai virus (a parainfluenza virus), pneumonia virus of mice (a paramyxovirus), and rat respiratory virus (a hantavirus), are minor respiratory pathogens that by themselves rarely cause overt disease. A coronavirus of rats, sialodacryoadenitis (SDA) virus, is highly infectious and causes overt disease confined to the eyes, ears, nose and throat. These minor respiratory pathogens interact synergistically as copathogens with the major respiratory pathogens to produce two major clinical syndromes: chronic respiratory disease (CRD) and bacterial pneumonia.

CRD is also known as murine respiratory mycoplasmosis because M. pulmonis is the major component of the disease. Clinical signs are highly variable, and initial infection occurs without any clinical signs. Both upper and lower respiratory tracts are involved. Signs may include snuffling, nasal discharge, red tears, rapid respiration, weight loss, hunched posture, ruffled coat, and head tilt. CRD varies greatly in disease expression because of many environmental, host, and organismal factors that influence the host-pathogen relationship: cage ammonia levels, concurrent infection (Sendai virus, SDA virus, pneumonia virus of mice, rat respiratory virus, CAR bacillus), genetic susceptibility of host, virulence of Mycoplasma strain, and vitamin A or E deficiency. Antibiotic therapy (enrofloxacin/doxycycline combination, Azithromycin) will not cure CRD, but may alleviate clinical signs; affected animals typically have persistent M. pulmonis infection. Removing cage litter and replacing with clean paper daily may help reduce ammonia levels. Bronchodilators and short-acting corticosteroids are also sometimes helpful.

Bacterial pneumonia, the other major clinical syndrome, is nearly always caused by Streptococcus pneumoniae, usually with the help of M. pulmonis, Sendai virus, or CAR bacillus coinfection. Corynebacterium kutscheri causes pneumonia only in severely immunosuppressed individuals, and is rare in pet rats. Pneumonia caused by S. pneumoniae can be of sudden onset. Young rats are more severely affected than older ones, and the only symptom may be sudden death. Signs in mature rats include dyspnea, snuffling, abdominal breathing, and purulent nasal exudate (nares and front paws). Tentative diagnosis can be made by a Gram stain of this exudate (will reveal numerous gram-positive diplococci). Because severe bacteremia and multiorgan abscesses/infarctions are common; antibiotic treatment must be aggressive. Beta-lactamase-resistant penicillins are recommended.

Recommended antibiotics for rats include azithromycin (15-30 mg/kg PO q 24 hr), enrofloxacin (15 mg/kg PO q 24 hr), chloramphenicol (30-50 mg/kg PO q 12 hr), doxycycline (5 mg/kg PO q 12 hr), amoxicillin (20 mg/kg PO q 12 hr), amoxicillin/clavulanate (15 mg/kg PO q 12 hr), tylosin (10 mg/kg PO q 12-24 hr).

Prognosis

The prognosis for pneumonia varies by etiology and severity of the disease at presentation. Pneumonia is often difficult to reverse. Affected animals often have underlying immunodeficiency and tend to decline rather than recover. Prognosis becomes guarded once there is obvious respiratory distress.

Prevention

Many of the causes of pneumonia in small exotic mammals are husbandry related and corrections need to be made in order to prevent disease. Keeping a closed colony will ensure that new diseases are not introduced. New arrivals should go into quarantine, and they should not be mixed with the general population until there has been a reasonable quarantine period, usually 30-90 days.

References

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Hrapkiewicz K, Medina L. Clinical Laboratory Animal Medicine: An Introduction, Third Edition. Blackwell Publishing: Ames, Iowa, 2007.

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Cohn LA. Infectious Disease of the Airways. Proc of the North Am Vet Conf. 2005:1049-1050

Harkness JE, Wagner JE. The Biology and Medicine of Rabbits and Rodents, Fourth Edition. Williams and Wilkins: Media, PA. 1995

Cohn LA. How I treat severe bacterial pneumonia. Proc of the North Am Vet Conf. 2005:1056-1057

Cohn LA. Aerosol Delivery of Medications to Small Animals. Proc of the North Am Vet Conf. 2006:183-1284