Definition

An infection and inflammatory process of the bronchioles, alveolar spaces, and interstitial tissue of the lung parenchyma.

Clinical Signs

May observe any of the following:

• Porphyrin (rust colored) stains about nose and/or eyes
• Wheezing
• Small coughs
• Congestion
• Sneezing
• Increase in rapid breathing
• Labored breathing (use of abdominal muscles to breathe)
• Gasping
• Hunched posturing
• Piloerection (ruffled, bristled fur)
• Lethargy
• Poor or loss of appetite
• Panic type movement related to inability to get enough oxygen into lungs
• Changes in behavior due to illness (e.g., nipping, biting, avoidance)
• Feet and tail tip cyanosis (as oxygen in blood decreases) may be a late sign

Other Clinical Signs

• May hear Rales (crackling, often sounds like Rice Krispies® in milk, or a bubbling sound) when listening to chest with stethoscope.
• May hear Rhonchi (loud rumbling indicating presence of thick fluid) with or without a stethoscope.
• If significant consolidation present in lungs breath sounds may be diminished even when listening with a stethoscope.
• The presence of head tilt if otitis media/interna (ear infection) is present.
• The presence of secondary illness (e.g., tumors).

Etiology

Pneumonia is the result of primary or secondary infections by organisms such as bacteria, viruses, or fungal and parasitic infections. These organisms may reach the lungs through droplet (aerosolization), contact, or hematogenous (in the blood) spread. Pneumonia can also result through the inhalation of chemical irritants, or due to the aspiration of food or of drugs being administered.

The inflammation, swelling, congestion or consolidation of the airways and lungs contributed to by these organisms, and irritants, decreases the ability to breathe effectively.

There are several classifications or types of pneumonia, such as focal, lobar, or Bronchopneumonia. Determination of the type is based on the area and pattern of distribution found in the lobes of the lungs or bronchi. It can be further described based on the pathophysiology of the various organisms that cause infection and or inflammation.

In bacterial infections, pneumonia is believed to be initiated when there is a change, alteration, or increase in the number of organisms normally residing in the nasopharynx that results in the overwhelming of the host’s immune system, or where normal defenses fail to protect the respiratory tree from filtering the organisms from the lungs.

In rats, where severe respiratory disease or pneumonia is present, more than one organism or infection is involved. The most prevalent and naturally occurring organism in the rat that contributes to the development of pneumonia is the bacterium, Mycoplasma pulmonis.

Other bacteria that contribute to the development of pneumonia in association with Mycoplasma pulmonis are Ciliated-Associated Respiratory (CAR) Bacillus (renamed filobacterium rodentium in 2016), Corynebacterium kutscheri, Streptococcus pneumoniae, Pasturella pneumotropica, Bordetella bronchiseptica, and Klebsiella pnuemoniae (klebsiella is a part of normal gut flora that under certain conditions result in an opportunistic infection).

Viruses such as SDA (sialodacryoadenitis) and Sendai (SeV) can also act in conjunction with Mycoplasma overwhelming the immune system and leading to the development of pneumonia.

In rats that are severely immunocompromised, pneumonia may be further complicated by the presence of opportunistic, species-specific strains of a fungal or protozoan organism such as Pneumocystis carinii and Pneumocystis wakefieldiae.

In aspiration pneumonia where food or liquids have entered the lungs, atelectasis (an airless lung) or pulmonary edema and hemorrhage can occur, especially if the substance aspirated is very acidic.

Lastly, some of the complications occurring in severe cases of pneumonia can be:

• Abscesses, in the lung tissue such as in aspiration pneumonia.
• Abscesses and empyema (pus filled fluid), or pus filled lumina in pneumonias with mixed organisms such as klebsiella, CAR bacillus (filobacterium rodentium), and Mycoplasma. Empyema in Pneumocystis carinii and Pneumocystis wakefieldiae.
• Bacteremia, where the infection has spread via blood, particularly in those pneumonias caused by Gram-negative organisms.
• Pleural effusion, when the small amount of fluid normally present that lubricates the pleural membranes starts to build up.

Figure

Photos of pneumonia in lung tissue of rat (*note: very graphic)

• Fig. 1: Photos of fibrotic, abscessed lungs, taken on necropsy from a rat with pneumonia due to Mycoplasmosis.

Diagnostics

Radiography exam of lungs may show the following:

• Mycoplasma: films in early stage may appear clear. Later may become patchy in lower lobes and show infiltrates in alveolar walls.
• Viral pneumonias: films may show infiltrates in the bronchi leading to consolidation
• Pneumocystis carinii and Pneumocystis wakefieldiae: diffuse, bilateral interstitial pneumonia
• Fungal pneumonias: consolidation, cavitation, and empyema

ELISA test. *Note: bacterial cultures may result in false negative for mycoplasma.*

Complete blood count with low WBC may indicate mycoplasma or viral illness.

Gram stain.

Blood cultures to rule out bacteremia.

Treatment

See the Rat Medication Guide for a listing of the following drugs, dosages, and use.

Giving Antimicrobials

Give broad-spectrum antibiotics, or if culture and sensitivity results are known, give specific antibiotic.

Preferred and alternate antimicrobial therapy in humans as recommended by CURRENT Medical Diagnosis & Treatment 2002, 41st Edition, Edited by: Lawrence M. Tierney,Jr.,MD.; Stephen J. McPhee,MD.; Maxine A. Papadakis,MD., for the following listed identified organisms. These antimicrobials are also helpful in rats:

• Streptococcus pneumoniae
  • Preferred: Amoxicillin
  • Alternatives: Macrolides, cephalosporins, doxycycline, fluoroquinolones, or clindamycin
• Klebsiella
  • Preferred: Third-generation cephalosporin. For severe infections add aminoglycoside
  • Alternatives: Beta-lactam/beta-lactamase inhibitor, or a fluoroquinolone
• Mycoplasma
  • Preferred: Doxycycline or erythromycin
  • Alternative: Clarithromycin; azithromycin, or a fluoroquinolone

The choice of treatment in Pneumocystis carinii and Pneumocystis wakefieldiae pneumonia is TMP/SMX (trimethoprim/sulfamethoxazole), along with a corticosteroid such as prednisone.

A treatment regimen for moderate, serious and advanced respiratory illness

The following treatment regimen for use in rats with moderate to advanced lung infection, or more serious respiratory illness with Mycoplasma as the suspected agent, is recommended by Dr. Michael Hutchinson, DVM; Animal General, Cranberry Township, PA., and is based on his experience treating rats and current literature:

Doxycycline 10 mg/kg, q12hr, PO (oral) for 10 to 30 days
Enrofloxacin (Baytril) 15 mg/kg, q12hr, PO (oral) for 10 to 30 days

Nebulization for 15 minutes, 2 to 3 times a day, for 14 days, with the following mixture:
8 mL sterile saline
0.5 mL Gentocin injectable 100 mg/mL
0.5 mL Albuterol 0.083% Inhalation
*Note: excess mixture for nebulization can be refrigerated for up to 3 days.

Dexamethasone 1 mg/lb BID, then weaned down as follows:
1 mg/lb BID injectable or PO (oral) for 3 days
1 mg/lb SID for 3 days
0.5 mg/lb SID for 3 days
0.5 mg/lb orally every other day, three doses

Other veterinary recommended dosing and reduction schedules for dexamethasone may also be used.

Additional antimicrobial choices

Besides the above recommended antimicrobial choices, and treatment regimens for pneumonia, the following drug choices may also be used:

• Tetracycline
• Cefadroxil (for secondary infections – best used in combination with Gentocin)
• Chloramphenicol
• Enrofloxacin (Baytril) and Doxycycline simultaneously.

An aminoglycoside: (such as amikacin or gentamicin) in combination with Cefadroxil.

*Note: Combination of drugs given simultaneously like enrofloxacin (Baytril) + doxycycline, azithromycin + doxycycline, clarithromycin + doxycycline, have been found to be very effective in rats.

The choice of an antibiotic/antimicrobial or combination can be more effective when selected based on culture and sensitivity of organism.

Bronchodilators and Corticosteroids In Therapy

The use of bronchodilators such as Aminophylline/Theophylline (given orally), or Albuterol (nebulized in normal or a 7% hypertonic saline which helps to break down mucus), may be added to help relax the smooth muscle and dilate the bronchi in the lungs to aid breathing.

Nebulized treatments involving antibiotics (e.g., fluoroquinolones: enrofloxacin (Baytril), aminoglycosides: amikacin or gentamicin (Gentocin), or a macrolide: tylosin), may be prescribed for rats that have difficulty taking the medications orally. Medications for nebulization need to be diluted in normal saline unless otherwise directed by the veterinarian.
Ratio for dilution of medication per normal saline recommended as follows:
Enrofloxacin(Baytril) 10 mg to 1 mL normal saline. ³
Gentamicin 5 mg to 1 mL normal saline. ³
All others a 1 to 10 solution. ³

For the nebulization formula using Gentocin and Albuterol in a treatment regimen, recommended by Dr. Michael Hutchinson, see above in the section: A treatment regimen for serious and advanced respiratory illness.
See Nursing Care below for more information on nebulizers.

In addition, a corticosteroid such as prednisone or dexamethasone may be added to the treatment regimen to help reduce inflammation of the bronchi and bronchioles in order to help the rat breathe easier.

For dexamethasone therapy, in a treatment regimen, for moderate to advanced lung infection, or more serious respiratory illness, see doses suggested above by Dr. Michael Hutchinson, listed under: A treatment regimen for moderate, serious and advanced respiratory illness.

*Note*
Dexamethasone has been shown, in the controlled studies cited below, to reduce plasma leakage, resolve Mycoplasma induced inflammation, and also reduce the number of Mycoplasma organisms even when used as the only therapy.

• Am. J. Respir. Crit. Care Med., Vol 150, No. 5, Nov 1994, 1391-1401; Dexamethasone and oxytetracycline reverse the potentiation of neurogenic inflammation in airways of rats with Mycoplasma pulmonis infection; J.J. Bowden, TR Schoeb, J. R. Lindsey and D.M. McDonald; Cardiovascular Research Institute and Department of Anatomy, UCSF.
• Am. J. Respir. Crit. Care Med., Vol 164, No. 10 Nov 2001, S39-S45; Angiogenesis and Remodeling of Airway Vasculature in Chronic Inflammation; Donald M. McDonald; Cardiovascular Research Institute and Department of Anatomy, UCSF.

It should be noted that based on dexamethasone’s long biologic activity of action it is advised to use the lowest dose for condition being treated which achieves the desired effect.

Length of Treatment and Maintenance

The prognosis for rats with pneumonia is very grave, and will require long term antibiotic therapy.

Due to the belief that Mycoplasma is probably never eliminated entirely from the airways in rats, and because it is a contributor to the development of pneumonia, it often becomes necessary to use pulse antibiotic therapy (long term, intermittent, dosing), or a continuing maintenance schedule of antibiotics for rats with chronic Mycoplasmosis.

Dr. Hutchinson has had some success with the long term, maintenance dosing of enrofloxacin 15 mg/kg, q12hr, PO (or in the presence of renal disease 8 mg/kg to 10 mg/kg, q12hr, PO) in conjunction with doxycycline 5 mg/kg to 10 mg/kg, q12hr, and based on his experience no discernible side effects have been noted.

For appropriate dosing in pulse antibiotic therapy for chronic illness, discuss with veterinarian.

Remember, it is important to give all doses of a prescribed medication even if clinical signs seem to lessen or disappear. If clinical signs seem to worsen or no improvement is seen, do not stop medication. Contact the veterinarian to discuss changes in medication.

Treatment in Pregnant and nursing does, and rats under 4 months of age:

Recommended antimicrobials are azithromycin (Zithromax) or tylosin (Tylan).
*Note: The use of enrofloxacin (Baytril) and doxycycline is not recommended for initial treatment in the pregnant and nursing Doe, or rats under 4 months of age.

However, where symptoms are progressing, these stronger antimicrobials may be necessary. The benefits of using a fluoroquinolone (such as enrofloxacin), doxycycline, or a combination of drugs, may outweigh the risks. Discuss with a veterinarian.

Additional Therapy

Keeping the rat adequately hydrated will prevent dehydration and help to liquefy and loosen secretions making it easier to remove from the lungs. Providing higher caloric foods and encouraging the rat to eat will help maintain strength to combat the effects of illness and to keep the gut mobile. Rats that are ill frequently tend to reduce intake of water and food, so it becomes important to monitor this.

If respiratory distress is present (gasping, or laboring to breathe), and/or gums, ears, feet, or tail appear to be cyanotic (blue tinge) or are very pale, Oxygen therapy should be initiated.

Nursing Care

• Use recommended nebulizers with a particle size of 0.5-5 micrometer when nebulizing medication in rats. Nebulizers with a larger particle size that are used for humans or small animals will not be as effective in delivering the medication to the rat.

  Nebulized treatment may take from 10 to 30 minutes depending on the volume to be given, and how well the rat tolerates the treatment. Observe for any signs of increased agitation or intolerance. If noted stop treatment and contact vet.

  Sites for purchasing nebulizers:

  • https://www.lambertvetsupply.com/medical-supplies-pet-respiratory.html
  • https://www.allvetsupply.com/nebulizer.html
    

    Examples of nebulizer set up:

  • https://www.rmca.org/Articles/albuterol.htm
  • See also: Fig. 3: of First Aid Supplies located in the Rat Health section of the Rat Guide.

• Provide humidification with a humidifier, or stay with rat in a closed cool misted bathroom for 10-to-15-minute intervals, to soothe inflamed irritated breathing passages, and loosen secretions.
  • *Note: cool mist humidifiers or vaporizers may be of more comfort to the rat than steam or heated mist if there is congestion with increased mucus production and swelling of airways.
  • It is important to remember to clean humidifiers or vaporizers following each use to prevent growth of organisms from standing water.
• When antibiotics are given remember to include Bene-Bac or yogurt with live active cultures, to prevent normal gut flora from being destroyed by the antibiotics.
• Provide additional warmth to maintain body temperature within normal limits. It is essential that the rat does not become overheated or dehydrated. The rat should also be able to move away from the heat source if it becomes uncomfortable. If the rat is unconscious or immobile extreme care must be taken to keep the heat low and stable.
  • You can use an isothermic product that is heated in the microwave such as SnuggleSafe®. Make sure to follow the product directions carefully and wrap in a towel before placing in the cage. SnuggleSafe® will provide heat for 12 hours before needing to be reheated. Other similar types of products may vary in re-heat time. Check directions for individual product.
  • If using a heating pad (good for long term use) use only the low heat setting, put a thick towel in between the pad and the cage bottom, and place beneath a corner of the cage.
  • If none of these options are available you can use a plastic bottle filled with hot water, and wrapped in a towel, in the corner of the cage.
• Assess nutritional status:
  • Provide additional nutritional supplement, such as soy baby formula, Ensure, Boost, NutriCal paste (for dogs and cats found in pet store), mashed avocado, and baby foods. If the rat is not willing to eat on its own, provide feeding in an oral syringe every 2 hours being careful to prevent aspiration. Providing small amounts of food in this fashion will help to promote intestinal motility during illness. Also, because so much energy is being expended to breathe in pneumonia, the added dietary supplements will keep up the rat’s strength.
    It is also helpful to include a multi-vitamin supplement (can be found in pet store) if food intake is poor.
  • Place food and water close and on same level with the rat to prevent from exerting itself. Over exertion in a rat who already has difficulty breathing will prevent the rat from wanting to eat.
  • Provide fluids to prevent dehydration. If the rat is willing to drink on its own or by syringe (using needleless syringe), the following are suggested: fresh water, or a glucose mixture of 3 teaspoons of honey in 1 pint of warm water (be sure water is warm enough to dissolve honey and then cooled just enough so as not to burn rat’s mouth), or Jell-O water, or electrolyte replacement drinks such as Pedialyte or Gatorade which can be found in local grocery stores.
  • Please note that Pedialyte is only good refrigerated for 24 hours after opened, but can be frozen as ice cubes and thawed as needed.
  • Care should be taken to prevent aspiration when giving fluids with an oral syringe. If the rat is not drinking discuss providing warmed SQ fluids with your vet.
• If possible, let rat remain with cage/litter mate for additional comfort, unless there is competition for food or undue stress.
• Contact veterinarian to discuss changes in treatment options if condition does not seem to be improving.
• In the event condition continues to deteriorate and precludes further comfort or quality, discuss euthanasia with veterinarian.

Outcome

• Airway remains clear
• Nutrition level adequate
• Comfort and quality of life maintained
• Emotional support for those having to consider euthanasia for their rat

Prevention

• Early treatment of upper respiratory symptoms as appropriate.
• Prevent ammonia build up by maintaining clean cage environment.
• Use dust free litter. Do not use pine or cedar due to phenols present in shavings.
• Locate cage or housing in draft free area.
• Quarantine all new rats for a minimum of two weeks prior to introducing into existing colony.
• Breeders should establish a system to record and track diagnosis and treatment in their lines.
• Do not smoke around your rats!

Consultation

• Michael Hutchinson, DVM
  Animal General
  Cranberry Township, PA.
• Thomas M. Donnelly, DVM, DACLAM
  Warren Institute | 712 Kitchawan Rd
  Ossining NY 10562-1118 USA

References

1. Donnelly TM. Symposium Konijnen & Knaagdieren (Rabbit & Rodents Symposium). Held November 27-29, 2008, Burgers Zoo, Arnhem, Netherlands. Proveto, Utrecht, Netherlands (2008). What are treatment options for Mycoplasma pulmonis in rats?
2. Cassell, G. (n.d.). Infectious Causes of Chronic Inflammatory Diseases and Cancer. Retrieved March 18, 2008, from http://www.emergingworlds.com/pro_article.cfm?link=Infectious_Causes_of_Chronic_Inflammatory_Diseases_and_Cancer.htm.
3. Manuelidis, E., & Thomas, L. (1973). Occlusion of brain capillaries by endothelial swelling in mycoplasma infections. Proc Natl Acad Sci U S A, 70(3), 706-9. Retrieved October 12, 2010, from https://www.jstor.org/stable/62340