Definition

Mycoplasma : a bacterium lacking a cell wall.

Mycoplasma pulmonis: a commensal species-specific organism carried by nearly all pet rats, and which colonizes the luminal surface of the respiratory epithelium.

Murine Mycoplasmosis: a disease entity caused by Mycoplasma pulmonis, and which is responsible for respiratory and genital infections in pet rats.

Clinical Signs

Clinical signs vary depending on virulence, and the site of infection. Also, because the course of disease caused by mycoplasma is chronic rather than fulminant signs of illness tend to increase as the rat ages. Any of the following clinical signs may be present:

Respiratory

• In upper respiratory illness signs may range from clinically silent to early signs of sneezing, snuffling, squinting, and porphyrin staining (rust colored) around eyes and nose. Inner ear infection may also be seen with signs of head tilt, rolling, and face or ear rubbing.

• In lower infection as disease advances along the respiratory passages causing bronchiolitis, bronchiectasis and bronchopneumonia, the signs may include rattling moist breath sounds, labored breathing, gasping, chattering, and coughing. Additional signs of illness are: hunched posturing with rough coat, weight loss, and changes in behavior due to illness (e.g., nipping, biting, avoidance).

• *Note: it is important to mention that either upper respiratory signs and / or lower respiratory signs may be seen in CRD (chronic respiratory disease) involving mycoplasma.

Genital

• In genital infections, the organism may be a cause of pyometra or purulent endometritis (inflammation of the lining of the uterus), salpingitis (inflammation of fallopian tubes), and perioophoritis (inflammation of ovaries). The signs may range from clinically inapparent symptoms to abdominal distention or signs of blood-tinged uterine discharge. Hematuria (blood-tinged urine) from a concurrent urinary tract infection may also be present. Where chronic uterine infections are attributed to Mycoplasma, decreased litter sizes may also result.

Etiology

The genus mycoplasma is a very small (smaller than some viruses), pleomorphic (neither cocci nor rod shape) bacterium, from the family of Mycoplasmataceae. There are over 95 different mycoplasma (Peirce, 1998) species that are distributed in nature. These also include several commensals that can be found in the mouth and genitourinary tract of humans and mammals (Harvey, Rouse, & Strohl, 2001).

Mycoplasma differs from other bacteria in that they lack a cell wall. They are, instead, enclosed by a simple cell membrane made of a lipid and protein bilayer. They are neither Gram-positive nor Gram-negative (Gladwin & Trattler, 2004). Because of this it is easy to see why some antibiotics like the penicillins and cephalosporins that are designed to inhibit cell wall synthesis are ineffective against mycoplasma, and why those antibiotics that inhibit protein synthesis at different stages of prokaryotic mRNA translation such as: aminoglycosides (e.g., gentamicin, amikacin), macrolides (e.g. azithromycin, erythromycin at bactericidal doses), and the tetracyclines (e.g., doxycycline, minocycline), as well as those antibiotics that disable bacterial enzymes such as the fluoroquinolones (e.g., enrofloxacin), are more effective against mycoplasma.

Mycoplasma that are pathogenic have an affinity for the respiratory tract, and urogenital tracts, and with some species of mycoplasma for articular cartilage. Those species that cause disease in animals and humans are able to colonize epithelial cell surfaces and attach to certain receptors on the host’s cell membrane. The ability of mycoplasma to have a cell membrane to cell membrane attachment with its host allows the organism to expose the host’s cells to peroxide metabolites and superoxide radicals (Suckow, Weisbroth, & Franklin, 2005). The disease course caused by mycoplasma tends to be chronic (over lifetime) rather than sudden.

The mycoplasma organism carried principally by rats and mice is Mycoplasma pulmonis. The organism is host specific and highly contagious among rats and mice being transmitted via direct contact between Doe and pups through intrauterine or sexual transfer, or via aerosol transmission over very short distances. It is the species M. pulmonis that is among the cause of chronic disease in rats and mice and is the etiology of Murine Respiratory Mycoplasmosis and Murine Genital Mycoplasmosis. Its ability to cause disease in these animals is very similar to the way Mycoplasma pneumoniae causes disease in humans.

M. pulmonis is non-pathogenic to humans, and even though it can be carried by humans in the nasal passages for short periods of time, you yourself cannot be infected. In addition, because mycoplasmas are very fragile organisms and rarely remain viable outside the host for long periods makes it nearly impossible for it to be transmitted through fomites (e.g., equipment in cages, or carried on clothing). However, how rapidly transmission occurs may vary among rats within a colony based on husbandry practices, environment, and how many rats within the colony.

Murine Mycoplasmosis (encompassing Murine Respiratory Mycoplasmosis and Murine Genital Mycoplasmosis) could be considered as a syndrome. What this means is that although the etiology is Mycoplasma pulmonis, the disease is frequently initiated, accompanied, or exacerbated by other bacterial infections that can act synergistically (act together) such as: CAR bacillus (Filobacterium rodentium), and Corynebacterium kutscheri, as well as viral infections like SDA (Sialodacryoadenitis) and Sendai (SeV), with recognizable clinical signs.

Murine respiratory mycoplasmosis is a slowly developing, chronic respiratory, disease process. Research indicates that while M. pulmonis has been shown to colonize ciliated epithelium of the upper and lower respiratory tracts, in rat pups, the small, microscopic lesions may not be detected until the rat reaches 2–6 months of age, and the chronic obstructive lung disease that results may not show until the rat is 12–18 months (Cassell, 2008).

Because the disease is chronic rather than sudden, animals that are older, immunocompromised, or that are susceptible, will often experience more severe signs of the illness.

Those factors that may contribute to the exacerbation of disease:

• Rats that are stressed
• Rats with secondary illnesses
• Over-crowding in cages
• Poor ventilation of the animal’s habitat that results in ammonia buildup from urine and feces
• Use of bedding or litter that contains phenols (e.g., pine and cedar)

*Note: It is reported (Barthold & Percy, 2001) that two other murine mycoplasmas, M. arthritidis (causing “arthritis”), and M. neurolyticum (causing “rolling disease”; or neurological signs in mice and rats²) appear to have antigenic heterogenecity (cross reacts) with M. pulmonis. The report further indicates that both strains have been isolated from the respiratory tract and middle ear, but that they do not appear to be a cause of clinical disease in rats.

To date, Mycoplasma pulmonis appears to remain the only significant species of Mycoplasma that is the cause of disease in rats.

While Mycoplasmosis cannot be effectively cured, at this point in time, responsible care and early persistent treatment of clinical signs can allow the animal to live a longer comfortable life.

Figures

Case Histories of Mycoplasmosis

• Fig 1: Renda Lynn’s case history and necropsy photos showing lung abscess present with mycoplasma (graphic).
• For lung tissue visualization in advanced Mycoplasmosis, see: Fig. 1: of Pneumonia in the Rat Health Guide.

Diagnostics

Based on history and findings.

Enzyme-linked immunosorbent assay (ELISA)

PCR assay (polymerase chain reaction assay measures the presence, or the amount, of DNA or RNA of an organism or virus that is in blood or tissue)

Treatment

The following listed treatments are those that have been successfully used in rats to control clinical signs of respiratory illness attributed to mycoplasmosis. For more information on the individual drugs, their dosages and usage see the Rat Medication Guide.

For mild upper respiratory illness or rhinitis, one of the following antibiotics such as:
Tylosin or the tetracyclines (e.g., tetracycline, doxycycline, or minocycline) or enrofloxacin, may be sufficient to control mild symptoms. In addition, the veterinarian based on assessment may choose to add a non-steroidal anti-inflammatory medication such as Metacam to reduce sinus inflammation where warranted.

However, if clinical signs become chronic or more serious with lung involvement the use of an additional antimicrobial, along with nebulization treatments, and the use of a corticosteroid may be required.

For treatment regimens see the section below on: Early or mild illness, or the section on: Moderate to Advanced or more difficult to treat illness.

Early or mild illness

The following medications for use in rats with early or mild infection suspected to have Mycoplasma as the pathogen, are recommended by Dr. Michael Hutchinson, DVM; Animal General, Cranberry Township, PA., and are based on his experience treating rats and current literature:

Enrofloxacin (Baytril) 15 mg/kg, q12hr, PO (oral) for 10 to 30 days
or
Doxycycline 5 mg/kg, q12h, PO (oral) for 10 to 30 days

If not responding within a reasonable time frame: give both enrofloxacin and doxycycline at the above doses for 10 to 30 days

If still not responding within a reasonable time frame continue the meds as described, and add nebulization with the following mixture:

Nebulize 15 minutes, 2 to 3 times a day, for 14 days
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.

If mild lung involvement is present, and the animal is not responding to antibiotics or nebulization, add dexamethasone at the following dosage schedule:

Dexamethasone at 0.5 mg/lb can be added to the treatment regimen, weaning down as follows:

0.5 mg/lb BID injectable or PO (oral) for 3 days
0.5 mg/lb SID for 3 days
0.25 mg/lb SID for 3 days
0.25 mg/lb orally every other day, three doses

Moderate to Advanced or more difficult to treat chronic illness

If no response or poor response to one of the above medications, or if illness or symptoms advance to include middle to inner ear infection or more serious lower respiratory infections medications such as: azithromycin (Zithromax), chloramphenicol, or combination therapy such as enrofloxacin (Baytril) plus doxycycline, azithromycin (Zithromax) plus doxycycline, or the addition of an aminoglycoside (like gentamicin), can be instituted.

You will note that enrofloxacin (a bactericidal antibiotic) plus doxycycline (a bacteriostatic antibiotic) are listed as one of the combination’s to be used in mycoplasmosis infection. Normally bactericidal agents and bacteriostatic agents are not used in combination. However, their efficacy in controlling clinical signs of illness, in rats, due to mycoplasmosis has been documented.

The following treatment regimen, for moderate, advanced or more serious difficult to treat respiratory illness with Mycoplasma as the suspected agent, has been used with great success by Dr. Michael Hutchinson:

Enrofloxacin (Baytril) 15 mg/kg, q12hr, PO (oral) for 10 to 30 days
Doxycycline 10 mg/kg, q12hr, PO (oral) for 10 to 30 days
Nebulize for 15 minutes, 2 to 3 times a day, for 14 days, with the following mixture:
8 mL sterile saline
0.5 mL gentamicin 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.

Use of Bronchodilators and Corticosteroids In Therapy

The use of bronchodilators such as Aminophylline/Theophylline (oral or injectable) ¹, or Albuterol (nebulized in normal or a 7% hypertonic saline which helps to break down mucus) may be added to the treatment regimen, when needed, to help relax the smooth muscle and dilate the bronchi in the lungs to aid breathing ¹.

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.
The following are recommended ratios for dilution of those medications in normal saline:
Enrofloxacin(Baytril) 10 mg to 1 mL normal saline. ³
Gentamicin (Gentocin) 5 mg to 1 mL normal saline. ³
All others a 1 to 10 solution. ³

For the nebulization formula using gentamicin and Albuterol, in a treatment regimen, recommended by Dr. Michael Hutchinson, see above in sections: Early or mild illness or Moderate to Advanced or more difficult to treat illness. For further information on nebulizers or how to nebulize see under Nursing Care.

Corticosteroids 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 either moderate or serious Mycoplasma based respiratory illness see doses suggested above by Dr. Michael Hutchinson.

*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.

• Bowden, J., Schoeb, T., Lindsey, J., & McDonald, D. (1994). Dexamethasone and oxytetracycline reverse the potentiation of neurogenic inflammation in airways of rats with Mycoplasma pulmonis infection. Am. J. Respir. Crit. Care Med., 150(5), 1391-1401.
• McDonald, D. (2001). Angiogenesis and Remodeling of Airway Vasculature in Chronic Inflammation. Am. J. Respir. Crit. Care Med., 164(10), S39-S45.

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

Because Mycoplasma is probably never eliminated entirely from the airways, in chronic respiratory disease involving mycoplasma, it often becomes necessary to extend antibiotic treatment 6 to 8 weeks where the antibiotics used are controlling the clinical signs, and then continuing a maintenance schedule at reduced dose.¹
Pulse antibiotic therapy (long term, intermittent, dosing) may also be a consideration, for rats, where chronic Mycoplasmosis is controlled while on antibiotics.

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) in conjunction with doxycycline 5 mg/kg to 10 mg/kg, q12hr, PO, 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.

*Note: it is important to complete the medication treatment or regimen prescribed. However, if the rat shows no improvement within five days of starting treatment, or should the rat’s condition worsen at any point during treatment, see a veterinarian to discuss alternative antimicrobial or appropriate combination drug therapy.

It is also important to give the correct dose of the medication, to not skip doses, and to give for the prescribed length of time in order to prevent resistance.

Additional treatments:

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.

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.

For more information on the treatment and therapies in advanced Mycoplasmosis where pneumonia, otitis media/interna is involved, or where genital or urinary tract infections are present, see the following located in the Rat Health Guide section of the Rat Guide:

• Pneumonia
• Otitis
• Pyometra

Treatment in pregnant and nursing Does, and rats less than 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 less than 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.

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 or heated mist bathroom for 10 to 15 minute intervals, to soothe 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.
• If 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.
• 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 needless 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. Include 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 needless 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 veterinarian.
• 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 in the event the condition does not seem to be improving. If condition continues to deteriorate, and precludes further comfort or quality, discuss euthanasia with veterinarian.

Outcome

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

Prevention

To date, elimination of mycoplasma is virtually impossible. Controlled Research Labs have through cesarean derivation, and strict barrier maintenance, been able to reduce infection focusing on mycoplasma free rats for breeding.

For the typical pet rat owner, the focus is on suppression of clinical signs and symptoms. This can be accomplished to some extent by doing the following:

• Breeders focusing on breeding from mycoplasma resistant rats.
• Early treatment of symptoms as appropriate.
• Good husbandry by preventing the buildup of ammonia from urine and feces, in cages, will help reduce severity of symptoms. Be sure to rinse cages, and cage equipment, with clean water following use of recommended cage cleaning agents, and dry well before returning rats to their cage.
• The use of dust and phenol free bedding and litter (e.g., found in some types of cedar and pine litters) will help reduce clinical symptoms.
• Locate cage or housing in draft free area.
• Refrain from smoking or the burning of candles around or near rats.
• Avoid the use of fabric softeners, and scented detergents or soaps when cleaning rat’s bedding.
• Quarantine all new rats for a minimum of two weeks prior to introducing into existing colony.
• 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