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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:

In upper respiratory disease, 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.
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).

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 approximately 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).

Mycoplasmas differ 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, and why those antibiotics that inhibit protein synthesis such as aminoglycosides, erythromycin (bacteriocidal doses), and the tetracyclines (which includes doxycycline), as well as those antibiotics that intefere with nucleic acid metabolism like the fluoroquinolones 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 life time) 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 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; eg: 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) is often referred to 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 such as CAR bacillus, and Corynebacterium kutscheri, as well as viral infections like SDA (Sialodacryoadenitis) and Sendai virus.

Murine mycoplasmosis is a slowly developing, chronic 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 to 6 months of age, and the obstructive lung disease that results may not show until the rat is 12-18 months (Cassell).
Because the disease is chronic rather than sudden, animals that are older, immunosuppressed, 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 including 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) 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 can not 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

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

Diagnostics

Based on history and findings.

Enzyme-linked immunosorbent assay (ELISA)

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 or doxycycline) or enrofloxacin, may be sufficient to control mild symptoms.
However, if clinical signs become chronic or more serious with lung involvement the use of an additional antimicrobial, along with nebulization treatments, and/or the addition of corticosteroids may be required.

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

Early to moderate illness

The following medications for use in rats with early to moderate 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 BID PO (oral) for 10 to 30 days
or
Doxycycline 5 mg/kg BID 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
0.5mL Gentocin injectable 100 mg/mL
0.5mL Albuterol 0.083% Inhalation
*Note: excess mixture for nebulization can be refrigerated for up to 3 days.

If mild to moderate 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

Advanced or more difficult to treat 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) and doxycycline, azithromycin (Zithromax) and 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 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 BID, PO (oral) for 10-30 days
Doxycycline 5 mg/kg BID PO (oral) for 10-30 days
nebulization for 15 minutes, 2 to 3 times a day, for 14 days, with the following mixture:
8 mL sterile saline
0.5mL gentamicin injectable 100 mg/mL
0.5mL 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 given orally, such as Aminophylline/Theophylline, or Albuterol,may be added to help relax the smooth muscle and dilate the bronchi in the lungs to aid breathing.
Nebulized treatments with these medications as well as certain antibiotics ( e.g., fluoroquinolones: enrofloxacin(Baytril), aminoglycosides: amikacin or gentamicin, or a macrolide: tylosin ), may be prescribed for rats that have difficulty taking the medications orally. Medications for nebulization are dosed at oral dosage recommendation, and need to be diluted in normal saline.
The following are recommended ratios for dilution of those medications in normal saline:
Enrofloxacin(Baytril) 10mg to 1 mL normal saline. ³
Gentamicin (Gentocin) 5mg 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 to moderate illness or 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 breath 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, 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 BID PO (or in the presence of renal disease 8 mg/kg to 10 mg/kg BID) in conjunction with doxycycline 5 mg/kg BID 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.

Treatment in pregnant and nursing does, and rats less than 4 months:

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

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:

http://www.petiatric.com/Medicalnebulizer.htm
http://www.lambertvetsupply.com/sbsite.php?search_query=nebulizer

Examples of nebulizer set up:

http://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 using a hot water bottle or heating pad, if needed, in order to maintain body temperature within normal limits. Use low heat settings and place under one half of cage to ensure rat does not become overheated or dehydrated.
• 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 Jello 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 if 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 or aquariums, will help reduce severity of symptoms.
• The use of dust and phenol free bedding and litter (e.g., cedar and pine litters) will help reduce clinical symptoms.
• Locate cage or housing in draft free area.
• Quarantine all new rats for a minimum of two weeks prior to introducing into existing colony.
• Do not smoke around your rats!

References

• 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.

Posted on June 25, 2003, 09:23, Last updated on July 7, 2010, 10:20 | Bacteria