Mycobacterial Infections in Dogs and Cats
Mycobacterium species are gram-positive, aerobic, non-spore forming, non-motile members of the order Actinomycetales that, when engulfed by phagocytes, cause a granulomatous immune response. Mycobacteria are ubiquitous in soil and water, and infections are increasingly reported in pets that are frequently exposed through ingestion of mycobacterium-contaminated substrates. Mycobacteria can cause a variety of clinical syndromes in dogs and cats, ranging from localized skin conditions to disseminated, often fatal, systemic infections.
To begin therapy, the mycobacteria species must be identified, treatment consists of a combination of surgical excision of lesions and long term medical therapy with at least 3 of the following antimicrobial agents: isoniazid, rifampin, ethambutol, pyrazinamide, clarithromycin, azithromycin, enrofloxacin, marbofloxacin, orbifloxacin, doxycycline or clofazimine. The complexity and non-palatability of multi-drug therapies can overwhelm pet owners and significantly reduce compliance.
Compounding pharmacists have many techniques and dosage forms to assist veterinarians and pet owners in delivering palatable combination drug therapies for mycobacterial infections. Likewise, compounding pharmacists are well-versed in preventing and monitoring for drug interactions.
Chapter 48: Mycobacterial Infections, in Infectious Diseases of the Dog and Cat, Craig Greene, DVM, MS, DipACVIM (Ed.), 4th Ed. Elsevier, St. Louis, MO. 2012.
Penicillin Gelatin Guttural Pouch LavageStreptococcus equi is the bacterial pathogen responsible for a highly contagious equine disease known as strangles. Strangles most commonly occurs in younger horses, but can be seen in horses of any age, particularly performance horses encountering sites where high density and high turnover of horses occurs (competition grounds, fairs, auctions, and boarding facilities). Infection by S. equi causes a severe inflammatory response manifesting as fever (102°-106°F), inappetance, lymphadenopathy with abscessation and resulting stridor, and a copious, mucopurulent nasal discharge. The guttural pouch has been identified as the site most likely to harbor S. equi organisms after infection due to draining abscesses from the mandibular lymph nodes. While systemic beta-lactam therapy has proven very valuable in treatment of active disease, antibiotics do not achieve high enough concentrations in the guttural pouch to eliminate organisms. Recently, the use of penicillin G sodium impregnated gelatin has been utilized to fill the guttural pouches following guttural pouch lavage in order to allow prolonged, bacteriocidal concentrations of penicillin in the guttural pouch after a single application. The penicillin sodium gel should be prepared in an aseptic environment and refrigerated for at least 24 hours prior to administration. Our compounding pharmacists are able to provide this preparation for equine veterinary patients.For further reading on equine strangles consult the American Association of Equine Practitioners at //www.aaep.org/strangles.htm.
Clotrimazole 1% in Pluronic Gel for Nasal AspergillosisNasal aspergillosis is a common fungal condition in dogs that results in massive turbinate destruction, pain and death or euthanasia due to lysis of surrounding skeletal structures such as the cribiform plate. Systemic treatment with oral antifungals is very expensive and often accompanied with serious adverse effects, and often is not successful (40-70% success). Traditionally, the treatment of choice for nasal aspergillosis in dogs was a one-hour intranasal irrigation of 1% clotrimazole solution while the patient was anesthetized. The prolonged anesthesia was necessary to allow maximal contact time of the 1% clotrimazole solutions that immediately ran out of the sinuses once introduced. This therapy resulted in a success rate of almost 70% after a single treatment, but many dogs require multiple treatments for complete resolution. Because of the expense and risk of multiple surgical and prolonged anesthetic procedures, a method to provide prolonged contact of 1% clotrimazole solutions in the nasal sinuses has been considered. A recent study assessed the retention, toxicity and stability of several viscous preparations of clotrimazole 1% in canine frontal sinus. Six compounds were evaluated including commercially available 1% clotrimazole cream, and 1% clotrimazole in varying concentrations of hydroxypropyl methylcellulose, carboxymethylcellulose, and poloxamer gel. Results of this study indicate that clotrimazole 1% delivered in 25% poloxamer gel resulted in the least amount of sinus inflammation and was accompanied by a reasonable retention time. Researchers concluded that use of poloxamer gels holds much promise for prolonged delivery of clotrimazole in nasal sinuses, potentially reducing anesthetic time as well as accomplishing fungal organism eradication after a single course of treatment. Veterinarians interested in pursuing use of this therapy for nasal aspergillosis can contact our compounding pharmacist to prescribe clotrimazole 1% in 25% poloxamer gel.
Am J Vet Res 2009:70:640–647
Assessment of clotrimazole gels for in vitro stability and in vivo retention in the frontal sinus of dogs.
Click here to access the PubMed abstract of this article.
Metronidazole
Metronidazole is effective against a variety of obligate anaerobic bacteria as well as anaerobic protozoa such as Giardia and Trichomonas. “Various salts of metronidazole with improved palatability are now available for veterinary patients… Cats and birds accept the benzoate salt much more willingly than they accept metronidazole HCl and do not seem to be stressed by its administration.”
Metronidazole should be used with caution in patients with hepatic dysfunction. Therapy should be promptly discontinued if abnormal neurological signs appear, including nystagmus, ataxia, seizures, and rigidity. All benzene moieties must be conjugated with glucuronide to facilitate elimination and this pathway is inefficient in cats. Therefore, doses of metronidazole benzoate above 200 mg/kg/day may produce signs of cumulative toxicity in cats within 48 to 72 hours.
Compendium Dec. 2000: 22(12); pp. 1104, 1105, 1107, 1130
Esophageal Strictures Secondary to Administration of Doxycycline Tablets
“The most common causes of esophageal strictures in dogs and cats are gastroesophageal reflux during anesthesia, persistent vomiting, or ingestion of foreign bodies or caustic agents. In humans, esophageal retention of oral medication is a common cause of severe esophagitis. Of the medications proven to lead to esophageal ulceration, doxycycline is most often implicated. It has been suggested that pill-induced esophagitis also could occur in small animals…” Drug-induced esophageal ulceration usually occurs when tablets are taken with little or no water and adhere to the esophageal mucosa. Once this occurs, flushing with large quantities of liquid fails to wash the medication into the stomach. Melendez et al. of Colorado State University College of Veterinary Medicine report on three cases of presumptive doxycycline-induced esophagitis in cats, with resultant stricture formation. All cats had been administered fractions of doxycycline tablets one to three weeks before presenting with a chief complaint of regurgitation. “Two of the cases developed regurgitation within 7 days after initiation of therapy with doxycycline. One cat, which was treated while at an animal shelter, was noted to be regurgitating the day that it was adopted, approximately 2 weeks after being treated with doxycycline. No other cause of esophageal stricture formation could be identified.” If a pet that has received a doxycycline tablet shows sign of esophagitis (dysphagia, excessive salivation, inappetence, and regurgitation), the doxycycline tablets should be discontinued. Suggested therapy for esophagitis includes sucralfate slurries, a prokinetic agent (i.e. cisapride) to increase lower esophageal sphincter tone, and anti-inflammatory doses of glucocorticoids to prevent stricture formation.
Doxycycline can be compounded as a stable flavored liquid preparation or other palatable dosage form to meet the specific needs of each animal and owner.
Feline Practice 28:2; 10-12 (Mar/Apr 2000)
Oral Itraconazole for Therapy of Dermatophytosis Caused by Microsporum canis
Itraconazole could be an effective alternative to griseofulvin that has toxic effects (particularly in puppies based on this author’s experience) and frequent therapeutic relapses. Itraconazole has also been used to successfully treat M. canis infection of cats and guinea pigs.
J Am Vet Med Assoc 1998;213:993-995
Chloramphenicol Suspension for Birds & Small Animals
by J. Terry McGrath, VMD, Pennsylvania
Since chloramphenicol palmitate is no longer commercially available, we contacted our compounding pharmacist for an alternative for use in our avian and other small patients, such as rabbits and rodents. The pharmacist prepared a cola flavored suspension containing 30 mg/ml of chloramphenicol palmitate, which could be administered using a small oral syringe. However, birds did not like the taste and it was reformulated into a tutti fruitti and pina colada syrup. The “animal appropriate” flavor has really helped with compliance, because now the birds and small animals like to take their medicine!
Note: To avoid potential antagonism, chloramphenicol should not be administered simultaneously with penicillin or streptomycin. Chloramphenicol-containing preparations should not be administered in conjunction with, or two hours prior to, the induction of general anesthesia with pentobarbital.
When administered orally in dogs, chloramphenicol is well-tolerated, has high clinical efficacy, and a low incidence of side effects. The recommended canine dosage is 25 mg/lb of body weight every six hours.
Precautions: Chloramphenicol should be administered cautiously to animals with hematopoietic dysfunction, or impaired kidney or liver function.
Antibiotic Treats for Feline Abscess
Submitted by: Michael Briggs, Pharm.D. Veterinarian: Rich Marchetti, D.V.M.
Patient: One year old non-castrated short-haired male cat with abscess from wound received in fight. The owner reported that the cat, who is usually affectionate and friendly toward the owner and house dog, had been withdrawn, on guard, and growling for approximately three days. A thorn-like projection near the tail was found by the owner, who immediately took the cat to the veterinarian. The cat was anesthetized and the veterinarian cleaned, debrided, and shaved the area of the wound, and prescribed amoxicillin 100 mg daily for ten days. The owner was instructed to keep the cat inside for the duration of therapy, to minimize the risk of superinfection and avoid additional injury.
Medication Problem: The cat refused to take liquids, and was also resistant to taking tablets (“pilling”). The required dose of antibiotic was too high for transdermal treatment (due to the amount of gel that would need to be applied for each dose).
Solution: The veterinarian called our compounding pharmacy and asked if we could come up with a palatable dosage form. We formulated a fish-flavored chewable treat containing amoxicillin 100 mg to be given once daily for ten days. This dosage form offers the advantage of ease of administration, decreases the potential for dosing errors, and greatly increases patient compliance. The cat readily consumed the amoxicillin “treat”. The wound did not heal in a ten day period, so five additional days of therapy were required.
Intranasal Clotrimazole for Treatment of Nasal Aspergillosis in Dogs
“Treatment of nasal aspergillosis with systemic antifungal medications, such as thiabendazole, ketoconazole, and fluconazole, has been disappointing because the response rate is only 43 to 60%. Response to oral administration of itraconazole has been approximately 60 to 70%… Topical administration of the imidazoles, enilconazole, and clotrimazole is more effective than orally administered antifungal medications.”
Topical administration of clotrimazole resulted in resolution of clinical disease in 65% of dogs after 1 treatment and 87% of dogs after one or more treatments. Topical administration of clotrimazole, using either technique, was an effective treatment for nasal aspergillosis in dogs. Use of non-invasive intranasal infusion of clotrimazole eliminated the need for surgical trephination of frontal sinuses in many dogs and was associated with fewer complications. Nasal discharge ceased in most dogs 2 weeks after topical treatment, and the authors now recommend re-treatment with clotrimazole if nasal discharge has not improved 2 weeks after treatment.
“[Damage] of the cribriform plate may contraindicate use of topical treatment; complications arising from leakage of antifungal medications into the CNS in dogs with fungal rhinitis have not been evaluated.”
J Am Vet Med Assoc 1998 Aug 15;213(4):501-6
Comparison of topical administration of clotrimazole through surgically placed versus nonsurgically placed catheters for treatment of nasal aspergillosis in dogs: 60 cases (1990-1996).
Click here to access the PubMed abstract of this article.
J Am Anim Hosp Assoc 1998 Nov-Dec;34(6):487-92
Management of nasal aspergillosis in a dog with a single, noninvasive intranasal infusion of clotrimazole.
Click here to access the PubMed abstract of this article.
Azithromycin
is a form of erythromycin with improved action against gram-negative organisms, resistance to acid degradation, improved tissue penetration, and a prolonged elimination half-life. Azithromycin shows potential for use in veterinary medicine, particularly in cats and certain avian and exotic species.
“Lacking the prokinetic action of erythromycin, azithromycin appears to cause fewer GI side effects and is generally well tolerated after oral administration. Cats appear to tolerate the drug particularly well… Animals with a history of arrhythmias should be monitored while receiving the drug. Some reduction in dose may be warranted in patients with hepatic or biliary dysfunction, although no reduction appears necessary in patients with renal dysfunction.” Please consult our compounding pharmacist regarding dosing.
Compendium of Continuing Education 23:3 (March 2001), pp. 242-7
Azithromycin for R. equi Infections in Foals
On the basis of pharmacokinetic values, minimum inhibitory concentrations of R. equi isolates, and drug concentrations in pulmonary epithelial lining fluid (PELF) and bronchoalveolar cells, a single daily oral dose of 10 mg/kg may be appropriate for treatment of R. equi infections in foals. Persistence of high azithromycin concentrations in PELF and bronchoalveolar cells 48 hours after discontinuation of administration suggests that after 5 daily doses, oral administration at 48-hour intervals may be adequate.
Am J Vet Res 2001 Dec;62(12):1870-5
Pharmacokinetics of azithromycin and concentration in body fluids and bronchoalveolar cells in foals.
Click here to access the PubMed abstract of this article.
The Capsule Report, Mixed Practice/Exotic Edition Jan 2002;15, 10: page 1
Itraconazole/DMSO for Fungal Keratitis in Horses
Fungal keratitis is a serious complication of trauma to the eye. Approximately one-half of the cases of fungal infections have involved the use of eye ointments containing corticosteroids after trauma to the globe of the eye.
“Itraconazole is a third generation triazole that has superior penetration properties and a wide spectrum of activity. A 1% solution of itraconazole in a 30% DMSO and petroleum base has been shown to reach high concentrations within the stroma of the cornea when administered every 4 to 6 hours. In general, every 6 hours is suitable for all but Fusarium sp which requires every 4 hour administration.”
Disease which is rapidly ulcerating “should also receive treatment that helps block the enzymes (collagenase) responsible for ulceration. A 5% acetylcysteine solution and autologous serum in which 4 mg/ml of EDTA has been added has been recommended. These need to be instilled hourly for best effect. The antimicrobial can be added to the serum.”
This information has been abstracted from an article by Robert N. Oglesby, DVM, which appears on his webpage, “The Horseman’s Advisor.”
For more information, references and complete text, see //www.horseadvice.com/horse/messages/4/5506.html
Idoxuridine Ophthalmic Drops for Cats
The ocular signs of feline herpesvirus I (FHV-1) infection include bilateral conjunctivitis, serous ocular discharge which may become mucoid or mucopurulent, and blepharospasm. If corneal involvement is present, topical antivirals are prescribed. Research indicates that idoxuridine is effective against FHV-1. Prolonged contact with the infected tissue is required. The 0.1% solution must be applied five times daily. Previously marketed as Stoxil®, the ophthalmic solution is not commercially available at this time.
Michael Zigler, DVM, Cert.V.Ophthal //www.eyevet.ca/herpes.html
Am J Vet Res 1989 Jan;50(1):158-60
In vitro susceptibility of feline herpesvirus-1 to vidarabine, idoxuridine, trifluridine, acyclovir, or bromovinyldeoxyuridine.
Click here to access the PubMed abstract of this article.
Feline Ocular Toxoplasmosis
“The anterior uveitis seen in cats with a positive serum titer to Toxoplasma gondii may result from immune-mediated mechanisms and not the presence or replication of the organism itself. As a result, it is unclear whether systemic antitoxoplasmic therapy is beneficial in these cases.” Michael G. Davidson, DVM, of North Carolina State University, College of Veterinary Medicine reports in Vet Clin N Amer, Sep 2000, that he “usually treats cats with ocular lesions and concurrent systemic findings of toxoplasmosis with systemic clindamycin (12.5 mg/kg PO twice daily for 14-21 days) and anti-inflammatory therapy. Other sources recommend clindamycin 10-12.5 mg/kg every 12 hours for 4 weeks. Oral trimethoprim-sulfonamide combination therapy (15 mg/kg every 12 hours for 2 to 4 weeks) can also be used to treat toxoplasmosis but is less suitable because of potential side effects caused by folic acid deficiency in cats.2 In T gondii seropositive cats exhibiting anterior uveitis alone and with no systemic signs, Dr. Davidson recommends topical steroids and atropine alone. If the cat fails to respond to topical therapy alone within 1-3 weeks, systemic clindamycin should be added to the treatment regimen. The rationale for the use of corticosteroids is to suppress the damaging inflammation in the retina, which may affect vision. Corticosteroids are typically administered 1-2 days after antibiotic therapy has been initiated to allow adequate tissue levels of the antimicrobial agent to be achieved. [Dr. Davidson] does not recommend systemic steroids in cats with suspected ocular toxoplasmosis because of the risk of exacerbating systemic replication of T gondii.”
Swift and aggressive treatment of uveitis is necessary to avoid such secondary complications as glaucoma, cataract formation, and retinal degeneration or detachment.
The Capsule Report 19:10 (Jan 2001), p. 4
Compendium of Continuing Education 23:3 (March 2001), pp. 258-66
