In the UK, the majority of mycobacterial infections in cats are caused by tuberculous mycobacteria. The only large culture study showed ~35% of infections to be caused by Mycobacterium microti (~20%) or M. bovis (~15%) (Gunn-Moore et al., 2011ab), with ~50% of case submissions failing to grow. The most common non-tuberculous mycobacteria (NTM) are in the M. avium complex (MAC), and a wide range of NTM can infect cats.

It is important to consider the factors below before undertaking treatment:

• There is a potential zoonotic risk – especially for the species of the tuberculosis (TB) complex group. All members of the affected cat’s household must be considered and it is important to determine any potentially immunosuppressed individuals (e.g. people with human immunodeficiency virus or who are undergoing chemotherapy). Treatment should be thoroughly considered where such individuals may be exposed, especially if the affected cat has generalized disease, cavitating lesions within the respiratory tract or extensive draining cutaneous lesions as these may increase the risk of transmission
• Treatment is almost always long term – this can be difficult to maintain if the patient is non-compliant, due to the inherent toxicity of some of the drugs and the financial costs involved. In some cases, the drugs may at best suppress disease and indefinite treatment may be required (Sieber-Ruckstuhl et al., 2007; Greene and Gunn-Moore, 2011). Uncomplicated cutaneous cases with or without diffuse pulmonary changes carry the most favourable prognosis; treatment is successful in over 80% of cases. Placement of a feeding tube may be required to improve compliance with medications
• Interim management – pending a definitive diagnosis, interim therapy with a fluoroquinolone is recommended in cases of localized cutaneous infection (Gunn-Moore et al., 2010).

Pradofloxacin (or moxifloxacin) is recommended as it is more effective against mycobacteria than the older fluoroquinolones, such as marbofloxacin (Govendir et al., 2011). With more extensive disease, the addition of azithromycin is indicated, pending confirmation, and rifampin should be added when TB is confirmed.

Treatment of mycobacterial disease

Previously, anti-TB treatment was given in an initial and then a continuation phase (Greene and Gunn-Moore, 2011). It is now known that it is better to give all three drugs for 4–6 months, depending on the extent of disease, and always for at least 2 months following complete resolution of the lesions. Extensive clinical experience supports using rifampin, pradofloxacin and azithromycin as a starting point; however, NTM infections may need different combinations.

Potentially useful drugs for the treatment of feline mycobacterial disease are given in the table below.

Treatment of Non-tuberculous mycobacteria (NTM): At a minimum, use of a fluoroquinolone is suggested while waiting for polymerase chain reaction or culture and susceptibility results. The new fluoroquinolones (e.g. pradofloxacin or moxifloxacin) are recommended as they have an extended spectrum of activity, which includes some NTM, and they are even effective against MAC infections (Govendir et al., 2011). MAC infections are particularly difficult to treat (Jordan et al., 1994).

Clarithromycin or azithromycin should be included (Piersimoni et al., 1995), ideally in combination with rifampin (Tomioka et al., 2002) ± another antibiotic according to culture and susceptibility testing, such as doxycycline (Baral et al., 2006) or, from human studies, ethambutol (Esteban et al., 2012).

Pyogranulomatous panniculitis usually requires long-term antibiotics prior to considering surgical management such as reconstructive surgery. Non-surgical cases may require double or triple therapy.

Feline leprosy-type infections (feline leprosy syndrome; FLS) can usually be treated with surgical removal of small nodules, which may be curative. Where medical management is needed, clarithromycin, pradofloxacin and rifampin or clofazimine are recommended.

Doxycycline, fluoroquinolones and aminoglycosides may also be useful (Mundell 1988; Malik et al., 2002, 2006a, 2013; Courtin et al., 2007). Dapsone is considered too toxic for use in cats (Hamanda et al., 1991) and is antagonistic to clofazimine. Treatment should be continued until the lesions have completely resolved, and ideally for a further 2–3 months to reduce the risk of recurrence; however, some cases require life-long clarithromycin to prevent recurrence (Malik et al., 2013).

TABLE: Susceptibility and resistance of mycobacterial species to potential drugs for the treatment of NTM in cats

Managing side effects

Cats may suffer side effects while receiving treatment for mycobacterial infections, especially with rifampin. While side effects can be concerning to owners and veterinary professionals, this drug is essential for optimizing the outcome of cats with TB and is the only drug in the triple therapy approach with activity against non-replicating bacteria.

To help manage dermatological side effects such as pruritus, antihistamines can be used. Chlorphenamine therapy has been reported but the ideal dose and interval is unknown and efficacy is not established clinically. Focal pruritic lesions can also be managed with topical hydrocortisone aceponate spray.

Hepatotoxicity is another possible side effect of rifampin, which may manifest clinically as hyporexia, nausea or vomiting, or may be identified with increased enzyme activities on serum biochemistry. S-Adenosylmethionine (20 mg/kg p.o. q24h) is a widely used hepatoprotective agent in cases of drug-induced liver toxicity. An intriguing alternative agent is N-acetylcysteine (NAC) (600 mg/cat p.o. q12h); while pharmacological data are lacking for its use in cats, it is safe and well tolerated. NAC has an unpleasant taste and smell, so giving whole capsules is usually advised. Nausea and vomiting are potential side effects, and drooling occurs when the capsule content is mixed with too little food. Since NAC can cause bronchial spasm, it should be used with caution in animals with asthma. NAC helps to restore blood glutathione concentrations, and thus antioxidant capacity. It has also been shown to reduce bacterial counts and the severity of lesions.

Restoration of antioxidant capacity helps reduce the toxic side effects of anti-TB drugs such as rifampin and isoniazid, which are mediated by oxidant-driven damage to the liver. Short-term studies have also shown that NAC has some direct antimycobacterial activity and can reduce growth of bacteria both in vitro and in vivo.

References

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