In the UK, the majority of mycobacterial infections in cats are caused by tuberculous mycobacteria. The initial large culture study showed ~35% of infections to be caused by Mycobacterium microti (~20%) or Mycobacterium bovis (~15%) (Gunn-Moore et al., 2011ab), with ~50% of cases failing to grow. However, further, as yet unpublished work using the more sensitive polymerase chain reaction (PCR) approach found a similar proportion of cases caused by M. bovis, but a higher proportion caused by M. microti (~35%) (Gunn-Moore and O’Halloran, unpublished data). 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 – the disease may be caused by a member of the tuberculosis (TB) complex. All members of the affected cat's household must be considered. It is important to determine any potentially immunosuppressed individuals (e.g. people with human immunodeficiency virus or who are undergoing chemotherapy). Treatment is not advised where such individuals may be exposed. Treatment is also not advised 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 given patient non-compliance, 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. Placement of a feeding tube may be required to improve compliance
• 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, double or triple therapy is advised (Greene and Gunn-Moore, 2011); i.e., start with pradofloxacin and azithromycin, pending confirmation, then add rifampin when TB is confirmed.

Treatment of mycobacterial disease

Previously, anti-tuberculosis treatment was given in an initial and then a continuation phase (Greene and Gunn-Moore, 2011); however, 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. In those cats where triple therapy is not feasible, treatment should still involve two drugs and should be given for a minimum of 6–9 months. 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. Second-line treatments for tuberculosis should be reserved for resistant infections. Ensure all aspects of cascade prescribing have been considered before using drugs only authorized for human use. Data from Kaufman et al., 1995; Gelatt et al., 2001; Bennett, 2007; Sieber-Ruckstuhl et al., 2007. FLS = feline leprosy syndrome; MAC =M. avium-intracellulare complex; NTM = non-tuberculous mycobacteria; TB = tuberculosis.aThe authors do not recommend enrofloxacin as it has been associated with retinal degeneration; other than the newer fluoroquinolones (pradofloxacin and moxifloxacin), most others are not effective against MAC infections.b These drugs may cause potentially serious side effects (e.g. hepatotoxicity or nephrotoxicity); it is advisable to monitor use closely, including routine haematology and serum biochemistry 2 weeks after starting treatment and again following any change in the cat’s demeanour.c M. tuberculosis and some NTM, potentially including MAC infections, can have inducible resistance genes to macrolides, meaning they appear susceptible in vitro but are resistant in vivo; where possible (limited by GI signs), use higher doses to reduce the risk of resistance.d Particularly useful when treating MAC infections.e Not effective against M. bovis infection.f Can be difficult to obtain.g Give with food or give water after the medication to avoid oesophageal injury.

Treatment of NTM

At a minimum, use of a fluoroquinolone is suggested while waiting for PCR or culture 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 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 requires long-term antibiotics and radical well planned surgery: e.g., doxycycline for several weeks, then radical surgical excision and local reconstruction plus parenteral gentamicin perioperatively for 3–5 days, followed by a prolonged course (3–6 months) of a new fluoroquinolone (White et al., 1983; Malik et al., 1994, 2000, 2004). 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; Courtin et al., 2007; Malik et al., 2013). 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).

Susceptibility and resistance of mycobacterial species to potential drugs for the treatment of NTM in cats. Data from Studdert and Hughes, 1992; Malik et al., 1994, 2000, 2004, 2006ab; Michaud, 1994; Kiehn et al., 1996; Foster et al., 1999; Smith et al., 2000; Jang and Hirsh, 2002; Tomioka et al., 2002; Dietrich et al., 2003; Govendir et al., 2011; Cho et al., 2012; van Ingen et al., 2012; Bennie et al., 2014.aOther studies have shown these drugs to be either more or less effective.

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 treating 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, oedema and erythema, chlorphenamine is advised (2–4 mg/cat p.o. q8–12h). 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 enzymes on serum biochemistry.S-Adenosylmethionine (SAMe) (20 mg/kg p.o. q24h) is one hepatoprotectant agent that is widely used in cases of drug-induced liver toxicity, as well as in cases of liver disease.

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 anti-mycobacterial activity and can reduce growth of bacteria both in vitro and in vivo.

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