Long-term cure of disseminated Mycobacterium avium infection in a cat

Mycobacterium avium-intracellulare, a member of the M avium complex (MAC), is a ubiquitous, saprophytic, slowgrowing, acid-fast bacillus that is widely distributed in the environment (Greene and Gunn-Moore 2006). Clinical signs associated with MAC infection are typically organ-specific, depending on the route of infection. Dissemination can occur in immunocompromised hosts. The treatment of localised disease consists of surgical removal of the infected tissue, with or without medical therapy (Kaufman and others 1995, Malik and others 1998). The treatment of disseminated MAC infection in cats has recently been reported to be successful with a variety of combination drug regimens, including clofazimine and clarithromycin as essential components (Baral and others 2006). This short communication describes the treatment of a cat with disseminated M avium infection with a multidrug regimen and the associated side effects. A five-year-old, male neutered Abyssinian cat was evaluated by a private veterinarian because of a history of weight loss and anorexia. Physical examination revealed an abdominal mass, which was removed surgically. Pyogranulomatous inflammation was observed on histopathological examination of the mass. Tests for feline leukaemia virus (FeLV) antigen and feline immunodeficiency virus (FIV) antibody were negative. Treatment with prednisone was initiated, but within two weeks the cat became tachypnoeic and was referred to the University of Georgia Veterinary Teaching Hospital. Thoracic radiography revealed a diffuse, nodular interstitial lung pattern. Pyogranulomatous inflammation without visible microorganisms was detected on bronchoalveolar lavage (BAL) and on transthoracic lung aspirates. The results of aerobic bacterial and fungal cultures and tests for cryptococcal antigen (latex agglutination test), toxoplasmosis antibodies (immunoglobulin M [IgM] and immunoglobulin G [IgG] ELISAs) and coronavirus antibody (immunoflourescent antibody test), were negative. On an empirical basis, the cat was discharged on 10 mg/kg clindamycin and 5 mg/kg itraconazole, both administered orally every 12 hours. Two months later, the cat was re-presented because of persisting anorexia and tachypnoea. At that time (day 0) the cat was thin (bodyweight 2·7 kg) and had a normal rectal temperature and a markedly increased respiratory rate, with increased expiratory effort. Thoracic auscultation revealed increased normal breath sounds bilaterally, and abdominal palpation revealed a 6 x 7 cm, irregular, non-painful mass in the mid-abdomen. Laboratory abnormalities included mild neutrophilia (15,768 cells/μl, reference range [RR], 2500 to 12,500 cells/μl) with left shift (bands, 1944 cells/μl, RR 0 to 300 cells/μl), hyperglobulinemia (51 g/l, RR 30 to 34 g/l) and hypercalcemia (total calcium 4·0 mmol/l, RR 2·25 to 2·7 mmol/l; ionised calcium 1·59 mmol/l, RR 1·22 to 1·3 mmol/ l). A severe bronchointerstitial lung pattern was detected on thoracic radiography (Fig 1). Abdominal ultrasonography revealed multiple irregularly marginated hypoechoic masses in the mesentery and/or omentum. The results of repeated FIV antibody, FeLV antigen, coronavirus antibody and toxoplasmosis antibody (IgM and IgG) tests were negative. An abdominal laparotomy revealed multiple nodular lesions within the omentum and moderate mesenteric lymphadenomegaly. A section of the omentum and two mesenteric lymph nodes were excised and submitted for aerobic, anaerobic, mycobacterial and fungal culture, direct fluorescent antibody testing for intralesional coronavirus, and routine histopathological evaluation, which demonstrated pyogranulomatous inflammation. The results of special staining (Giemsa, acid-fast, periodic acid-Schiff) for bacteria and fungi and the fluorescent antibody test on serum for coronavirus were negative. The cat was discharged from the hospital six days later. Over the next two months, the cat was clinically stable. No growth was reported on the aerobic, anaerobic or fungal cultures. After 65 days’ culture carried out by the Centers for Disease Control and Prevention [CDC], the mycobacterial culture yielded growth of an organism. Pending definitive identification, it was considered to be a member of the MAC because of its very slow growth and the clinical presence of gastrointestinal involvement with respiratory dissemination (Greene and Gunn-Moore 2006). Treatment was started with a multidrug regimen consisting of 4·4 mg/kg clarithromycin every 12 hours, 50 mg clofazimine every 24 hours and 12·5 mg/kg doxycycline every 12 hours, all administered orally. A dramatic clinical improvement was seen; four weeks later (94 days after the cat had been re-presented), the pulmonary densities had a markedly decreased opacity on radiography. Abdominal ultrasonography revealed that the masses had disappeared, although the mesenteric lymphadenomegaly persisted. On day 120, the isolate was identified as M avium-intracellulare by the CDC, which was sensitive only to rifampin. Because of the obvious clinical and radiographic improvements, the treatment protocol was not altered. On day 134, the cat’s appetite suddenly decreased. Increased serum activities of alanine aminotransferase (ALT) (727 U/l, RR 31 to 104 U/l) and alkaline phosphatase (ALP) (73 U/l, RR 0 to 50 U/l) were noted. Hepatotoxicity due to the medications was suspected, and the clarithromycin was discontinued. On day 146, the serum ALP activity was within the reference range (45 U/l) and the serum ALT activity had decreased to 301 U/l. Enroflaxacin (2·5 mg/kg every 12 hours, administered orally) was added to the protocol. At re-evaluation 20 days later, the cat was clinically healthy and serum liver enzyme activities were within reference limits. The radiographic lung densities had continued to decrease, and mesenteric lymphadenomegaly was no longer detected ultrasonographically (Fig 2). Eight weeks later (day 230), the owner chose to discontinue all medications. At the time of writing, the cat has been reevaluated on a periodic basis for approximately 900 days, and had remained clinically healthy. Reports of M avium infection in cats are uncommon, leading to the suspicion that cats have some resistance to this Veterinary Record (2007) 160, 131-132