33-35: Nontuberculous Mycobacterial Diseases

About 10% of mycobacterial infections are caused by nontuberculous mycobacteria. Nontuberculous mycobacterial infections are among the most common opportunistic infections in advanced HIV disease. These organisms have distinctive laboratory characteristics, occur ubiquitously in the environment, are not communicable from person to person, and are often resistant to standard antituberculous drugs.

Mycobacterium avium complex (MAC) causes a chronic, slowly progressive pulmonary infection resembling tuberculosis in immunocompetent patients who typically have underlying pulmonary disease. Susceptibility testing for macrolide-resistance should be performed on clinical isolates. Treatment of nodular or bronchiectatic pulmonary disease is clarithromycin (1000 mg orally three times per week) or azithromycin (500 mg orally three times per week) plus rifampin (600 mg orally three times per week) or rifabutin (300 mg orally three times per week) plus ethambutol (25 mg/kg orally three times per week). Patients with fibrocavitary lung disease or severe nodular or bronchiectatic disease should receive three-drug therapy with clarithromycin (500–1000 mg orally daily) or azithromycin (500 mg orally daily) plus rifampin (600 mg orally daily) or rifabutin (300 mg orally daily) plus ethambutol (15 mg/kg orally daily). Therapy is continued for at least 12 months after sterilization of cultures.

M kansasii can produce clinical disease resembling tuberculosis, but the illness progresses more slowly. Most such infections occur in patients with preexisting lung disease, though 40% of patients have no known pulmonary disease. Microbiologically, M kansasii is similar to M tuberculosis and is sensitive to the same drugs except pyrazinamide, to which it is resistant. Therapy with isoniazid, ethambutol, and rifampin for 2 years (or 1 year after sputum conversion) has been successful.

Less common causes of pulmonary disease include M xenopi, M szulgai, and M gordonae. These organisms have variable sensitivities, and treatment is based on results of sensitivity tests. The rapid growing mycobacteria, M abscessus, M chelonae, and M fortuitum, also can cause pneumonia in the occasional patient.

Most cases of lymphadenitis (scrofula) in adults are caused by M tuberculosis and can be a manifestation of disseminated disease. In children, the majority of cases are due to nontuberculous mycobacterial species, with MAC being the most common followed by M scrofulaceum in the United States and M malmoense and M haemophilum in Northern Europe. M kansasii, M bovis, M chelonae, and M fortuitum are less commonly observed. Infection with nontuberculous mycobacteria can be successfully treated by surgical excision without antituberculous therapy.

Skin and soft tissue infections such as abscesses, septic arthritis, and osteomyelitis can result from direct inoculation or hematogenous dissemination or may occur as a complication of surgery.

M abscessus, M chelonae, and M fortuitum are frequent causes of these types of infections. Most cases occur in the extremities and initially present as nodules. Ulceration with abscess formation often follows. The organisms are resistant to the usual antituberculosis drugs and may have susceptibility to clarithromycin, azithromycin, doxycycline, amikacin, cefoxitin, sulfonamides, imipenem, and ciprofloxacin. Given the multidrug-resistant nature of these organisms, obtaining antibiotic susceptibility testing is recommended. Therapy often includes surgical debridement along with at least two active antibiotics. Antibiotic therapy is usually continued for 3 months, although this must be determined based on clinical response.

M marinum infection (“swimming pool granuloma”) presents as a nodular skin lesion following exposure to nonchlorinated water. The lesions respond to therapy with clarithromycin, doxycycline, minocycline, or trimethoprim-sulfamethoxazole.

M ulcerans infection (Buruli ulcer) is seen mainly in Africa and Australia and produces a large ulcerative lesion. Therapy consists of surgical excision and skin grafting.

MAC causes disseminated disease in immunocompromised patients, most commonly in patients in the late stages of HIV infection, when the CD4 cell count is less than 50/mcL (see Pulmonary Disease caused by Nontuberculous Mycobacteria, Chapter 9, for a discussion of the infection in immunocompetent persons). Persistent fever and weight loss are the most common symptoms. The organism can usually be cultured from multiple sites, including blood, liver, lymph node, or bone marrow. Blood culture is the preferred means of establishing the diagnosis and has a sensitivity of 98%.

Agents with proved activity against MAC are rifabutin, azithromycin, clarithromycin, and ethambutol. Amikacin and ciprofloxacin work in vitro, but clinical results are inconsistent. A combination of two or more active agents should be used to prevent rapid emergence of secondary resistance. Clarithromycin, 500 mg orally twice daily, plus ethambutol, 15 mg/kg/day orally as a single dose, with or without rifabutin, 300 mg/day orally, is the treatment of choice. Azithromycin, 500 mg orally once daily, may be used instead of clarithromycin. Insufficient data are available to permit specific recommendations about second-line regimens for patients intolerant of macrolides or those with macrolide-resistant organisms. MAC therapy may be discontinued in patients who have been treated with 12 months of therapy for disseminated MAC, who have no evidence of active disease, and whose CD4 counts exceed 100 cells/mcL for 6 months while receiving antiretroviral therapy (ART).

Antimicrobial prophylaxis of MAC prevents disseminated disease and prolongs survival. It is the standard of care to offer it to all HIV-infected patients with CD4 counts of 50/mcL or less. In contrast to active infection, single-drug oral regimens of clarithromycin, 500 mg twice daily, azithromycin, 1200 mg once weekly, or rifabutin, 300 mg once daily, are appropriate. Clarithromycin or azithromycin is more effective and better tolerated than rifabutin, and therefore preferred. Primary prophylaxis for MAC infection can be stopped in patients who have responded to antiretroviral combination therapy with elevation of CD4 counts of greater than 100 cells/mcL for 3 months.