Current Diagnosis & Treatment in Infectious Diseases

Section V - Bacterial Infections

62. Other Mycobacteria

Julie Brahmer MD

Yenjean Hwang MD

Merle A. Sande MD

Essentials of Diagnosis

  • Demonstration of the acid-fast bacillus.
  • Infections more common in immunocompromised hosts.
  • Infections mainly pulmonary or soft tissue.

General Considerations

The increasingly relative importance of the atypical mycobacteria, many of which are ubiquitous in the environment, was recognized with the decline in tuberculous disease. Generally, atypical mycobacteria are unusual causes of disease in patients who are immunocompetent but can in immunocompromised hosts such as AIDS and cancer patients. Most infections caused by atypical mycobacteria are skin and soft tissue abscesses, sometimes following pulmonary infection or implantation of prosthetic devices. There have been a few reports of epidemics of iatrogenic infection with atypical mycobacteria, associated with injection of contaminated materials.

  1. Epidemiology.Atypical mycobacteria may account for 35% of isolations of potentially pathogenic mycobacteria in the United States; the rate of infection from atypical mycobacteria, however, ranges from 0.5% to 30% of all infections caused by mycobacteria. An estimated 3 million of the 6 million cases of leprosy worldwide remain untreated.
  2. Microbiology.The atypical mycobacteria are classified into four groups according to their growth characteristics, as well as pigment production in culture. Runyon class I includes organisms such as Mycobacterium kansasii, which are characterized by pigment production upon exposure to light (photochromogens). Runyon class II, including Mycobacterium scrofulaceum, are scotochromogens, which produce pigment in the light or in the dark. Runyon class III includes nonpigment producers (nonchromogens) such as Mycobacterium aviumcomplex (MAC). Runyon class IV organisms, such as Mycobacterium abscessus, are characterized by rapid growth in culture, on the order of 2–30 days, as compared with the other mycobacteria, which often take 6–8 weeks to cultivate.
  3. Pathogenesis.Sources of the atypical mycobacteria include soil, water, and domestic and wild animals (see Table 62-1 for habitats of common medically important mycobacteria). Most infections are acquired through aspiration or inoculation of atypical mycobacteria from the environment. Incubation periods are very long, averaging 5 years. Affected patients are of all age groups, but the peak age of onset is in young adults; children are rarely affected.

Pulmonary disease often results from inhalation of organisms, whereas direct inoculation of the organism or a foreign body contaminated with the organism results in soft-tissue disease. Ingestion of organisms can result in gastrointestinal involvement. Person-to-person transmission does not usually occur, with the exception of Mycobacterium leprae, which is transmitted by nasal droplets, although there is some evidence that transmission may occur by soil. Disseminated disease does not usually occur except in immunocompromised hosts.

CLINICAL SYNDROMES

MYCOBACTERIUM AVIUM COMPLEX (DISSEMINATED & PULMONARY DISEASE)

M avium is the most common atypical mycobacterium to cause disease in humans. In immunocompetent patients, M avium can cause pulmonary disease (Box 62-1). It is the most common pulmonary pathogen of all the atypical mycobacteria. There are several risk factors for pulmonary M avium infection besides AIDS. Patients with underlying pulmonary disease, those who have had a gastrectomy, and those with cystic fibrosis can develop pulmonary infection. Pulmonary disease can also develop in a subgroup of women without pulmonary disease but with mitral valve prolapse, pectus excavatum, and thoracic scoliosis.

In immunocompromised patients such as those with AIDS who have a CD4 lymphocyte count of < 100, M avium can cause osteomyelitis, peritonitis, oral lesions, and disseminated disease (Box 62-2). It may also cause colonization without disease in these patients. In children with AIDS, MAC is also common, occurring in 24% of children with a CD4 count of < 100. Patients with underlying malignancies and defects of cell-mediated immunity and those on chronic steroids or cytotoxic chemotherapy are also susceptible.

Table 62-1. Mycobacterium species, their habitats, and the diseases they cause. 1

Mycobacterium species

Habitat

Common Diseases in Humans

Tuberculosis complex

   M tuberculosis

· Humans

· Bronchopulmonary

   M bovis

· Humans, cattle

· Soft tissue & gastrointestinal tract

Photochromogens

   M kansasii

· Water, cattle

· Skeletal

   M marinum

· Fish, water

· Skin and soft tissue

   M simiae

· Primates

· Bronchopulmonary

   M asiaticum

· Primates

· Pulmonary (rare)

Scotochromogens

   M scrofulaceum

· Soil, water, foodstuffs

· Lymphadenitis

   M szulgai

· Unknown

· Bronchopulmonary

   M gordonae

· Water

· Pulmonary (rare)

   M flavescens

· Soil, water

· Pulmonary (rare)

   M xenopi

· Water

· Bronchopulmonary

Nonchromogens

   M avium-intracellulare

· Soil, water, swine, cattle, birds

· Pulmonary, lymphadenitis, disseminated

   M ulcerans

· Unknown

· Skin and soft tissue

   M gastri

· Soil, water

· Pulmonary (rare)

   M terrae

· Soil, water

· Pulmonary (rare)

Rapid growers

   M fortuitum

· Soil, water, animals, marine life

· Skin, soft tissue, disseminated

   M abscessus

· Soil, water, animals, marine life

· Skin, soft tissue, disseminated, skeletal

   M chelonae

· Soil, water, animals, marine life

· Skin, soft tissue, disseminated, skeletal

   M smegmatis

· Moist surfaces, urogenital flora

· Pulmonary (rare)

M leprae

· Humans, nine-branded armadillos

· Skin, soft tissue, disseminated (rare)

1Adapted from Long SS (editor): Principles and Practice of Pediatric Infectious Diseases, Churchill Livingstone, 1997.

M avium can cause other disease syndromes, including skeletal infections, lymphadenitis, deep subcutaneous nodules, fascitis, panniculitis, and synovitis. In children, it can cause superficial lymphadenitis and cutaneous disease such as ulcers, abscesses, or plaques, and intracerebral infection has been reported.

Clinical Findings

  1. Signs and Symptoms.Patients with pulmonary disease caused by M aviuminfection can present with a productive cough, fever, weight loss, and, less commonly, hemoptysis (Table 62-2). Symptoms of disseminated disease are constitutional, such as fever, weight loss, and malaise. MAC very rarely causes pneumonia in AIDS patients. Hepatosplenomegaly and adenopathy can be noted by physical exam. Gastrointestinal involvement in AIDS patients can present with three different syndromes, including chronic diarrhea and abdominal pain, chronic malabsorption, and extrabiliary obstructive jaundice secondary to periportal lymphadenopathy. MAC should be suspected in AIDS patients who exhibit all of the following signs or symptoms: CD4 counts of < 100, fever lasting for > 30 days, a hematocrit of < 30%, and an albumin concentration of < 3.0 mg/dL.
  2. Imaging.MAC involving the lung can classically cause pulmonary infiltrates seen on chest x-ray in the upper lobes or disseminated. Chest x-ray findings in these patients can vary from small thin-walled cavities to lobar infiltrates and isolated nodules. In older women, x-ray abnormalities include fibronodular and interstitial abnormalities with upper-lobe predominance. Chest x-rays can mimic reactivation tuberculosis with cavitation.

BOX 62-1 MAC in Immunocompetent Patients

 

Children

Adults

More Common

· Superficial lymphadenitis

· Cutaneous ulcers, abscesses and plaques

· Colonization

· Pulmonary infection—productive cough hemoptysis in <25%, fever and weight loss in 33%

Less Common

· Pulmonary

· Disseminated disease

· Cutaneous lesions

· Lymphadenitis

· Disseminated disease

BOX 62-2 MAC in AIDS Patients (CD4 <100)

 

Children

Adults

More Common

· Disseminated disease

· Pulmonary disease

· Colonization-gastrointestinal and respiratory tracts

· Fever, drenching night sweats, weight loss, diarrhea, abdominal pain, anorexia, hepatosplenomegaly, adenopathy, and anemia

Less Common

· Isolated lymphadenitis

· Isolated cutaneous lesions

· Pulmonary infection

· Osteomyelitis, peritonitis, oral lesions, appendicitis

MYCOBACTERIUM LEPRAE (LEPROSY)

M leprae is the etiologic agent of Hansen's Disease or leprosy. Although not a common problem in the United States, it is in other parts of the world. With the advent of effective antimicrobial agents, the number of cases of leprosy worldwide has fallen from 12 million in 1982 to 6 million in 1991. It remains a significant problem, however, because the incidence of new cases has not yet declined, and much of the affected population lives in areas where effective medical treatment is difficult to obtain. Leprosy is endemic in Asia, Africa, Latin America, and the Pacific.

In the United States, Canada, and Europe, there are virtually no cases of leprosy except those that are imported from areas where leprosy is endemic. Risk factors for acquisition of leprosy in endemic areas include poverty and rural residence. However, even in endemic areas, the distribution of leprosy can vary greatly, sometimes with significant differences in incidence of leprosy in adjacent villages. In North America, armadillo contact has been reported as a risk factor for acquisition. Other risk factors that have been reported in certain populations are the human leukocyte antigens HLA-DR3 (with the tuberculoid or paucibacillary form of disease) and HLA-MTI (with the lepromatous or multibacillary form of disease). Interestingly, the proportions of the lepromatous and tuberculoid types of leprosy (Box 62-3) vary geographically; in Mexico, 90% are lepromatous, whereas, in India and Africa, 90% are tuberculoid.

Table 62-2. Clinical findings in Mycobacterium avium complex infection.1

Acid-fast bacillus, nonphotochromogen
Slow grower (10–21 days) at 36°C
CXR findings vary from small thin-walled cavities to lobar in filtrates and isolated nodules.
Diagnosis clinically:

· Presence of pulmonary cavities not attributable to another disease and 2 or more positive sputum or bronchial wash specimens with moderate to heavy growth of MAC

· Infiltrate present but no cavities present, with failure of sputum cultures to convert to negative with either pulmonary toilet or 2 weeks of specific antimicrobial therapy

· Lung biopsy with histological confirmation and positive culture

· One positive blood culture

· Isolation of MAC from any other sterile body site

· Positive bone marrow, lymph node, or liver biopsy

1For clinical findings in AIDS patients, see BOX 62-7.

Clinical Findings

  1. Signs and Symptoms.The manifestations of leprosy involve the skin, upper respiratory system, peripheral nerves, and, in men, testes (Table 62-3). The peripheral neuropathy that is seen in leprosy results in impaired sensation of fine touch, temperature, and pain, whereas proprioception and vibratory sensation are intact. Such loss of sensation leads to recurrent trauma and ulceration in the extremities. For example, loss of sensation in the feet can lead to chronic nonhealing ulcers, especially at the metatarsal heads. Large nerve trunks may also be affected. A common nerve trunk that is affected in leprosy is the ulnar nerve at the elbow, which results in clawing of the fourth and fifth digits of the hand, dorsal interosseus muscle atrophy, and loss of sensation in the hand along the ulnar nerve distribution.

The lepromatous or multibacillary form of leprosy is characterized by symmetric skin nodules, plaques, and thickened dermis. Usually, the ear lobes and extremities are affected. Diffuse lepromatosis is seen usually in patients from Mexico, who show areas of diffuse dermal infiltration and no focal lesions. Untreated, lepromatous leprosy results in a high level of continuous bacteremia. Peripheral neuropathy is symmetric and generalized. There is a characteristic deformity associated with this type of leprosy, “saddle-nose deformity,” which occurs because of infiltration of the upper respiratory system and nasal cartilage. Other upper respiratory system effects include chronic nasal congestion and epistaxis.

The tuberculoid, or paucibacillary, form of leprosy is characterized by one or few hypopigmented macules, which are anesthetic and variable in size. These macules have distinct and elevated borders. Peripheral neuropathy in this form of leprosy is usually asymmetric and affects large nerves. Neural leprosy is characterized by functional impairment of large nerve trunks without skin lesions. The upper respiratory system is not involved.

  1. Laboratory Findings.M lepraeis an acid-fast, Gram-stain-variable bacillus. Its size varies from 1 to 8 µm long by 0.3 to 0.5 µm wide. It cannot be distinguished morphologically from other mycobacteria. M leprae's distinguishing characteristics include loss of acid fastness by pyridine extraction, presence of dopa-oxidase activity, and a doubling time of 12 days in the mouse footpad. It is an obligate intracellular parasite but can remain viable outside its natural hosts, i.e. humans and the nine-banded armadillo, for several days. Doubling time of the bacillus is very slow, but, by the time of diagnosis in a lepromatous patient, the number of bacilli present, 1015, is enormous, greater than any human bacterial infectious agent. M leprae has a predilection for cooler areas of the body because it grows best at temperatures under 37°C, hence its characteristic effects on extremities, the nose, and the pinna of the ears.

Table 62-3. Clinical findings in Mycobacterium leprae infection.

o   Acid-fast bacillus, Gram stain variable

o   Presence of dopa-oxidase activity, loss of acid fastness by pyridine extraction

o   Multiplies in mouse foot with doubling time of 12 d

o   Hematoxylin and eosin stain of skin biopsy shows organisms; sometimes silver stain positive

  1. Complications.Leprosy patients may develop Lepra type 1 reaction (downgrading and reversal reactions), Lepra type 2 reaction (erythema nodosum leprosum), or a reaction called Lucio's reaction. Lepra type 1 reactions usually occur in borderline leprosy patients, before therapy (downgrading reaction) or after initiation of therapy (reversal reaction). The reaction consists of inflammation within previous skin lesions, new multiple-satellite maculopapular skin lesions, neuritis, and low-grade fever. Irreversible nerve damage can occur unless therapy with corticosteroids is started promptly. The recommended treatment is prednisone, 40–60 mg daily, tapered over 2–3 months. Lepra type 2 reactions affect nearly half of lepromatous patients, usually within 2 years of instituting antimicrobial therapy. Painful papules on the extensor surface of extremities, neuritis, fever, uveitis, lymphadenitis, orchitis, and glomerulonephritis can occur. Treatment of erythema nodosum leprosum requires a short course of corticosteroids. Lucio's reaction is seen in patients with diffuse lepromatosis and consists of shallow recurrent ulcerations on the lower extremities. Occasionally, the lesions can be generalized, and, in that case, Lucio's reaction can be fatal.

BOX 62-3 Mycobacterium leprae Syndromes

Lepromatous Forms

Tuberculoid Forms

· Symmetrical skin plaques, nodules, or thickened dermis, usually on cooler parts of the body

· Infiltration of upper respiratory system and nasal cartilage, resulting in “saddle nose” deformity

· Symmetric and generalized peripheral neuropathy

· Diffuse lepromatosis seen in Mexican patients, diffuse dermal infiltration without focal lesions

· Normal-looking skin will show organisms in clumps, foam cells in deep dermis, and granulomas in liver, spleen, and lymph nodes

· Few hypopigmented anesthetic macules with distinct elevated and erythematous borders

· Large and asymmetric peripheral nerve involvement

· Neural leprosy causes large functionally impaired nerve trunks without skin lesions

· Lesions and rims should be biopsied (normal-looking skin will not have abnormalities); granulomas with invasion and destruction of dermal nerves

MYCOBACTERIUM KANSASII (CHRONIC PULMONARY INFECTION)

M kansasii is the most common nontuberculous mycobacterium after MAC to be isolated in tertiary care centers. M kansasii is a pathogen worldwide, and in the United States the incidence is highest in the Midwest and Southwest. It commonly affects individuals in certain occupations, such as miners, welders, and sandblasters. Patients with underlying pulmonary pathology can be infected also. However, M kansasii rarely causes disease in children. Children who are affected tend to be immunocompetent and without an underlying pulmonary disease.

Clinical Findings

The most common clinical syndrome caused by M kansasii is a chronic pulmonary infection that resembles pulmonary tuberculosis.

  1. Signs and Symptoms.Symptoms of infection are nonspecific and can include cough, fatigue, and shortness of breath. Uncommonly, M kansasiican cause local lymphadenitis, a skin infection that resembles sporotrichosis. With disseminated infections, skin lesions can be present, such as erythema nodosum, erythema multiforme, and induration.

In AIDS patients, M kansasii is the second most common infection caused by atypical mycobacterium. It tends to produce a disseminated disease similar to MAC. M kansasii-disseminated disease was present at the time of the index AIDS diagnosis in 0.2% of patients. M kansasii can also produce isolated oral ulcers, osteomyelitis, soft tissue infections, tenosynovitis, and arthritis. It may also produce necrotizing pulmonary nodules.

  1. Laboratory Findings.Nonspecific.
  2. Imaging.On chest x-ray, M kansasiiis difficult to distinguish from M tuberculosis. In children, mediastinal and hilar lymph nodes are commonly enlarged.
  3. Differential Diagnosis.Atypical mycobacterium should be suspected if a patient does not respond to conventional therapy for M tuberculosis.

MYCOBACTERIUM SCROFULACEUM (LYMPHADENITIS)

M scrofulaceum is a ubiquitous scotochromogenic mycobacterium that commonly exists in soil and water and contaminates reagents and foodstuffs. It readily colonizes respiratory secretions of healthy children and adults. The most common clinically evident disease in humans is lymphadenitis, which is commonly seen in children < 12 years old.

Clinical Findings

  1. Signs and Symptoms.The clinical presentation is a single node or cluster of nodes in the submandibular area. The nodes slowly enlarge over weeks. The patient experiences very few local or systemic symptoms except for mild lymph node tenderness on palpation. Over weeks to months, if left untreated, the infection comes to the surface, ruptures, and forms a draining sinus, which then calcifies.
  2. Laboratory Findings.Nonspecific.

MYCOBACTERIUM BOVIS (TUBERCULOSIS IN ANIMALS)

M bovis is considered to be part of the M tuberculosis complex. It is a nonchromogen and generally takes 21–40 days to isolate in culture. Its natural reservoir is humans and cattle, and it generally causes tuberculosis in cattle, goats, cats, dogs, primates, and other wildlife. It is rarely a cause of tuberculosis in humans, although there are reports of it causing 3% of the tuberculosis cases in certain places such as San Diego, California. An attenuated strain of M bovisis used for bacille Calmette-Guérin (BCG) vaccine. Transmission of the organism occurs by inhalation of aerosol or by direct inoculation. Transmission by ingestion of contaminated milk from infected cows did occur prior to routine pasteurization. Clinical syndromes associated with M bovis include soft tissue infection. Soft tissue infection has been reported after accidental self-inoculation with BCG by a health care worker.

Clinical Findings

M bovis will cause pulmonary infection indistinguishable from that caused by M tuberculosis. Bacteremia, mycotic aortic aneurysm, vertebral osteomyelitis, and granulomatous hepatitis have been reported as complications of bladder instillation of BCG for the treatment of bladder cancer.

  1. Laboratory Findings.Nonspecific.

MYCOBACTERIUM MARINUM (CLASSIC FISH TANK GRANULOMA)

M marinum is an acid-fast bacillus that is in Runyon class I, the photochromogens. It grows optimally at 32°C and inhabits water and marine organisms. Infection of humans generally occurs after a trauma that takes place in water (eg, fish spines, nips by crustaceans); it can be acquired through open skin that comes into contact with swimming pools, aquariums, domestic fish tanks, or stagnant bodies of water.

Clinical Findings

  1. Signs and Symptoms.The typical lesions of M marinuminfection, which can resemble cutaneous sporotrichosis, are small papules on the extremities that enlarge, turn blue-purple, and then suppurate and ulcerate. Dissemination is rare, although it can occur in immunocompromised hosts.
  2. Laboratory Findings.A skin biopsy should be taken for culture. Pathology shows granulomatous inflammation, but it is rare to find acid-fast bacilli on stain.
  3. Differential Diagnosis.M marinumcan resemble sporotrichosis.

Diagnosis

The diagnosis of atypical mycobacterial infections may be difficult to make with certainty. It is often unclear whether the presence of an atypical mycobacterium in a clinical specimen indicates infection or colonization. The diagnosis of an infection with mycobacteria should be made only in the presence of an illness associated with mycobacteria and when other causes of disease have been excluded. Another clue that helps distinguish colonization from infection is the quantity of growth in culture. Heavy growth of one organism in culture is more suggestive of infection than of colonization; light growth is suggestive of colonization, unless the organism was isolated from a normally sterile body fluid. It is often helpful to notify the microbiology laboratory when infection with an atypical mycobacterium is suspected, because the nontuberculous mycobacteria often have very specialized culture requirements.

Experience is needed for accurate interpretation of the appearance of mycobacteria in stained specimens. Typically, fluorochrome, Kinyoun, and Ziehl-Neelsen stains are used. Cultures are incubated at 37°C in 10% carbon dioxide and 90% air, usually for ≥ 6–8 weeks. (More detailed information regarding laboratory diagnosis can be found in a standard microbiology text.) Typically, detection of growth in culture can be made within 2 weeks, but identification and speciation may take ≤ 2–4 weeks. Susceptibility testing has not been standardized, and all significant isolates need to be tested for antibiotic susceptibility. However, susceptibility to an antibiotic in vitro has not been directly correlated to clinical efficacy.

Diagnosis of MAC, M bovis, and M marinum infections is determined by acid-fast bacillus smear and culturing from the infected tissue. Diagnosis of M scrofulaceum infection is made by identification of granulomatous inflammation in skin biopsy and isolation of the organism from culture. Diagnosis of M kansasii infection is difficult, especially since there can be a concurrent infection with M tuberculosis.

Diagnosis of leprosy depends on clinical information as well as biopsy of affected dermis; viable organisms stain brightly and uniformly (see Table 62-3). Nonviable organisms stain in an irregular manner. A skin biopsy taken from a patient with suspected leprosy should be stained with hematoxylin and eosin, as well as with Fite stain for acid fastness.

The two polar forms of leprosy are the lepromatous, or multibacillary, and the tuberculoid, or paucibacillary (see Box 62-3 for features of both). Most patients will have intermediate forms. In lepromatous patients, skin biopsies should be taken at sites of skin lesions, but normal looking skin will also have pathologic changes. Lesions will show many bacilli in clumps and foam cells loaded with bacilli in the dermis. Granulomatous changes may be seen in the liver, spleen, and lymph nodes. In tuberculoid patients, biopsies should be done only at sites of lesions because biopsies of normal appearing skin will be nondiagnostic. Skin biopsies from tuberculoid patients will show few or no organisms but will show granulomas of epithelial cells, lymphocytes, and foreign-body giant cells near dermal appendages, especially dermal nerves. The pathognomic lesion for tuberculoid leprosy is acute granulomatous invasion and destruction of dermal nerves. Most patients, however, have intermediate, or borderline, forms of leprosy, and their biopsies will show a mixture of findings.

An intradermal skin test is available that uses heat-killed M leprae. However, use of the skin test to make the diagnosis of leprosy is unreliable. Although the skin test will be positive in tuberculoid patients, treated lepromatous patients and unaffected individuals in endemic areas will show positive results as well. Lepromatous patients will be anergic specifically to M leprae but will have a normal response to intradermal recall antigens, such as purified protein derivative. Various M leprae lipid and carbohydrate constituents are believed to impair macrophage and T-lymphocyte function specifically against M leprae. There also seems to be an increase in the number of T-suppressor cells. Cytokines such as interleukin 2 (IL-2), interferon γ (IFN-γ), IL-4, IL-5, and IL-10 are also thought to play a role in expression of disease.

Treatment of Atypical Mycobacterial Infections

MAC Infection. Treatment of pulmonary disease, disseminated disease, subcutaneous infections, and bone infections in immunocompetent patients consists of a regimen of three drugs (Box 62-4). Clarithromycin at a dose of 500 mg by mouth two times a day is given with ethambutol at a dose of 15–25 mg per kg by mouth every day. These two drugs are also then given with rifabutin, 300 mg by mouth every day for ≤ 24 months. If there is an isolated lung lesion, surgical removal of the nodule is a treatment option. Other second-line drugs include azithromycin, clofazimine, ciprofloxacin, and amikacin. The regimen used should be tailored to in vitro susceptibility tests. Patients with pulmonary disease should have sputum samples tested every month during the course of treatment. In 80–90% of patients, the sputum should convert to negative in 1–2 months. The therapy should be extended for 12 months after the sputum conversion.

HIV-positive patients with disease can be treated with a three-drug regimen that includes clarithromycin or azithromycin, ethambutol, and/or rifabutin (Box 62-5). An alternative regimen includes clarithromycin or azithromycin, ethambutol, plus/ minus rifabutin and one of the following: ciprofloxacin, ofloxacin, or amikacin. A recent study of treatment regimens showed that therapy with rifabutin, ethambutol, and clarithromycin resulted in a longer mean survival than did therapy with rifampin, ethambutol, clofazimine, and ciprofloxacin. The efficacy of these regimens in children with HIV infection has not been well established.

 

BOX 62-4 Treatment of MAC in Immunocompetent Patients

 

Adults

Children

First Choice

Clarithromycin 500 mg PO twice daily + ethambutol 15–25 mg/kg PO + rifabutin 300 mg PO once daily for as many as 24 months, treat for at least 12 months after sputum conversion; surgical excision if one isolated pulmonary nodule

Clarithromycin, 7.5 mg/kg PO twice daily (max. dose 500 mg/dose) in children >6 months old + ethambutol, 15 mg/kg/d as a single dose in children >13 years old + rifabutin

Second Choice

Rifampin + ethambutol + clofazamine + ciprofloxacin, 750 mg PO twice daily

 

Once immunosuppressed patients with AIDS are treated, they must be placed on lifelong suppressive therapy that includes clarithromycin or azithromycin plus ethambutol. Alternative drugs include clarithromycin or azithromycin alone or rifabutin.

AIDS patients who do not have documented active MAC disease and whose CD4 count is < 100 may be placed on primary prophylactic therapy, which consists of a single drug (Box 62-6). Those drugs used in primary prophylaxis are clarithromycin, azithromycin, or rifabutin. Clarithromycin reduces the MAC infection rate by 68% and was associated with a 38% mortality rate as compared with 47% with placebo.

M leprae Infection. Leprosy generally requires a long duration of treatment, and compliance is a major problem. Lepromatous leprosy requires a longer treatment time course than tuberculoid leprosy because of the greater number of organisms involved. Currently, the recommended treatment is dapsone and rifampin for 6 months for tuberculoid leprosy (Box 62-7). Dapsone alone is not recommended because of reports of emerging resistance. For lepromatous leprosy, dapsone with rifampin or clofazimine for 24 months is recommended. Nonetheless, there have been reports of relapses even after such long courses of treatment. Other agents such as ethionamide, prothionamide, the aminoglycosides, minocycline, clarithromycin, and the fluoroquinolones may also prove to be beneficial.

BOX 62-5 Treatment of MAC in AIDS patients

First Choice

Same regimen as adult treatment of MAC in immunocompetent patients. May substitue azithromycin (500 mg once daily) for clarithromycin

Second Choice

Clarithromycin or azithromycin + ethambutol + rifabutin + 1 or more of the following

· Ciprofloxacin, 750 mg PO twice daily

· Ofloxacin, 400 mg PO twice daily

· Amikacin, (7.5–15 mg/kg) IV or IM

Pediatric Considerations

Treatment regimens for pediatric AIDS patients are not well established.

M kansasii Infection. Response to antimycobacterial therapy tends to be poor, but there have been reports of clinical responses. Treatment must be tailored to each individual patient depending on the in vitro sensitivities of M kansasii and whether immunosuppression is present. Treatment should consist of a three- to five-drug regimen depending on sensitivities. A common regimen for M kansasii includes rifampin (10 mg/kg/d for a maximum of 400 mg/d), isoniazid (5 mg/kg/d for a maximum of 300 mg/d), and ethambutol (15–25 mg/kg/d). Treatment should be continued for ~ 18 months and has been shown to have about a 90% response rate.

BOX 62-6 Control of MAC Infection in AIDS Patients

Prophylactic Measures

· Lifelong prophylaxis in AIDS patients with CD4 <100: clarithromycin, 500 mg PO twice daily or azithromycin, 1200 mg PO weekly, or rifabutin, 300 mg PO once daily.

· Secondary prophylaxis in AIDs patients after treatment of MAC disease: clarithromycin OR azithromycin PLUS ethambutol (15 mg/kg/d)

Isolation Precautions

· None

BOX 62-7 Treatment of Mycobacterium leprae

 

Adults

Children

First Choice: Tuberculoid

Dapsone, 100 mg once daily unsupervised + rifampin, 600 mg once per month supervised for 6 months

Correspondingly lower dose

First Choice: Lepromatous

Dapsone, 100 mg once daily + clofazamine, 50 mg once daily unsupervised OR rifampin, 600 mg once daily + clofazamine, 300 mg every month supervised for 24 months

Correspondingly lower doses

Alternative Choice

Ethionamide, 250 mg once daily or prothionamide, 375 mg once daily in place of clofazamine; minocycline, clarithromycin, or fluoroquinolone reportedly bactericidal

 

M kansasii has been shown to be sensitive in vitro to clarithromycin, erythromycin, amikacin, and the fluoroquinolones. These medications, along with sulfamethoxazole or bactrim, are second-line drugs. If lymphadenitis is present, the lymph node should be totally excised. There is no rationale for incision and drainage. In AIDS patients with disseminated disease, treatment should be extended for 15 months after cultures are negative. Treatment regimens in children have not been well established.

M scrofulaceum Infection. Antituberculosis drugs are not helpful. The treatment of choice is surgical excision of involved nodes. Clarithromycin may be useful in patients not responsive to excision.

M bovis Infection. Treatment of M bovis is the same as for M tuberculosis, although M bovis is uniformly resistant to pyrazinamide.

M marinum Infection. Treatment of M marinum infection consists of rifampin and ethambutol.

Prevention & Control of Atypical Mycobacterium Infection

No isolation measures are needed since the organisms are found in the environment. Prophylaxis is needed only in AIDS patients with MAC (see Box 62-6).

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