• Information
  1. Species of Mycobacteria
  2. Characteristics of Mycobacterium Avium Complex
  3. Diagnosis
  4. Treatment of MAC
  5. Prophylaxis Against MAC
  6. Mycobacterium bovis

A. Species of Mycobacteria

1. Common Typical Mycobacteria
   1. M. tuberculosis
   2. M. bovis (see below)
   3. M. leprae (isolated infected areas)
2. Atypical Mycobacteria
   1. M. avium complex (MAC; see below)
   2. M. marinum (see below)
   3. M. chelonae - may cause cellulitis and other subcutaneous infections [1]
   4. M. haemophilum - skin and soft tissue infection in immunocompromised patients
   5. M. scrofulaceum - can cause lymphadenitis; uncommon in the USA (scrofula agent)
   6. M. kansasii - pulmonary disease similar to tuberculosis
   7. M. xenopi - pulmonary disease similar to TB, mainly Canada and Southern Europe
   8. M. malmoense - pulmonary disease similar to TB, mainly Scandinavia and North Europe
   9. M. ulcerans (mainly Africa; see below)
   10. M. avium paratuberculosis (MAP; see below)
3. M. marinum [2]
   1. Originally called "swimming pool granuloma" now "fish tank granuloma"
   2. Infection transmitted from fresh and salt water, usually through skin breaks
   3. Increasing incidence with popularity of fish tank hobby
   4. Mainly causes superficial skin infections on limbs: nodules, ulcers, abscesses
   5. Can penetrate deeper structures causing tenosynovitis, arthritis, osteomyelitis
   6. Disseminated infections very uncommon
   7. Treatment requires drug combinations: rifampin and clarithromycin most effective
   8. Ethambutol, doxycycline (minocyline), also effective and may be included in combination
   9. Ofloxacin, ciprofloxacin, TMP/SMX, are also effective
   10. Susceptibility testing should be carried out on all isolates
   11. Therapy should extend for a minimum of 6-8 weeks even with rapid healing
4. M. kansasii [3,4]
   1. Causes pulmonary disease indistinguishable from M. tuberculosis
   2. Increasing incidence in both HIV+ and HIV- persons
   3. Overall, 2.4 cases per 100,000 adults per year
   4. About 115 cases per 100,000 HIV+ persons per year
   5. 94% of cases from respiratory isolates
   6. About 10% of HIV+ persons with M. kansasii have mycobactermia (0% of HIV- persons)
   7. About 40% of HIV- persons with M. kansasii had no underlying disease
   8. Association with transverse myelopathy reported [4]
5. M. ulcerans [5,18]
   1. Third most common mycobacterial disease in immunocompetent persons
   2. Causes Buruli ulcer disease, mainly in Africa, some parts of South America
   3. Transmitted from environment (believed to be mainly insects) through mild traumatic injuries or abraded skin
   4. Produce ulcerations through secretion of mycolactones, highly inflammatory lipids
   5. Mycolactones destroy cells in subcutis causing large ulcers with undermined edges
   6. Painless nodules may resolve or progress
   7. Large unseemly but generally painless ulceration can occur
   8. Systemic symptoms are minimal even with large ulcers
   9. Large ulcers can slowly resolve, or surgery can be used
   10. Rifampicin + amikacin or streptomycin for 12 weeks is recommended
   11. Treatment for 8 weeks with daily rifampicin 10mg/kg po and streptomycin 15mg/kg IM leads to conversion of cultures from positive to negative within 4 weeks [5]
   12. Trimethoprim-sulfamethoxazole and clofazimine do not appear to be effective
   13. Excision of <5cm ulcers under local anesthetic is curative in 84% of cases
   14. BCG vaccination may afford some protection from infection / symptoms
   15. Additional vaccines are being developed including DNA based vaccines
6. Mycobacterium avium paratuberculosis (MAP) [16]
   1. Similar pathology between paratuberculosis caused by MAP and Crohn's disease
   2. MAP (Mycobacterium avium subspecies paratuberculosis) causes chronic enteritis in cows
   3. MAP DNA found in 45% of CD patients' white blood cells
   4. Viable MAP cultured from 50% of CD, 22% of UC, and none in normal persons

B. Characteristics of Mycobacterium Avium Complex (MAC)

1. MAC is most common atypical mycobacterial species
2. Usually affects lungs and/or gastrointestinal (GI) tract
3. MAC is found primarily in immunocompromised patients
   1. Most patients have AIDS with CD4 <100/µL
   2. Many persons are colonized with these organisms
   3. AIDS and other causes of immunosuppression can cause reactivation and dissemination
4. GI disease is most commonly affected in immunocompromised patients
   1. Diarrhea is most common symptom in these patients
   2. Usually in HIV+ persons (CD4 T cell count <100/µL)
   3. Watery diarrhea, large volumes
5. Pulmonary Mycobacteria [7]
   1. Most common in patients with underlying chronic lung disease
   2. Symptoms: hypoxia, tachypnea, chest pain, cough, sputum production
   3. Interstitial Pneumonia, often with nodular opacities
6. Systemic Symptoms in AIDS Patients
   1. Fatigue and malaise
   2. High fevers
   3. Bacteremia
7. Hypersensitivity Pneumonitis [19]
   1. May occur in immunocompetent patients
   2. Exposure to MAC in high levels
   3. "Hot-tub" lung - MAC accumulates in standing water
   4. May progress to ARDS but have self-resolving course

C. Diagnosis

1. Purified Protein Derivative (PPD)
   1. Mild cross reaction with MAC infection using standard PPD from M. tuberculosis
   2. PPD skin test is usually positive in infected patients unless they are anergic
2. Sputum Culture and Gram Stain
3. Blood Cultures (mycobacterial isolator tubes) - sometimes positive in AIDS patients
4. Invasive Testing
   1. Gastrointestinal biopsy - stain and culture
   2. Bronchealveolar Lavage (BAL) with biopsy for possible lung infection
5. Careful speciation and drug sensitivity testing are required in all cases

D. Treatment of MAC [8,9]

1. Treatment of active infection requires combination antimicrobacterial agents
   1. Rapid resistance to all drugs develops when single agents are used
   2. Combination of agents with different mechanisms is required
   3. Chronic suppressive therapy generally required unless CD4 counts increase to >200/µL
   4. Suppressive therapy may be discontinued with HIV treatment to CD4 >200/µL [17]
2. The following agents are active against MAC (with doses)
   1. Clarithromycin 500mg po bid - single most potent agent [9,10]
   2. Azithromycin 500mg po qd (1200mg weekly for prophylaxis) [11]
   3. Ethambutol 15-25mg/kg/d po (may cause optic neuritis)
   4. Rifabutin 300mg po qd
   5. Ciprofloxacin 750mg po bid or Ofloxacin 400mg po bid
   6. Amikacin Sulfate 10mg/kg/d intravenous
3. Disseminated MAI in AIDS patients with AIDS [10]
   1. Rifabutin, ethambutol and clarithromycin is current treatment of choice
   2. More effective than rifampin, ethambutol, clofazamine and ciprofloxacin
   3. Rifabutin at 300mg/d was not as effective as 600mg/d dose, but better tolerated
   4. Clarithromycin may increase serum concentrations of rifabutin and decrease ZDV
4. Treatment of other atypical mycobacteria depends on susceptibility testing [1,2]

E. Prophylaxis Against MAC

1. Azithromycin [11]
   1. Dose of 1200mg po weekly is more effective prophylaxis than 300mg qd rifabutin
   2. Azithromycin is well tolerated and rarely selects for resistance
   3. Azithromycin cost-benefit is $35,000 per QALY (quality adjusted life year) [12]
   4. Azithromycin also reduced incidence of pneumocystis infections by 45% when given with rifampin for MAI prophylaxis [13]
   5. Azithromycin prophylaxis may be discontinued in patients with durable increases in CD4 counts to >100/µL on antiretroviral therapy [14,15]
2. Clarithromycin [9]
   1. Dose of 500mg bid prophylaxis reduces infection rate by ~70%
   2. Improves survival by ~30%
   3. Most effective agent for prophylaxis
   4. Higher pill burden than qd agents
3. Rifabutin [8]
   1. 300mg po qd reduces infection rate by 55%
   2. Frequency of disseminated MAI, fever and fatigue decreased in HIV patients
   3. Bactermia from ~18% in controls to ~9% in treated patients
   4. Side effects include uveitis and decreased serum AZT levels
   5. Rifabutin cost-benefit is $74K per QALY, more than twice as much as azithromycin [12]
4. Azithromycin + rifabutin very effective but less well tolerated than single agents [11]
5. Combination therapy recommended only for active infections
6. Breakthrough common in HIV disease with CD4<50/µL
7. Baseline cultures should be obtained prior to initiating prophylaxis
8. These baseline cultures insure that there is no occult mycobacteremia

F. Mycobacterium bovis

1. Usually only in advanced HIV infection, the elderly, other immunosuppresion
2. Also causes tuberculosis in normal patients and animals in underdeveloped countries
3. M bovis transmission between humans in UK (cluster of 6 cases) reported [6]
4. Bacillus Calmette-Guerin (BCG) preparation of M. bovis given intravesicularly is a common treatment for bladder cancer
5. Mycobacteremia can occur after BCG treatment for bladder cancer
6. Highly drug resistant, untreatable nosocomial outbreak has been described recently [20]

References

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19. Systrom DM and Wittram C. 2005. NEJM. 352(12):1238 (Case Record)
20. Jasmer RM, Nahid P, Hopewell PC. 2002. NEJM. 347(23):1860