Mycobacterium Avium Complex Flashcards
What organisms are included in the Mycobacterium avium complex (MAC)?
Includes M. avium subspecies hominissuis, M. colombiense, M. genavense, M. kansasii, M. simiae, M. mycogenicum, and others.
What percentage of people with HIV and advanced immunosuppression historically acquired disseminated MAC disease before effective ART?
> 95%
What is the estimated prevalence of MAC infection in adults with HIV?
7% to 12%
What factors are associated with an increased risk for MAC disease in people with HIV?
- CD4 count <50 cells/mm3
- Ongoing HIV viral replication despite ART
- Previous or concurrent opportunistic infections
- Reduced lymphoproliferative immune responses
- Genetic predisposition
What is the typical clinical presentation of MAC disease in people with advanced HIV immunosuppression?
Disseminated, multi-organ infection with symptoms like fever, night sweats, weight loss, fatigue, diarrhea, and abdominal pain.
What laboratory abnormalities are particularly associated with disseminated MAC disease?
- Anemia
- Elevated liver alkaline phosphatase levels
What is the diagnosis criterion for confirmed disseminated MAC disease?
Isolation of MAC from cultures of blood, lymph fluid, bone marrow, or other normally sterile tissue.
True or False: Person-to-person transmission of MAC disease is likely.
False
What is the preferred therapy for primary prophylaxis against disseminated MAC disease?
- Azithromycin 1,200 mg PO once weekly
- Clarithromycin 500 mg PO twice daily
- Azithromycin 600 mg PO twice weekly
When should primary prophylaxis for MAC disease be discontinued?
If the patient is continuing on a fully suppressive ART regimen.
What is the recommended duration of therapy for treating disseminated MAC disease?
At least 12 months
Fill in the blank: MAC disease typically occurs in people with HIV with CD4 T lymphocyte counts < ______ cells/mm3.
50
What are the preferred initial drugs for treating disseminated MAC disease?
- Clarithromycin 500 mg PO twice daily plus ethambutol 15 mg/kg PO daily
- Azithromycin 500–600 mg plus ethambutol 15 mg/kg PO daily
What should be ruled out before initiating primary prophylaxis for MAC disease?
Disseminated MAC disease
What is the impact of effective ART on the incidence of MAC disease?
The overall incidence has declined to <2 cases of MAC per 1,000 person-years.
What is the association between immune function and localized MAC disease?
Localized MAC disease occurs more often in people with HIV on suppressive ART with increased CD4 counts.
What is the risk of developing MAC disease after stopping primary prophylaxis in patients on effective ART?
0.6 to 0.8 per 100 person-years
What alternative therapy is suggested for those who cannot tolerate azithromycin or clarithromycin?
Rifabutin 300 mg PO daily
What factors may necessitate adding a fourth drug to MAC treatment?
- More severe disease manifestations
- High risk of mortality
- Emergence of drug resistance
- CD4 count <50 cells/mm3
- High mycobacterial loads
What is the role of molecular techniques in diagnosing MAC?
Species identification should be performed using molecular techniques.
What is the recommended approach for treating asymptomatic colonization with MAC organisms?
Routine screening and preemptive treatment are not recommended.
What are some localized syndromes associated with MAC disease?
- Cervical lymphadenitis
- Intraabdominal lymphadenitis
- Pneumonia
- Pericarditis
- Osteomyelitis
- Skin abscesses
What is the significance of a positive culture for MAC from sputum specimens?
It is part of the diagnostic criteria for MAC disease limited to the lung.
What is the recommended action if active tuberculosis (TB) is suspected before starting rifabutin?
Active TB should be ruled out.
What is the general recommendation for the use of aminoglycosides in MAC treatment?
Generally avoided unless in the setting of refractory disease when other alternatives are not available or tolerated
Which drugs have demonstrated in vitro activity against clinical isolates of MAC?
- Bedaquiline
- Tedizolid
- Linezolid
- Omadacycline
What is the minimum duration of therapy for MAC disease?
At least 12 months
What CD4 count is required for discontinuation of MAC therapy?
CD4 count should be >100 cells/mm3 for ≥6 months
What is the same as treatment regimens for chronic maintenance therapy?
Same as treatment regimens
What are the criteria for discontinuing chronic maintenance therapy?
- Completed at least 12 months of therapy
- No signs or symptoms of MAC disease
- Sustained (≥6 months) CD4 count >100 cells/mm3 in response to ART
When should chronic maintenance therapy be restarted?
If a fully suppressive ART regimen is not possible and CD4 is consistently <100 cells/mm3
What is the preferred drug combination for secondary prophylaxis during pregnancy?
- Azithromycin
- Ethambutol
What may be used for moderate to severe symptoms attributed to IRIS?
NSAIDs
How long can systemic corticosteroid therapy be used for IRIS symptoms?
4–8 weeks
What is the initial treatment for MAC disease?
Consist of two or more antimycobacterial drugs
What are the preferred first agents for MAC treatment?
- Clarithromycin
- Azithromycin
What is associated with increased mortality in MAC treatment?
Doses of clarithromycin >1 g/day
What should be tested for MAC isolates?
Susceptibility to clarithromycin or azithromycin
What is the recommended second drug for the initial treatment of MAC disease?
Ethambutol
What can be used as a third drug in MAC treatment?
Rifabutin
What are the injectable aminoglycosides mentioned?
- Amikacin
- Streptomycin
What is the risk associated with advanced immunosuppression in MAC treatment?
High risk of mortality and emergence of drug resistance
What is the recommended duration of treatment for people with HIV and disseminated MAC disease?
Minimum duration of 12 months
When should ART be initiated in relation to MAC disease diagnosis?
As soon as possible after the diagnosis
What should be monitored after initiating antimycobacterial therapy?
Repeat blood culture for MAC
What are some adverse effects of clarithromycin and azithromycin?
- GI upset
- Metallic taste
- Elevations in liver transaminase levels
- Hypersensitivity reactions
What can increase clarithromycin levels?
Protease inhibitors (PIs)
What is IRIS associated with MAC disease?
A systemic inflammatory syndrome with signs and symptoms clinically indistinguishable from active MAC infection
What is the definition of MAC treatment failure?
Absence of a clinical response and persistence of mycobacteremia after 4 to 8 weeks of treatment
What should be done if MAC isolates show resistance?
Repeat testing for susceptibility and construct a new multidrug regimen
What should not be continued despite resistance to clarithromycin or azithromycin?
Continuing clarithromycin or azithromycin
What is the recommendation for primary prophylaxis for MAC disease in pregnant people?
Not recommended
What should be done if ART does not result in immune reconstitution?
Continue chronic maintenance therapy
What is the recommendation for primary prophylaxis for MAC disease in pregnant people who immediately initiate ART?
Not recommended (AIII)
This means that if a pregnant person starts ART immediately, they do not need primary prophylaxis for MAC disease.
What is the preferred agent for primary prophylaxis in a pregnant person not treated with effective ART?
Azithromycin (BIII)
Azithromycin is favored when primary prophylaxis is necessary for pregnant individuals not on effective ART.
What is the recommended drug combination for secondary prophylaxis in pregnant individuals?
Azithromycin plus ethambutol (BIII)
This combination is used for chronic maintenance therapy.
Why is clarithromycin not recommended as the first-line agent for prophylaxis or treatment of MAC in pregnancy?
Increased risk of birth defects based on animal studies (BIII)
Animal studies have shown that clarithromycin may lead to birth defects, leading to its avoidance in pregnancy.
What did two studies with first-trimester exposure to clarithromycin show regarding defects?
No increase in specific pattern of defects, but one noted increased risk of spontaneous abortion
This indicates that while defects weren’t specifically linked to clarithromycin, there might be a risk of miscarriage.
What did azithromycin studies find regarding defects in animal studies?
Did not produce defects
However, human experience with azithromycin in the first trimester is limited.
What association was found in a nested case-control study regarding azithromycin use?
Association with spontaneous miscarriage
The study could not adjust for infection severity, which is an important factor.
What have multiple studies found about azithromycin use in the first trimester and major congenital malformations?
No association found
Studies included large cohort studies that looked into this specific issue.
What did a systematic review of pregnancy outcomes following macrolide use reveal?
No significant increased risks for major congenital malformations
However, a small but significant increased rate of major congenital malformations with azithromycin could not be excluded due to maternal confounders.
What was the conclusion of a Cochrane systematic review regarding azithromycin and other agents for treating Chlamydia trachomatis infection in pregnancy?
No apparent difference in efficacy and pregnancy complications
This suggests that azithromycin is comparable to other treatments for this condition during pregnancy.
