Leprosy and Atypical Mycobacterial Infections Flashcards
Leprosy or Hansen’s Disease is primarily a chronic granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract, caused by the mycobacteria, Mycobacterium Leprae and Mycobacterium Lepromatosis. What is the treatment for this disease?
Dapsone, Clofazimine and Rifampin
—resistance to dapsone developed very quickly and it was only the introduction of combo therapy that has lead to treatment of disease
What are the WHO treatment recommendations for Leprosy?
Type:
- Pauci-bacillary (PB): 1-5 skin lesions — Rifampin + Dapsone for 6 months
- Multi-bacillary: greater than 5 skin lesions – Rifampin, Clofazimine and Dapsone (12 months)
First lets discuss dapsone for tx of Leprosy. What is the MOA?
Related to sulfa
–mechanism involves the inhibition of folate synthesis (via dihydropteroate synthethase inhibition)
What is the clinical application and spectrum of activity for dapsone?
Used in combo with rifampin +/- clofazimine
Alternative in the tx of AIDS related PCP
What are the pharmacokinetics for Dapsone?
Acedapsone is a repository form of dapsone that provides inhibitory plasma concentrations for several months
Can be given orally and penetrates tissue well
What are the adverse effects of Dapsone?
Hemolysis: esp in G6PD patients
Erythema Nodosum Leprosum : inflammatory condition of leprosy – painful skin lesions on the arms and legs and face.
Cytochrome P450 inhibitior
The other drug for the treatment of Leprosy is Clofazimine. What is the MOA?
Phenazine Dye
- -binds to DNA to inhibit replications
- -redox properties that lead to generation of cytotoxic oxygen radicals
What is the spectrum of activity and clinical applications of Clofazimine?
Bactericidal to M. Leprae
Some activity to M. Avium-intracellulare complex
Used in combo with dapsone and rifampin for tx
What are adverse effects of Clofazimine?
Red brown discoloration of the skin
GI irritation
Eosinophilic enteritis
Finally a bit on drugs for Atypical Mycobacterial Infections. What are some features?
M. Avium and M. Kansaii: present in the environment but are not communicable from person to person
- -susceptible to different drugs to those used for both the treatment of TB and leprosy
- -combo therapy is recommended
What is the tx for M. Kansaii?
Resembles TB
–Isoniazid + Rifampin + Ethambutol
What is the tx for M. Marinum?
Granulomatous Cutaneous Disease
Rifampin, ethambutol, clarithromycin, minocycline, doxycycline or sulfa
2 drug combo therapy
What is the tx for M. Avium Complex?
Pulmonary Disease
-Clarithromycin + Ethambutol +/- Rifabutin
What is the tx for M. Chelonae?
Abscess, Sinus Tract, Ulcer, Bone/Joint/Tendon Infection
–Clarithromycin (monotherapy usually works fine)
What is the tx for M. Fortuitum?
Abscess, Sinus tract, Ulcer, Bone/Joint/Tendon Infection
–Amikacin, Cefoxitin, Levofloxacin, Sulfa, Imipenem
