Drugs active against atypical mycobacteria Introduction About 10% of mycobacterial infections seen in clinical practice in USA are not cozed by M tuberculosis or M tuberculosis complex organisms But they are cozed nontuberculous or so-called "atypical" mycobacteria. Atypical mycobacteria have distinctive lab x-tics They are present in the environment & are not communicable frm person to person. As a rule, these mycobacterial species are less susceptible than M tuberculosis to antituberculous drugs.

1. Dr. NDAYISABA CORNEILLE
CEO of CHG
MBChB,DCM,BCSIT,CCNA
Supported BY
DRUGS FOR ATYPICAL
MYCOBACTERIUM &
LEPROSY

2. Drugs active against atypical mycobacteria
Introduction
 About 10% of mycobacterial infections seen in
clinical practice in USA are not cozed by M
tuberculosis or M tuberculosis complex organisms
 But they are cozed nontuberculous or so-called
"atypical" mycobacteria.
Dr Ndayisaba Corneille

3.  Atypical mycobacteria have distinctive lab x-tics
 They are present in the environment & are not
communicable frm person to person.
 As a rule, these mycobacterial species are less
susceptible than M tuberculosis to antituberculous
drugs.
Dr Ndayisaba Corneille

4.  Instead agents such as erythromycin,
sulfonamides, or tetracycline may be effective for
infections cozed by atypical strains.
 Emergence of resistance during therapy is also a
problem with these mycobacterial spp & active
infection shld be Rx with combinations of drugs.
Dr Ndayisaba Corneille

5.  M kansasii is susceptible to R & E, partially
resistant to IHZ & completely resistant to
pyrazinamide.
 A three-drug combination of RHE is the
conventional Rx for M kansasii infection.
Dr Ndayisaba Corneille

6. Examples of atypical mycobacterium
 M kansasii
 M marinum
 M scrofulaceum
 M avium complex
 M chelonae
 M fortuitum
 M ulcerans
Dr Ndayisaba Corneille

7. M marinum
Clinical presentation
 Granulomatous
cutaneous disease
Treatment options
 Amikacin
 Clarithromycin
 Ethambutol
 Doxycycline
&minocycline
 Rifampin
 Trimethoprim-
sulfamethoxazole
Dr Ndayisaba Corneille

8. M kansasii
Clinical presentation
 Resembles
tuberculosis
Treatment options
 Ciprofloxacin
 Clarithromycin
 Ethambutol
 Isoniazid
 Rifampin
 Trimethoprim-
sulfamethoxazole
Dr Ndayisaba Corneille

9. M scrofulaceum
Clinical presentation
 Cervical adenitis in
children
Treatment options
 Amikacin
 Erythromycin (or other
macrolide)
 Rifampin
 Streptomycin
 Surgical excision is
often curative & Rx of
choice.)
Dr Ndayisaba Corneille

10. M avium complex
Clinical presentation
 Pulmonary disease in
pts with chronic lung
disease
 Disseminated
infection in AIDS
Treatment options
 Amikacin
 Azithromycin
 Clarithromycin
 Ciprofloxacin
 Ethambutol
 Rifabutin
Dr Ndayisaba Corneille

11. M chelonae
Clinical presentation
 Abscess
 Sinus tract infection,
 Ulcer;
 Bone infection,
 Joint infection
 Tendon infection
 Amikacin
 Doxycycline
 Imipenem
 Macrolides
 Tobramycin
Treatment options
Dr Ndayisaba Corneille

12. M fortuitum
Clinical presentation
 Abscess
 Sinus tract infection
 Ulcer infection
 Bone infection
 Joint infection
 Tendon infection
Treatment options
 Amikacin
 Cefoxitin,
 Ciprofloxacin,
 Doxycycline,
 Ofloxacin,
 Trimethoprim-
sulfamethoxazole
Dr Ndayisaba Corneille

13. M ulcerans
Clinical presentation
 Skin ulcers
Treatment options
 Isoniazid
 Streptomycin
 Rifampin
 Minocycline
 (Surgical excision
may be effective.)
Dr Ndayisaba Corneille

14. M. avium complex(MAC)
 Includes both M avium & M intracellulare
 An important & common coz of disseminated
disease in late stages of AIDS,CD4 counts <
50/mm³.
 MAC is much less susceptible than M. tuberculosis
to most anti-cocks
Dr Ndayisaba Corneille

15. Rx of MAC
 Combinations of agents are required to suppress
the disease.
 Azithromycin500 o.d or Clarithromycin 500 mg BD
 Plus ethambutol 15–25 mg/kg/d, is an effective &
well-tolerated regimen for Rx of disseminated
disease.
Dr Ndayisaba Corneille

16.  Some authorities recommend use of a 3rd agent,
such as ciprofloxacin 750 mg BD or rifabutin, 300
mg OD.
 Other agents that may also be useful.
 Rifabutin 300 mg o.d has been shown to reduce
incidence of MAC bacteremia in AIDS pts with CD4
less than 100/ mm³
Dr Ndayisaba Corneille

17.  Clarithromycin also effectively prevents MAC
bacteremia in AIDS pts.
 But if a breakthrough bacteremia occurs, isolates
often are resistant to both clarithromycin &
azithromycin.
 This precludes use of these most effective drugs
for Rx of MAC
Dr Ndayisaba Corneille

18. Drugs used in Leprosy
 Mycobacterium leprae has never been grown in
vitro.
 But animal models have permitted growth.
 Only drugs that have the widest clinical use are
presented here.
 Bcoz of increasing reports of dapsone resistance,
Rx of leprosy with combinations of the drugs is
recommended. Dr Ndayisaba Corneille

19. Examples drugs used in leprosy
 Dapsone
 Clofazimine
 Rifampicin
Dr Ndayisaba Corneille

20. 1. Dapsone & other sulfones
 Several drugs closely related to sulfonamides have
been used effectively in long-term Rx of leprosy
 The most widely used is dapsone
(diaminodiphenylsulfone).
Mechanism of action
 Like the sulfonamides, it inhibits folate synthesis.
Dr Ndayisaba Corneille

21.  Resistance can emerge in large popns of M leprae,
eg, in lepromatous leprosy, if very low doses are
given.
 Thus, the combination of Dapsone, rifampin &
Clofazimine is recommended for initial therapy.
Dr Ndayisaba Corneille

22. Pharmacokinetics
 Well absorbed frm the gut & widely distributed
throughout body fluids &tissues.
 Half-life is 1–2 days
 Drug tends to be retained in skin, muscle, liver &
kidney.
 Skin heavily infected with M leprae may contain
several times more drug than normal skin.
Dr Ndayisaba Corneille

23.  Excreted into bile & reabsorbed into intestine.
 Excretion into urine is variable & most excreted
drug is acetylated.
 In renal failure, the dose may have to be adjusted.
 Dosage in leprosy is 100 mg/d.
 For children, the dose is less depending on weight.
 Usually well tolerated
Dr Ndayisaba Corneille

24. Indications for Dapsone
 Rx of leprosy
 Prophylaxis against PJP I pts intolerant to septrine
 Rx of Pneumocystis jiroveci pneumonia (PJP) in
AIDS pts.
Dr Ndayisaba Corneille

25. S/E
 Some hemolysis, esp if pts have G6PD deficiency.
 Methemoglobinemia is common, but rarely a prob
clinically.
 GI intolerance
 Fever
 Pruritus & various rashes
Dr Ndayisaba Corneille

26.  Erythema nodosum leprosum during therapy of
lepromatous leprosy
 Erythema nodosum leprosum may Rx by
corticosteroids or thalidomide.
*It is sometimes difficult to distinguish reactions to
dapsone frm manifestations of the underlying
illness.
Dr Ndayisaba Corneille

27. 2. RIFAMPIN
 600 mg/d is highly effective in lepromatous leprosy.
Bcoz of the probable risk of emergence of
rifampin-resistant M leprae.
 Given in combination with dapsone or another
antileprosy drug.
Dr Ndayisaba Corneille

28. 3. Clofazimine
 Phenazine dye that can be used as an alternative
to dapsone.
Mechanism of action
 Is unknown but may involve DNA binding.
Pharmacokinetics
 A common dosage is 100 mg/d orally.
 Absorption frm the gut is variable & a major portion
of the drug is excreted in feces.
Dr Ndayisaba Corneille

29.  Stored widely in reticuloendothelial tissues & skin
& its crystals can be seen inside phagocytic
reticuloendothelial cells.
 It is slowly released frm these deposits, so that
serum half-life may be 2 months.
S/E
 Skin discoloration ranging frm red-brown to nearly
black.(Most prominent S/E)
 GI intolerance Dr Ndayisaba Corneille

30. Indications for Clofazimine
 Sulfone-resistant leprosy
 Pts are intolerant to sulfones.
Dr Ndayisaba Corneille

31. END
BY
DR NDAYISABA CORNEILLE
MBChB,DCM,BCSIT,CCNA,Cyber Security
contact: amentalhealths@gmail.com ,
ndayicoll@gmail.com
whatsaps :+256772497591 /+250788958241
THANKS FOR LISTENING
Dr Ndayisaba Corneille