Antimycobacterial

Antimycobacterial: medications designed to treat infections caused by mycobacteria, a group

of bacteria that includes:

1. Mycobacterium tuberculosis (causes tuberculosis).

2. Mycobacterium leprae (causes leprosy).
3. Mycobacterium avium complex (MAC) (causes lung disease, especially in
immunocompromised individuals).

Medications Contraindicated in Pregnancy:

● Streptomycin
● Amikacin
● Capreomycin
● Fluoroquinolones

Black Box Warnings for Fluoroquinolones:

● Tendinitis and tendon rupture.

● Peripheral neuropathy.
● Central nervous system effects (e.g., seizures, psychiatric symptoms).

Isoniazid and Neuropathy (Mechanism and Prophylaxis):

● Mechanism: Isoniazid interferes with vitamin B6 (pyridoxine) metabolism, causing a

deficiency that leads to peripheral neuropathy.
● Prophylaxis: Concomitant administration of pyridoxine (vitamin B6) is recommended,
especially for at-risk groups (e.g., diabetes, alcoholism, HIV).

Black Box Warning for Isoniazid:

● Severe and sometimes fatal hepatitis, with higher risk in patients consuming alcohol,
those with liver disease, and postpartum Black or Hispanic women.

Rifamycins - Discoloration of Body Fluids:

● Rifamycins (e.g., Rifampin) cause red-orange discoloration of body fluids, including

urine, tears, and sweat.
Pyrazinamide - Contraindications (Acute Gout):

● Pyrazinamide is contraindicated in patients with acute gout or severe hepatic damage.

Ethambutol - Contraindications (Optic Neuritis):

● Ethambutol is contraindicated in patients with optic neuritis, especially if they cannot

report visual changes.

Genetic Testing - Aminoglycosides - Ototoxicity:

● Patients with mutations in the MT-RNR1 gene (e.g., m.1555A>G) are at increased risk
of aminoglycoside-induced ototoxicity, potentially causing irreversible hearing loss.

Clofazimine - Skin Discoloration:

● Clofazimine can cause brownish skin pigmentation in 75-100% of patients.

Clavulanate - Role in MDR TB Treatment:

● Combination with Carbapenems: Clavulanate is a β-lactamase inhibitor that enhances

the efficacy of carbapenems by overcoming bacterial resistance.
● Rationale for Use: Mycobacterium tuberculosis produces β-lactamase, which degrades
β-lactam antibiotics. Clavulanate inhibits this enzyme, allowing carbapenems to act
effectively.
● Mechanism: Provides synergy with carbapenems by preventing enzymatic degradation.
● Use of Amoxicillin-Clavulanate Alone: Amoxicillin-clavulanate is not effective alone
and is considered "salvage therapy" in combination with carbapenems.

1. Differences Between Latent and Active TB:

○ Latent TB:
■ Infection is present, but bacteria are inactive.
■ No symptoms or signs of disease.
■ Cannot transmit TB to others.
■ Can progress to active TB if the immune system weakens.
○ Active TB:
■ Infection becomes active → symptoms.
■ Transmittable to others.
 ■ affects the lungs and may involve other organs (e.g., lymph nodes,
meninges, kidneys).
2. Five Treatment Options for Latent TB:
○ 3HP: Weekly Isoniazid (INH) + Rifapentine for 3 months.
○ 4R: Daily Rifampin for 4 months.
○ 3HR: Daily INH + Rifampin for 3 months.
○ 6H or 9H: Daily Isoniazid (INH) for 6 or 9 months → less preferred/ alternative
○
3. Preferred Treatment Options for Latent TB:
○ 3HP (Isoniazid + Rifapentine).
○ 4R (Rifampin)
○ 3HR: (Isoniazid + Rifampin)
4. Advantages of Preferred Regimens for Latent TB:
○ Lower risk of hepatotoxicity
○ Shorter & more compliance
5. Disadvantages of 3HP (INH and Rifapentine) Treatment:
○ Increased cost & Requires taking numerous pills simultaneously.
○ Associated with systemic drug reactions– influenza-like syndrome.
○ Neutropenia– low level of neutrophils, a type of white blood cell essential for
fighting infections
○ elevated liver enzymes.

6. Alternative to 4R (Rifampin) When Contraindicated and INH Can’t Be Used:

○ Rifabutin can be used as an alternative when drug interactions make Rifampin
unsuitable.
7. Regimen Adjustments for Fast Acetylators Starting INH Therapy:
○ Fast acetylators metabolize INH more quickly, reducing its therapeutic effect.
Increased dosage to achieve therapeutic levels.
8. Drug Interaction Between Simvastatin and INH:
○ Increased risk of muscle pain
9. Mechanism by Which INH Causes Neuropathy:
○ INH interferes with vitamin B6 metabolism, leading to a deficiency and
subsequent peripheral neuropathy– damage to the peripheral nerves, which are
the nerves outside the brain and spinal cord → numbness
10. Black Box Warning Associated with INH:
○ Risk of hepatitis. This risk increases with age, daily alcohol consumption, and in
certain demographic groups (e.g., Black and Hispanic women, especially
postpartum).
11. Dietary Supplements with INH:
○ Vitamin B6 to prevent peripheral neuropathy.
○ Increase intake of folate, niacin, and magnesium.
12. Foods to Avoid with INH Therapy:
○ Tyramine: cheese, cured meat, chocolate, coffee, fish, wine.
○ histamine-containing foods
14. Mechanism of Action of Rifamycins:
○ Rifamycins inhibit RNA polymerase, preventing bacterial RNA synthesis.
15. Medications Contraindicated with Rifampin:
○ Atazanavir, darunavir, fosamprenavir, ritonavir/saquinavir, saquinavir,
○ These are antiviral medications used primarily to treat HIV and hepatitis C
infections.
16. Class of Medications Causing Red-Orange Discoloration of Body Fluids:
○ Rifamycins (e.g., Rifampin).
17. Counseling Female Patients About Rifampin and Oral Contraceptives:
○ Rifampin is a potent inducer of drug-metabolizing enzymes and may reduce the
effectiveness of oral contraceptives. Alternative contraception methods are
recommended.
18. Advantage of Rifapentine Over Rifampin:
○ Rifapentine has a longer half-life → less frequent dosing.
19. Drugs Included in the 4-Month Regimen for Active TB:
○ Moxifloxacin (MOX), isoniazid (INH), Rifapentine (RPT), Pyrazinadine (PZA)
○ MIRP
20. Who Should Receive the 4-Month Active TB Regimen:
○ Patients 12 years or older with a body weight ≥ 40 kg.
○ Patients with a low mycobacterial burden and no contraindications to this
regimen.
○ HIV-positive patients with CD4 counts ≥ 100, on efavirenz-based ART, and no
drug-drug interactions.
○ Basically less sick pts
21. What Does the 6-9 Month Active TB Treatment Consist Of?
● Consists of a two-phase regimen:
○ Intensive phase: Includes rifampin (RIF), isoniazid (INH), pyrazinamide (PZA),
and ethambutol (EMB). RIPE
○ Continuation phase: Includes isoniazid (INH) and rifampin (RIF) → 6-9 months
22. How Long is the Intensive Phase of 6-9 Month Active TB Treatment?
● intensive phase lasts for 2 months.
23. Who Should Receive 9 Months of Active TB Treatment?
● Individuals with cavitary pulmonary TB whose sputum culture remains positive
after the initial 2 months of treatment → treatment isn't working as well as it
should
● Those whose intensive phase treatment did not include pyrazinamide.
● HIV-positive individuals not receiving antiretroviral therapy during TB treatment.
● Patients treated with once-weekly INH + rifapentine whose sputum culture
remains positive after the intensive phase.
● Low CD4 count & higher viral load

24. Acute Gout is a Contraindication to Which TB Treatment?

● Pyrazinamide (PZA).
25. Optic Neuritis is a Contraindication to Which TB Treatment?
● Ethambutol (EMB).
26. Which Regimen Should Not Be Used in Pregnant Patients Treated for Latent TB?
● 3HP (isoniazid + rifapentine).
27. What is the Preferred Regimen for Treatment of Active TB in Pregnancy?
● Isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide (PZA).
● PIRE
28. Which TB Treatments Are Contraindicated in Pregnancy?

active TB in pregnancy – treatment typically involves a combination of

● Streptomycin.
● Amikacin.
● Capreomycin.
● Fluoroquinolones
■ But latent TB while pregnant – Isoniazid (INH) alone
29. What Regimen is Preferred for the Treatment of Latent TB in Children >2 Years
Old?
● Once-weekly INH + rifapentine for 12 weeks.
30. Which Regimen Should Not Be Used to Treat Active TB in Children <12 Years or
<40 kg?
● The 4-month rifapentine-moxifloxacin regimen is not recommended for
children under 12 years or under 40 kg.

31. Which Oral Agents Are Used to Treat Multi-Drug-Resistant (MDR) TB?
● Levofloxacin.
● Moxifloxacin.
● Bedaquiline.
● Linezolid.
● Clofazimine.
● Cycloserine.
32. Which Injectable Agents Can Be Used to Treat Multi-Drug-Resistant TB?
● Amikacin.
● Streptomycin.
● Capreomycin.
33. Which Agents Used to Treat MDR TB Are Associated with Glucose Dysregulation?
● Fluoroquinolones (e.g., moxifloxacin, levofloxacin).
34. What is the Boxed Warning for Fluoroquinolones?
● Tendinitis and tendon rupture.
● Peripheral neuropathy.
● Central nervous system effects (e.g., seizures, psychiatric symptoms).
○
35. What is the Boxed Warning for Bedaquiline?
● QT prolongation – delay in the heart's electrical cycle– the QT interval
● Increased risk of mortality compared to the placebo group in trials.
○
36. Bedaquiline Exhibits Cross-Resistance with Which Medication?
● Clofazimine.
37. Linezolid is Contraindicated with Which Medications?
● Monoamine oxidase inhibitors (MAOIs).
● Serotonin reuptake inhibitors (SSRIs).
● Tricyclic antidepressants (TCAs).
● Buspirone.
○
38. Patients Receiving Linezolid Have a Risk of Thrombocytopenia if They Have Which
Concomitant Conditions?
● Liver cirrhosis.
● Renal impairment.
39. Which Medication to Treat MDR TB is Associated with Brownish Skin Pigmentation?
● Clofazimine.
40. Which Medication to Treat MDR TB is Associated with Ichthyosis?
● Clofazimine.
41. Clofazimine may result in accumulation of crystals in the intestinal mucosa, spleen, and
liver. What may this result in?
● May lead to obstruction or other complications in the affected tissues.
42. This medication can result in B-12 deficiency. Cycloserine is contraindicated in which
patients?
● Cycloserine can cause B-12 deficiency.
● Contraindications for Cycloserine:
○ Patients with epilepsy.
○ Severe anxiety, depression, or psychosis.
○ Severe renal insufficiency.
○ Excessive concurrent use of alcohol.
43. How do the aminoglycosides work?
● Mechanism of action: Aminoglycosides inhibit bacterial protein synthesis by binding to
the 30S ribosomal subunit, leading to:
○ Prevention of initiation complex formation.
○ Misreading of mRNA, causing faulty protein production.
○ Inhibition of translocation.
44. What boxed warnings are associated with aminoglycosides?
● Neurotoxicity.
● Ototoxicity (hearing loss or balance issues).
● Renal impairment.
● Neuromuscular blockade and respiratory paralysis.

45. Patients with which genetic mutation are at increased risk of ototoxicity with
aminoglycoside use?
● Patients with mutations in the MT-RNR1 gene (e.g., m.1555A>G).
46. How should patients with genetic mutations be treated for MDR TB?
● Avoid aminoglycosides if possible to prevent irreversible ototoxicity. Use
alternative therapies that do not pose the same risk.
47. When should capreomycin be used?
● Capreomycin should be reserved for cases where there is resistance to
aminoglycosides or limited treatment options.
○
48. Which electrolyte disorders may occur with capreomycin use?
● Hypocalcemia.
● Hypokalemia.
● Hypomagnesemia.
49. Why is clavulanate added to carbapenem therapy?
● Clavulanate inhibits β-lactamase enzymes, enhancing the activity of carbapenems
against M. tuberculosis by overcoming resistance mechanisms.
50. What is the role of amoxicillin-clavulanate monotherapy in MDR TB treatment?
● Amoxicillin-clavulanate monotherapy is not effective. It is used only in
combination with carbapenems to provide synergy.
○
51. Which agents are used as 1st line treatment for primary prophylaxis for MAC?
● Azithromycin
● Clarithromycin
● Azithromycin (alternative). Make acronym
52. How do the macrolides work to treat MAC?
● Mechanism of action: Macrolides inhibit bacterial protein synthesis by binding to
the 50S ribosomal subunit, blocking elongation of the protein chain.

53. Which agent is preferred for primary prophylaxis for MAC in the pregnant patient?
● Azithromycin is preferred.
54. Which two medications are started for disseminated MAC?
● Clarithromycin or Azithromycin plus Ethambutol.

55. What agent should be added to initial therapy if more severe disease manifestations are
present?
● Rifabutin should be added.
56. What unique side effects are associated with rifabutin?
● Neutropenia.
● Thrombocytopenia.
● Dermatologic reactions (e.g., Stevens-Johnson syndrome).
● Uveitis.
● Reddish-orange discoloration of urine and body fluids.
○
57. When should a fourth drug be added to the MAC treatment regimen?
● A fourth drug should be added for:
○ Severe disease.
○ High mycobacterial load (>2 log10 CFU/mL of blood).
○ CD4 count <50 cells/μL.
○ Lack of effective antiretroviral therapy (ART).

58. What are the options for the fourth drug for severe disease for MAC treatment?
● Fluoroquinolones (e.g., levofloxacin, moxifloxacin).
● Injectable aminoglycosides (e.g., amikacin, streptomycin).
● Bedaquiline or linezolid may also be considered.

59. How is leprosy treated?

● Daily dapsone and rifampin once per month.
60. Which treatment may artificially lower HbA1c?
● Dapsone.