Tuberculosis

Question 1

Situations in which TB treatment duration is extended

Answer 1

Treatment may be extended in certain situations: a. Pulmonary TB with a positive 2-month sputum culture b. Bone and joint involvement c. Central nervous system (CNS) involvement d. Patient with HIV not receiving antiretroviral therapy during TB treatmen

Question 2

Active TB intensive phase: conditions to allow intermittent dosing

Answer 2

intermittent dosing may be considered if: a. Patient has completed the initial 2 weeks of daily therapy b. Patient has a low risk of relapse i. MTB is drug-susceptible ii. Noncavitary TB and/or smear is negative at start of treatment c. Patient is HIV negative

Question 3

When to start TB therapy in HIV patients

Answer 3

Treatment should begin as soon as possible. The START and TEMPRANO trials showed that earlier treatment resulted in reduced AIDS-defining illnesses and death.

Question 4

Rifampin interactions with modern ART

Answer 4

DTG - increase to BID
EVG/c - avoid
RAL - increase to 800 BID
ATV/r - avoid
DRV/r -  avoid
LPV/r - avoid
EFV- consider increasing dose

Question 5

RFB interactions with modern ART

Answer 5

DTG - no change
EVG/c - avoid
RAL - no change
ATV/r - RFB 150 qd
DRV/r - RFB 150 qd
LPV/r - RFB 150 qd
EFV - increase RFB - 450 daily

Question 6

Conditions to use INH + RFP for latent TB

Answer 6

Isoniazid 900 mg once weekly in combination with rifapentine 900 mg once weekly a. Treatment for individuals older than 12 years b. Currently, must be given directly observed therapy c. Not recommended for: iii. Individuals younger than 2 years iv. Patients with HIV/AIDS v. Women who are pregnant, or expecting to become pregnant during treatment vi. Individuals believed to be infected with isoniazid- or rifampin-resistant MTB

Question 7

Early bactericidal activity in TB definition

Answer 7

EBA refers to the first 2–5 days of treatment but can refer to a period of up to 2 weeks (extended EBA).

Question 8

INH drug interactions

Answer 8

Drug interactions a. Isoniazid can inhibit CYP2E1, CYP2C19, and CYP3A. b. Isoniazid can induce CYP2E1. c. Examples of medications that may be affected: Warfarin, phenytoin, carbamazepine

Question 9

Is EMB ocular toxicity irreversible?

Answer 9

If optic neuritis is recognized promptly, vision usually returns to baseline.

Question 10

Treatment principles for MDR-TB (RIF-R, INH-R)

Answer 10

FIVE effective medications should be used in treating MDR-TB (standard regimen). a. Pyrazinamide should be included, if isolate is susceptible. b. Intensive phase is recommended for 8 months. c. Continuation phase is 12 months of at least three or four effective medications

Patients should receive: a. Pyrazinamide b. One medication from group A c. One medication from group B d. Two medications from group C

Question 11

WHO second-line TB agents: Group A

Answer 11

Group A: A fluoroquinolone i. Levofloxacin ii. Moxifloxacin

Question 12

WHO second-line TB agents: group B

Answer 12

Group B: Aminoglycosides and capreomycin

Question 13

WHO second-line TB agents: group C

Answer 13

Group C: Other core second-line agents i. Ethionamide/prothionamide ii. Cycloserine/terizidone iii. Linezolid iv. Clofazimine

Question 14

WHO second-line TB agents: group D (add-on agents)

Answer 14

Group D: Add-on agents i. D1: Pyrazinamide ii. D1: Ethambutol iii. D1: High-dose isoniazid iv. D2: Bedaquiline v. D2: Delamanid vi. D3: Para-aminosalicylic acid vii. D3: Imipenem/cilastin viii. D3: Meropenem ix. D3: Amoxicillin/clavulana

Question 15

RIF-moxi interaction

Answer 15

Drug interactions i. Rifampin decreases moxifloxacin’s AUC by 27%. A 600-mg moxifloxacin dose may be neces- sary to overcome this reduction.

Question 16

Characteristics of PAS

Answer 16

Para-aminosalicylic acid a. Mechanism of action: Unknown; has activity against folic acid pathway b. Dose i. 4 g three times daily (twice daily has been used as an alternative)

GI upset most common; newer aminosalicylic acid (Paser) granules are better than older dos- age forms. Diarrhea is still a common adverse effect, but this usually improves within the first 2 weeks of administration. ii. Hypothyroidism iii. Steatorrhea

Question 17

Characteristics of cyclosporine

Answer 17

Cycloserine
a. Mechanism of action: Disrupts the incorporation of d-alanine into peptidoglycan during cell wall
synthesis
b. Dose
i. 10–20 mg/kg twice daily (typically 250–500 mg)
ii. Pediatric dose typically 10–20 mg/kg/day in two divided doses
iii. Cmax of 20–35 mcg/mL 1–2 hours post-dose
iv. Dosage adjustment necessary in patients with renal dysfunction, with target concentrations
less than 30 mcg/mL (not recommended in patients with a CrCl of less than 50 mL/minute/
1.73 m2
)
c. Adverse effects:
i. Most common CNS adverse effects: Anxiety, confusion, depression, dizziness, difficulty con-
centrating, drowsiness, lethargy, hyperexcitability, paresthesias, seizures, tremor, vertigo
ii. CNS toxicity may be greater at higher concentrations (greater than 35 mcg/mL), and concen-
trations should be maintained below 30 mcg/mL to reduce the risk of adverse effects.

Question 18

Characteristics of ethionamide

Answer 18

Ethionamide
a. Mechanism of action
i. Inhibition of mycolic acid synthesis
ii. Cross-resistance with isoniazid possible
b. Dose
i. 250–500 mg twice daily is typical.
ii. Pediatric dose is 15–20 mg/kg/day divided twice daily.
iii. Cmax is 1.5–3.0 mcg/mL 2 hours post-dose.
c. Adverse effects
i. GI adverse effects (can be severe): Can reduce by splitting the dose initially, or starting with
lower doses and increasing gradually
ii. Other, less common adverse effects
(a) Hepatotoxicity
(b) Visual disturbances
(c) Goiter
d. Metabolism
i. Sulfoxidation, desulfurization, and deamination, followed by methylation
ii. 250–500 mg orally daily recommended in patients with a CrCl less than 30 mL/minute/1.73 m2
e. Drug interactions: No significant drug interactions

Question 19

Recommended TDM for TB

Answer 19

May be used to assess patient adherence, maximize efficacy, or minimize adverse events
3. For the first- and second-line TB drugs, two concentration time points can be measured to help individ-
ualize therapy: a 2-hour sample (3 hours for rifabutin) and a 6-hour sample. The 2-hour sample captures
the Cmax (see Table 3).
4. A 6-hour sample is used to determine malabsorption or delayed absorption.
a. Malabsorption: Both 2- and 6-hour concentrations are below the expected range (increased dose
may be necessary)
b. Delayed absorption: The 2-hour concentration is below the expected range, but the 6-hour concen-
tration is within range (no dose adjustment necessary)