Pharmacotherapy III: Tuberculosis and Opportunistic Infections

mycoplasma tuberculosis

Which bug causes tuberculosis?

atypical

What type of bug is m.tuberculosis?

droplets

How is TB spread?

F (latent TB can NOT be spread)

T or F: Latent TB is also infectious and can be spread via droplets.

infection, disease

(Infection/Disease) means an organism is present in the body, while (infection/disease) means that organism is causing illness.

latent TB

A form of TB where the immune system contains the infection, and the patient has no symptoms and is not contagious.

active TB

A contagious form of TB where organisms are replicating and symptoms develop.

latent

When a person becomes infected with TB, 90% of all infections become (active/latent).

at-risk for acquiring TB, at risk for progressing to active TB

What are the 2 criteria for testing people for TB?

HIV patients, immunosuppression, children, comorbidities

Who is at a higher risk for progressing from latent TB to active disease?

TST, IGRA

What are the two tests we can use to identify an exposure to TB?

TST (Tuberculin Skin Test)

A TB skin test that requires returning to the clinic for evaluation. A positive result means the patient has been exposed to TB at some point.

IGRA

A blood assay for TB that when Abs are positive, indicates exposure to TB at some point.

F (neither can differentiate)

T or F: Both the TST and the IGRA can differentiate between active and latent TB.

symptoms, chest xray

If the TST or IGRA is positive, what are the next steps in determining whether TB is latent or active?

cough, fever/night sweats, weight loss, hemoptysis

What are some classic symptoms of active TB?

consolidation/infiltrates

If TB is active, what will be found on a chest x-ray?

active

If the patient has symptoms of TB or infiltrates upon chest x-ray, we should consider them to have (active/latent) TB.

latent

If a patient has a positive TST/IGRA but NO symptoms or infiltrates, we should consider them to have (active/latent) TB.

AFB smear, NAAT, cultures

If the patient has active TB, what three tests can we run on a specimen to confirm the diagnosis?

AFB smear

The fastest microbiology assay for TB akin to a gram-stain, but is not specific for TB.

NAAT

An assay that rapidly detects TB and may identify resistance markers as well.

cultures

The slowest identification method that provides definitive confirmation of TB and provides susceptibility testing.

Isoniazid/Rifapentine, Rifampin

There are 4 main treatments for latent TB. Which 2 regimens are preferred?

once weekly for 3 months

How is Isoniazid/Rifapentine administered for latent TB treatment?

pyridoxine

What should be added to regimens with Isoniazid?

combats peripheral neuropathy

Why do we give pyridoxine with Isoniazid?

daily for 4 months

How is Rifampin monotherapy used for latent TB treatment?

Isoniazid/Rifapentine

Which one of the preferred regimens for latent TB should NOT be used in children younger than 2 or pregnancy?

Isoniazid/Rifampin, Isoniazid monotherapy

List the 2 non-preferred regimens in latent TB treatment.

daily for 3 months

How is Isoniazid/Rifampin administered?

daily for 6-9 months

How is Isoniazid monotherapy administered?

resistance

Active TB must be combated with multiple drugs to avoid _________, and it is usually given in two phases: intensive and continuation.

RIPE therapy

What regimen is preferred when treating an active TB infection?

Rifampin, Isoniazid, Pyrazinamide, Ethambutol

What meds make up RIPE therapy?

2 months

How long do we administer RIPE therapy in its intensive phase?

Isoniazid and Rifampin

What medications do we administer after completing 2 months of RIPE therapy for the continuation phase?

4 months

How long do we administer Isoniazid and Rifampin as the continuation phase of active TB treatment?

RIPM therapy

What alternate regimen to RIPE therapy can be used if needed?

Rifapentine, Isoniazid, Pyrazinamide, Moxifloxacin

What drugs make up RIPM therapy?

2 months

How long do we continue RIPM therapy as the intensive phase?

Rifapentine, Isoniazid, Moxifloxacin

What drugs are used after completing 2 months of RIPM therapy as the continuation phase of therapy?

9 weeks

How long do we continue Rifapentine, Isoniazid, and Moxifloxacin?

symptoms, weight, sputum

How do we check and see if the TB infection is improving?

F (NOT used to track treatment response)

T or F: TST or IGRA is repeated after therapy to confirm the infection is gone.

optic neuritis (ethambutol --> E for eyes)

We should also monitor the treatment for toxicity. What are some toxicities associated with Ethambutol?

hepatotoxicity, peripheral neuropathy

We should also monitor the treatment for toxicity. What are some toxicities associated with Isoniazid?

pyridoxine

How do we prevent peripheral neuropathy with Isoniazid?

gout (hyperuricemia), hepatotoxicity

We should also monitor the treatment for toxicity. What are some toxicities associated with Pyrazinamide?

drug induction, orange-red fluids

We should also monitor the treatment for toxicity. What are some toxicities associated with Rifampin/Rifapentine/Rifabutin?

CNS effects, QTc prolongation, tendon rupture

We should also monitor the treatment for toxicity. What are some toxicities associated with Moxifloxacin?

opportunistic infections (OIs)

Infections that emerge when host defenses are impaired.

HIV patients

Which population is the most at-risk for OIs?

transplant patients, immunocompromised, chemo, glucocorticoid use

What other factors may make someone more at risk for OIs?

PJP (pneumocysti jirovecii pneumonia)

an opportunistic fungus with protozoan characteristics.

HIV patients

Who is traditionally more at-risk for PJP?

dyspnea, fever, nonproductive cough, hypoxemia, thrush

What are some symptoms of a PJP infection?

opacities upon CT (better than CXR), PCR for specimen, B-D-glucan test

How can we diagnose PJP?

CD4 < 200 NOT on ART, CD4 < 100 while on ART, other immunosuppression markers

Who is indicated for PJP prophylaxis?

TMP/SMX

What medication is largely used for both HIV and non-HIV PJP prophylaxis?

Dapsone, Pentamidine, Atovaquone

What are some other options for prophylaxis if the patient has a sulfa allergy to TMP/SMX?

Dapsone

Which second-line medication requires a G6PD status test before initiation?

TMP/SMX

If the patient has an active PJP infection, the DOC is...

Prednisone

If a patient has a more severe PJP infection, such as PaO2 < 70, they should add ____________ to their TMP/SMX regimen.

ASAP (usually within 2 weeks)

If the patient is not already on ART, when can ART be initiated while the patient has PJP?

Primaquine + Clinda, Atovaquone, IV Pendtamidine

What other medications can be used for PJP treatment if the patient has a sulfa allergy?

T

T or F: If PJP infection is severe, TMP/SMX can be given IV and transitioned to po as necessary.

toxoplasma

A protozoan parasite found in undercooked meat or cat feces.

toxoplasmic encephalitis

What is the most concerning complication with toxoplasmosis?

brain lesions with edema, IgG-positive serology

How can we diagnose Toxoplasmosis?

IgG-positive, CD4 < 50

Who is eligible for toxoplasmosis prophylaxis?

TMP/SMX

What medication do we give for toxoplasmosis prophylaxis?

Atovaquone

What medication can we give for toxoplasmosis prophylaxis if the patient has a sulfa allergy?

CD4 > 200 for 3 months on ART

When can we d/c prophylaxis for toxoplasmosis?

pyrimethamine + sulfadiazine + leucovorin

If the patient has an active infection of toxoplasmosis, what medications are first-line for treatment?

reduces BMS from Pyrimethamine

Why is Leucovorin administered in this regimen?

TMP/SMX

What other medication can be used for toxoplasmosis treatment?

continue until immune recovery or CD4 > 200

How long should we treat the patient for toxoplasmosis?

MAC (mycobacterium avium complex)

A group of non-tuberculous mycobacteria comprised of M.intracellulare and M.avium found in water, soil, and animals and can be incurred through ingestion or inhalation.

pulmonary, lymphadenitis, disseminated

MAC can cause three associated disease states:

disseminated

The type of MAC associated with advanced HIV and a CD4 count below 50.

fever, drenching night sweats, unintentional weight loss, anemia

What are some symptoms of disseminated MAC?

CD4 < 50 while NOT on ART

Who is at-risk for MAC and should receive prophylaxis?

no

Should patients on ART receive MAC prophylaxis at any time?

Azithromycin/Clarithromycin

What medications are used for MAC prophylaxis when indicated?

Rifabutin

If macrolides cannot be used for some reason for MAC prophylaxis, what can we adminiser?

macrolide + ethambutol

What treatment is indicated in a positive MAC diagnosis?

12 months

How long do we treat active MAC?

asymptomatic, CD4 > 100 after 6 months on ART

When can we d/c MAC treatment?

cryptococcus

An encapsulated environmental yeast from bird droppings, soil, and decaying wood.

meningoencephalitis

What is the most concerning consequence of a cryptococcus infection?

advanced HIV, immunocompromised patients

Who is most at-risk for a cryptococcus infection?

fever, high ICP, altered mental status

What are some symptoms of cryptococcus meningoencephalitis?

CrAg (antibodies)

How do we definitively diagnose a cryptococcus infection?

LP (check for CNS disease)

If a patient is positive for CrAg, what next step should be taken before treating for cryptococcus?

there isn't one (not routinely recommended)

What regimen is recommended for cryptococcus prophylaxis?

liposomal Amphotericin B (1 dose) + flucytosine + fluconazole

What meds are administered in the induction phase of cryptococcus treatment in an HIV patient?

amphotericin + fluconazole daily

What meds are administered in the induction phase of cryptococcus treatment in a non-HIV patient?

2 weeks

How long do we treat cryptococcus in the induction phase?

high dose fluconazole

Which drug do we administer in the consolidation phase of cryptococcus treatment?