Opportunistic Infections

What type of bug is Pneumocystitis jirovecci?

opportunistic fungus with protozoan characteristics

What are the risk factors for Pneumocystitis jirovecci pneumonia (PJP)?

HIV with CD4

What are the clinical manifestations of Pneumocystitis jirovecci pneumonia (PJP)?

progressive dyspnea, fever, non-productive cough, and chest discomfort lasting for days-to-weeks, hypoxemia (pO2

How is Pneumocystitis jirovecci pneumonia (PJP) diagnosed?

CXR/ CT abnormalities, organism identification by staining or polymerase chain reaction, 1,3-B-D-glucan elevation

When is prophylaxis for Pneumocystitis jirovecci pneumonia (PJP) indicated in patients with HIV?

CD4 count 100-200 with a detectable HIV RNA load

OR

CD4 count

What are the preferred prophylactic regimens for Pneumocystitis jirovecci pneumonia (PJP)?

TMP/SMX 1 DS PO QD

OR

TMP/SMX 1 SS PO QD

What are the alternative prophylactic regimens for Pneumocystitis jirovecci pneumonia (PJP)?

TMP/SMX 1 DS PO 3x/week

OR

Dapsone

OR

Aerosolized pentamidine via Respigard

OR

Atovaquone

When should Pneumocystitis jirovecci pneumonia (PJP) prophylaxis be discontinued?

When CD4 count >200 for >/= 3 months on ART

OR

(consider) when CD4 count 100-200 and suppressed HIV RNA for >/= 3-6 months

What is the preferred treatment for mild-to-moderate Pneumocystitis jirovecci pneumonia (PJP)?

TMP/SMX 15-20mg/kg PO in 3 divided doses x21d

What is the alternative treatment for mild-to-moderate Pneumocystitis jirovecci pneumonia (PJP)?

Primaquine + Clinamycin or Atovaquone x21d

What is considered moderate-to-severe Pneumocystitis jirovecci pneumonia (PJP)?

pO2

What is the preferred treatment for moderate-to-severe Pneumocystitis jirovecci pneumonia (PJP)?

TMP/SMX 15-20mg/kg IV q6-8h, then switch to PO when possible x21d + 21 day prednisone taper

What are the alternative treatments for moderate-to-severe Pneumocystitis jirovecci pneumonia (PJP)?

Primaquine + Clindamycin or IV Pentamidine x21d

PLUS

Prednisone taper for 21 days

If a patient with HIV who is not on ART is diagnosed with PJP, when should ART be initiated?

Within 2 weeks of diagnosis

What type of bug is Toxoplasma gondii?

ubiquitous intracellular protozoan parasite

What are the risk factors for Toxoplasma gondii?

HIV with CD4

What are the clinical manifestations of Toxoplasma gondii?

HA, confusion, motor weakness, fever, (+) IgG in most cases, ring-enhancing brain lesions +/- edema

How is Toxoplasma gondii diagnosed?

Serology (IgG), imaging with CT/MRI showing contrast-enhancing brain lesions, organism ID

When is prophylaxis for Toxoplasma gondii indicated in patients with HIV?

IgG positive and CD4 count

What is the preferred prophylactic regimen for Toxoplasma gondii?

TMP/SMX 1 DS PO QD

What are the alternative prophylactic regimens for Toxoplasma gondii?

TMP/SMX 1 DS PO three times a week

OR

TMP/SMX 1 SS PO QD

OR

Atovaquone

When should Toxoplasma gondii prophylaxis be discontinued?

When CD4 count >200 for >/= 3 months on ART

OR

(consider) when CD4 count 100-200 and suppressed HIV RNA for >/= 3-6 months

What is the preferred therapy for the acute treatment phase of toxoplasmosis?

Pyrimethamine + sulfadiazine + leucovorin >/= 6 weeks

What are the alternative therapies for the acute treatment phase of toxoplasmosis?

Pyrimethamine + leucovorin + Clindamycin >/= 6 weeks

OR

TMP/SMX IV or PO q12h >/= 6 weeks

What is the preferred therapy for the chronic maintenance of toxoplasmosis?

Pyrimethamine + Sulfadiazine + Leucovorin

What are the alternative therapies for the chronic maintenance of toxoplasmosis?

Pyrimethamine + leucovorin + clindamycin

OR

TMP/SMX DS 1 tablet once or twice daily

When can chronic maintenance therapy for toxoplasmosis be discontinued?

Initial therapy has been completed

Pt is asymptomatic

CD4 >/= 200 cells/mm^3 for >/= 6 months on ART

If a patient with HIV who is not on ART is diagnosed with Toxoplasmosis, when should ART be initiated?

Within 2-3 weeks of diagnosis

What type of bug is Mycobacterium avium complex (MAC)?

non-tuberculosis mycobacterium

What are the risk factors for Mycobacterium avium complex (MAC)?

COPD, CF, prior pneumonia, chronic glucocorticoids, older women w/o risk factors, children

What are the clinical manifestations of Mycobacterium avium complex (MAC)?

Fever, night sweats, weight loss fatigue, diarrhea, abdominal pain, hepatomegaly, splenomegaly, lymphadenopathy, anemia, leukopenia, increased ALP

How is Mycobacterium avium complex (MAC) diagnosed?

Compatible s/sx + isolation of the bug from the blood, bone marrow, lymph, or other sterile tissue/fluid

When is prophylaxis for Mycobacterium avium complex (MAC) indicated in patients with HIV?

CD4 count

Before starting MAC prophylaxis, you should make sure that

The patient does not have disseminated MAC

What are the preferred prophylactic regimens for Mycobacterium avium complex (MAC)?

Azithromycin PO QW

OR

Azithromycin PO twice weekly

OR

Clarithromycin PO BID

What is the alternative prophylactic regimen for Mycobacterium avium complex (MAC)?

Rifabutin PO QD

When should Mycobacterium avium complex (MAC) prophylaxis be discontinued?

Once the patient is on effective ART

What are the preferred treatments for Mycobacterium avium complex (MAC) in patients with HIV?

Azithromycin + Ethambutol >/=12 months

OR

Clarithromycin + Ethambutol >/=12 months

When is it appropriate to consider adding a 3rd/4th drug to treat Mycobacterium avium complex (MAC) in patients with HIV?

CD4

What 3rd/4th drugs could you add to a Mycobacterium avium complex (MAC) treatment regimen?

Rifabutin

OR

Amikacin/Streptomycin

OR

Levofloxacin/Moxifloxacin

When is it appropriate to discontinue treatment of Mycobacterium avium complex (MAC)?

Asymptomatic and CD4 count is >100 cells/mm^3 for >6 months on ART

What type of bug is Cryptococcus neoformans?

Encapsulated yeast; ubiquitous

How is Cryptococcus neoformans transmitted?

Inhalation of infectious propagules

What are the risk factors for Cryptococcus neoformans?

HIV with CD4 < 100 cells/mm3

Pts on immunosuppressive drugs

Underlying immunosuppressive diseases

What are the clinical manifestations of Cryptococcus neoformans? (sx and labs)

subacute meningitis/meningoencephalitis: fever, malaise, HA

classic meningal signs: neck stiffness, photophobia

encephalopathic sx from increased intracranial pressure: lethargy, altered mentation, memory loss

CSF findings:

pleocytosis (lymphocyte predominant, may be minimal in advanced HIV)

mild protein elevation

low-normal glucose

opening pressure often elevated (≥25cm H20 in 60-80%)

How is Cryptococcus neoformans diagnosed?

Culture (CSF, sterile sites) and cryptococcal antigen (CrAg)

CSF CrAg: highly sensitive in meningoencephalitis

Serum CrAg: positive in most cases (can precede sx)

Positive serum CrAg: LP to rule out CNS disease

When is prophylaxis for Cryptococcal neoforman indicated in patients with HIV?

We do not initiate ppx for Cryptococcal neoformans.

What medications are used for induction therapy in Cryptococcus meningoencephalitis treatment in patients with HIV? Include induction therapy duration.

Duration: ≥2 weeks

Liposomal amphotericin B (HD) X 1 dose + flucytosine PO q6h x 14 days + fluconazole HD daily x 14 days

OR

Liposomal amphotericin B IV daily x 14 days + flucytosine PO 16h x 14 days

What medications are used for consolidation therapy in Cryptococcus meningoencephalitis treatment in patients with HIV? Include consolidation therapy duration.

Fluconazole HD daily for 8 weeks following induction therapy

What medications are used for maintenance therapy in Cryptococcus meningoencephalitis treatment in patients with HIV? Include maintenance therapy duration.

Fluconazole daily for ≥12 months and until immune reconstitution after consolidation therapy

When is it appropriate to discontinue therapy for Cryptococcal meningoencephalitis treatment in patients with HIV?

After patient has completed ≥12 months of maintenance therapy

Patient is asymptomatic

CD4 count ≥ 100 cells/mm3 for ≥ 3 months on ART with virologic suppression

If a patient with HIV who is not on ART is diagnosed with Cryptococcal meningoencephalitis, when should ART be initiated?

delay until after induction (≥2 weeks)

sometimes deferred until after consoliation (~10 weeks)

Increasing intracranial pressure in cryptococcal meningoencephalitis will continue to deteriorate despite anti-fungal response. Pts are at risk of this if their pressure is ≤ 25 cm H2O

False

How do we manage increased intracranial pressure in cryptococcal meningoencephalitis?

Measure opening pressure at diagnosis and repeat LPs or CSF shunting if symptomatic

What medications are not effective in the management of intracranial in cryptococcal meningoencephalitis?

glucocorticoids, mannitol, acetazolamide

What are the toxicities of Amphotericin B?

Nephrotoxicity: azotemia, decreased potassium, magnesium

infusion reactions: chills, fever, HA, vomiting

rare: hypotension, neuro or hepatotoxicity

How do we manage the toxicities of Amphotericin B?

Mitigate nephrotoxicities with IV saline pre- and post-infusion

Infusion reactions: premedicate with APAP, diphenhydramine, hydrocortisone, meperidone (rigors)