Opportunistic Infections

Question 1

Immunosuppresive Effects of Common meds

Answer 1

Corticosteroids: Lymphopenia (predominantly T-cell), impaired chemotaxis, others
Tacrolimus/cyclosporine: Depressed T-cell response
Rituximab: B-cell apoptosis
Alemtuzumab: Profound lymphopenia
Antithymocyte globulin: Profound T-cell lymphopenia
Conventional chemotherapy: Significant leukopenia

Question 2

Antibiotic prophylaxis in Neutropenic Cancer patients?

Answer 2

• Gram-positive infections (e.g., Staphylococcus epidermidis, oral streptococci) most common
• Gram-negative causes most morbidity and mortality.
• Antibiotic prophylaxis in afebrile neutropenic patients significantly reduces all-cause mortality
• Prophylaxis recommended in patients with hematologic malignancy (fluoroquinolones preferred—most studied option and associated with best benefit)

Question 3

What are the agents of choice for abx prophy in neutropenic patients?

Answer 3

1) Levaquin
2) Cipro - alternative, not good G(+) coverage

*Moxi doesn’t cover psuedomonas well.

Question 4

Who should get abx prophy for neutropenic pts?

Answer 4

Anticipated duration of profound neutropenia (<100 cells/mm3) for > 7 days. Levaquin is first line. (Cipro is an alternative, but has minimal G+ coverage.
Oral PCN rec’d for pts with GVHD.

Question 5

Treatment of Neutropenic Fever?

Answer 5

Monotherapy with anti-pseudomonal beta-lactam is sufficient: Cefepime, Zosyn, Merrem, Primaxin, Ceftaz (not often used due to poor G(+) activity.

*Some pt’s need staph coverage

Question 6

What pts with neutropenic fever need G+ coverage?

Answer 6

• Hemodynamically unstable (just in case)
• Pneumonia (don’t know why)
• Blood culture is positive for G+ bac (duh)
• Clinically suspected CVC infx (usually these are G+)
• SSTI infection (also generally G+)
• Colonization with MRSA (duh)
• Severe mucositis, if ceftaz used AND pt got FQ prophy (accidentally selected for strep viridans group)

*Stop the G+ agent in 2-3 days if no specific need identified.

Question 7

Which azoles are “Mold active,” meaning they are active against aspergillus?

Answer 7

Voriconazole, Posaconazole, and Isavuconazonium.

But NOT Fluconazole
*Vori lacks mucor activity.

Question 8

What three Virus’s establish a latent infection which can re-emerge during periods of immunosuppresion?

Answer 8

Herpes (HSV), Vericella Zoster (VZV), cytomegalovirus (CMV).

Question 9

What agents are used for viral prophylaxis in neutropenic patients

Answer 9

High risk patients should get either:
-Acyclovir, Famciclovir, Valacyclovir to prevent HSV and VZV.

CMV-seropositive allogenic HSCT recipients and patients receiving alemtuzumab should receive Letermovir through the first 100 days (a new agent that is only active against CMV).

Question 10

What is the significance of a UL97 gene mutation in CMV?

Answer 10

It confers resistance to ganciclovir and valganciclovir.

These drugs require a viral kinase to phosphorylate them intracellularly in order to be active. The mutant UL97 gene no longer has this kinase activity.

Foscarnet and cidofovir retain activity. Foscarnet is generally preferred.

Question 11

What is the significance of a UL54 mutation in CMV?

Answer 11

May confer resistance to any or all of the following: foscarnet, ganciclovir, valganciclovir, and cidofovir.

Treatment of choice is highly dependent on the specific mutation present.

Question 12

Treatment of choice for pulmonary invasive aspergillosis?

Answer 12

First Line is Voriconazole: 6 mg/kg BID x 2 doses, then 4 mg/kg q12h.

Alternative: amphotericin (poor side-effect profile) or isavuconazonium (non-inferior to vori and fewer side-effecs too!).

Salvage therapy? ampho, caspo, mica, posa, itra

Question 13

Voriconazole trough target?

Answer 13

Therapeutic is between 1 to 4-6 mcg/ml

Question 14

What is a common side effect of Voriconazole?

Answer 14

Visual disturbances and hallucinations. Just keep treating through it.

Question 15

What is a target trough for posazonazole?

Answer 15

Prophy: > 700 ng/ml
Therapuetic: > 1,000 ng/ml

Question 16

Which antacid does voriconazole interact with?

Answer 16

Omeprazole: it’s a CYP-2C19 inhibitor.

Question 17

Is Moxifloxacin a good choice for pseudomonas?

Answer 17

No. Among the FQ’s, Moxi has the least activity against pseudomonas aeruginosa.

Question 18

What fungus specie are most likely to infect patients in the pre-engraftment phase of a stem cell transplant (when they are profoundly neutropenic)?

Answer 18

Candida spp. (yeast)

Question 19

Is aspergillus a yeast or a mold?

Answer 19

Mold!

Question 20

Does antimicrobial prophy actually help neutropenic patients without fever?

Answer 20

According to a Cochrane review, it reduces all cause mortality.

Question 21

What are some drug interaction considerations for the Azoles?

Answer 21

They are substrates and inhibitors of some CYP enzymes. Also p-gp interactions.

• Posaconazole: Strong 3A4 inhibitor
• Voriconazole: Strong 2C19 inhibitor and substrate. Moderate 3A4 and 2C9 inhibitor too. *This is probably the most relevant. Don’t take with omeprazole (2C19)

Fluconazole: Moderate inhibition. Not a substrate.

Question 22

Who gets antifungal prophylaxis (in neutropenic pts) and what should they receive?

Answer 22

Low-Risk: No prophy (solid tumor, autlogous HSCT w/o mucositis)

Any allogenic HSCT, or anyone with mucositis: Fluconazole or Micafungin. (most worried about candida).

Allogenic + GVHD: (worried about Mold) 1st line = posaconazole. Alternatives = Vori, echino, ampho

Acute Myeloid Leukemia/myelodysplastic syndrome on chemotherapy: Same as above: First = posa, alt = vori, echin, ampho.

Question 23

What neutropenic patients should get PCP prophy?

Answer 23

Anyone in high risk group: Allogenic HSCT, ALL, pts getting Alemtuzumab, High-dose steroids.

Prophy with Bactrim.

*anyone with T-cell depletion probably should be considered for prophy. Just like HIV.

Question 24

What’s the deal with Letermovir?

Answer 24

It’s an antiviral that is active only against CMV. Still need another agent to cover HSV and VZV. Recommended for prophylaxis follow allogenic CMV-seropositive HSCT for first 100 days.

*Not rec’d for prophy following solid organ transplant

Question 25

Which antivirals can be used to TREAT cmv?

Answer 25

Valganciclovir (cytopenias), ganciclovir (cytopenias), foscarnet (kidney damage), cidofovir (kidney damage).

*Letermovir is only for prophy! Not for treatment!

Question 26

Which antivirals can be used to TREAT CMV?

Answer 26

Valganciclovir (cytopenias, poor absorption), ganciclovir (cytopenias), foscarnet (kidney damage, lyte disturbances), cidofovir (kidney damage, worse than foscarnet).

*Letermovir is only for prophy! Not for treatment!

Question 27

What is the treatment of choice for ganciclovir resistance CMV (UL97 positive)?

Answer 27

Foscarnet.

Question 28

What does a positive serum galactomannan indicate?

Answer 28

Presence of invasive aspergillosis (mold). Need to treat with an anti-mold agent, like posaconazole, voriconazole, or isavuconazonium.

Question 29

What is the treatment of choice for invasive mold (aspergillus)?

Answer 29

Voriconazole: RCT showed better outcomes.

*Side effect = visual disturbances/hallucinations. Just treat through it.