NAPLEX Question of the Week: Prophylactic Tactics

This week's question will test your knowledge on an important prophylactic agent.
NAPLEX Question of the Week: Prophylactic Tactics
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HB is a 45-year-old female that presents to your pharmacy to pick up 2 new medications: Abacavir/Dolutegravir/Lamivudine and Trimethoprim/Sulfamethoxazole (TMP/SMX). She tells you that she was recently diagnosed with HIV/AIDS and is confused about why she has to take these medications when she "doesn’t feel sick."

PMH:
Hypertension

Hyperlipidemia

HIV/AIDS (no history of AIDS-defining conditions)

Allergies: No known drug allergies

Medications:

-Abacavir/Dolutegravir/Lamivudine 1 tablet PO QD

-Losartan 50 mg PO QD

-TMP/SMX 1 double-strength tablet PO QD

-Hydrochlorothiazide 12.5 mg PO QD

-Pravastatin 40 mg PO QD

Vitals and Labs:

HR: 75 BPM
RR: 20 BPM
Temp: 98.5 F
BP: 128/78 mmHg
Na: 141 mEq/L
K: 4.7 mEq/L
SCr: 0.8 mg/dL

HIV-1 RNA Viral load: 200,000 copies/mL
CD4 count: 120 cells/uL

Which of the following is true regarding this patient’s TMP/SMX? Select all that apply.
A - TMP/SMX alone is adequate opportunistic infection prophylaxis based on this patient’s CD4 cell count.

B - This patient will require lifelong treatment with TMP/SMX.

C - TMP/SMX is available as an oral tablet, oral suspension, and intravenous solution.

D - Possible adverse reactions of TMP/SMX include a delayed hypersensitivity reaction and hypokalemia.

E - TMP/SMX’s mechanism of action involves the inhibition of bacterial cell wall synthesis.

Human Immunodeficiency Virus (HIV) is transmitted via body fluids and attacks CD4+ cells, weakening the immune system when left untreated. Acquired Immunodeficiency Syndrome (AIDS) is the most advanced stage of HIV infection and is diagnosed in patients with a CD4 cell count < 200 cells/uL or if they have an AIDS-defining condition, such as cytomegalovirus retinitis. Our patient has AIDS due to their CD4 count in conjunction with HIV. ART is recommended in all HIV-positive patients, but patients with AIDS should also be started on appropriate antibiotic prophylaxis for opportunistic infections depending on their CD4 cell count. 

For HIV-infected patients with a CD4 cell count < 200 cells/uL, primary prophylaxis against Pneumocystis pneumonia (PCP) is recommended. PCP infection is characterized by dry cough, fever, and chest discomfort and infected patients may have chest x-rays that show diffuse bilateral infiltrates resembling a butterfly pattern. The preferred agent for PCP prophylaxis is TMP/SMX. Sulfa allergy is more common in the HIV population, so knowledge of alternatives is prudent in case prophylaxis is required. Several potential agents in a patient with this presentation if a sulfa allergy was present would be dapsone, pentamidine, or atovaquone. 

Answer choice A is correct. This patient’s CD4 cell count is 120 cells/uL so they only require primary prophylaxis against PCP. Other opportunistic infections that require prophylaxis based on CD4 counts are Toxoplasma gondii when CD4 cell count < 100 cells/uL and Mycobacterium avium complex (MAC) when CD4 cell count < 50 cells/uL. TMP/SMX is the preferred agent for Toxoplasma gondii prophylaxis and use of either azithromycin or clarithromycin is preferred for MAC prophylaxis.

Answer choice B is incorrect. This patient only requires PCP prophylaxis with TMP/SMX until their CD4 cell count stays above 200 cells/uL for at least 3 months. If their cell count ever drops below this level again, they will have to restart prophylactic therapy.

Answer choice C is correct. TMP/SMX is available in a variety of dosage forms. Dosing for TMP/SMX is based on the trimethoprim component and all available dosage forms contain trimethoprim to sulfamethoxazole in a fixed 1:5 ratio. Intravenous use is rare in clinical practice due to the high volume required to maintain TMP/SMX in solution. If the patient had active PCP pneumonia that required high dose treatment with TMP/SMX, this is often a situation where the IV dosage form would be used. 

Answer choice D is incorrect. Although delayed hypersensitivity reactions may be seen with TMP/SMX, this medication may cause hyperkalemia and not hypokalemia. TMP/SMX may cause immediate or delayed hypersensitivity reactions. Immediate reactions include angioedema and anaphylaxis and develop within a few hours of administration, and delayed reactions include skin rashes and severe cutaneous adverse reactions (SCARs) that may develop within days to weeks of drug exposure. Delayed reactions are much more common.  Hyperkalemia associated with TMP/SMX is due to the trimethoprim component inhibiting renal potassium excretion and may occur within 5 to 10 days of exposure, especially with higher doses or other medications that promote hyperkalemia, such as renin-angiotensin-aldosterone acting agents.

Answer choice E is incorrect. TMP/SMX does not impact cell wall synthesis.  Trimethoprim inhibits dihydrofolate reductase, preventing the production of tetrahydrofolic acid from folic acid and sulfamethoxazole inhibits folic acid synthesis. When these agents are used together, bacteria can’t make folic acid or use their current stores of folic acid and are unable to synthesize DNA.

Medications: Trimethoprim-Sulfamethoxazole (Bactrim or Septra); Abacavir, Dolutegravir, Lamivudine (Triumeq); Losartan (Cozaar); Hydrochlorothiazide (Microzide); Pravastatin (Pravachol)

Naplex Competencies:

Area 2 - Identify Drug Characteristics

2.1 - Pharmacology, mechanism of action, or therapeutic class

Area 3 - Develop or Manage Treatment Plans

3.4 - Drug dosing or dosing adjustments; duration of therapy

3.5 - Drug route of administration, dosage forms, or delivery systems

3.7 - Adverse drug effects, toxicology, or overdose

3.11 - Evidence-based practice

Area 6 - Develop or Manage Practice or Medication-Use Systems to Ensure Safety and Quality

6.3 - Disease prevention or screening program; or stewardship

6.4 - Vulnerable populations, special populations, or risk prevention programs

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