What medications should be prioritized in immunocompromised patients?

From the Guidelines

Immunocompromised patients should receive prophylactic antimicrobials, including trimethoprim-sulfamethoxazole (TMP-SMX) at 160/800 mg daily or three times weekly for Pneumocystis jirovecii pneumonia prevention, particularly when CD4 counts fall below 200 cells/μL or during high-dose steroid therapy, as recommended by the most recent guidelines 1. When CD4 counts are <200 cells/ml, prophylaxis against Pneumocystis jirovecii pneumonia (PcP) and antiviral prophylaxis with acyclovir or valacyclovir in patients with a history of herpes simplex virus or varicella zoster virus infection are strongly recommended 1. Some key points to consider:

• Antiviral prophylaxis with acyclovir 400 mg twice daily or valacyclovir 500 mg daily is recommended for herpes virus prevention in severely immunocompromised patients.
• For those at risk of fungal infections, fluconazole 100-200 mg daily may be indicated, especially in stem cell transplant recipients.
• Patients with latent tuberculosis should receive isoniazid 300 mg daily with pyridoxine 25-50 mg daily for 9 months.
• Additionally, immunocompromised patients often require pneumococcal vaccines (both PCV13 and PPSV23), annual influenza vaccination, and hepatitis B vaccination if not immune.
• Inactivated vaccines are generally safe, though live vaccines are typically contraindicated.
• G-CSF (filgrastim) at 5 μg/kg daily may be needed for neutropenic patients until neutrophil recovery. These medications are crucial because immunocompromised patients have impaired ability to fight infections, and prophylactic therapy significantly reduces morbidity and mortality from opportunistic pathogens that rarely cause disease in immunocompetent individuals.

From the FDA Drug Label

For patients co-infected with HIV, screening of antimycobacterial drug levels, especially in patients with advanced HIV disease, may be necessary to prevent the emergence of MDRTB. The response of the immunologically impaired host to treatment may not be as satisfactory as that of a person with normal host responsiveness.

In immunocompromised patients, antimycobacterial medications such as isoniazid and rifampin should be prioritized, and their levels should be monitored, especially in patients with advanced HIV disease, to prevent the emergence of multi-drug resistant tuberculosis (MDRTB) 2.

• Isoniazid and rifampin are key medications for the treatment of tuberculosis in immunocompromised patients.
• Monitoring of drug levels is crucial in patients with advanced HIV disease to ensure effective treatment and prevent the emergence of MDRTB.

From the Research

Medications for Immunocompromised Patients

• Antimicrobial chemoprophylaxis is an important part of preventive strategies used in immunocompromised patients, with regimens available against bacteria, protozoa, fungi, and viruses 3
• Trimethoprim-sulfamethoxazole (TMP-SMX) is the antimicrobial treatment of choice for Pneumocystis jirovecii pneumonia (PJP), a common and highly morbid infection in immunocompromised patients 4
• Reduced doses of TMP-SMX (≤10 mg/kg/d of trimethoprim) may be effective and carry an improved safety profile, with similar rates of mortality and fewer treatment-emergent severe adverse events compared to standard doses 4, 5

Prioritization of Medications

• Patients with severe neutropenia, patients receiving bone-marrow or organ transplants, and patients with AIDS are important candidates for prophylaxis 3
• The choice of medication should be based on the individual patient's needs and the potential risks and benefits of each regimen, with consideration of the cost and potential side effects 3, 6
• A low-dose prophylactic regimen of sulfamethoxazole/trimethoprim (SMX/TMP) may be well tolerated in kidney transplant recipients, with lower discontinuation rates compared to higher-dose regimens 7

Considerations for Medication Use

• The net state of immunosuppression and epidemiologic exposures should be considered when determining the risk of infection in immunocompromised patients 6
• Antimicrobial agents can be used therapeutically, prophylactically, or pre-emptively to prevent or treat clinical infection in immunocompromised patients 6
• The potential for adverse events, such as hypersensitivity reactions, drug-induced liver injury, cytopenias, and renal failure, should be considered when selecting medications for immunocompromised patients 5