While immunosuppressives can be lifesaving in patients with immune-mediated hematological disorders, this benefit comes with a price, which includes the development of bacterial and viral infections and reactivation of tuberculosis, toxoplasmosis, varicella zoster, or viral hepatitis. A recent critical review incorporating recommendations from the CDC, regulatory agencies, and expert panels offered strategies to help prevent infectious complications in patients undergoing treatment for nonmalignant, immune-mediated hematological disorders. The review featured guidance on vaccination and infectious-disease screening in adults receiving rituximab, eculizumab, corticosteroids, antimetabolites (azathioprine or mycophenolate mofetil), cyclosporine, and cyclophosphamide or undergoing splenectomy.
A point stressed in the review was the need for patient counseling on proper hand hygiene and avoiding contact with persons who can pose a risk of infection.
Depending on the dose and duration of corticosteroids, patients on as little as 7.5 mg daily of prednisone are at risk of developing infections, such as Pneumocystis jirovecii pneumonia, herpes zoster reactivation, tuberculosis, strongyloidiasis, and mycobacterial, Candida, and cryptococcal infections. For patients on chronic or high-dose corticosteroids (e.g., >10-20 mg of prednisone equivalents daily for >4 weeks), it has been suggested to screen for hepatitis B (HBV), hepatitis C (HCV), latent tuberculosis, and strongyloidiasis. High-risk patients (i.e., those with a >10% risk of reactivation of HBV), those on chronic, moderate doses (10-20 mg prednisone-equivalents), and those on high doses (>20 mg prednisone equivalents) for >4 weeks of corticosteroids should receive HBV prophylaxis with an antiviral with a high barrier to resistance, such as entecavir or tenofovir.
If patients are on >10 mg daily of prednisone equivalents and have other risk factors, such as advanced age, pulmonary disease, or treatment with cyclophosphamide or rituximab, trimethoprim-sulfamethoxazole prophylaxis (or atovaquone, dapsone, or nebulized pentamidine in those intolerant to the sulfa antibiotic) against Pneumocystis jiroveccii pneumonia should be considered. All patients on chronic corticosteroids should receive the influenza vaccine yearly, and those aged 50 years and older should also receive the herpes zoster vaccine.
Rituximab primarily places patients at risk of developing HBV or HCV reactivation. Patients on rituximab and their family members should be taught the warning signs of progressive multifocal leukoencephalopathy, which include neurotoxicity. Late-onset neutropenia, hypogammaglobulinemia, and opportunistic infections such as reactivation of tuberculosis, cytomegalovirus, Epstein-Barr virus, parovirus, echo virus, varicella zoster, and fungal infections have been reported in patients on steroids. Patients taking rituximab should be tested for HBV (in particular, hepatitis B surface antigen [HBsAg] or anti–hepatitis B core antibody [anti–HBc Ab]). Patients who are HBsAg-positive/anti–HBc Ab-positive or HBsAg-negative/anti–HBc Ab-positive should receive antiviral therapy. The recommendations for HCV testing and treatment are not as strong. Patients on rituximab should be vaccinated against pneumococcus, Haemophilus influenzae type b, and meningococcal infection using polysaccharide vaccines.
Patients treated with eculizumab are primarily at risk of meningococcal infections. These patients should be prophylaxed with both quadrivalent meningococcal conjugate and serogroup B meningococcal vaccines. Antibiotic prophylaxis is recommended if eculizumab is administered prior to meningococcal vaccination or if the risks of delaying eculizumab therapy for two weeks following the administration of the vaccine outweigh the risks of meningococcal infection. First-line prophylactic therapy is penicillin VK 500 mg orally twice daily. Ciprofloxacin, rifampin, or azithromycin can be used in those who are penicillin allergic. Others have prophylaxed all patients on eculizumab for the duration of treatment. Patients on eculizumab should also be enrolled in the FDA’s Risk Evaluation and Mitigation Strategy program, which is monitoring for meningococcal signals among other adverse events.
Antimetabolites, such as azathioprine and mycophenolate mofetil, can be associated with the development of atypical bacterial, fungal, parasitic, and viral infections as well as the reactivation of parasitic and viral reactivations. These drugs also increase the risk of John Cunningham virus–associated progressive multifocal leukoencephalopathy. Cyclosporine use can also result in reactivation of viral infections, whereas cyclophosphamide can cause serious, sometimes fatal, bacterial, fungal, viral, protozoal, and parasitic infections.
While there are no specific recommendations for antibiotic prophylaxis for patients on either azathioprine or mycophenolate mofetil, it has been suggested to prophylaxis against Pneumocystis jiroveci pneumonia in those on concurrent cyclophosphamide and corticosteroid therapy. The use of live attenuated vaccines should be avoided in these populations. Those patients aged 50 years or older should receive recombinant herpes zoster vaccination.
Recommendations are also provided on infection risk, infection-prevention strategies, antimicrobial prophylaxis, and other supportive considerations in surgical splenectomy patients.
The pharmacist can take a proactive role monitoring for signs and symptoms of infection in patients with nonmalignant, immune-mediated hematological disorders. They can also recommend prophylaxis and promote immunizations.
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Published February 27, 2020