Infectious complications and preventive strategies with the use of systemic corticosteroids
| Pathogen . | Risk factors for infection . | Preventive strategy . |
|---|---|---|
| PJP | A. Corticosteroid dose ≥ 30 mg PEQ daily given for ≥4 wk B. Corticosteroids ≥ 15 mg to <30 mg PEQ daily given for ≥8 wk uninterrupted or in intermittent doses C. Combination of medium-dose corticosteroids (ie, ≥15 mg to <30 mg PEQ daily) and CP (oral or IV pulses) D. Corticosteroids ≥ 10 mg PEQ daily and ≥2 of the following: advanced age > 65 y, coexisting lung disease (eg, COPD, lung fibrosis), use of immunotherapeutics (eg, rituximab, anti-TNF). | Antimicrobial prophylaxis: • For all patients in (A) through (D), PJP prophylaxis is indicated. • TMP/SMX, 1 single-strength tablet (80 mg of TMP and 400 mg of SMX) daily, or TMP/SMX, 1 double-strength tablet 3 times weekly. • If TMP/SMX intolerance or contraindicated, alternative therapies are atovaquone, dapsone, or once-monthly nebulized pentamidine. • For patients in (D), PJP prophylaxis should be continued until the corticosteroid dose is ≤5 mg PEQ daily. |
| HZ (shingles) | A. Advanced age > 60 y B. Corticosteroid dose > 7.5 mg to 10 mg PEQ C. History of recurrent shingles | Immunization: • RZV (ie, SHINGRIX) preferred over ZVL (ie, Zostavax) • Indicated in all adults aged ≥ 50 y, including those who received ZVL in the past; had chickenpox or do not recall whether they had chickenpox; had shingles, but not an active flare at the time of vaccination; and have chronic comorbidities (eg, chronic renal failure, diabetes mellitus, autoimmune diseases, COPD) • In adults aged ≥ 50 y anticipating immunosuppression or currently on immunosuppressive therapy, important considerations are to vaccinate ideally ≥4 wk before treatment; okay in patients taking low-dose immunosuppressive therapy (eg, <20 mg/d prednisone or equivalent, or using inhaled or topical steroids, azathioprine, mycophenolate mofetil); and okay in patients who have recovered from an immunocompromising illness • Adults aged < 50 y: ACIP does not have a recommendation to administer either zoster vaccine to people younger than 50 y. However, based on the available evidence, clinicians may choose to administer a vaccine off-label, if, in their clinical judgment, they think that the vaccine is indicated (eg, history of shingles). The patient should be informed that the use is off-label and that efficacy and safety of the vaccine have not been tested in people younger than 50 y. Antimicrobial prophylaxis: • No evidence outside of the transplant setting exists on the use of antiviral prophylaxis. However, it might be reasonable that patients with history of recurrent shingles or heavily treated with immunosuppressive agent should consider antiviral prophylaxis. Doses as low as 400 mg of acyclovir daily have shown to an effective strategy in immunocompromised patients. |
| TB reactivation | A. Corticosteroid dose < 15 mg PEQ daily has a 2.8-fold increased risk B. Corticosteroid dose > 15 mg PEQ daily has a 7.7-fold increased risk | TB screening testing: • Patients taking corticosteroids at a dose ≥ 10 mg PEQ daily for ≥4 wk should be screened for latent TB using tuberculin skin test or interferon-γ release assays; the latter is preferred in patients with altered T-cell function (eg, HIV/AIDS), history of BCG immunization, and ongoing corticosteroid therapy or other immunosuppressive agents • If positive test, refer to an infectious disease specialist |
| Disseminated SS hyperinfection syndrome | A. Major risk factor is provenance/travel history: tourists, military, and immigrant populations coming from high prevalence areas, such as Africa (Ghana, Zambia, Gabon, Sudan), Asia (Thailand, Cambodia), Central America (Guatemala), and South America (Peru, Venezuela, Brazil). B. There are no clear data on the dosage or duration of corticosteroid therapy that triggers the risk for severe strongyloidiasis. | SS screening testing: • Given the available data, any patient coming from a high-risk area and scheduled to start corticosteroids at a dose > 10-15 mg PEQ daily for ≥4 wk should be screened with stool sample for ova and parasites and serum IgG against SS. Antimicrobial prophylaxis: • Given the poor sensitivity and high cost of SS screening, empiric therapy with ivermectin represents a safe and cost-effective approach in patients at high-risk for severe strongyloidiasis (ie, people walking barefoot in endemic areas). |
| HBV reactivation | A. High-dose corticosteroids (>20 mg PEQ daily) for >4 wk B. Chronic (≥8 wk) medium-dose corticosteroids (10-20 mg PEQ daily) | HBV screening testing: • Patients in (A) and (B) need hepatitis B screening with anti-HBc and HBsAg. Results interpretation: • Patients in (A) or (B) with positive anti-HBc and positive HBsAg have a high risk for HBV reactivation (≥10% risk for reactivation). • Patients in (A) with positive anti-HBc, but negative HBsAg, have a moderate risk for HBV reactivation (1-10% risk of reactivation). Antimicrobial prophylaxis: • Patients with high risk for HBV reactivation require antiviral prophylaxis. • For patients with moderate risk for HBV reactivation, 2 options are available: preemptive therapy guided by serial HBV DNA monitoring, with antiviral therapy initiated as soon as HBV DNA becomes detectable, and routine prophylactic antiviral therapy. • Entecavir or tenofovir is the preferred agent because of the low risk of resistance. • Infectious disease input is encouraged. |
| Pathogen . | Risk factors for infection . | Preventive strategy . |
|---|---|---|
| PJP | A. Corticosteroid dose ≥ 30 mg PEQ daily given for ≥4 wk B. Corticosteroids ≥ 15 mg to <30 mg PEQ daily given for ≥8 wk uninterrupted or in intermittent doses C. Combination of medium-dose corticosteroids (ie, ≥15 mg to <30 mg PEQ daily) and CP (oral or IV pulses) D. Corticosteroids ≥ 10 mg PEQ daily and ≥2 of the following: advanced age > 65 y, coexisting lung disease (eg, COPD, lung fibrosis), use of immunotherapeutics (eg, rituximab, anti-TNF). | Antimicrobial prophylaxis: • For all patients in (A) through (D), PJP prophylaxis is indicated. • TMP/SMX, 1 single-strength tablet (80 mg of TMP and 400 mg of SMX) daily, or TMP/SMX, 1 double-strength tablet 3 times weekly. • If TMP/SMX intolerance or contraindicated, alternative therapies are atovaquone, dapsone, or once-monthly nebulized pentamidine. • For patients in (D), PJP prophylaxis should be continued until the corticosteroid dose is ≤5 mg PEQ daily. |
| HZ (shingles) | A. Advanced age > 60 y B. Corticosteroid dose > 7.5 mg to 10 mg PEQ C. History of recurrent shingles | Immunization: • RZV (ie, SHINGRIX) preferred over ZVL (ie, Zostavax) • Indicated in all adults aged ≥ 50 y, including those who received ZVL in the past; had chickenpox or do not recall whether they had chickenpox; had shingles, but not an active flare at the time of vaccination; and have chronic comorbidities (eg, chronic renal failure, diabetes mellitus, autoimmune diseases, COPD) • In adults aged ≥ 50 y anticipating immunosuppression or currently on immunosuppressive therapy, important considerations are to vaccinate ideally ≥4 wk before treatment; okay in patients taking low-dose immunosuppressive therapy (eg, <20 mg/d prednisone or equivalent, or using inhaled or topical steroids, azathioprine, mycophenolate mofetil); and okay in patients who have recovered from an immunocompromising illness • Adults aged < 50 y: ACIP does not have a recommendation to administer either zoster vaccine to people younger than 50 y. However, based on the available evidence, clinicians may choose to administer a vaccine off-label, if, in their clinical judgment, they think that the vaccine is indicated (eg, history of shingles). The patient should be informed that the use is off-label and that efficacy and safety of the vaccine have not been tested in people younger than 50 y. Antimicrobial prophylaxis: • No evidence outside of the transplant setting exists on the use of antiviral prophylaxis. However, it might be reasonable that patients with history of recurrent shingles or heavily treated with immunosuppressive agent should consider antiviral prophylaxis. Doses as low as 400 mg of acyclovir daily have shown to an effective strategy in immunocompromised patients. |
| TB reactivation | A. Corticosteroid dose < 15 mg PEQ daily has a 2.8-fold increased risk B. Corticosteroid dose > 15 mg PEQ daily has a 7.7-fold increased risk | TB screening testing: • Patients taking corticosteroids at a dose ≥ 10 mg PEQ daily for ≥4 wk should be screened for latent TB using tuberculin skin test or interferon-γ release assays; the latter is preferred in patients with altered T-cell function (eg, HIV/AIDS), history of BCG immunization, and ongoing corticosteroid therapy or other immunosuppressive agents • If positive test, refer to an infectious disease specialist |
| Disseminated SS hyperinfection syndrome | A. Major risk factor is provenance/travel history: tourists, military, and immigrant populations coming from high prevalence areas, such as Africa (Ghana, Zambia, Gabon, Sudan), Asia (Thailand, Cambodia), Central America (Guatemala), and South America (Peru, Venezuela, Brazil). B. There are no clear data on the dosage or duration of corticosteroid therapy that triggers the risk for severe strongyloidiasis. | SS screening testing: • Given the available data, any patient coming from a high-risk area and scheduled to start corticosteroids at a dose > 10-15 mg PEQ daily for ≥4 wk should be screened with stool sample for ova and parasites and serum IgG against SS. Antimicrobial prophylaxis: • Given the poor sensitivity and high cost of SS screening, empiric therapy with ivermectin represents a safe and cost-effective approach in patients at high-risk for severe strongyloidiasis (ie, people walking barefoot in endemic areas). |
| HBV reactivation | A. High-dose corticosteroids (>20 mg PEQ daily) for >4 wk B. Chronic (≥8 wk) medium-dose corticosteroids (10-20 mg PEQ daily) | HBV screening testing: • Patients in (A) and (B) need hepatitis B screening with anti-HBc and HBsAg. Results interpretation: • Patients in (A) or (B) with positive anti-HBc and positive HBsAg have a high risk for HBV reactivation (≥10% risk for reactivation). • Patients in (A) with positive anti-HBc, but negative HBsAg, have a moderate risk for HBV reactivation (1-10% risk of reactivation). Antimicrobial prophylaxis: • Patients with high risk for HBV reactivation require antiviral prophylaxis. • For patients with moderate risk for HBV reactivation, 2 options are available: preemptive therapy guided by serial HBV DNA monitoring, with antiviral therapy initiated as soon as HBV DNA becomes detectable, and routine prophylactic antiviral therapy. • Entecavir or tenofovir is the preferred agent because of the low risk of resistance. • Infectious disease input is encouraged. |
Data are from Youssef et al,17 Cavallasca et al,23 Dooling et al,24 Yun et al,25 Loomba and Liang,26 Katsuyama et al,27 and Center for Disease Control and Prevention.28
ACIP, Advisory Committee on Immunization Practices; anti-HBc, anti–hepatitis B core antibody; anti-TNF, anti–tumor necrosis factor inhibitors; BCG, bacillus Calmette-Guérin; HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; HZ, herpes zoster; IgG, immunoglobulin G; PJP, P jirovecii pneumonia; RZV, recombinant zoster vaccine; SMX, sulfamethoxazole; SS, Strongyloides stercoralis; TB, tuberculosis; TMP, trimethoprim; ZVL, zoster vaccine live.