Corticosteroids, cytotoxic agents, and infection

Infection Corticosteroid therapy
Acute bacterial meningitis caused by Haemophilus influenzae type B in children or Streptococcus pneumoniae in adults Dexamethasone 0.15 mg/kg q6h × 4 d
Pneumocystis jirovecii pneumonia, P02 70 mm Hg in HIV-infected patients Prednisone 40 mg BID × 5 d, then 40 mg qd × 5 d, then 20 mg qd for 11 d
Acute severe laryngotracheobronchitis (croup) Dexamethasone >0.3 mg/kg qd × 3–4 d
Allergic bronchopulmonary aspergillosis Prednisone 45–60 mg qd until infiltrate clears then taper
Typhoid fever, critically ill with mental status changes or shock High-dose dexamethasone × 2–3 d
Tuberculous pericarditis and meningitis Prednisone 60–80 mg qd for several weeks followed by taper

Abbreviations: HIV = human immunodeficiency virus.

Corticosteroids and risk of infection

Myriad pathogens are associated with impaired cellular immunity and corticosteroid use (Table 87.2). Most of the organisms listed rarely cause significant or life-threatening infections in the immunocompetent patient. Some, such as P. jirovecii, cause disease only in immunocompromised individuals.

Table 87.2 Pathogens associated with corticosteroid use or other causes of cellular immunodeficiency

Legionella pneumophilia
Listeria monocytogenes
Mycobacterium tuberculosis
Nocardia species
Salmonella species
Rhodococcus equi
Blastomyces dermatitidis
Candida species
Coccidioides immitis
Histoplasma capsulatum
Cryptococcus neoformans
Aspergillus species
Strongyloides stercoralis
Cryptosporidium parvum
Pneumocystis jirovecii
Toxoplasma gondii
Plasmodium species
Herpes simplex
Hepatitis B

Patients with severe opportunistic infections often have concurrent underlying impairment of cellular immunity separate from the iatrogenic impairment secondary to steroid use. Thus, the risk of infection varies by underlying disease process. For instance, patients with acquired immunodeficiency syndrome (AIDS) or childhood acute lymphocytic leukemia have higher rates of PCP than patients without these diseases but receiving chronic corticosteroid therapy. For patients requiring chronic corticosteroid therapy, the infection rate for many of the pathogens listed in Table 87.2 is actually quite low. Overall, the risk increases with the dose and duration of use and may be increased by concomitant administration of other immunosuppressants. Patients who require 15 mg of prednisone or an equivalent dose of other corticosteroids for more than 1 month should receive prophylaxis against PCP and other infections with trimethoprim–sulfamethoxazole. Alternative agents include dapsone, atovaquone, and inhaled pentamidine. Skin induration 5 mm after tuberculin skin test is indicative of latent tuberculosis in this population.

Cytotoxic antineoplastic agents

Mechanisms of action

Cancer itself is associated with immune suppression such as neutropenia in acute leukemia or numerical/functional lymphocyte impairment in lymphoma patients. However, clinically significant infections in cancer patients are often related to the effects of cytotoxic antineoplastic agents.

The oldest class of cytotoxic drugs comprises alkylating agents, such as cyclophosphamide, busulfan, melphalan, and chlorambucil. The purine

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Jun 18, 2016 | Posted by in INFECTIOUS DISEASE | Comments Off on Corticosteroids, cytotoxic agents, and infection

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