What is the best management approach for a patient with severe adenoviral infection, considering factors such as age, immune status, and underlying health conditions?

Management of Severe Adenoviral Infection

For severe adenoviral infections in immunocompromised patients with pneumonia, hepatitis, disseminated disease, or severe gastroenteritis, initiate cidofovir as the antiviral of choice, while for immunocompetent patients, provide aggressive supportive care as the mainstay of treatment since antivirals have not proven effective in this population. 1

Initial Risk Stratification

Determine immune status immediately, as this fundamentally dictates management approach:

• Immunocompromised patients (stem cell transplant recipients, solid organ transplant recipients, HIV/AIDS, congenital immunodeficiency) face mortality rates exceeding 50% with untreated severe disease and require antiviral therapy 2
• Immunocompetent patients typically experience self-limited disease, though rare cases of severe pneumonia requiring ECMO support have been reported with poor outcomes despite aggressive intervention 3

Diagnostic Confirmation

Obtain rapid diagnostic testing immediately using PCR or rapid antigen detection (sensitivity 88-89%, specificity 91-94%):

• Collect nasopharyngeal swabs for respiratory disease 1
• Collect conjunctival swabs for ocular disease 1
• Monitor serial stool samples in pediatric stem cell transplant recipients, as the gastrointestinal tract serves as the primary site of viral persistence and replication preceding invasive infection 4
• Monitor peripheral blood specimens in adult immunocompromised patients 4

Treatment Algorithm by Patient Population

Immunocompromised Patients with Severe Disease

Initiate cidofovir immediately for patients presenting with:

• Adenoviral pneumonia
• Hepatitis
• Disseminated infection
• Severe gastroenteritis 1

Dosing options (select based on severity and renal function):

• Low-dose regimen: 1 mg/kg three times weekly 1
• Standard-dose regimen: 5 mg/kg once weekly for 2 weeks, then once every other week 1

Critical monitoring requirement: Nephrotoxicity is the primary dose-limiting adverse effect—monitor renal function closely throughout treatment 1

Timing is paramount: Early initiation of antiviral treatment is required for prevention or successful control of disseminated disease, as established adenovirus disease is difficult to treat even with effective antivirals 5, 4

Immunocompetent Patients with Severe Disease

Provide aggressive supportive care only, as antivirals have not proven effective in this population 3:

• Maintain adequate hydration, particularly with gastrointestinal manifestations 1
• Provide supplemental oxygen and mechanical ventilation as needed
• Consider ECMO support for refractory respiratory failure, though outcomes are significantly worse than other viral pneumonias 3
• Monitor for secondary bacterial infections without using prophylactic antibiotics 1

Severe Adenoviral Keratoconjunctivitis Management

For severe ocular disease with marked chemosis, lid swelling, epithelial sloughing, or membranous conjunctivitis, consider topical corticosteroids (fluorometholone, rimexolone, or loteprednol) with mandatory close ophthalmology follow-up 6, 1:

• Monitor intraocular pressure and perform periodic pupillary dilation to evaluate for glaucoma and cataract 6, 1
• Taper slowly to minimum effective dose 1
• Critical caveat: Corticosteroids may prolong viral shedding in animal models, though human data are lacking 6
• Never use corticosteroids without confirming the diagnosis is not herpes simplex virus, as this can cause corneal scarring and vision loss 1

Debride membranes in membranous conjunctivitis to prevent corneal epithelial abrasions or permanent cicatricial changes 6, 1

Re-evaluate within 1 week for patients with severe disease, corneal epithelial ulceration, or membranous conjunctivitis 6

Infection Control Measures (Critical for All Patients)

Implement strict precautions immediately, as adenovirus survives for weeks on surfaces without proper disinfection 1:

• Standard, contact, and droplet precautions in healthcare settings 1
• Place patients in private rooms or cohort with other adenovirus-infected patients 6, 1
• Wear gloves when entering patient rooms 1
• Wear gowns when soiling with respiratory secretions is anticipated 1
• Wear surgical mask and eye protection or face shield when within 3 feet of patient 1
• Hand hygiene with soap and water or alcohol-based hand rubs 1
• Disinfect surfaces with EPA-registered hospital disinfectants or sodium hypochlorite (1:10 dilution of household bleach) 1

Educate patients to minimize contact with others for 10-14 days from symptom onset 6, 1

Restrict healthcare personnel with acute upper respiratory tract infections from caring for high-risk patients (infants, immunocompromised, cardiac patients, premature infants) 6, 1

Common Pitfalls to Avoid

Do not prescribe antibiotics for adenovirus infection in immunocompetent patients—they provide no benefit and contribute to antimicrobial resistance 1

Do not underestimate contagiousness—the virus survives for weeks on surfaces, requiring rigorous infection control measures 1

Do not treat all immunocompromised patients with antivirals—reserve cidofovir for severe or disseminated disease given its nephrotoxicity 1

Do not use topical corticosteroids for conjunctivitis without confirming the diagnosis is not HSV, as this can worsen HSV infections and lead to corneal scarring 1

Do not delay antiviral therapy in immunocompromised patients with severe disease—timely initiation is required for successful control, as established disease is difficult to treat 5, 4