What is the recommended treatment for a patient with severe adenoviral infection?

Treatment of Severe Adenoviral Infection

For severely ill immunocompromised patients with adenovirus-associated disease (pneumonia, hepatitis, disseminated infection, or severe gastroenteritis), cidofovir is the drug of choice, while immunocompetent patients should receive supportive care unless they develop life-threatening disease with organ failure. 1, 2

Treatment Algorithm by Patient Population

Immunocompromised Patients with Severe Disease

Cidofovir should be initiated for severe manifestations including pneumonia, hepatitis, disseminated infection, or severe gastroenteritis. 1

Dosing regimens:

• Standard dosing: 5 mg/kg IV once weekly for 2 weeks, then every other week 1, 2, 3
• Low-dose alternative: 1 mg/kg three times weekly (based on severity and renal function) 1
• Continue until 3 consecutive negative samples from all previously involved sites 3

Mandatory monitoring for nephrotoxicity is required as this is the primary dose-limiting adverse effect. 1, 3 Concurrent probenecid should be administered for renal protection. 4

Clinical efficacy data: In pediatric HSCT patients, cidofovir achieved complete resolution of clinical symptoms in 98% of patients (56/57) with no dose-limiting nephrotoxicity observed. 3 Early treatment prevents the poor outcomes associated with adenovirus disease, which can exceed 50% fatality rates in untreated severe pneumonia or disseminated disease. 2

Immunocompetent Patients

Supportive care is the cornerstone of management for the vast majority of immunocompetent patients, with infections typically resolving within 7-10 days. 2

Supportive measures include:

• Adequate hydration, particularly with gastrointestinal manifestations 1, 2
• Oral analgesics for pain management 1
• Antipyretics for fever 2
• Respiratory support (oxygen, nebulizers) as needed 2
• Cold compresses and artificial tears for conjunctivitis 1

Exception for cidofovir use: Consider cidofovir in previously healthy patients who develop fulminant infection with multiple organ failure, persistent viremia >560,000 copies/mL despite supportive care, or lymphopenia. 4 A case report demonstrated successful use in an immunocompetent child with adenovirus type 7 requiring ECMO support, with viral clearance after 3 doses. 4

Early cidofovir administration (median 48 hours from admission, 7.1 days from symptom onset) in non-immunocompromised patients with severe AdV-B55 pneumonia and progressive respiratory failure resulted in complete symptomatic improvement after a median of 12 days without complications. 5

Diagnostic Approach

Rapid diagnostic testing should be performed promptly on patients admitted with symptoms to facilitate early treatment initiation when indicated. 1

• PCR testing (sensitivity 88-89%, specificity 91-94%) or rapid diagnostic tests 1
• Nasopharyngeal swabs for respiratory disease 1
• Conjunctival swabs for ocular disease 1
• Quantitative real-time PCR for peripheral blood screening in HSCT patients 3

Special Clinical Scenarios

Adenoviral Keratoconjunctivitis

Topical corticosteroids (fluorometholone, rimexolone, or loteprednol) should be considered for severe disease with subepithelial infiltrates causing blurred vision or photophobia, with mandatory close ophthalmology follow-up. 1

• Monitor for increased intraocular pressure and cataract formation 1
• Taper slowly to minimum effective dose 1
• Debride membranes in membranous conjunctivitis to prevent corneal epithelial abrasions or permanent cicatricial changes 1

High-Risk Pediatric Oncology/BMT Patients

A clinical algorithm can identify high-risk patients who merit cidofovir therapy versus low-risk patients who can be observed. 6 In one study, cidofovir reduced adenovirus-related mortality in high-risk patients from 80% to 11% (relative risk 0.14, P<0.05), with all treated patients clearing their virus. 6

ARDS with ECMO Support

Cidofovir combined with early ECMO therapy may be a therapeutic option in adenoviral ARDS. 7 Three cases showed positive clinical response to cidofovir with 28-day survival. 7

Infection Control Measures

Rigorous infection control is essential as adenovirus survives for weeks on surfaces and remains infectious for 10-14 days from symptom onset. 1, 2

• Standard, contact, and droplet precautions in healthcare settings 1
• Hand hygiene with soap and water or alcohol-based hand rubs 1, 2
• Gloves when entering patient rooms; gowns when soiling anticipated 1
• Surgical mask and eye protection within 3 feet of patients 1
• Private rooms or cohorting with other adenovirus-infected patients 1
• Disinfect surfaces with EPA-registered disinfectants or sodium hypochlorite (1:10 dilution of household bleach) 1, 2

Critical 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 use topical corticosteroids for conjunctivitis without confirming the diagnosis is not herpes simplex virus, as corticosteroids worsen HSV infections and lead to corneal scarring. 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 cidofovir—reserve for severe or disseminated disease given nephrotoxicity risk. 1

Do not delay cidofovir in high-risk patients with persistent organ failure and high viral loads, as early treatment (within 48 hours of admission) improves outcomes. 5