eMedicine Specialties > Infectious Diseases > Viral Infections

Adenoviruses: Treatment & Medication

Author: Sandra G Gompf, MD, FACP, FIDSA, Section Chief, Associate Professor of Infectious Diseases and International Medicine, Infectious Diseases, James A Haley Veterans Hospital
Coauthor(s): Richard L Oehler, MD, FACP, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases and Tropical Medicine, Univ of South Florida College of Medicine; Assistant Epidemiologist, Division of Infectious Diseases, Tampa VA Medical Center
Contributor Information and Disclosures

Updated: Dec 3, 2007

Treatment

Medical Care

Currently, specific therapy for adenovirus infection, other than supportive and symptomatic treatment, remains a matter of debate.

  • Several case reports of successes with ribavirin therapy have been cited for serious adenoviral disease in immunocompromised patients; however, the number of failed treatments that have not been reported remains uncertain.
    • Attempts to shed light on this issue have included retrospective reviews of adenoviral disease in recipients of bone marrow transplants.18 Some benefit of both ribavirin and cidofovir has been documented in case series, as demonstrated by decreased viremia and concomitant clinical improvement with antiviral therapy.19,20,21  Cidofovir treatment resulted in complete clinical resolution in 56 of 57 pediatric recipients of hematopoietic stem cell transplants in whom the virus became undetectable, without dose-limited nephrotoxicity.22
    • Engraftment or recovery of T-cell–specific immunity has been suggested as vital to recovery from pulmonary or disseminated infection, regardless of antiviral therapy.23 In one study involving children who underwent hematopoietic stem cell transplantation, all patients who died from adenoviral infection lacked specific T cells against adenovirus.23
    • Clinical trials are warranted to determine the role and possible sequencing of ribavirin and cidofovir, as well as to document the adverse events that may be unique to specific transplantation populations.
  • No available studies adequately address issues such as which syndromes are most likely to respond to treatment, which patients develop limiting hematologic toxicity from ribavirin or nephrotoxicity from cidofovir, or which patients, if any, may benefit from adjunctive therapy with leukocyte transfusions.
    • Certainly, given the increasing recognition of the impact of adenovirus infection in immunosuppressed persons, the increasing use of immune modulators and transplantation for various illnesses, and the attendant likely rise in the incidence of adenovirus infection, more attention will be paid to effective treatment.
    • Prospective controlled trials and the development of new antiviral agents must address the critical issue of treating adenoviral infections in immunocompromised patients.
    • Because successful outcomes and evidence of viremic control with antiviral therapy has been described, the benefits of treating individual patients should be carefully considered. The risks of serious morbidity and mortality related to adenoviral disease must also be weighed carefully against those related to its treatment.
    • No evidence-based guidelines for or against specific antiviral therapies in this setting are available, and treatment decisions should be individualized; current evidence somewhat favors treatment.
  • Fortunately, most infections are self-limited in the setting of a normal immune response and do not warrant specific therapy.

Consultations

  • Consultation with an ophthalmologist should be sought in the follow-up care of persons with keratoconjunctivitis, preferably early, but particularly if they develop corneal opacities.
  • If hemorrhagic cystitis does not resolve within 5 days, consider noninfectious etiologies and consultation with a urologist or nephrologist, as appropriate.
  • Immunosuppressed patients may present with various adenoviral syndromes, ranging from afebrile hemorrhagic cystitis to fulminant disseminated disease (followed by shock and death). Consultation with an infectious disease specialist is helpful in this setting.

Medication

Medical therapy is not indicated in healthy hosts. However, adenoviral keratitis has been treated with early topical steroids to avoid loss of sight; refer to the available ophthalmologic literature for details on the management of adenoviral ophthalmologic infections.

Ribavirin and cidofovir therapy have been used with variable success in immunosuppressed hosts. Anecdotal evidence suggests success against adenoviral infection with combined intravenous ribavirin and pooled human intravenous immunoglobulin. Also anecdotally, intravesical cidofovir has been reported to be successful in persons with adenoviral hemorrhagic cystitis; the latter delivery method may obviate the systemic toxicity of this agent and warrants investigation.24

Weighing the severity of illness, the likelihood of response in a given setting, and the possibility of adverse events, decisions regarding treatment should be individualized at this time. Evidence-based standardized treatment guidelines currently are lacking, and consultation with an infectious diseases clinician is recommended.

Antivirals

These agents inhibit viral DNA and protein synthesis.


Ribavirin (Virazole)

Inhibits viral replication by inhibiting DNA and RNA synthesis. Antiviral against RSV, influenza virus, herpes simplex virus, and hepatitis C virus. The latter requires adjunctive treatment with interferons.
The likelihood that most adenovirus infections in immunosuppressed hosts are disseminated warrants intravenous rather than inhalational therapy, including in the setting of adenoviral pneumonia.

Adult

IV ribavirin is available on a compassionate use and investigational basis from US Centers for Disease Control and Prevention (CDC); suggested dosing based on available literature follows; however, dose may be altered based on individual circumstance or further research; consultation with CDC and an infectious diseases clinician recommended
30 mg/kg IV (not to exceed 2 g) loading dose, followed by 16 mg/kg IV (not to exceed 1 g) q6h for 4 d, followed by 8 mg/kg IV (not to exceed 500 mg) for 3-6 d

Pediatric

Administer as in adults

Decreases effects of zidovudine

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution in hemolytic anemia (monitor hemoglobin during therapy); be aware of teratogenicity, teratogenic in all animal species in which adequate studies are available, and, although clinical studies are not available, may harm human fetus; concentrates in red blood cells and persists for life of the cell; terminal half-life for systemic elimination is expected to be that of circulating red blood cells; after exposure, minimum safe interval for which conception must be avoided is not known; as appropriate, screening for pregnancy is recommended prior to administration, as is counseling both men and women regarding avoidance of conception for a reasonable interval after exposure; patient should be encouraged to seek preconception counseling prior to attempting to conceive


Cidofovir (Vistide)

Nucleotide analog that selectively inhibits viral DNA production in CMV and other herpes viruses. Indicated for CMV retinitis.

Adult

Available dosing guidelines refer to management of CMV retinitis, for which cidofovir is FDA approved; available literature suggests lower dosing schedule may be adequate for adenovirus infection; however, dose may be altered based on individual circumstance or further research; consultation with an infectious diseases clinician recommended
1 mg/kg IV over 1 h qd, 3 times/wk for minimum of 3 wk

Pediatric

Available literature suggests lower dosing schedule may be adequate for adenovirus infection; however, dose may be altered based on individual circumstance or further research; consultation with an infectious diseases clinician recommended
1 mg/kg IV over 1 h qd, 3 times/wk for minimum of 3 wk

Coadministration of aminoglycosides, amphotericin B, pentamidine IV, and foscarnet may increase nephrotoxicity

Documented hypersensitivity; coadministration with other nephrotoxic agents; serum creatinine level >1.5 mg/dL; CrCl <55 mL/min; urine protein level >100 mg/dL

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor neutrophil counts; renal toxicity is major adverse effect; prehydrate with normal saline IV and coadminister probenecid with each infusion to minimize nephrotoxicity (monitor renal function); monitor serum creatinine and urine protein 48 h prior to treatment (adjust dose accordingly); granulocytopenia may occur

More on Adenoviruses

Overview: Adenoviruses
Differential Diagnoses & Workup: Adenoviruses
Treatment & Medication: Adenoviruses
Follow-up: Adenoviruses
Multimedia: Adenoviruses
References
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Further Reading

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Keywords

adenoviruses, acute respiratory disease, ARD, pharyngoconjunctival fever, epidemic keratoconjunctivitis, acute hemorrhagic cystitis, nephritis, gastroenteritis, adenoviral infection, immunocompromise, immunosuppression, transplantation, transplants, transplantation complications, transplant complication, gene therapy, adenovirus, Mastadenovirus, viral gene therapy, cystic fibrosis, osteoporosis, lytic infection

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Contributor Information and Disclosures

Author

Sandra G Gompf, MD, FACP, FIDSA, Section Chief, Associate Professor of Infectious Diseases and International Medicine, Infectious Diseases, James A Haley Veterans Hospital
Sandra G Gompf, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Richard L Oehler, MD, FACP, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases and Tropical Medicine, Univ of South Florida College of Medicine; Assistant Epidemiologist, Division of Infectious Diseases, Tampa VA Medical Center
Richard L Oehler, MD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America, and Society for Healthcare Epidemiology of America
Disclosure: Nothing to disclose.

Medical Editor

David Hall Shepp, MD, Program Director, Fellowship in Infectious Diseases, Department of Medicine, North Shore University Hospital; Associate Professor, New York University School of Medicine
David Hall Shepp, MD is a member of the following medical societies: Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Richard B Brown, MD, FACP, Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine
Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, and Massachusetts Medical Society
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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