eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease
Cytomegalovirus Infection: Treatment & Medication
Updated: May 8, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
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Treatment
Medical Care
Medical care consists of good nutritional support, vigorous supportive care for end-organ syndromes (particularly pneumonia in immunocompromised patients), and specific antiviral therapy in select circumstances.
Surgical Care
Some children with congenital cytomegalovirus (CMV) require orthopedic interventions (cerebral palsy) and gastrostomy placement for enteral nutrition.
Consultations
Depending on the patient and associated risk factors, CMV disease is encountered by obstetricians, pediatricians, infectious disease specialists, oncologists, and critical care physicians. Appropriate consultations with surgeons, developmental specialists, pathologists, otolaryngologists, ophthalmologists, neurologists, and gastroenterologists may be necessary.
Medication
Experience with antiviral agents for cytomegalovirus (CMV) prophylaxis and CMV therapy is limited in children. Administer anti-CMV therapy only after consultation with an expert familiar with dosage and adverse effects. Antiviral agents may be administered therapeutically for established CMV disease or prophylactically (ie, preemptive therapy) when the risk of development of CMV disease is high (eg, in transplant recipients).
Antiviral agents
Nucleosides are the only true antiviral agents active against CMV, although immunoglobulins may provide some antiviral effect, particularly in combination with these agents. These agents share a common molecular target, namely, the viral DNA polymerase. Biochemically, ganciclovir is an acyclic nucleoside analog, whereas cidofovir is an acyclic nucleoside phosphonate. Each compound must be phosphorylated to a triphosphate form before it can inhibit the CMV polymerase. A viral gene product, the UL97 phosphotransferase, mediates the monophosphorylation step for ganciclovir. In contrast to these 2 agents, foscarnet is not a true nucleoside analog but can also directly inhibit the viral polymerase.
Ganciclovir is commonly used as preemptive therapy in transplant recipients at high risk of developing disease (eg, a CMV-seronegative recipient of an organ transplant from a CMV-seropositive donor). Oral and intravenous acyclovir has also been used successfully as prophylaxis for solid organ transplantation (seronegative recipient); however, never use acyclovir for CMV therapy in active disease. An oral formulation is approved for use in adult patients infected with HIV who have CMV retinitis; however, the bioavailability is poor, and no data support use in children.
Relatively little information concerning the use of ganciclovir in the setting of congenital CMV infection is available. Because some of the neurological sequelae of congenital CMV, particularly sensorineural hearing loss, progress postnatally, the presentation of results from a terminated nationwide collaborative trial are of interest. Intravenous ganciclovir led to improvement or stabilization of hearing in a significant number of 6-month-old infants. Case reports have suggested the efficacy of ganciclovir for acutely ill neonates with life-threatening CMV disease (eg, pneumonia).
Alternatives to ganciclovir include trisodium phosphonoformate (PFA) and cidofovir. Pediatric experience with these agents is limited. Although potentially useful in the setting of ganciclovir resistance, the toxicities of these antivirals are significant. Use these agents only in pediatric patients in exceptional circumstances. Although they have only a modest level of activity against CMV, high-dose oral acyclovir and valacyclovir have been used for prophylaxis of CMV in high-risk individuals but are not suitable for therapy of active disease. Oral therapy with valganciclovir is considered to be investigational in children.
Ganciclovir (Cytovene)
First compound licensed for treatment of CMV infections. A synthetic acyclic nucleotide structurally similar to guanine. Its structure is similar to that of acyclovir; like acyclovir, it requires phosphorylation for antiviral activity. The enzyme responsible for phosphorylation is the product of the viral UL97 gene, a protein kinase. Resistance may occur with long-term use, generally because of mutations in UL97. Indicated in immunocompromised children (eg, HIV infection, posttransplant, other immunocompromised states) when clinical and virological evidence of specific end-organ disease (eg, pneumonitis, enteritis) is present.
In infants, antiviral therapy with ganciclovir may be of benefit in reducing the prevalence of neurodevelopmental sequelae, in particular sensorineural hearing loss (Schleiss, 2004). A study sponsored by the National Institutes of Allergy and Infectious Diseases demonstrated improved hearing-related outcomes in infants with symptomatic congenital CMV treated with ganciclovir (Kimberlin, 2003). Therefore, therapy in newborns with documented infection should be considered; however, consult an expert.
Adult
Induction: 5 mg/kg IV bid for 2-3 wk, followed by maintenance dose
IV maintenance: 5 mg/kg IV qd for the duration of therapy; 2.5 mg/kg/dose IV q8h has been used in some patients with CMV pneumonitis
PO maintenance: 1 g PO q8h limited to those with HIV who are need of long-term anti-CMV therapy for CMV retinitis
PO prophylaxis in liver transplant recipients: 1 g PO q8h pc; typically administered through week 14 posttransplantation, depending on duration and degree of immunosuppression
Pediatric
Newborns with congenital CMV infection: Consult specialist for investigational protocol; one example is 6 mg/kg IV q12h for 6 wk
Life-long prophylaxis in children with history of CMV disease: 30 mg/kg PO q8h
Bone marrow transplant: 5 mg/kg IV q12h; protocols vary for duration and maintenance treatment depending on recipient's risk and type of HSCT (ie, autologous vs allogeneic)
Concomitant administration with cytotoxic drugs (eg, dapsone, vinblastine, doxorubicin, pentamidine, flucytosine, vincristine, amphotericin B, cotrimoxazole, other nucleoside analogs) may result in additive toxicity in bone marrow, spermatogonia, and germinal layers of skin and GI mucosa (coadminister only if potential benefits outweigh risks); coadministration with imipenem-cilastatin may cause generalized seizures (use only if potential benefits outweigh risks); serum creatinine may increase following concurrent use with either cyclosporine or amphotericin B; renal clearance is reduced when coadministered with probenecid; didanosine increases bioavailability when administered either 2 h before or simultaneously; bioavailability may decrease in presence of zidovudine, whereas bioavailability of zidovudine is increased in presence of ganciclovir
Documented hypersensitivity
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
Myelosuppression (eg, granulocytopenia, anemia, thrombocytopenia) is often a dose-limiting toxicity in immunocompromised patients who often are on other myelosuppressive agents; PO administration associated with higher rate of CMV retinitis progression compared with IV formulation, use only when benefits outweigh risks (eg, advanced HIV disease); half-life and plasma/serum concentrations may increase as a result of reduced renal clearance; dosages >6 mg/kg IV may result in increased toxicity; rapid IV infusions may result in increased toxicity; initially, reconstituted IV solutions have a high pH (ie, 11), phlebitis or pain may occur at IV infusion site may occur despite further dilution in IV fluids; administration should be accompanied by adequate hydration; photosensitization (eg, photoallergy, phototoxicity) may occur
Cidofovir (Vistide)
Nucleotide analog that selectively inhibits viral DNA production in CMV and other herpes viruses.
Adult
Induction: 5 mg/kg IV infusion over 1 h qwk for 2 wk with probenecid (2 g PO 3 h before cidofovir, 1 g PO 2 h immediately after dose, and 1 g PO 8 h after dose)
Maintenance: 5 mg/kg IV infusion over 1 h q2wk; give with probenecid (described above)
Adequately hydrate by administering an IV infusion of 1 L 0.9% NaCl 1 h before HPMPC infusion
Pediatric
Not established
Coadministration of aminoglycosides, amphotericin B, IV pentamidine, or PFA may increase nephrotoxicity
Documented hypersensitivity; coadministration with other nephrotoxic agents; serum creatinine >1.5 mg/dL; a CrCl <55 mL/min; urine protein >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; IV prehydration with NS and coadministration of probenecid can minimize nephrotoxicity; monitor serum creatinine and urine protein 48 h before treatment (adjust dose accordingly)
Foscarnet (Foscavir)
Organic analog of inorganic pyrophosphate that inhibits replication of known herpesviruses, including CMV, HSV-1, and HSV-2. Inhibits viral replication at pyrophosphate-binding site on virus-specific DNA polymerases.
Adult
CMV retinitis:
Induction: 90 mg/kg IV q12h infused over a minimum of 1.5-2 h for 14-21 d
Maintenance: 90-120 mg/kg/d IV infused over 2 h
Pediatric
<12 years: Not established
>12 years: Administer as in adults
Coadministration with potentially nephrotoxic drugs (eg, aminoglycosides, amphotericin B, IV pentamidine) may increase nephrotoxicity (do not administer unless potential benefits outweigh risks); coadministration with IV pentamidine may cause hypocalcemia
Documented hypersensitivity
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
May cause decline in renal function; for correct dosing, obtain 24-h serum creatinine at baseline and continue to monitor (discontinue if serum creatinine <0.4 mL/min/kg); hydration may reduce nephrotoxicity
Carefully monitor electrolytes (eg, calcium, magnesium); assess for electrolyte and mineral level abnormalities if mild perioral numbness, paresthesias symptoms, or seizures; granulocytopenia and anemia may occur (regularly monitor CBC count)
Infuse PFA solutions into veins with adequate blood flow to avoid local irritation; to avoid toxicity, do not administer by rapid or bolus IV injection
Immunoglobulins
These agents are used as passive immunization for the prevention of symptomatic CMV disease. This strategy has been useful in the control of CMV disease in immunocompromised patients in the prenucleoside antiviral era. Evidence in pregnancy suggests that the infusion of CMV immune globulin in women with evidence of a primary CMV infection can prevent transmission and improve outcomes in newborns.
Immune globulin intravenous (Carimune, Gamimune, Gammagard S/D, Gammar-P, Polygam S/D)
The observation that random donor IVIG appears to be equal in efficacy to CMV hyperimmunoglobulin suggests that the benefit may be derived from an immunomodulatory effect unrelated to virus neutralization.
Adult
500 mg/kg IV qod for 10 doses in combination with ganciclovir, followed by 500 mg/kg IV 2 times per wk for 8 additional doses
Pediatric
CDC recommendation in stem cell transplant recipients: 400 mg/kg IV qmo; increase dose or frequency to maintain IgG levels >400 mg/dL
May decrease immune response to live virus vaccines
Documented hypersensitivity; IgA deficiency; anti-IgE/IgG antibodies
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
Check serum IgA before IVIG (use an IgA-depleted product [eg, Gammagard S/D]); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-5 d postinfusion to 30 d)
Increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease; lab result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia
CMV-Ig (CytoGam)
A CMV hyperimmunoglobulin has been shown to decrease prevalence of CMV disease when administered posttransplant to high-risk transplant recipients when administered alone or in combination with nucleoside antivirals. May be administered therapeutically for CMV disease in combination with ganciclovir.
Adult
Prophylaxis posttransplantation: 100-150 mg/kg IV initiated within 3 d posttransplant, then repeated q2-4 wk for 4 mo
Pediatric
Not established
May decrease the immune response to live virus vaccines.
Documented hypersensitivity; IgA deficiency
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
Caution in renal dysfunction; may cause facial flushing, nausea, vomiting, muscle cramps, wheezing, diaphoresis, or aseptic meningitis; monitor blood pressure during infusion
More on Cytomegalovirus Infection |
| Overview: Cytomegalovirus Infection |
| Differential Diagnoses & Workup: Cytomegalovirus Infection |
 Treatment & Medication: Cytomegalovirus Infection |
| Follow-up: Cytomegalovirus Infection |
| Multimedia: Cytomegalovirus Infection |
| References |
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Further Reading
Keywords
cytomegalovirus, CMV, CMV disease, human CMV, HCMV, cytomegalic inclusion disease, CID, cytomegalovirus disease, inclusion body disease, salivary gland virus, herpes, herpesvirus, human herpesvirus 5, HHV-5, Betaherpesvirinae, human immunodeficiency virus, HIV, mental retardation, cytomegalia, human herpesvirus, herpes simplex virus, hepatitis, toxoplasmosis, rubella, TORCH infection, congenital cytomegalovirus infection, congenital CMV infection
intrauterine growth retardation, hepatosplenomegaly, thrombocytopenia, blueberry muffin baby, microcephaly, ventriculomegaly, cerebral atrophy, chorioretinitis, sensorineural hearing loss, intracerebral calcifications, lymphadenopathy, pneumonitis, CMV mononucleosis, Epstein-Barr virus, EBV, pharyngitis, retinitis, esophagitis, gastritis, gastroenteritis, pyloric obstruction, pancreatitis, colitis, cholecystitis, highly active antiretroviral therapy, HAART, Menetrier disease, atherosclerosis, immunosenescence
