CMV and ganciclovir
also see CMV
Cytomegalovirus (CMV) is an opportunistic infection that occurs among immunocompromised persons, such as the girl described in the vignette. Pneumonia, colitis, and retinitis are the most frequent clinical manifestations in the immunocompromised host. Particularly at risk are those who have human immunodeficiency virus infection or who are receiving treatment for malignant neoplasms or immunosuppressive therapy following organ transplantation.
Ganciclovir was the first antiviral compound approved by the United States
Food and Drug Administration for use in the treatment of severe infections
caused by CMV. It is an analog of guanine and structurally
similar to acyclovir, which has not been effective against CMV. As a
virostatic agent, ganciclovir suppresses viral
replication but does not eliminate it. Accordingly, the drug
must be continued indefinitely in patients who have
acquired immunodeficiency syndrome (AIDS) and CMV retinitis. In addition
to retinitis, ganciclovir is indicated in CMV-induced colitis,
meningoencephalitis, esophagitis, and hepatitis. Although its effectiveness in
treating pneumonitis following bone marrow transplantation has been
disappointing, it is more effective in CMV pneumonitis following organ
transplantation and in patients who have AIDS.
Studies on the use of ganciclovir in congenital CMV infection are in progress. It is hoped that antiviral treatment of some infants who have congenital disease will modulate the progressive central nervous system (CNS) damage caused by this virus. Because intrauterine CNS damage is irreversible, the most that can be expected is a containment of existing damage. It remains to be seen whether ganciclovir will play a significant role in the treatment of congenital CMV, although the odds are against this possibility because of the irreversibility of congenital CNS damage and the virostatic nature of the drug.
The most frequent adverse events noted in patients treated with ganciclovir are hematologic and include granulocytopenia, neutropenia, and thrombocytopenia. Administration of ganciclovir to patients who have AIDS has resulted in a total absolute neutrophil count (ANC) of less than 1,000/cu mm (1 x 109/L) in about 40% of cases and of less than 500/cu mm (0.5 x 109/L) in about 20% of cases. Thrombocytopenia developed in 13% of cases. In most instances, withdrawal of the drug resulted in rapid normalization of the neutrophil and platelet counts. Rarely, patients have experienced irreversible neutropenia or died from severe bacterial or fungal infections during episodes of neutropenia.
Accordingly, patients receiving ganciclovir should have neutrophil and platelet counts monitored every 2 days during the initial treatment period and weekly thereafter. Severe neutropenia (ANC <500/cu mm [<0.5 x 109/L]) or thrombocytopenia (platelet count <25,000/cu mm [<25 x 109/L]) requires interruption of therapy until there is evidence of bone marrow recovery (ANC > 1,000/cu mm [>1 x 109/L]).
Another adverse effect of ganciclovir is renal toxicity, which typically produces elevated creatinine levels, especially when the drug is used in combination with other nephrotoxic agents. The effect is transient in most cases. Abnormal liver function test results are seen in 2% of patients receiving ganciclovir, and cardiac arrhythmias have been reported in 1% of patients. Urticaria and diarrhea are not observed in patients receiving ganciclovir.
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Diseases. 25th ed. Elk Grove Village, Ill: American Academy of
Hanshaw JB. Cytomegalovirus infections. Pediatr Rev. 1995;16:43-48
Prober CG. Antiviral agents and interferons. In: Long SS, Pickering
LK, Prober CG, eds. Principles and Practice of Pediatric Infectious
Diseases. New York, NY: Churchill Livingstone; 1997:1682-1703