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.
References:
American Academy of Pediatrics. Cytomegalovirus infection. In:
Pickering LK, ed.2000 Red Book: Report of the Committee on Infectious
Diseases. 25th ed. Elk Grove Village, Ill: American Academy of
Pediatrics; 2000:227-230
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