Treatment With Ganciclovir of Adenovirus Pneumonia in a Cardiac Transplant Patient

doi:10.1016/S0002-9343(97)85997-9

The American Journal of Medicine

Volume 103, Issue 5, November 1997, Pages 439-440

https://doi.org/10.1016/S0002-9343(97)85997-9 Get rights and content

Section snippets

Case Report

A 58-year-old woman was admitted with acute onset of fever and dry cough. Her past medical history was significant for viral cardiomyopathy with cardiac transplantation 5 years before admission and chronic renal failure. One day before admission the patient developed nausea without vomiting, malaise, dry cough, and fever of 101.5°F (38.6°C). On admission the physical exam was unremarkable. Laboratory studies revealed a hemoglobin of 11.9 gm/dL, white blood cell count of 3500/μL (61%

Discussion

We believe this immunocompromised patient developed severe adenovirus pneumonia which responded promptly to treatment with ganciclovir and a single dose of intravenous immunoglobulin. Immunocompromised patients with adenovirus pneumonia can present with the abrupt onset of fever, rigors, malaise, nonproductive cough, nausea, vomiting, diarrhea, abdominal pain, headache, and arthralgia. Physical examination is often unremarkable.[6]Chest roentgenogram usually shows bilateral diffuse interstitial

References (24)

JM Zahradnik et al.
Adenovirus infection in the immunocompromised patient
Am J Med.
(1980)
RM Buchdahl et al.
Nebulised ribavirin for adenovirus pneumonia
Lancet.
(1985)
GF Murphy et al.
Adenovirus-associated hemorrhagic cystitis treated with intravenous ribavirin
J Urol.
(1993)
DL Taylor et al.
The susceptibility of adenovirus infection to the anti-cytomegalovirus drug, ganciclovir (DHPG)
FEMS Microbiol Lett.
(1988)
H Schmitz et al.
Worldwide epidemiology of human adenovirus infections
Am J Epidemiol.
(1983)
AF Shields et al.
Adenovirus infections in patients undergoing bone-marrow transplantation
NEJM.
(1985)
JM Zahradnik
Adenovirus pneumonia
Sem Resp Infect.
(1987)
GT Valainis et al.
Respiratory failure complicated by adenovirus serotype 29 in a patient with AIDS
J Infect Dis.
(1989)
DJ Anderson et al.
Viral pneumonia in recipients of solid organ transplants
Sem Resp Infect.
(1990)
JD Shanley et al.
Viral pneumonia in the immunocompromised patient
Sem Resp Infect.
(1986)

MG Michaels et al.

Adenovirus infection in pediatric liver transplant recipients

J Infect Dis.

(1992)

B Koneru et al.

Adenoviral infections in pediatric liver transplant recipients

JAMA.

(1987)

Cited by (39)

Disseminated adenovirus infection twenty-five years post heart-lung transplant complicated by haemophagocytic lymphohistiocytosis
2021, Clinical Infection in Practice
Citation Excerpt :
Different adenovirus subtypes are more associated with specific clinical syndromes, for example subtypes 40 and 41 with gastrointestinal infection. However, disseminated infection may occur in any solid organ or haematopoietic stem cell transplant recipients, carrying a high mortality (Duggan et al., 1997). This is most common within the first year post-transplant but has been described up to six years later in the literature (Willems et al., 2008).
Disseminated adenovirus infection is well recognised in transplant patients and carries a high mortality. Treatment options are limited and potentially hepatotoxic and nephrotoxic. Adenovirus is one of many known triggers for haemophagocytic lymphohistiocytosis (HLH), a life-threatening hyper-inflammatory response. We present a patient with disseminated adenovirus-driven HLH occurring 25 years after a heart-lung transplant, the longest documented in the literature.
A 75-year-old man presented to the emergency department with a two week history of fever, cough and diarrhoea. Past medical history included heart-lung transplant. He was febrile and tachycardic but appeared well. Blood tests showed acute kidney injury, transaminitis and pancytopenia. Chest radiograph was unremarkable. Initial treatment was with co-amoxiclav and intravenous fluids. Computerised tomography of thorax and abdomen showed moderate splenomegaly.
After 48 h, he remained febrile and hypotensive with worsening renal and hepatic function. Antibiotic therapy was broadened to meropenem and amikacin. Nasopharyngeal swabs returned positive for adenovirus PCR and subsequently, the preliminary diagnosis was adenovirus gastroenteritis with hypovolaemia. Blood cultures were negative with undetectable cytomegalovirus and Epstein-Barr Virus DNA in blood samples.
On day 4 he developed fulminant multi-organ failure. HLH was suspected, given bone marrow and splenic involvement with laboratory investigations showing hyperferritinemia, hypertriglyceridemia and haemophagocytosis on bone marrow biopsy. Cidofovir/Brincidofovir were discussed as potential treatments but were difficult to obtain with concern regarding toxicity. Intravenous immunoglobulins were commenced for HLH on day 6. Adenovirus was later detected by PCR in urine, stool and blood samples. He continued to deteriorate and died on day 8.
This case highlights the importance of considering a broad range of infectious aetiologies in all transplant recipients, even those on stable immune suppression. Immune senescence in an increasingly older transplant population may represent an additional risk factor to consider. Early diagnosis is crucial in such cases.
Emerging antiviral therapeutics for human adenovirus infection: Recent developments and novel strategies
2021, Antiviral Research
Citation Excerpt :
However, much like ribavirin, most evidence suggests little value for ganciclovir as a HAdV therapeutic. This is unsurprising as ganciclovir requires activation by a viral thymidine kinase to be most effective, which HAdV does not encode (Chen et al., 1997; Duggan et al., 1997; Matthes-Martin et al., 2012; Matthews and Boehme, 1988; Naesens et al., 2005; Ying et al., 2014). Interestingly, in vitro studies of HAdV co-infection with human cytomegalovirus (CMV) suggests improved anti-HAdV activity of ganciclovir, which is proposed to be due to CMV viral kinase-mediated activation of ganciclovir (Aguilar-Guisado et al., 2020).
Human adenoviruses (HAdV) are ubiquitous human pathogens that cause a significant burden of respiratory, ocular, and gastrointestinal illnesses. Although HAdV infections are generally self-limiting, pediatric and immunocompromised individuals are at particular risk for developing severe disease. Currently, no approved antiviral therapies specific to HAdV exist. Recent outbreaks underscore the need for effective antiviral agents to treat life-threatening infections. In this review we will focus on recent developments in search of potential therapeutic agents for controlling HAdV infections, with a focus on those targeting post-entry stages of the virus replicative cycle.
A case of severe pneumonia with viremia caused by adenovirus B7 identified by off-label use of a multiplex PCR system
2021, IDCases
Citation Excerpt :
Evidence regarding ganciclovir treatment in vivo is scarce. A case report described the successful use of ganciclovir and IVIG in a cardiac transplant patient with severe HAdV pneumonia [19]. In addition, a few retrospective studies demonstrated the potential prophylactic benefit of ganciclovir in HSCT patients [20].
Severe infection with human adenovirus (HAdV) is uncommon in adults, and the lack of reliable point-of-care testing makes the diagnosis challenging. A 39-year-old immunocompetent Indian man developed severe pneumonia, and his condition became life-threatening despite antimicrobial therapy. While sputum and blood cultures remained negative, a multiplex PCR respiratory panel (Filmarray Respiratory Panel), which is only approved for use with nasopharyngeal samples, detected HAdV in the serum and tracheal aspirates on day 5. We therefore initiated ganciclovir, steroids, and intravenous immunoglobulin. The patient’s respiratory condition improved significantly, and he eventually recovered without complications. We later confirmed that conventional PCR of serum detected HAdV-B7. Our case illustrated that a respiratory panel using multiplex PCR successfully detected HAdV in unapproved samples. Such off-label analyses may support the early diagnosis of infections caused by pathogens that are difficult to identify by routine microbiological examination.
In vitro co-infection by cytomegalovirus improves the antiviral activity of ganciclovir against human adenovirus
2020, International Journal of Antimicrobial Agents
Citation Excerpt :
The use of GCV to treat HAdV infections does not have a mechanistic basis as HAdV does not encode for such protein kinases; however, evaluation of the in vivo efficacy of GCV led to its recommended use to treat HAdV infections in transplant recipients [8]. Moreover, other authors suggest that the use of GCV as prophylaxis for HCMV infection was significantly associated with a lower risk of developing HAdV infections [9–14]. In addition, the presence of HSV TK has been shown to increase the anti-HAdV activity of GCV [7].
Human adenovirus (HAdV) infection has an important clinical impact in the immunosuppressed population and is associated with high morbidity and mortality rates. The lack of a specific, safe and effective antiviral treatment against HAdV makes necessary the search for new therapeutic options. The aim of this study was to evaluate the in vitro activity of ganciclovir (GCV) against HAdV in co-infection by human cytomegalovirus (HCMV) and HAdV in cellular cultures. Quantitative real-time polymerase chain reaction (qPCR) was used to measure HAdV and HCMV DNA replication efficiency in monocultures and in co-infection situations in the presence of both cidofovir (CDV) and GCV. The effects of GCV and CDV were also evaluated in a burst assay (used to measure the production of virus particles) for both viruses, alone and in combination. GCV decreased by 1-log the HAdV DNA replication efficiency in co-infection with HCMV compared with its activity in HAdV monoculture. The burst assay showed that the reductions in virus yield in the presence of GCV were higher for HCMV and co-infection than for HAdV in monoculture (145.2±35.5- vs. 116.4±27.3- vs. 23.0±10.0-fold, respectively, P<0.05). The improved anti-HAdV activity of GCV during co-infection may be because of the more efficient phosphorylation of GCV by the HCMV protein kinase, UL97. Patients treated with GCV as pre-emptive therapy for HCMV infection may be considered as low-risk for developing HAdV infections; however, further evaluations are required to confirm these results.
Adenovirus DNA polymerase: Structure, function, and prospects in diagnostics and therapeutics
2018, Viral Polymerases: Structures, Functions and Roles as Antiviral Drug Targets
Adenoviruses cause variety of infections in mammals and birds leading to high morbidity and mortality in immunocompromised hosts. Adenoviruses replicate in hosts cell nucleus and code their own DNA polymerase. The first eukaryotic DNA replication system for which both initiation and elongation could be reconstituted in vitro was that of the adenovirus. Three viral proteins are required for adenovirus genome replication: (1) adenovirus DNA polymerase (Ad pol), (2) the precursor terminal protein (pTP), and (3) the DNA-binding protein (DBP). The chapter presents a detailed account of Ad pol, which is a 140 kDa protein that belongs to protein-primed polymerases of family B (Alpha like) of DNA-dependent DNA polymerases. It is functionally conserved with the polymerase activity located at C terminals and has molecular architecture similar to DNA polymerase of bacteriophage RB69. Ad pol is a processive enzyme and in addition to a polymerase activity also possesses 3ʹ–5ʹ exonuclease activity. In recent years, it has emerged as a promising target for development of diagnostic and therapeutic agents against adenoviral diseases.
Adenovirus in solid organ transplantation
2013, American Journal of Transplantation

View all citing articles on Scopus

View full text

Brief Clinical ObservationsTreatment With Ganciclovir of Adenovirus Pneumonia in a Cardiac Transplant Patient

Section snippets

Case Report

Discussion

Am J Med.

Lancet.

J Urol.

FEMS Microbiol Lett.

Worldwide epidemiology of human adenovirus infections

Am J Epidemiol.

Adenovirus infections in patients undergoing bone-marrow transplantation

NEJM.

Adenovirus pneumonia

Sem Resp Infect.

Respiratory failure complicated by adenovirus serotype 29 in a patient with AIDS

J Infect Dis.

Viral pneumonia in recipients of solid organ transplants

Sem Resp Infect.

Viral pneumonia in the immunocompromised patient

Sem Resp Infect.

Adenovirus infection in pediatric liver transplant recipients

J Infect Dis.

Adenoviral infections in pediatric liver transplant recipients

JAMA.

Brief Clinical Observations
Treatment With Ganciclovir of Adenovirus Pneumonia in a Cardiac Transplant Patient