Journal of Clinical Virology - Volume 82 - Supplement 1 - September 2016

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Abstracts / Journal of Clinical Virology 82S (2016) S1–S142 S97
competent hosts but can lead to life-threatening conditions in
immunosuppressed patients.
We report a case of a fatal CMV infection in a 4-month old patient
with primary immunodeficiency and consecutive hematopoietic
stem cell transplantation.
Case report: A 4-month old girl was referred for fever, failure
to thrive and bloody diarrhea. Since she was a child of consan-
guineous parents, severe immunodeficiency was presumed. CMV
was detected in the blood (day −82) with a viral load of 3.77
10E6 copies/mL (in-house real-time PCR) and treatment with gan-
ciclovir was started. As the CMV viral load still increased, therapy
was switched to foscarnet (day −33) and patient received CMV-
specific immunoglobulins. Antiviral resistance testing (genotyping
the UL97 protein kinase, responsible for ganciclovir phosphoryla-
tion, and the UL 54 DNA polymerase) in a blood sample on day −19
revealed the presence of a mixed population of M460V-mutant and
wild-type virus in the UL97 protein kinase, known to confer resis-
tance to ganciclovir with susceptibility to foscarnet and cidofovir.
Despite treatment, patient deteriorated further anddevelopedCMV
encephalitis with positivity of CMV PCR on cerebrospinal fluid (day
−14), which showed a similar resistance profile as previously ana-
lyzed blood samples and nasopharyngeal fluid (NPA) samples.
An allogeneic stem cell transplantation from a haploidentical
donor was performed, with both donor and acceptor being CMV IgG
positive (day 0). Because of progression of neurologic encephalitic
disturbances suggestive of central CMV infection, cidofovir was
added empirically to the foscarnet antiviral treatment. Antiviral
resistance testing of a blood sample on day +1 showed, in addi-
tion to a mixed population of M460V-mutant and wild-type virus
at the UL97 protein kinase, also the presence of a mixed popula-
tion of 981–982 deletion mutant and wild-type virus in the UL 54
DNA polymerase. This is known to confer resistance to ganciclovir,
foscarnet and cidofovir. On day +19, only the mixed population of
DNA polymerase mutant virus bearing the 981–982 deletion was
present in blood. Three days later, the mutant virus totally replaced
the wild-type in multiple blood, urine and NPA samples, indicating
a generalized multidrug-resistance CMV infection. On day +23, cid-
ofovir was stopped due to severe cytopenia and further increase of
viral load. Since respiratory and liver function deteriorated further
and the patient developed an uncontrollable sepsis, palliative care
was initiated and the patient deceased on day +36.
Conclusions: An immunosuppressed pediatric patient devel-
oped a multidrug-resistant CMV disease to currently approved
anti-CMV drugs. This case report highlights the importance of rapid
drug-resistance monitoring and indicates the urgent need for the
development of new anti-CMV drugs.
Abstract no: 172
Presentation at ESCV 2016: Poster 154
Changing time line of CMV infection in
seropositive live donor Liver Transplant
recipients: A prospective study from a tertiary
care liver center
Ekta Gupta ∗, Nadeem Hasnain , Yogita Verma ,
Niteen Kumar , Ajeet Singh Bhadoria ,
Viniyendra Pamecha
1 Department of Clinical Virology, Institute of Liver
and Biliary Sciences, India
2 Department of HPB Surgery, Institute of Liver and
Biliary Sciences, India
3 Department of Clinical Research, Institute of Liver
and Biliary Sciences, India
Background:To study the incidence and timeline of CMV infec-
tions in seropositive live donor liver transplant (LTx) recipients and
correlate the risk of infection with pre-transplant CMV immunity.
Methods: A total of 155 consecutive LTx recipients from our
Institute, a tertiary care Liver Institute in Delhi, North India
were included from March 2010 to April 2012. Patients were not
on anti-CMV prophylaxis. Nine cases died during the follow-up,
and thus the final analysis included 146 patients. Pre-transplant
donor (D) and recipient (R) CMV IgG titers were estimated by
Chemiluminescence based immunoassay (Architect, Abbott). Post
transplant, follow up was done weekly for 1 month, and then
monthly up to one year. Median time of followupwas 299 (±126.7)
days. CMV DNA was quantitated in plasma samples using the
LightCycler® 480 II Real-Time PCR System (Roche Life Science, US).
CMV infection and disease were defined according to the standard
criteria. CMV DNA positivity in blood (DNAemia) was considered
as the evidence of CMV infection.
Results: Out of 146, 114 (78%) were males, 132 were adults and
14 were pediatric recipients. Pre-Tx 142 (97.3%) were D+R+ and
4(2.7%) were D−R+. Post-Tx CMV infection was seen in 54 (36.9%)
recipients. CMV disease was seen in 14 (9.5%) cases. Median CMV
viral loadwas 3.6 × 103 (IQR: 3.4 × 102 –4.6× 106) copies/ml. Signif-
icant viremia of ≥500 copies/ml was seen in 45 (29%) cases. CMV
infection was higher in pediatric patients 10 (71.4%) than adults
44 (33.3%) (p value = 0.004). Monthly incidence of CMV infection
post-Tx was: 32 (59.2%) in 1st, 13 (24%) in 2nd, 5 (9.2%) in 3rd, 2
(3.7%) in 4th, 1 (1.8%) each in 5th & 6th months. Rejection was seen
in 30 (19.5%) recipients and was higher when CMV infection was
also present 18 (32.7%) as compared to without CMV infection 12
(12%), p = 0.002. A total of 113 (77.4%) cases had pre-Tx IgG titers
of ≥ 250 AU/ml. Post-Tx CMV infection in titers <250 AU/mL and
≥250 AU/mL were 42.4% and 34.5%, respectively (p = 0.99). There
was no difference in the time of occurrence of CMV infection in
both the groups (<250 AU/mL vs ≥250 AU/mL).
Conclusions: Early CMV infections were seen mostly within 1st
month of post-transplant period in high seropositive population.
CMV infection does not correlate with pre-transplant CMV immu-
nity but may contribute in rejection of the transplanted organ.