Developed Cytomegalovirus Pneumonitis Research Articles

Ganciclovir-Resistant Cytomegalovirus Infections among Lung Transplant Recipients Are Associated with Poor Outcomes despite Treatment with Foscarnet-Containing Regimens

Ganciclovir-resistant cytomegalovirus (CMV) infections are reported infrequently among lung transplant recipients receiving extended valganciclovir prophylaxis. We performed a single-center, retrospective review of ganciclovir-resistant CMV infections in a program that employed valganciclovir prophylaxis for ≥6 months after lung transplant. CMV infections were diagnosed in 28% (170/607) of patients. UL97 mutations were detected in 9.4% (16/170) of CMV-infected patients at a median of 8.5 months posttransplant (range, 5 to 21) and despite prophylaxis for a median of 7 months (range, 4 to 21). UL97 mutations were canonical; 25% (4/16) of strains carried concurrent UL54 mutations. Ganciclovir-resistant CMV was more likely with breakthrough infections (75% [12/16] versus 19% [30/154]; P = 0.00001) and donor positive/recipient negative (D+/R-) serostatus (75% versus 45% [69/154]; P = 0.03). The median whole-blood CMV load was 4.13 log10 copies/cm(3) (range, 2.54 to 5.53), and 93% (14/15) of patients had low-moderate immune responses (Cylex Immunoknow). Antiviral therapy was successful, failed, or eradicated viremia followed by relapse in 12% (2/16), 31% (5/16), and 56% (9/16) of patients, respectively. Eighty-seven percent (14/16) of patients were treated with foscarnet-containing regimens; toxicity developed in 78% (11/14) of these. Median viral load half-life and time to viremia eradication among foscarnet-treated patients were 2.6 and 23 days, respectively, and did not correlate with protection from relapse. Sixty-nine percent (11/16) of patients developed CMV pneumonitis, and 25% (4/16) died of it. Serum viral load was independently associated with death among foscarnet-treated patients (P = 0.04). In conclusion, ganciclovir-resistant CMV infections remained a major cause of morbidity and mortality following lung transplantation. Foscarnet-based regimens often eradicated viremia rapidly but were ineffective in the long term and limited by toxicity.

237 Ganciclovir Resistant Cytomegalovirus in a Renal Transplant Recipient: A Medical Challenge

GANCICLOVIR RESISTANT CYTOMEGALOVIRUS IN A RENAL TRANSPLANT RECIPIENT: A MEDICAL CHALLENGE Aashish K Pandey, David B. Butcher Department of Nephrology and Hypertension St. John Hospital & Medical Center, Detroit, Michigan The PV 16000 study reported ganciclovir resistant cytomegalovirus (CMV) in 1.9% renal transplant recipients. The resistant strain may present amino acid deletions or substitutions in conserved regions of the UL97 protein, point mutation in the DNA polymerase (UL54) or both. We describe a case of a 54 year old African American female, who received a deceased donor renal allograft in August, 2009. CMV serology status was seronegative for the recipient and seropositive for donor. Patient had intermittent lapses in CMV prophylaxis due to missing medication followed by leucopenia. Her Immunosuppressant medications included Tacrolimus, Mycophenolate Mofetil and prednisone. One month post transplant, patient developed Acute AntibodyMediated rejection, and received treatment with Plasmapheresis, IV Immunoglobulin and Rituximab. A week later she developed CMV pneumonitis, and was started on Valganciclovir. A viral load of 381,000 was detected that progressively decreased to 44,800 over a period of 4 months. Patient continued to feel lethargic and was admitted again in the hospital. Her viral load had increased to 80,300. A genotypic testing for drug resistance was performed, and patient found to have a UL97 mutation with resistance at site L595S. Treatment was initiated on a combination synergistic regimen of one half dose of ganciclovir and one half dose of Foscarnet, which helped bring the viral load down to 17,300 in 3 weeks. Renal function remained stable with IV hydration. The intensity of immunosuppression, CMV seronegative status and intermittent CMV prophylactic treatment contributed to the development of ganciclovir resistant CMV infection in our renal transplant patient.

Ganciclovir for Cytomegalovirus: a Call for Indefinite Prophylaxis in Lung Transplantation

Universal ganciclovir (GCV) prophylaxis is a strategy aimed at reducing cytomegalovirus (CMV) infection and delaying the development of bronchiolitis obliterans syndrome (BOS). However, the optimal duration of GCV prophylaxis remains unclear. We report our experience with GCV prophylaxis administered indefinitely and its effect on CMV pneumonitis, BOS and survival after lung transplantation (LT). One hundred fifty-one patients surviving >100 days after LT were analyzed. GCV was given to 130 CMV donor- or recipient-seropositive patients. Data from 90 patients who received indefinite GCV prophylaxis (IND) and 40 patients who discontinued their GCV prophylaxis (STOP) were compared. CMV pneumonitis occurred in 16%, 8%, 17% and 19% of patients in the D+R+, D-R+, D+R- and D-R- groups, respectively. In the STOP cohort, 15 of 40 patients developed CMV pneumonitis (median time 79 days) after GCV was stopped. Ten of these 15 patients developed BOS (median time 116 days) after discontinuing GCV. The risk of CMV pneumonitis in the STOP cohort was significantly higher when GCV prophylaxis was discontinued within the first year. Cumulative incidence of CMV pneumonitis in the IND and STOP groups at 5 years was 2% and 57%, respectively (p < 0.001). BOS-free survival and survival were similar across both groups. Indefinite GCV prophylaxis prevents CMV pneumonitis in 98% of LT recipients. Thirty-eight percent of patients discontinuing prophylaxis developed CMV pneumonitis, 50% of whom progressed to BOS within 1 year. Continuing ganciclovir prophylaxis indefinitely after lung transplantation should be considered.

CMV Pneumonitis in an Immunosuppressed Patient With C-ANCA Positive Glumerulonephritis

Cytomegalovirus (CMV) pneumonitis is an important cause of morbidity and mortality in HIV and post-transplant patients, and is rare in patients with autoimmune diseases treated with immunosppressive therapy. We report the first case of a patient with Cytoplasmic anti neutrophil cytoplasmic antibodies positive glomerulonephritis who developed CMV pneumonitis after treatment with cyclophosphamide and prednisone. The CMV infection developed simultaneously with bacterial respiratory infection. All symptoms resolved rapidly under treatment with gancyclovir and immunoglobulins.

Deletion 22q11.2 syndrome—Implications for the intensive care physician*

To report on the experience of a pediatric intensive care unit (PICU) with patients with deletion 22q11.2 syndrome: 1) to delineate the clinical characteristics and management of these patients; 2) to assess whether these patients were managed appropriately, especially in terms of blood transfusion; and 3) to make recommendations for PICU management. Retrospective assessment of medical records of patients with fluorescent in situ hybridization-proven 22q11 deletion admitted to the PICU at the Children's Hospital at Westmead, Sydney. PICU in a tertiary university-affiliated children's hospital. Sixty-five consecutive admissions in 40 patients with diagnosis of 22q11 deletion over a 4-yr period. None. Thirty-seven (57%) of 65 admissions were postoperative cardiac surgical and accounted for the most common reason for admission to the PICU. Thirteen (20%) admissions were for velopharyngeal/laryngeal problems. Four (6%) admissions were associated with hypocalcemia, with two being first presentations. Five (12.5%) of 40 patients had immune dysfunction, one of whom developed cytomegalovirus pneumonitis. Twenty-nine (72.5%) patients received blood products either immediately before PICU admission or in the PICU. Of these, 16 received nonirradiated cellular blood products. There were two deaths from complications of congenital heart disease. PICUs need to be familiar with deletion 22q11.2 syndrome, especially the recommended use of irradiated and cytomegalovirus-seronegative blood components in these immunocompromised patients. The guidelines were inconsistently followed in the cohort of patients reported here. The extent of this problem may be more widespread in PICUs, and we recommend that individual units review their practice in this regard. Hypocalcemia may manifest at any time, and a regular survey of the calcium status is required in the intensive care setting. Admission to PICU should afford the opportunity to invite subspecialty referral and optimize extended care.

Relation Between Polymerase Chain Reaction Findings and Morphological Changes During Cytomegalovirus Infection in Transplanted Lung

Cytomegalovirus (CMV) can be present as a latent or productive infection resulting in disease. The polymerase chain reaction (PCR) is a sensitive technique to document the presence of CMV (DNA). Negative reactions are indicative of its absence. The presence of CMV (DNA) was assessed longitudinally in 261 transbronchial lung biopsy (TBB) specimens from 37 patients over a 6-month period. The TBB specimens from six serologically CMV-negative recipients who received lungs from serologically CMV-negative donors never showed a positive CMV-PCR(DNA) reaction during the study. Based on a study of their TBB specimens, 10 serologically CMV-positive recipients who received lungs from serologically CMV-negative donors all developed a CMV-PCR(DNA)-positive reaction and five (50%) morphologically manifested CMV disease. The remaining 21 serologically CMV-positive recipients who received lungs from serologically CMV-positive donors all developed a CMV-PCR(DNA)-positive reaction and 15 (71%) developed CMV pneumonitis. The data show that development of a positive CMV-PCR(DNA) reaction in a TBB sample within the first month after transplantation indicates a greatly increased risk of developing CMV disease. In addition, a positive CMV-PCR(DNA) reaction preceded morphologically manifest disease on average by 2 weeks. Comparisons between TBB and bronchoalveolar lavage show the former to provide a more dependable template.

The impact of blood transfusion on the occurrence of pneumonitis in primary cytomegalovirus infection after liver transplantation.

The influence of blood transfusion, and particularly the transfusion of blood from cytomegalovirus (CMV)-seropositive donors, on the incidence of primary CMV infection following liver transplantation was studied prospectively in 29 consecutive CMV-seronegative adult liver transplant recipients. Fourteen patients received a liver graft from a CMV-seropositive donor (Group A), whereas for 15 patients, the donor was CMV seronegative (Group B). Eleven patients (79%) in Group A but only two (13%) in Group B developed CMV infection (odds ratio, 23.8; 95% confidence interval, 3.5-169.4). In five Group A patients, primary CMV infection resulted in pneumonitis. There was no statistical difference in the total number of blood units and the number of units of CMV-seropositive blood given to patients who did or did not develop CMV infection in both Groups A and B (odds ratio for unit of CMV-seropositive blood transfused, 1.07; 95% confidence interval, 0.96-1.19). However, Group A patients who developed CMV pneumonitis received a higher total number of blood units (median, 44) and of CMV-seropositive blood units (median, 18) than did patients who developed other CMV infections (asymptomatic CMV, CMV syndrome, or CMV hepatitis), who received a median of 9 total units of blood and 5 units of CMV-seropositive blood (p = 0.004). It is concluded that the total number of blood units and of CMV-seropositive blood units transfused does not have an effect on the incidence of primary CMV infection after liver transplantation, but it does have an impact on the severity of the infection in recipients of a CMV-seropositive allograft.