The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG-Study Group. Cytogam, MedImmune, Inc. Gaithersburg, Maryland.

PURPOSE: To assess impact of cytomegalovirus (CMV) donor-recipient serostatus, infection, or disease on development of invasive fungal infection in orthotopic liver transplant recipients. PATIENTS AND METHODS: An analysis of prospectively collected data in 146 liver transplant recipients (intention to treat cohort) from 4 tertiary care, university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation). Patients were observed for 1 year after transplantation for the development of CMV infection, CMV disease, CMV pneumonia, as well as for the development of opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine and throat and every other week of buffy coat for CMV for 2 months, then monthly for 6 months, at 1 year, and at the time of any clinical illness. Pre- and posttransplant variables including CMV-serostatus of donor and recipient, fungal isolation from sterile body sites, fungemia, bacteremia, antibiotic use, immunosuppression, treatment for rejection, and volumes of blood products were measured. RESULTS: Survival analysis demonstrated that 36% of patients with CMV disease developed invasive fungal disease within the first year post-transplant compared with 8% of those without CMV disease (P < 0.0001). One-year mortality in patients with invasive fungal disease was 15 of 22 (68%) compared with 23 of 124 (19%) in those without invasive fungal disease (P < 0.001). A multivariable, time-dependent analysis demonstrated that being a CMV-seronegative recipient of a CMV-seropositive donor organ (P < 0.001), having bacteremia (P = 0.001), UNOS (United Network for Organ Sharing) status 4 (need for life support measures) at transplant (P = 0.002), and volume of platelets (P = 0.002) were independently associated with invasive fungal disease. Restriction of cases of invasive fungal disease to those that occurred more than 2 weeks after transplant demonstrated an association with CMV disease (P = 0.003), bacteremia (P = 0.003), need for life support (P = 0.03), and volume of blood products transfused (P = 0.02). CONCLUSION: CMV disease or being a CMV-seronegative recipient of a CMV-seropositive donor organ is an important predictor for invasive fungal disease following orthotopic liver transplantation.

Respiratory syncytial virus immunoprophylaxis: impact on epidemiology.

OBJECTIVE: To better understand the spectrum of disease among hospitalised children infected with respiratory syncytial virus (RSV) and to assess the potential impact of passive immunoprophylaxis on RSV hospitalisation rates, we analysed all patients infected with RSV who were admitted to a paediatric teaching hospital over a 3-year period. DESIGN: We performed a retrospective chart review of all paediatric patients from whom RSV was isolated between October 1, 1994 and April 30, 1997. RESULTS: A total of 255 children infected with RSV were hospitalised during this 3-year period. 246 (96%) patients had community acquired infections and 9 (4%) had nosocomial infections. Excluding patients with nosocomial infections, the mean length of hospital stay was 4.7 days. 70 (28%) children were admitted to the intensive care unit, 32 (13%) were intubated and there was a total of 4 deaths (1.6%). 48% of hospitalised patients were in 1 of 4 previously recognised high risk groups. Of the 52% of patients not in a defined high risk category, 42% were otherwise healthy infants (>6 weeks of age) and 10% had chronic underlying illnesses generally not associated with an increased risk of severe RSV disease. Patients not in a defined high risk category accounted for 46% of total hospital days. CONCLUSION: In order to reduce overall RSV hospitalisation rates and the economic burden to society, programmes for disease prevention must be directed at healthy infants as well as children in recognised high risk categories. Even if all currently eligible candidates were to have received passive immunoprophylaxis, which yields about a 50% reduction in hospitalisation rates, the number of RSV hospitalisations in our 3-year study would have been reduced by no more than 9%. Without development and widespread use of an effective RSV vaccine, a major impact on RSV-induced hospitalisation is unlikely.

Cytomegalovirus immune globulin prophylaxis in liver transplantation. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To study the effect of cytomegalovirus immune globulin (CMVIG) on prevention of cytomegalovirus (CMV) disease and its complications in patients receiving liver transplants. DESIGN: Randomized, multicenter, placebo-controlled, double-blind trial. SETTING: Four university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation). PATIENTS: One hundred forty-one liver transplant recipients completed the study. INTERVENTION: CMVIG or placebo (1% albumin) given in a dose of 150 mg/kg body weight within 72 hours of the transplant, then at weeks 2, 4, 6, and 8, and at 100 mg/kg at weeks 12 and 16. MEASUREMENTS: Patients were observed for 1 year after transplantation for the development of CMV infection, disease, pneumonia, as well as for opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine, buffy coat, and throat wash for CMV for 2 months, then monthly, and at any clinical illness. RESULTS: Using a Cox proportional hazards model, CMVIG was shown to reduce severe CMV-associated disease (multi-organ CMV disease, CMV pneumonia, or invasive fungal disease associated with CMV infection) from 26% to 12% (relative risk, 0.39; 95% CI, 0.17 to 0.89). When we controlled for the use of monoclonal antibodies to T cells (OKT3), CMVIG use was still protective (relative risk, 0.39; CI, 0.17 to 0.90). Rates of CMV disease were reduced from 31% to 19% (relative risk, 0.56; CI, 0.3 to 1.1) in CMVIG recipients although no effect on rates of CMV infection, graft survival, or patient survival at 1 year were shown. When we controlled for the urgency of transplantation and OKT3 use, a reduction in CMV disease (relative risk, 0.22; CI, 0.06 to 0.81) was shown for globulin recipients for all serologic groups except for the highest risk group (the CMV-seropositive donor, CMV-seronegative group). CONCLUSION: CMVIG reduced the rate of severe CMV-associated disease in patients undergoing orthotopic liver transplantation. No effect of CMVIG on CMV donor-positive, recipient-negative liver transplant recipients was shown, suggesting a need for additional prophylactic strategies.