Evaluation of a Cytomegalovirus Prophylaxis Protocol in Cytomegalovirus-IgG Positive Renal Transplant Recipients (R+)

BackgroundThe aim of the study was to evaluate the efficacy of a unique cytomegalovirus- (CMV) prophylaxis protocol in terms of CMV infection and disease progression in CMV IgG positive kidney transplant recipients.MethodsAchievement of negative CMV load, using concurrent prophylactic intravenous ganciclovir therapy during induction immunosuppression, combined with a 6-month prophylactic course of acyclovir, would yield a reduced incidence of early CMV infection and disease. CMV DNA was tested for at discharge, at the third, and sixth post-op months, and at the occurrence of any event that could be associated with CMV infection. CMV DNA positive patients received ganciclovir treatment until the viral load became negative. CMV replication was monitored using a quantitative PCR method capable of detecting as few as 42.5 copies/mL. All patients were given a maintenance dose of acyclovir.ResultThe file data of 267 patients who had undergone kidney transplantation between 2007 to 2016 were examined. Thirty-four patients were excluded from the study for various reasons, unrelated to the protocol. Of the remaining 233 patients, 42 (18%) had CMV DNA infection. Three patients had CMV disease (1.3%), 1of whom died of pneumonia. Diabetes mellitus (DM) was a risk factor for CMV DNA positivity (P < .004).ConclusionThe incidence of CMV infection and disease is low in renal transplant recipients whose CMV viral load is eliminated after concurrent ganciclovir administration with induction immunosuppression.     

Randomized controlled trial of oral ganciclovir versus oral acyclovir after induction with intravenous ganciclovir for long-term prophylaxis of cytomegalovirus disease in cytomegalovirus-seropositive liver transplant recipients

BACKGROUND: Without effective antiviral prophylaxis, cytomegalovirus (CMV) disease is a common cause of morbidity and mortality after liver transplantation. In this randomized, controlled trial, we compared the efficacy and safety of oral ganciclovir with oral acyclovir after induction with intravenous (IV) ganciclovir for long-term prophylaxis of CMV disease in CMV-seropositive liver transplant recipients. METHODS: Patients were initially administered IV ganciclovir at a dose of 6 mg/kg per day from day 1 to day 14 after transplantation followed by either oral ganciclovir (1 g every 8 hr) or oral acyclovir (800 mg every 6 hr) from day 15 to day 100 after transplantation. RESULTS: CMV disease occurred in only 1 of 110 patients (0.9%) receiving ganciclovir compared with 8 of 109 patients (7.3%) receiving acyclovir within the first year after transplantation (P =0.019). There was one case of CMV colitis in the ganciclovir group, whereas four cases of CMV syndrome, three cases of CMV pneumonia, and one case of CMV hepatitis developed in the acyclovir group. The only death from CMV disease occurred in an acyclovir-treated patient with CMV pneumonia. Both oral ganciclovir and oral acyclovir were generally well tolerated. Reversible leukopenia (decline in white blood cell count to <3.0 x 10(9)/L) was more common with oral ganciclovir (38/110 patients, 35%) than with oral acyclovir (20/109 patients, 18%) (P =0.009). The emergence of ganciclovir-resistant strains of CMV was not found during the study. CONCLUSIONS: A prophylactic regimen of 2 weeks of IV ganciclovir followed by an additional 12 weeks of oral ganciclovir is superior to a similar regimen of IV ganciclovir followed by oral acyclovir and almost completely eliminates CMV disease after liver transplantation. This superior protection against CMV disease extends up to 1 year after transplantation and is not associated with ganciclovir resistance.     

Acyclovir plus CMV immunoglobulin prophylaxis and early therapy with ganciclovir are effective and safe in CMV high-risk renal transplant pediatric recipients

Cytomegalovirus (CMV) infection is still a major cause of morbidity in high-risk renal transplant recipients. In the present report, we have reviewed our records of renal transplant pediatric recipients (RTPR; mean age 14.1 ± 4.9 years) since 1991, when we started a policy of CMV prophylaxis constituting high-dose oral acyclovir plus CMV hyperimmune immunoglobulins (Hlg) followed by early i. v. ganciclovir therapy in high-risk patients (i. e., CMV donor + / recipient ?). Four patients received a kidney from a living relative (LR), 2 patients had one previous transplant, and 1 had a combined liver – kidney transplant. Thirty-three patients who were negative for CMV antibodies (ab) before transplantation received a kidney from CMV ab positive donors. The immunosuppressive regimen included cyclosporine A and steroids, with the addition of azathioprine in the 4 patients who received an LR kidney. Serial assessments for CMV antigenemia (pp 65) were routinely performed for 6 months after transplantation to define CMV infection. Among the 33 CMV seronegative recipients (R ?) who received the graft from a CMV seropositive donor (D +), 18 (54.5 %) experienced CMV infection, whereas among the 28 CMV R +, who received a graft from a CMV D +, 11 (39.3 %) experienced CMV infection. With regard to CMV ? related symptoms, only 2 patients suffered from a CMV syndrome (fever and leukopenia in 1 patient, fever and arthralgia in the other). In no case did the spectrum of CMV disease occur; only minor symptoms were present in 7 of the remaining CMV-infected patients (fever in 6 and leukopenia in 1). Rejection episodes and renal function did not differ between CMV-infected and non-CMV-infected patients. Our experiences support the use of prophylactic acyclovir plus CMV HIg followed by early therapy with i. v. ganciclovir to combat the risk of increased morbidity in high risk RTPR.     

Retrospective review of the incidence of cytomegalovirus infection and disease after liver transplantation in pediatric patients: comparison of prophylactic oral ganciclovir and oral valganciclovir

Cytomegalovirus (CMV) is the most common viral infection after solid organ transplantation (SOT). Safe and effective prophylactic regimens that decrease its incidence after SOT are essential for long-term graft survival. Although valganciclovir is not Food and Drug Administration-approved for CMV prophylaxis in liver transplant recipients, postmarketing studies have shown valganciclovir to be as effective as ganciclovir in high-risk adult patients undergoing SOT. Currently, data are lacking for pediatric liver transplantation. The purpose of this study was to compare the efficacy and safety of valganciclovir and ganciclovir for CMV infection prophylaxis in pediatric liver transplant recipients. This was a retrospective study of 56 pediatric liver transplant recipients who were prescribed either oral ganciclovir (n = 37) or valganciclovir (n = 19). Patients were followed until 200 days after transplantation or death. The primary outcome measure compared the rates of early-onset CMV infection and CMV disease in the 2 medication groups. Secondary outcome measures identified patient-specific factors that contributed to CMV acquisition and the incidence of late-onset CMV infection or disease. The rates of adverse drug effects and discontinuation were also evaluated. Early-onset CMV disease was documented in 0% of valganciclovir patients and in 5.4% of ganciclovir patients (P = 0.54). There were no statistically significant differences in the secondary outcomes. An increased incidence of late-onset CMV disease was seen in the valganciclovir group versus the ganciclovir group (22.2% versus 8.1%, P = 0.23). No differences in adverse events were reported. In conclusion, no statistically significant differences were found in the incidence of CMV infection or disease between patients receiving oral valganciclovir and patients receiving oral ganciclovir.     

Acyclovir plus CMV immunoglobulin prophylaxis and early therapy with ganciclovir are effective and safe in CMV high-risk renal transplant pediatric recipients

Abstract Cytomegalovirus (CMV) infection is still a major cause of morbidity in high-risk renal transplant recipients. In the present report, we have reviewed our records of renal transplant pediatric recipients (RTPR; mean age 14.1 ± 4.9 years) since 1991, when we started a policy of CMV prophylaxis constituting high-dose oral acyclovir plus CMV hyperimmune immunoglobulins (Hlg) followed by early i.v. ganciclovir therapy in high-risk patients (i.e., CMV donor +/ recipient -). Four patients received a kidney from a living relative (LR), 2 patients had one previous transplant, and 1 had a combined liver -kidney transplant. Thirty-three patients who were negative for CMV antibodies (ab) before transplantation received a kidney from CMV ab positive donors. The immunosuppressive regimen included cyclosporin A and steroids, with the addition of azathioprine in the 4 patients who received an LR kidney. Serial assessments for CMV antigenemia (pp 65) were routinely performed for 6 months after transplantation to define CMV infection. Among the 33 CMV seronegative recipients (R -) who received the graft from a CMV seropositive donor (D +), 18 (54.5 %) experienced CMV infection, whereas among the 28 CMV R +, who received a graft from a CMV D +, 11 (39.3 %) experienced CMV infection. With regard to CMV - related symptoms, only 2 patients suffered from a CMV syndrome (fever and leukopenia in 1 patient, fever and arthralgia in the other). In no case did the spectrum of CMV disease occur; only minor symptoms were present in 7 of the remaining CMV-infected patients (fever in 6 and leukopenia in 1). Rejection episodes and renal function did not differ between CMV-infected and non-CMV-infected patients. Our experiences support the use of prophylactic acyclovir plus CMV HIg followed by early therapy with i.v. ganciclovir to combat the risk of increased morbidity in high risk RTPR.     

Cytomegalovirus prophylaxis using oral ganciclovir or valganciclovir in kidney and pancreas-kidney transplantation under antibody preconditioning

We investigated retrospectively the risk factors for cytomegalovirus (CMV) infection under ganciclovir or valganciclovir prophylaxis (oral ganciclovir 1 g tid, valganciclovir 450 mg/d) in our kidney and simultaneous pancreas-kidney (SPK) transplant patients undergoing transplantation between July 1, 2001 and February 28, 2003. Two hundred eleven patients receiving prophylactic oral ganciclovir or valganciclovir were included in the study. All patients were given antibody preconditioning (thymoglobulin 178, alemtuzumab 33). Duration of prophylactic treatment was between 3 and 8 months. Fifteen (7.1%) patients developed a positive CMV antigenemia in the first 6 months after transplantation, and 18 of 176 (10.2%) patients developed a positive CMV antigenemia during the first year. No patient developed tissue invasive CMV disease. At 6 months after transplantation, valganciclovir was slightly more effective than ganciclovir prophylaxis (P=.052). Positive donor CMV serology significantly increased the risk of CMV infection compared to CMV-negative donors (P=.014 and P=.003 at 6 and 12 months, respectively). Duration of CMV prophylaxis for more than 3 months decreased the risk of CMV infection (P=.04 and P=.009 at 6 and 12 months, respectively). Either valganciclovir prophylaxis (450 mg/d) or high-dose oral ganciclovir (1 g tid) is effective in preventing tissue-invasive CMV disease, and results in a low incidence of CMV antigenemia in patients undergoing kidney and SPK transplantation.     

Intravenous ganciclovir prophylaxis for cytomegalovirus in heart, heart-lung, and lung transplant recipients

Cytomegalovirus (CMV) disease has had a significant clinical impact on the heart, heart-lung and lung transplant recipients in our centre. CMV disease has been so severe with CMV antibody-negative heart-lung transplant patients receiving organs from CMV antibody-positive donors (CMV-mismatched patients) that in 1986 we adopted the policy of not transplanting CMV-positive organs into CMV-negative heart-lung or lung recipients. In December 1992, we instituted a policy of providing intravenous ganciclovir (5 mg/kg twice a day for 28 days) during the immediate postoperative period for CMV-mismatched heart recipients and CMV antibody-positive heart-lung and lung patients, who have been the patients at greatest risk of severe CMV disease in our centre. A placebo group was not employed because of ethical considerations, ganciclovir having been shown to be effective for the treatment of CMV infections among transplant patients. Compared with a historical control group of patients receiving no prophylaxis, prophylactic ganciclovir reduced the incidence of CMV infection (39 % vs 91 %, P = 0.0006) and CMV disease (17 % vs 74 %, P = 0.0004) among CMV antibody-positive heart-lung recipients. Prophylactic ganciclovir did not significantly reduce the incidence of CMV infection or disease among heart or isolated lung recipients. Ganciclovir was well tolerated, with few adverse reactions. In the case of heart-lung transplant patients, one month of intravenous prophylactic ganciclovir significantly reduced the incidence of both CMV infection and disease when compared with patients who received no prophylaxis. With the lung transplant and heart transplant patients, there were no significant differences between the prophylaxis and nonprophylaxis groups, although there was a consistent trend towards less infection and disease in the prophylaxis groups. Received: 14 April 1998 Received after revision: 24 September 1998 Accepted: 18 December 1998     

Cytomegalovirus prophylaxis with ganciclovir in kidney transplant recipients receiving induction antilymphocyte antibodies

BACKGROUND: Cytomegalovirus (CMV) is one of the serious viral infections after organ transplantation, especially in patients receiving anti-lymphocyte antibodies. Prevention of the infection using antiviral chemotherapy (ganciclovir) has gained interest in the transplant community due to the availability of quantitative methods for viral detection and monitoring. METHODS: Forty-six CMV seropositive kidney transplant recipients were assigned to receive induction immunosuppression with anti-thymocyte globulin (ATG, Fresenius). Prophylactic intravenous ganciclovir was administered for 2 weeks at a dose of 5 mg/kg/d (adjusted to kidney function) starting from the day of surgery. Patients were monitored regularly for CMV infection or disease over 1 year posttransplant. The time to CMV manifestation, the number of antigenemia assay-positive cells, the clinical severity of infection, the incidence of acute rejection, the graft function, and the duration of hospital stay were evaluated. This group was compared to a historical matched control cohort (n = 37) transplanted earlier who did not receive prophylactic ganciclovir. RESULT: The incidence of CMV disease was significantly less among the prophylaxis than the control group (6/46 patients [13%] vs 16/37 patients [43.2%], P = <.004). The time to develop CMV manifestations was much longer in the prophylaxis group than in the control group (median 92 vs 32 days, P 相似文献   

Two grams daily of oral acyclovir reduces the incidence of cytomegalovirus disease in CMV-seropositive liver transplant recipients

Our objective in this study was to determine the efficacy of 2 grams a day of oral acyclovir administered for 16 weeks after transplantation for the prevention of cytomegalovirus (CMV) infection and disease in CMV-seropositive liver transplant recipients. Seventy-three adult liver transplant recipients, seropositive for CMV, were randomized to receive either 2 grams a day of oral acyclovir for 16 weeks after transplantation or no prophylaxis. The incidence of CMV disease was significantly lower in the acyclovir group (5 %) than in the control group (27 %; P < 0.05). By log-rank analysis, the differences in the probability of presenting CMV disease over the first 16 weeks and over the 1st year were also significant (P < 0.05). We conclude that 2 grams a day of oral acyclovir provides effective prophylaxis against CMV disease in CMV-seropositive liver transplant recipients. Received: 14 March 1997 Received after revision: 30 May 1997 Accepted: 9 June 1997     

Efficacy and Safety of Maribavir Dosed at 100 mg Orally Twice Daily for the Prevention of Cytomegalovirus Disease in Liver Transplant Recipients: A Randomized,Double‐Blind,Multicenter Controlled Trial

Maribavir is an oral benzimidazole riboside with potent in vitro activity against cytomegalovirus (CMV), including some CMV strains resistant to ganciclovir. In a randomized, double‐blind, multicenter trial, the efficacy and safety of prophylactic oral maribavir (100 mg twice daily) for prevention of CMV disease were compared with oral ganciclovir (1000 mg three times daily) in 303 CMV‐seronegative liver transplant recipients with CMV‐seropositive donors (147 maribavir; 156 ganciclovir). Patients received study drug for up to 14 weeks and were monitored for CMV infection by blood surveillance tests and also for the development of CMV disease. The primary endpoint was Endpoint Committee (EC)‐confirmed CMV disease within 6 months of transplantation. In a modified intent‐to‐treat analysis, the noninferiority of maribavir compared to oral ganciclovir for prevention of CMV disease was not established (12% with maribavir vs. 8% with ganciclovir: event rate difference of 0.041; 95% CI: ?0.038, 0.119). Furthermore, significantly fewer ganciclovir patients had EC‐confirmed CMV disease or CMV infection by pp65 antigenemia or CMV DNA PCR compared to maribavir patients at both 100 days (20% vs. 60%; p < 0.0001) and at 6 months (53% vs. 72%; p = 0.0053) after transplantation. Graft rejection, patient survival, and non‐CMV infections were similar for maribavir and ganciclovir patients. Maribavir was well‐tolerated and associated with fewer hematological adverse events than oral ganciclovir. At a dose of 100 mg twice daily, maribavir is safe but not adequate for prevention of CMV disease in liver transplant recipients at high risk for CMV disease.     

Long-term oral ganciclovir prophylaxis for prevention of cytomegalovirus infection and disease in cytomegalovirus high-risk renal transplant recipients

BACKGROUND: Although specific therapy is available with ganciclovir, cytomegalovirus (CMV) disease remains a major problem after renal transplantation especially in CMV seronegative recipients of organs of seropositive donors (D+R-). METHODS: In an open-labeled prospective controlled trial we evaluated the effect of long-term oral ganciclovir prophylaxis (3 g/day for 3 months posttransplantation) in a cohort of 31 CMV-high risk (D+R-) renal transplant recipients (GC) compared with a cohort of 28 high-risk patients with targeted CMV prophylaxis (CO) receiving i.v. ganciclovir during antirejection therapy. Primary end-points were CMV infection, diagnosed by pp65 antigenemia assay or serologic method, and CMV disease. Additionally severity of CMV disease quantified by a scoring system was evaluated. RESULTS: CMV prophylaxis significantly reduced the incidence of CMV infection (CO: 75%, GC: 45%; P<.05) and CMV disease (CO: 60%, GC: 29%; P<.05) without relevant side effects and without any clinical suspicion of ganciclovir resistance. Severity of CMV disease as quantified by a scoring system was reduced from 8.3+/-6.7 points in controls to 3.3+/-2.6 points in ganciclovir-treated patients (P<.05). Mortality did not differ significantly between the two groups (CO: n=3, GC: n=1; NS). However, there was one lethal CMV disease and a second death possibly attributable to CMV disease in the control group, whereas in ganciclovir-treated patients there was no CMV-associated fatal outcome. CONCLUSION: Long-term oral ganciclovir prophylaxis is effective and safe in CMV high-risk renal transplant recipients.     

The economic impact of cytomegalovirus infection after liver transplantation

BACKGROUND: We studied the economic impact of cytomegalovirus (CMV) disease and its effective reduction with antiviral prophylaxis in liver transplant recipients. METHOD: Analysis of institutional charge data accumulated during a prospective, randomized, controlled trial comparing oral acyclovir 800 mg four times daily for 120 days (ACV) and intravenous ganciclovir 5 mg/kg every 12 h for 14 days followed by ACV for 106 days (GCV) was performed. RESULTS: Liver transplant recipients who developed CMV disease had significantly higher charges (median: $148,300) than those who developed asymptomatic CMV infection ($119,600) or experienced no CMV infection ($114,100) (P<0.01). A multiple linear regression analysis indicated that CMV disease is associated with a 49% increase in charges, independent of other factors influencing increased hospitalization charges. In CMV-seronegative patients who received a CMV-seropositive donor organ, GCV prophylaxis was associated with a significant reduction in charges, as compared to ACV prophylaxis ($113,900 vs. $153,300, respectively; P=0.02). CONCLUSIONS: CMV disease is an independent risk factor for increased resource utilization associated with liver transplantation. The use of an effective prophylactic antiviral regimen provides savings in health care resources, particularly in patients at high risk for developing CMV disease.     

Long-term outcomes of cytomegalovirus infection and disease after lung or heart–lung transplantation with a delayed ganciclovir regimen

Abstract: Background: Information is limited on long‐term outcomes after preemptive use of ganciclovir to control cytomegalovirus (CMV) infection in lung transplantation. Methods: We studied 78 lung recipients who received antithymocyte globulin induction from 1994 to 2000. All patients received six months of oral acyclovir (800 mg TID). This was interrupted three wk post transplantation for a two‐wk course of IV ganciclovir. Additional courses of ganciclovir were administered based on serial virological monitoring. CMV‐mismatched patients (R?D+) also received four doses of CMV immunoglobulin between weeks 2 and 8. Results: The one yr cumulative risk of CMV disease was 2% (1/61) in CMV seropositive (R+) patients, but was 37% (6/17) in R?D+ patients (p < 0.0001). Over 4.3 yr of follow‐up, patients with CMV infection developed more chronic graft dysfunction caused by bronchiolitis obliterans or bronchiolitis obliterans syndrome than patients without CMV infection (p = 0.012). This effect was also apparent in the subgroup of R+ recipients (p = 0.043). Acute rejection and overall survival were not associated with CMV infection. Conclusions: The use of prophylactic acyclovir and short preemptive courses of ganciclovir effectively controlled CMV disease in R+ patients, but was a relative failure in R?D+ patients. CMV infection was significantly associated with chronic graft dysfunction, even in R+ recipients who had good control of CMV symptoms.     

Impact of cytomegalovirus hyperimmune globulin on outcome after cardiothoracic transplantation: a comparative study of combined prophylaxis with CMV hyperimmune globulin plus ganciclovir versus ganciclovir alone.

BACKGROUND: Cytomegalovirus (CMV) disease was previously shown to be unaltered by a 28-day course of ganciclovir compared with placebo in seronegative recipients of hearts from seropositive donors (D+/R-). This study tests the hypothesis that a combination of ganciclovir plus CMV hyperimmune globulin (CMVIG) is more effective than ganciclovir alone for preventing acute CMV illness and its long-term sequelae. METHODS: The study population receiving CMVIG (n=80) included 27 heart transplant recipients (D+/R-) and 53 heart-lung and lung transplant recipients (R+ and/or D+). Each group was matched with historical controls who underwent transplantation within the preceding 2-3 years. Outcome measures compared were as follows: 3-year incidence of CMV disease; fungal infection; acute rejection; survival; rates and severity of transplant coronary artery disease (in heart patients) defined by intimal thickness (ultrasound) and coronary artery stenosis (angiographic); and incidence and death from obliterative bronchiolitis defined by pathological criteria on endobronchial biopsy specimens (in heart-lung/lung patients). RESULTS: Patients treated with CMVIG had a higher disease-free incidence of CMV, lower rejection incidence, and higher survival rate compared with the patients treated with ganciclovir alone. The coronary artery intimal thickness and the prevalence of intimal thickening were lower in the patients receiving CMVIG. Heart-lung and lung transplant patients treated with CMVIG had lower incidences of obliterative bronchiolitis and death from obliterative bronchiolitis and longer survival compared with the patients treated with ganciclovir alone. CONCLUSIONS: CMVIG plus ganciclovir seems to be more effective that ganciclovir alone for preventing the sequelae of CMV infection. A prospective randomized study is required to confirm these observations.     

Long-term results of CMV hyperimmune globulin prophylaxis in 377 heart transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) has emerged as the most important pathogen to affect the post-operative course after heart transplantation. We performed a retrospective analysis to evaluate the efficiency of CMV hyperimmune globulin (CMVIG) prophylaxis in preventing CMV disease in aggressively immunosuppressed patients after heart transplantation. METHODS: We studied 377 heart transplant recipients who received quadruple-immunosuppressive therapy and CMVIG as sole CMV prophylaxis. The study population was categorized into 4 groups according to donor and recipient CMV serology at the time of transplantation (D+/R+, D+/R-, D-/R+, D-/R-) and was monitored for CMV immediate early antigen in peripheral blood cells, in urine sediments, and in throat washings; for the presence of serum CMV immunoglobulin M and CMV immunoglobulin G; and for clinical evidence of CMV-related symptoms. In addition, we compared the incidence of cardiac allograft vasculopathy and infection among the groups. RESULTS: During the first 5 years after transplantation, CMV disease developed in 79 patients (20.96%). Comparison among the groups showed significantly increased risk for CMV disease in allograft recipients of organs from seropositive donors (D+, 27.31%; D-, 11.33%; p = 0.0003). We observed 6 CMV-associated deaths, all in CMV-antibody-negative recipients. Additionally CMV-positive recipients had a greater incidence of cardiac allograft vasculopathy (p = 0.048), and a greater overall infection rate (p = 0.0034). CONCLUSIONS: Cytomegalovirus hyperimmune globulin administration prevents CMV disease and infection in aggressively immunosuppressed heart transplant recipients. Because fatal CMV disease in CMV-negative recipients of organs from seropositive donors could not be prevented with CMVIG alone, we recommend the additional use of prophylactic ganciclovir in this CMV-mismatched population.     

Unusual case of severe late-onset cytomegalovirus-induced hemorrhagic cystitis and ureteritis in a renal transplant patient

Cytomegalovirus (CMV) infection is common in solid organ transplant recipients and accounts for the majority of graft compromise. Major risk factors include primary exposure to CMV infection at the time of transplantation and the use of antilymphocyte agents such as OKT3 (the monoclonal antibody muromonab-CD3) and antithymocyte globulin. It most often develops during the first 6 months after transplantation. Although current prophylactic strategies and antiviral agents have led to decreased occurrence of CMV disease in early posttransplant period, the incidence of late-onset CMV disease ranges from 2% to 7% even in the patients receiving prophylaxis with oral ganciclovir. The most common presentation of CMV disease in transplant patients is CMV pneumonitis followed by gastrointestinal disease. Hemorrhagic cystitis is a common complication following hematopoietic stem cell transplantation. The condition is usually due to cyclophosphamide-based myeloablative regimens and infectious agents. Even in these settings, CMV-induced cases occur only sporadically. Ureteritis and hemorrhagic cystitis due to CMV infection after kidney transplantation is reported very rarely on a case basis in the literature so far. We report here a case of late-onset CMV-induced hemorrhagic cystitis and ureteritis presenting with painful macroscopic hematuria and ureteral obstruction after 4 years of renal transplantation. The diagnosis is pathologically confirmed by the demonstration of immunohistochemical staining specific for CMV in a resected ureteral section. We draw attention to this very particular presentation of CMV hemorrhagic cystitis with ureteral obstruction in order to emphasize atypical presentation of tissue-invasive CMV disease far beyond the timetable for posttransplant CMV infection.     

Cytomegalovirus disease latent and active infection rates during the first trimester after kidney transplantation

Cytomegalovirus (CMV) infection is the single most frequent infectious complication in renal transplant recipients. The aim of this study was to determine the incidence of latent and active infections with CMV during the first 3 months after kidney transplantation. From January 2000 to December 2001, 203 consecutive adult renal transplant recipients underwent weekly measurements of pp65 CMV antigen from the 4th to the 12th posttransplantation week. Latent infection (seropositivity) was found in 92% of the population. Primary infection occurred in 4.9% (10 of 203), among whom 66% were previously seronegative patients. Among the primary infection patients, 70% (7 of 10) developed severe disease. The overall incidence of viremia was 69.5%, being more frequent among cadaver recipients (79% vs 59%; P =.02). The overall incidence of CMV disease was 38.4% (78 of 203) with 24.6% classified as severe disease requiring antiviral therapy. In conclusion, our population showed a high prevalence of latent infection with viremia. Not all patients developed clinical disease. Most subjects experienced a mild spectrum of symptoms, probably due to the prospective search for active infection during the major risk period after kidney transplantation.     

Prophylaxis of CMV disease by ganciclovir (DHPG) in seronegative recipients of renal allograft from seropositive donors

In an open-label randomized study of prophylactic treatment by ganciclovir, 23 seronegative recipients of kidney allograft from seropositive donors were randomized to receive from day 14 to day 28 after transplantation either no treatment (n = 11) or ganciclovir, 5 mg/kg twice daily (n = 12). Both groups were similar in age, immunosuppressive therapy, number of acute rejections and in steroid bolus. Seroconversion occurred in ten patients of the control group (91%) and in ten of the ganciclovir group (84%). CMV disease occurred in ten patients of the control group (91%) and in eight patients of the ganciclovir group (66%), three of whom had asymptomatic viraemia. The delay between transplantation and onset of CMV disease was significantly increased by ganciclovir prophylaxis (78.5 ± 7.7 vs 46.5 ± 7.5 days, P < 0.05). We conclude that in renal transplant recipients at risk of CMV disease, ganciclovir prophylaxis delays the onset of the disease and seems to decrease its incidence and its severity.     

Cytomegalovirus antigenemia directed pre-emptive prophylaxis with oral versus I.V. ganciclovir for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, controlled trial

BACKGROUND: The efficacy of pre-emptively administered oral ganciclovir in preventing cytomegalovirus (CMV) disease has not been documented in liver transplant recipients. We sought to compare the efficacy of pre-emptive oral ganciclovir with that of i.v. ganciclovir for the prevention of CMV disease after liver transplantation, and to determine whether withholding prophylaxis in the absence of CMV antigenemia, reliably identified patients in whom no prophylaxis was necessary. METHODS: Surveillance cultures for CMV pp65 antigenemia were performed in all patients at weeks 2, 4, 6, 8, 12, and 16. Patients with CMV antigenemia were randomized into two study groups. The experimental group received oral ganciclovir for 6 weeks (2 g t.i.d. for 2 weeks, then 1 g t.i.d. for 4 weeks), and the control group received i.v. ganciclovir (5 mg/kg q 12 hr) for 7 days. RESULTS: Of 72 consecutive liver transplant recipients studied, CMV antigenemia occurred in 31% (22 of 72). Twenty-two patients with asymptomatic antigenemia were randomized to two study groups. CMV disease (viral syndrome) occurred in 9% (1 of 11) of the patients in the i.v. ganciclovir group and in 0% (0 of 11) of the patients in the oral ganciclovir group. None of the study patients developed tissue invasive CMV disease. The median reduction in antigenemia level with oral ganciclovir was 55% at week 1, and 100% at week 2. Overall, 64% of the patients by week 1, 93% by week 2, and 100% by week 4 had antigenemia levels below the baseline after oral ganciclovir. Of 50 patients without CMV antigenemia, none developed CMV disease. CONCLUSIONS: Pre-emptive prophylaxis based on CMV antigenemia can effectively target the patients for CMV prophylaxis; 69% of the patients never received antiviral prophylaxis and did not develop CMV disease. Antiviral therapy instituted upon detection of antigenemia prevented tissue invasive CMV in both ganciclovir groups. Pre-emptively administered oral ganciclovir was effective as prophylaxis for CMV disease after liver transplantation.     

A Multicenter Study of Valganciclovir Prophylaxis up to Day 120 in CMV-Seropositive Lung Transplant Recipients

Seventy-six cytomegalovirus (CMV)-seropositive lung transplant recipients receiving valganciclovir (900 mg/day) for CMV prophylaxis were compared with a group of 87 patients receiving oral ganciclovir (3000 mg/day). Prophylaxis was administered to day 120 post-transplantation and follow-up was 1 year. In addition, a study was conducted on risk factors for CMV infection/disease. CMV disease incidence was 7.9% and 16.1% for valganciclovir and oral ganciclovir, respectively (p = 0.11). Patients receiving valganciclovir had fewer viral syndromes (2.6% vs. 11.5%, p < 0.05), a similar rate of tissue-invasive disease (5.2% vs. 4.6%, p = ns), longer time-to-onset of CMV infection/disease (197.5 vs. 155.2 days, p < 0.05), and a lower probability of infection/disease while on prophylaxis (1.3% vs. 12.6%, p < 0.01). Nonetheless, leukopenia incidence was higher with valganciclovir (15.8% vs. 2.3%, p < 0.01), as was the need for treatment withdrawal due to adverse effects (11.8% vs. 1.1%, p < 0.01). CMV infection was similar in both groups (32.9% vs. 34.5%). Induction therapy with basiliximab and glucocorticosteroid treatment were independent risk factors for developing CMV infection/disease. In conclusion, valganciclovir prophylaxis results in a low incidence of CMV disease in lung transplant recipients and appears more effective than oral ganciclovir. Despite the comparatively higher incidence of adverse events with valganciclovir, the drug can be considered safe for prophylaxis.