valganciclovir and Opportunistic-Infections

Leukopenia and neutropenia (L/N) may affect treatment decisions, potentially resulting in poor clinical and economic outcomes among kidney transplant recipients (KTRs). The burden of L/N is poorly quantified systematically. This systematic literature review aimed to summarize the incidence of, risk factors for, and clinical and economic outcomes associated with L/N post-KT.. We systematically searched MEDLINE, Embase, and the Cochrane Library (from database inception-June 14, 2021) and conferences (past 3 years) to identify observational studies examining epidemiology, risk factors, or outcomes associated with L/N among adult KTRs.. Of 2081 records, 82 studies met inclusion criteria. Seventy-three studies reported the epidemiology of L/N post-KT. Pooled incidence of neutropenia, defined as absolute neutrophil counts (ANC) <1000/μl, ranged from 13% to 48% within 1-year post-transplant; ANC <500/μl ranged from 15% to 20%. Leukopenia, defined as white blood cell counts <3500/μl, was 19% to 83%. Eleven studies reported independent risk factors associated with L/N post-KT. D+/R- cytomegalovirus status, mycophenolic acid (MPA), and tacrolimus use were the most consistent risk factors across studies. Fourteen studies reported L/N-associated clinical outcomes. We noted a trend toward a positive association between neutropenia and acute rejection/opportunistic infections. Mixed findings were noted on the association between L/N and graft failure or mortality. Dosage modifications of valganciclovir, MPA, cotrimoxazole, and anti-thymoglobulin and the need for granulocyte colony-stimulating factor (G-CSF) use were common with L/N.. Findings suggest post-transplant L/N were common and associated with frequent modifications of immunosuppressive agents, requiring G-CSF use, and rejection or opportunistic infections. Findings highlight the need for interventions to reduce risk of L/N post-KT.

Topics: Adult; Anemia; Graft Rejection; Granulocyte Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukopenia; Mycophenolic Acid; Neutropenia; Opportunistic Infections; Transplant Recipients; Valganciclovir

Topics: Animals; Antiviral Agents; Cytomegalovirus Infections; Drug Monitoring; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Opportunistic Infections; Transplant Recipients; Valganciclovir

Cytomegalovirus is the most important pathogen causing opportunistic infections in kidney allograft recipients. The occurrence of CMV disease is associated with higher morbidity, higher incidence of other opportunistic infections, allograft loss and death. Therefore, an efficient strategy to prevent CMV disease after kidney transplantation is required. Two options are currently available: pre-emptive therapy based on regular CMV PCR monitoring and generalized antiviral prophylaxis during a defined period. In this review, we describe those two approaches, highlight the distinct advantages and risks of each strategy and summarize the four randomized controlled trials performed in this field so far. Taken this evidence together, pre-emptive therapy and anti-CMV prophylaxis are both equally potent in preventing CMV-associated complications; however, the pre-emptive approach may have distinct advantages in allowing for development of long-term anti-CMV immunity. We propose a risk-adapted use of these approaches based on serostatus, immunosuppressive therapy and availability of resources at a particular transplant centre.

Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Opportunistic Infections; Post-Exposure Prophylaxis; Pre-Exposure Prophylaxis; Randomized Controlled Trials as Topic; Transplantation, Homologous; Valganciclovir

Bendamustine is one of the new key drugs for patients with indolent lymphoma. Bendamustine, together with rituximab, significantly improves the treatment outcomes of these patients. In addition, previous clinical studies have shown the complication rate of severe infection in bendamustine-containing regimens to be relatively low as compared to those of conventional chemotherapeutic regimens such as CHOP. However, some clinical case reports have raised the possibility that bendamustine may abrogate the immune responses of patients and trigger opportunistic infections including cytomegalovirus reactivation. Herein, we report three indolent lymphoma cases becoming positive on cytomegalovirus antigenemia assay during bendamustine monotherapy. All events occurred after more than three courses of treatment with bendamustine. One patient showed decreased CD4 positive T lymphocytes before the development of cytomegalovirus antigenemia. All three patients were successfully treated with valganciclovir. Although the precise risk is unknown, it should be noted that bendamustine can potentially cause reactivation of/infection with cytomegalovirus and physicians should pay attention to the possibility of this infection during treatment with bendamustine-containing regimens.

Topics: Adult; Aged; Antigens, Viral; Antiviral Agents; Bendamustine Hydrochloride; Biomarkers; CD4 Lymphocyte Count; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Lymphoma, B-Cell; Male; Middle Aged; Nitrogen Mustard Compounds; Opportunistic Infections; Treatment Outcome; Valganciclovir; Virus Activation

Cytomegalovirus (CMV) infection is a common infectious complication after solid organ transplantation (SOT) and is associated with the increased risk of opportunistic infections and allograft rejection, as well as decreased patient survival. Ganciclovir has been the mainstay antiviral agent for prevention and treatment of CMV; however, its clinical use is hampered by the poor oral bioavailability and the need for intravenous access. Valganciclovir, an oral prodrug of ganciclovir, is up to 10 times more bioavailable than oral ganciclovir and has replaced ganciclovir as a first-line agent in the management of CMV in adult SOT patients.. This article examines the safety and efficacy of valganciclovir in pediatric SOT patients, with a particular focus on prophylaxis of CMV infections. An in-depth review of the literature, including pertinent data from the adult SOT population, and a discussion of unmet needs are provided. The pharmacokinetics and pharmacodynamics of valganciclovir in the pediatric population are also discussed.. Existing evidence supports the use of valganciclovir in pediatric SOT patients for CMV prophylaxis. Although comprehensive data are lacking, valganciclovir is a treatment option for CMV infection in pediatric SOT patients. The role of valganciclovir in pediatrics is expected to grow given its demonstrated efficacy in a variety of clinical settings and its advantages over ganciclovir.

Topics: Administration, Oral; Adult; Antiviral Agents; Biological Availability; Child; Cytomegalovirus Infections; Ganciclovir; Humans; Opportunistic Infections; Organ Transplantation; Prodrugs; Valganciclovir

Cytomegalovirus is the most common viral pathogen that affects solid organ transplant recipients. It directly causes fever, myelosuppression, and tissue-invasive disease, and indirectly, it negatively impacts allograft and patient survival. Nucleic acid amplification testing is the preferred method to confirm the diagnosis of CMV infection. Prevention of CMV disease using antiviral prophylaxis or preemptive therapy is critical in the management of transplant patients. Intravenous ganciclovir and oral valganciclovir are the first line drugs for antiviral treatment. This article provides a comprehensive review of the current epidemiology, diagnosis, prevention and treatment of CMV infection in solid organ transplant recipients.

Topics: Antiviral Agents; Chemoprevention; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Immunocompromised Host; Molecular Diagnostic Techniques; Opportunistic Infections; Polymerase Chain Reaction; Transplantation; Transplants; Treatment Outcome; Valganciclovir; Viral Load

Prevention of cytomegalovirus (CMV) infection is an important part of clinical care provided to patients after solid organ transplantation. While the optimal preventive strategy has not been defined, most centers rely on universal prophylaxis or pre-emptive therapy. This article comments on recent studies designed to identify strategies that effectively reduce the incidence of late-onset CMV disease as the main problem associated with prophylaxis, and on recent data regarding the development of CMV-specific immunity depending on the CMV-preventive regimen used. Despite an apparent trend to prefer prophylaxis in clinical practice, this approach does not seem to be based on robust evidence.

Topics: Acyclovir; Antiviral Agents; Clinical Protocols; Cytomegalovirus Infections; Ganciclovir; Humans; Immunosuppressive Agents; Opportunistic Infections; Organ Transplantation; Randomized Controlled Trials as Topic; Valacyclovir; Valganciclovir; Valine

For patients with chronic inflammatory disease treated by immunosuppressive agents (for example: rheumatoid arthritis or systemic lupus erythematosus), there are no available guidelines in medical literature on the use of antiviral agents for the management of symptomatic cytomegalovirus (CMV) infection.. A patient treated by methotrexate for a spondylarthritis presented a CMV infection manifested with persistent fever and pneumonia. CMV pp65 antigenemia was of 120 positive nuclei for 100,000 cells. Treatment with valganciclovir allowed a prompt recovery, while treatment by methotrexate was maintained.. Symptomatic CMV infection evolution is unpredictable and potentially severe in patients with chronic inflammatory diseases receiving immunosuppressive agents. Although there is no data issued from clinical trials, the observation reported in this article and the publications of similar cases in the medical literature indicate that treatment with valganciclovir seems worth to be used in this context. Stopping immunosuppressive therapy does not seem mandatory.

Topics: Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Immunosuppressive Agents; Methotrexate; Middle Aged; Opportunistic Infections; Spondylarthritis; Valganciclovir

Cytomegalovirus (CMV) is the most common opportunistic viral infection to occur following solid-organ transplantation. This review will discuss the current strategies of management of CMV in solid-organ transplantation and their challenges. There are two principal approaches for preventing CMV disease in recipients of solid-organ transplants: prophylactic and pre-emptive. Ganciclovir is the most studied and used antiviral for both treatment and prevention, and is the first-line treatment for CMV infection and CMV disease in transplant recipients. There is no consensus regarding the most appropriate prevention method and the approach to CMV disease prevention differs among transplantation centers owing to the paucity of data comparing the two strategies head-to-head. Currently, the recommended treatment for CMV disease is intravenous ganciclovir.

Topics: Animals; Antiviral Agents; Cytomegalovirus Infections; Disease Management; Ganciclovir; Humans; Opportunistic Infections; Organ Transplantation; Valganciclovir

Valganciclovir (Valcyte) is an orally administered prodrug of the standard anti-cytomegalovirus (CMV) drug ganciclovir. Valganciclovir is as effective as intravenous ganciclovir for the treatment of AIDS-related CMV retinitis, and oral ganciclovir for the prophylaxis of CMV infection and disease in high-risk solid organ transplant recipients. The drug is generally well tolerated and has a similar tolerability profile to that of oral or intravenous ganciclovir, but is devoid of adverse events related to intravenous or indwelling catheter access associated with the use of intravenous ganciclovir, cidofovir and foscarnet. The simple and convenient once-daily valganciclovir regimen offers potential for improved patient compliance. It provides greater systemic ganciclovir exposure than oral ganciclovir, thus reducing the risk of viral resistance when used for prophylaxis in high-risk solid organ transplant recipients. Furthermore, the use of valganciclovir instead of intravenous ganciclovir may provide significant cost savings, based on data comparing oral versus intravenous regimens for the treatment of AIDS-related CMV retinitis. Overall, valganciclovir appears to have some advantages over ganciclovir. Therefore, when used as prophylaxis against CMV infection and disease in high-risk solid organ transplant recipients or as induction and maintenance therapy of CMV retinitis in patients with AIDS, oral valganciclovir is an attractive alternative to other available anti-CMV drugs.

Topics: Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Immunocompromised Host; Opportunistic Infections; Valganciclovir

Herpes virus infections, particularly those caused by cytomegalovirus (CMV), lead to significant and, sometimes severe, clinical problems for the immunocompromised host. As effective agents have become available, several treatment and prevention strategies have evolved over the past decade, first in intra-venous form and more recently, as oral preparations. Valganciclovir, the valine ester of ganciclovir, is an orally administered, potent, antiviral agent active against all herpes viruses. When taken orally, valganciclovir has much-improved bioavailability compared with oral ganciclovir and achieves ganciclovir exposures similar to intravenous ganciclovir. Clinical trials evaluating the safety and efficacy of valganciclovir for the treatment of new AIDS-associated CMV retinitis showed equivalency to intravenous ganciclovir and prevented progression of quiescent disease. In solid organ recipients, once-daily valganciclovir has been proven equivalent to oral ganciclovir for the prevention of CMV infection. The high bioavailability and convenient dosing formulation make valganciclovir an attractive option for these indications.

Topics: AIDS-Related Opportunistic Infections; Antiviral Agents; Clinical Trials as Topic; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Ganciclovir; Humans; Opportunistic Infections; Organ Transplantation; Valganciclovir

The pharmacology, pharmacokinetics, safety, and efficacy of valganciclovir, an oral prodrug for ganciclovir, used to prevent cytomegalovirus (CMV) disease in solid organ transplant recipients are described. Valganciclovir was developed to overcome the disadvantages associated with ganciclovir, which include low oral bioavailability, limited efficacy because of the development of viral resistance, and the need for frequent administration, which can adversely affect patient adherence. Valganciclovir is rapidly converted to ganciclovir; systemic exposure to the parent drug is low and short in duration. The oral bioavailability of ganciclovir from valganciclovir is 10 times higher than that from the original ganciclovir formulation. Food increases the oral bioavailability of valganciclovir. In a four-way, randomized, crossover pharmacokinetic study of 28 liver transplant recipients, single doses of valganciclovir 900 mg and intravenous ganciclovir 5 mg/kg resulted in a similar ganciclovir systemic exposure. The systemic exposure was proportionately lower with a single 450-mg dose of valganciclovir but similar to that of oral ganciclovir 3 g administered in three divided doses. In the recent multicenter, randomized, double-blind, double-dummy PV16000 trial in 364 solid organ transplant recipients at high risk for CMV disease (i.e., CMV-negative recipients of CMV-positive donor organs), valganciclovir 900 mg once daily was as effective in preventing CMV-disease as oral ganciclovir 1 g three times daily. Resistance was reported with ganciclovir but not with valganciclovir. Both drugs were well tolerated.

Topics: Administration, Oral; Antibiotic Prophylaxis; Antiviral Agents; Biological Availability; Cytomegalovirus Infections; Ganciclovir; Humans; Liver Transplantation; Opportunistic Infections; Randomized Controlled Trials as Topic; Valganciclovir

Prophylaxis for cytomegalovirus infection is highly recommended for kidney transplant recipients. The use of daily 900 mg valganciclovir is the usual prophylactic dose, whereas 450 mg daily is under investigation. We evaluated the outcome of using 2 different doses of valganciclovir prophylaxis for cytomegalovirus infection after kidney transplant.. We randomized kidney transplant recipients (1:1) to receive 450 mg daily valganciclovir (group 1) or 900 mg daily valganciclovir (group 2) for the first 6 months after kidney transplant. Serologically, all patients were at moderate risk for cytomegalovirus infection. Patients were studied for incidence of cytomegalovirus disease, leukopenia attacks, rejection episodes, and graft outcomes for 1 year.. Demographic features of group 1 (98 patients) and group 2 (98 patients) were comparable. More than 50% of patients received thymoglobulin induction therapy without difference between the groups. There were more leukopenia attacks in group 2 (P = .03) requiring higher doses of granulocyte colony-stimulating factor (P = .03). Group 2 patients received lower doses of mycophenolate mofetil (P= .04) and required reduced doses of valganciclovir (P = .045). Compared with group 1, the high-dose group developed numerically more rejection episodes (P = .057) and more cytomegalovirus infections requiring full treatment (P = .17). Graft and patient outcomes were satisfactory in both groups.. Six months of low-dose valganciclovir prophylaxis for intermediate-risk kidney transplant recipients was as effective as high-dose valganciclovir with a better safety profile.

Topics: Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Administration Schedule; Female; Ganciclovir; Graft Rejection; Graft Survival; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Leukopenia; Male; Middle Aged; Opportunistic Infections; Risk Factors; Time Factors; Treatment Outcome; Valganciclovir; Virus Activation

Cytomegalovirus (CMV) is the most prevalent opportunistic infection after lung transplantation. Current strategies do not prevent CMV in most at-risk patients.. To determine whether extending prophylaxis with oral valganciclovir from the standard 3 months to 12 months after lung transplantation is efficacious.. Randomized, clinical trial. Patients were randomly assigned by a central automated system to treatment or placebo. Patients and investigators were blinded to treatment status. (ClinicalTrials.gov registration number: NCT00227370). Multicenter trial involving 11 U.S. lung transplant centers.. 136 lung transplant recipients who completed 3 months of valganciclovir prophylaxis.. 9 additional months of oral valganciclovir (n = 70) or placebo (n = 66).. The primary end point was freedom from CMV disease (syndrome or tissue-invasive) on an intention-to-treat basis 300 days after randomization. Secondary end points were CMV disease severity, CMV infection, acute rejection, opportunistic infections, ganciclovir resistance, and safety.. CMV disease occurred in 32% of the short-course group versus 4% of the extended-course group (P < 0.001). Significant reductions were observed with CMV infection (64% vs. 10%; P < 0.001) and disease severity (110 000 vs. 3200 copies/mL, P = 0.009) with extended treatment. Rates of acute rejection, opportunistic infections, adverse events, CMV UL97 ganciclovir-resistance mutations, and laboratory abnormalities were similar between groups. During the 6 months after study completion, a low incidence of CMV disease was observed in both groups.. Longer-term effects of extended prophylaxis were not assessed.. In adult lung transplant recipients who have received 3 months of valganciclovir, extending prophylaxis by an additional 9 months significantly reduces CMV infection, disease, and disease severity without increased ganciclovir resistance or toxicity. A beneficial effect with regard to prevention of CMV disease seems to extend at least through 18 months after transplantation.

Topics: Administration, Oral; Adult; Antiviral Agents; Cytomegalovirus Infections; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Ganciclovir; Humans; Lung Transplantation; Male; Middle Aged; Opportunistic Infections; Pneumonia, Viral; Prospective Studies; Valganciclovir; Viremia

Pre-emptive treatment of CMV infection in transplant recipients aims at prevention of clinical disease by early detection. However, current treatment requires the intravenous (iv) administration of ganciclovir for 2 weeks, which is a considerable burden for the patient. In this observational study, the efficacy of the new oral prodrug valganciclovir was compared with iv ganciclovir.. To facilitate the introduction of valganciclovir, a therapeutic guideline was developed to use this drug under controlled conditions with regard to safety in renal/renal-pancreas transplant recipients requiring CMV therapy. Subsequently, a group of 57 consecutive transplant recipients was evaluated. Onset and treatment of CMV infections were followed by frequent monitoring of CMV DNA in plasma by quantitative real-time PCR. Details of antiviral therapy were documented.. In 15 out of 57 transplant recipients, a total of 27 anti-CMV treatment episodes were recorded: 18 with valganciclovir (900 mg twice daily) and nine with iv ganciclovir (5 mg/kg twice daily) as initial treatment. Median CMV DNA load reduction during treatment was 0.12 log10/day in the valganciclovir group and 0.09 log10/day in the ganciclovir group. There were no haematological side effects in any group and no patient developed signs of clinical CMV disease.. Similar reduction of CMV DNA load was observed during pre-emptive treatment with oral valganciclovir and iv ganciclovir in transplant recipients. Oral valganciclovir would provide an attractive and safe alternative for pre-emptive CMV treatment in renal/renal-pancreas transplant patients, however, confirmation in larger randomized studies would be desirable.

Topics: Administration, Oral; Adult; Aged; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Female; Ganciclovir; Humans; Injections, Intravenous; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Pancreas Transplantation; Safety; Valganciclovir

The most common opportunistic viral pathogen after lung transplantation is cytomegalovirus (CMV). Oral valganciclovir, a prodrug of ganciclovir, has been introduced as a potential drug for prophylaxis and treatment of CMV infection and disease in lung transplantation. The goal of this study was to describe our initial experience with oral valganciclovir for pre-emptive treatment of CMV infections after lung transplantation.. We summarize our experience with 19 patients who underwent lung transplantation and received pre-emptive oral valganciclovir therapy in the situation of positive CMV polymerase chain reaction (PCR) in either plasma or bronchoalveolar lavage. None of the patients presented with manifest CMV disease. Treatment dosage of valganciclovir was 450 mg to 1800 mg daily, depending on renal function and white blood count. Treatment was continued until the CMV PCR became negative, in any case for a period of at least 14 days.. Three patients received two courses of pre-emptive oral valganciclovir; 16 patients were treated once. Eleven patients (57.9%) were treated because of a positive plasma CMV PCR; in eight patients (42.1%) the PCR was positive only in bronchoalveolar lavage. Therapy was initiated 896 +/- 1186 days (range, 108-3911) after transplantation with a mean CMV PCR of 45,536 +/- 149,294 copies (range, 426-706,000). In all cases the PCR fell below detectability (<400 copies) after a period of 22 +/- 10 days of treatment (range, 7-50 days). Mild to moderate leucopenia was observed in seven patients (36.8%) during treatment. None of the patients developed new onset of other potentially drug-related disorders such as neutropenia, anemia, deterioration of renal function or gastrointestinal disorder.. Pre-emptive therapy with oral valganciclovir for CMV infections detected by PCR in either plasma or bronchoalveolar lavage after lung transplantation seems to be efficacious and safe. However, regular blood counts should be performed to detect developing leucopenia.

Topics: Administration, Oral; Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Lung Transplantation; Male; Middle Aged; Opportunistic Infections; Pilot Projects; Postoperative Care; Treatment Outcome; Valganciclovir

Few studies have directly compared preemptive therapy (PET) and antiviral prophylaxis (AP) for prevention of cytomegalovirus (CMV) disease in CMV seropositive (R+) orthotopic liver transplant (OLT) recipients.. We prospectively assessed CMV disease and clinical outcomes among 160 consecutive R+ OLT recipients who received PET (weekly plasma CMV PCR for 3 months, oral valganciclovir 900 mg twice daily for CMV viremia >250 IU/mL, until 2 consecutive negative weekly PCR results) and compared them with a historical cohort of 156 R+ recipients who received AP (valganciclovir, 900 mg daily for 3 months).. Patient characteristics were similar between PET and AP cohorts (P > 0.05 all comparisons). In the PET group, 24% (39/160) developed CMV viremia greater than 250 IU/mL at a median of 42 (range, 7-93) days post-OLT. CMV monitoring adherence in the PET cohort was 85% (1488/1760 required tests) and 86% (30/36) initiated PET within 3 days of the CMV result. By 12 months post-OLT, the incidence of CMV disease, acute allograft rejection, major infection, or death in the PET and AP cohorts was not significantly different: 2% versus 2%, 19% versus 16%, 10.5% versus 10.8%, and 5% versus 8%, respectively (P > 0.05 all comparisons). The estimated proportion of drug-exposed patients and average antiviral drug exposure were significantly lower with PET versus AP: 24% versus 100%, P < 0.001, and 15.8 versus 81 g per patient, P < 0.001, respectively.. PET is feasible in a nonresearch setting and is associated with similar CMV disease rates and other clinically relevant outcomes to AP in CMV seropositive liver transplant recipients.

Topics: Administration, Oral; Adult; Aged; Antibodies, Viral; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Administration Schedule; Feasibility Studies; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Opportunistic Infections; Prospective Studies; RNA, Viral; Time Factors; Treatment Outcome; Valganciclovir; Viral Load; Young Adult

Liver transplantation recipients (LTRs) who are seropositive for cytomegalovirus (CMV) (recipient seropositive [R+]) are at intermediate risk for CMV disease. A preventative strategy following transplant is considered standard of care. Current guidelines recommend high-dose valganciclovir (VGCV; 900 mg/day adjusted for renal function) for prophylaxis given limited data on the efficacy and safety of low-dose VGCV (450 mg/day adjusted for renal function). We describe our experience using low-dose VGCV prophylaxis for R+ LTRs at our institution. A single-center, retrospective study was conducted using a database of 364 LTRs over a 4-year period (2011-2014). Adult first-time R+ LTRs receiving low-dose VGCV prophylaxis were included. The primary endpoint was CMV disease at 1 year after transplant. Patients were compared with historical controls receiving high-dose VGCV prophylaxis. Secondary endpoints were biopsy-proven rejection and leukopenia on VGCV. With respect to leukopenia, patients receiving low-dose VGCV were compared with a group of D+R- patients from the database receiving high-dose VGCV. Univariate analyses were performed using chi-squared, Fisher's exact, and Wilcoxon rank sum tests. A total of 200 R+ LTRs met inclusion criteria. Median age was 60 years (interquartile range [IQR], 54-66 years), and 129 (65%) LTRs were male. Median Model for End-Stage Liver Disease score was 22 (IQR, 14-31), and 178 (89%) patients received deceased donor transplants. CMV disease occurred in only 9 (5%) patients, similar to rates in previous studies of LTRs receiving high-dose VGCV. Biopsy-proven rejection occurred in 18 (9%) patients. Patients received VGCV prophylaxis for a median of 3.4 (IQR, 3.1-4.3) months; 151 (76%) R+ LTRs receiving low-dose VGCV developed leukopenia. Premature VGCV discontinuation and granulocyte-colony stimulating factor use were infrequent and not significantly different between the 2 groups. In conclusion, low-dose VGCV was safe and effective for prevention of CMV disease in our cohort of 200 R+ LTR and should be considered as an option in future guidelines. Liver Transplantation 24 616-622 2018 AASLD.

Topics: Aged; Antiviral Agents; Chi-Square Distribution; Cytomegalovirus Infections; Databases, Factual; Female; Ganciclovir; Graft Rejection; Humans; Immunocompromised Host; Immunosuppressive Agents; Leukopenia; Liver Transplantation; Male; Middle Aged; New York City; Opportunistic Infections; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Valganciclovir

Cytomegalovirus (CMV) replication and disease, with its associated morbidity and poor transplant outcome, represents a serious threat to transplant recipients. The pediatric kidney transplant population is at a particularly increased risk of CMV infection.. We therefore analyzed CMV epidemiology in a large cohort of pediatric renal transplant recipients (n = 242) and assessed the impact of antiviral chemoprophylaxis with valganciclovir (VGCV) or ganciclovir (GCV) on CMV replication and morbidity.. While antiviral chemoprophylaxis with VGCV or GCV in patients with a high (D+/R-) or intermediate (D+/R+) CMV risk (n = 82) compared to preemptive therapy (n = 47) had no significant effect on the incidence of CMV syndrome or tissue-invasive disease, chemoprophylaxis was associated with a better preservation of transplant function at 3 years posttransplant (loss of estimated glomerular filtration rate in the chemoprophylaxis cohort, 16.0 ± 3.4 vs. 30.1 ± 4.7 mL/min per 1.73 m(2) in the preemptive therapy cohort, P < 0.05).CMV replication was associated with a more pronounced decline of graft function (difference in estimated glomerular filtration rate of 9.6 mL/min per 1.73 m(2) at 3 years) compared to patients without CMV replication. However, patients undergoing VGCV or GCV chemoprophylaxis had more leukocytopenia.. Antiviral chemoprophylaxis with VGCV or GCV in recipients with a high or moderate CMV risk is associated with a better preservation of transplant function. Hence, the prevention of CMV replication in this patient population has the potential to improve transplant outcome.

Topics: Adolescent; Age Factors; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections; Drug Administration Schedule; Europe; Female; Ganciclovir; Graft Survival; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Opportunistic Infections; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Valganciclovir

Cytomegalovirus (CMV) is a highly complex pathogen which, despite modern prophylactic regimens, continues to affect a high proportion of thoracic organ transplant recipients. The symptomatic manifestations of CMV infection are compounded by adverse indirect effects induced by the multiple immunomodulatory actions of CMV. These include a higher risk of acute rejection, cardiac allograft vasculopathy after heart transplantation, and potentially bronchiolitis obliterans syndrome in lung transplant recipients, with a greater propensity for opportunistic secondary infections. Prophylaxis for CMV using antiviral agents (typically oral valganciclovir or intravenous ganciclovir) is now almost universal, at least in high-risk transplants (D+/R-). Even with extended prophylactic regimens, however, challenges remain. The CMV events can still occur despite antiviral prophylaxis, including late-onset infection or recurrent disease, and patients with ganciclovir-resistant CMV infection or who are intolerant to antiviral therapy require alternative strategies. The CMV immunoglobulin (CMVIG) and antiviral agents have complementary modes of action. High-titer CMVIG preparations provide passive CMV-specific immunity but also exert complex immunomodulatory properties which augment the antiviral effect of antiviral agents and offer the potential to suppress the indirect effects of CMV infection. This supplement discusses the available data concerning the immunological and clinical effects of CMVIG after heart or lung transplantation.

Topics: Antiviral Agents; Consensus Development Conferences as Topic; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Heart Transplantation; Host-Pathogen Interactions; Humans; Immunization, Passive; Immunocompromised Host; Immunoglobulins; Immunoglobulins, Intravenous; Immunosuppressive Agents; Lung Transplantation; Opportunistic Infections; Treatment Outcome; Valganciclovir; Virus Activation

Topics: Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Drug Packaging; Ganciclovir; Humans; Liver Transplantation; Opportunistic Infections; Valganciclovir

The cytomegalovirus (CMV) donor-positive/recipient-positive (D+/R+) population is the largest proportion of renal transplant recipients (RTR). Guidelines for prevention of CMV in the intermediate-risk D+/R+ population include prophylaxis with valganciclovir (VGCV) 900 mg/day for 3 months. This study is the first head-to-head analysis, to our knowledge, comparing the efficacy and safety CMV prophylaxis of VGCV 450 vs 900 mg/day for 3 months in D+/R+ RTR.. A multicenter, retrospective analysis evaluated 478 adult RTR between January 2008 and October 2011. Study participants received VGCV 450 mg/day (Group 1; n=398) or 900 mg/day (Group 2; n=89)×3 months for CMV prophylaxis. All VGCV was adjusted for renal function. All groups included in this study received study-approved induction and maintenance immunosuppression regimens. The primary endpoint was incidence of CMV disease at 12 months.. The rates of graft loss, patient survival, T-cell and/or antibody-mediated rejection, hematological adverse events, opportunistic infections, and early VGCV discontinuation were evaluated. Patient demographics were comparable, but had significant differences in ethnicity and donor type between the groups.. The occurrence of CMV disease at 12 months was similar between the groups (3.5% vs 3.4%; P=1.000). Log-rank test found no statistically significant difference in the time to development of CMV between the 2 groups (P=.939).

Topics: Adult; Allografts; Antibiotic Prophylaxis; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Follow-Up Studies; Ganciclovir; Graft Rejection; Humans; Immunosuppression Therapy; Incidence; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Practice Guidelines as Topic; Retrospective Studies; Serologic Tests; Transplant Recipients; Treatment Outcome; Valganciclovir

Skin grafting has been evolving as an important application in reconstructive surgery. Mixed reports about the survival of allogeneic and xenogeneic keratinocytes require further substantiation to determine the role of these cells in wound healing.. Rabbit and rat skins were recovered and cultured in vitro. Full-thickness wounds were created on the dorsum of rabbits (2 cm × 2 cm; n = 4). Cultured epithelial autograft, allograft, and xenograft cells were sprayed onto 3 freshly created wounds, with 1 wound acting as a control. The wounds were monitored every 2 days for 4 weeks. After 4 weeks, the rabbits were killed; skin biopsies were taken from each healed wound and stained with hematoxylin and eosin, and epidermal thickness was measured.. All examined grafts showed favorable healing outcomes because the wounds appeared similar to normal skin upon healing. The only observed significant difference was the thickness of the epidermis layer, which was thinner in the xenograft (P = .002) than the autograft or allograft. Morphologic evaluation of the skin surface showed that the rat skin was thinner than the rabbit skin. The graft that achieved the best result was the autograft because the thickness was similar to and mimicked normal skin.. All 3 grafts (autograft, allograft, and xenograft) have the potential to reconstitute epithelial defects. This approach can overcome the limitation of autologous skin donor sites, especially in burn cases.

Topics: Adult; Allografts; Antiviral Agents; Biopsy; Cytomegalovirus Infections; Female; Ganciclovir; Gastritis; Humans; Immunocompromised Host; Immunohistochemistry; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Opportunistic Infections; Risk Factors; Time Factors; Treatment Outcome; Valganciclovir

Despite proven efficacy of prolonged cytomegalovirus (CMV) prophylaxis using valganciclovir 900 mg/day, some centers use 450 mg/day due to reported success and cost savings. This multicenter, retrospective study compared the efficacy and safety of 6 months of low-dose versus high-dose valganciclovir prophylaxis in high-risk, donor-positive/recipient-negative, renal transplant recipients (RTR).. Two hundred thirty-seven high-risk RTR (low-dose group = valganciclovir 450 mg/day [n = 130]; high-dose group = valganciclovir 900 mg/day [n = s7]) were evaluated for 1-year CMV disease prevalence. Breakthrough CMV, resistant CMV, biopsy-proven acute rejection (BPAR), graft loss, opportunistic infections (OI), new-onset diabetes after transplantation (NODAT), premature valganciclovir discontinuation, renal function and myelosuppression were also assessed.. Patient demographics and transplant characteristics were comparable. Induction and maintenance immunosuppression were similar, except for more early steroid withdrawal in the high-dose group. Similar proportions of patients developed CMV disease (14.6% vs 24.3%; P = 0.068); however, controlling CMV risk factor differences through multivariate logistic regression revealed significantly lower CMV disease in the low-dose group (P = 0.02; odds ratio, 0.432, 95% confidence interval, 0.211-0.887). Breakthrough and resistant CMV occurred at similar frequencies. There was no difference in renal function or rates of biopsy-proven acute rejection, graft loss, opportunistic infections, or new-onset diabetes after transplantation. The high-dose group had significantly lower mean white blood cell counts at months 5 and 6; however, premature valganciclovir discontinuation rates were similar.. Low-dose and high-dose valganciclovir regimens provide similar efficacy in preventing CMV disease in high-risk RTR, with a reduced incidence of leukopenia associated with the low-dose regimen and no difference in resistant CMV. Low-dose valganciclovir may provide a significant cost avoidance benefit.

Topics: Acute Disease; Adult; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Graft Rejection; Graft Survival; Humans; Immunocompromised Host; Kaplan-Meier Estimate; Kidney Transplantation; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Opportunistic Infections; Prevalence; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; United States; Valganciclovir

In solid organ transplantation, human cytomegalovirus (HCMV) is considered to be the most important viral pathogen. We report a case of a CMV R-/D+ small intestine transplant recipient with a primary CMV infection on valganciclovir prophylaxis. Sequencing of the HCMV DNA for drug resistance-associated mutations revealed the UL97 mutation N510S. This mutation has been initially reported to confer ganciclovir resistance. Based on in vitro recombinant phenotyping, this assumption has recently been questioned. Switching the antiviral treatment to an intravenous regimen of ganciclovir eliminated HCMV DNAemia, showing the in vivo efficacy of ganciclovir for the UL97 mutation N510S. Hence, knowledge of drug efficacy is crucial for an adequate choice of antiviral medication, carefully balancing antiviral potency versus the risk of harmful side effects.

Topics: Antiviral Agents; Chemoprevention; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Drug Resistance, Viral; Ganciclovir; Humans; Immunocompromised Host; Male; Middle Aged; Mutation, Missense; Opportunistic Infections; Phosphotransferases (Alcohol Group Acceptor); Sequence Analysis, DNA; Transplantation; Treatment Outcome; Valganciclovir

Cytomegalovirus (CMV) is a major cause of morbidity and mortality following solid organ transplantation (SOT). Two strategies, prophylactic, and preemptive have emerged for the prevention of CMV infection and disease after SOT. This retrospective chart review of two liver transplant cohorts: prophylactic and preemptive, compares the clinical impact of transitioning from prophylactic to preemptive strategy. The primary outcome is the incidence of CMV viremia at 3-and 6-months post-transplant. Secondary outcomes include: incidence of CMV tissue-invasive disease, acute cellular rejection, leukopenia and neutropenia, opportunistic infection rates, hospital readmission rates, and mortality at 3-and 6-months post-transplant. A total of 109 patients were included in the analysis. The incidence of CMV viremia was 4.9% and 50.0% (P < 0.001) in the prophylactic versus preemptive cohort, respectively, at 3 months post-transplant. The incidence of CMV viremia was 24.6% and 8.3% (P = 0.026) in the prophylactic versus preemptive cohort, respectively, at 6 months post-transplant. There were no statistical significant differences in the secondary outcomes between both cohorts. In conclusion, there is a statistical significant difference in time to onset of CMV viremia; however, the use of either prophylactic or preemptive strategy was not associated with significant negative clinical outcomes of CMV.

Topics: Adult; Aged; Antiviral Agents; Cohort Studies; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Liver Transplantation; Male; Middle Aged; Neutropenia; Opportunistic Infections; Retrospective Studies; Treatment Outcome; Valganciclovir; Viremia

Topics: Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Liver Transplantation; Male; Opportunistic Infections; Valganciclovir; Viremia

Cytomegalovirus (CMV) is the most common opportunistic infection following lung transplantation. CMV replication in the lung allograft is described as accelerating the development of bronchiolitis obliterans syndrome (BOS). Finding a strategy to prevent CMV infection is an important issue.. We performed a retrospective, single-centre study of 114 lung transplant recipients (LTRs) who underwent lung transplantation from January 2001 to December 2006. In a smaller cohort of 88 CMV seropositive (R+) LTRs, three months of valganciclovir prophylaxis (2004-2006) was compared to three months of oral ganciclovir (2001-2003) with respect to the incidence of CMV infection/disease, the severity of CMV disease, acute rejection, BOS-free 4 year survival and 4 year survival. In the whole group of 114 LTRs the impact of CMV infection on long-term survival (BOS free 4 year survival and 6 year survival) was assessed.. For the cohort of 88 CMV seropositive LTRs, the incidence of CMV infection/disease at one year was lower in the valganciclovir group compared to the ganciclovir group (24% vs. 54%, p = 0.003). There was a tendency towards reduced CMV disease, from 33% to 20% and a significant lower incidence of asymptomatic CMV infection (22% vs. 4%, p = 0.005). A lower incidence of acute rejection was observed in the valganciclovir group. However, there was no significant difference between the two groups in BOS free 4 year survival and 4 year survival.For the entire group of 114 LTRs, BOS-free 4 year survival for recipients with CMV disease was (32%, p = 0.005) and among those with asymptomatic CMV infection (36%, p = 0.061) as compared with patients without CMV infection (69%). Six year survival was lower among patients with CMV disease, (64%, p = 0.042) and asymptomatic CMV infection (55%, p = 0.018) than patients without CMV infection (84%).. A lower incidence of CMV infection/disease and acute rejections was observed with valganciclovir (3 months) when compared to oral ganciclovir (3 months). The long-term impact of CMV infection/disease was significant for BOS-free survival and survival.

Topics: Adolescent; Adult; Aged; Antibiotic Prophylaxis; Antiviral Agents; Bronchiolitis Obliterans; Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Graft Rejection; Humans; Incidence; Lung Transplantation; Male; Middle Aged; Opportunistic Infections; Retrospective Studies; Valganciclovir; Young Adult

Cytomegalovirus (CMV) infection remains a major problem in recipients with heart transplantation (HTx), because it may play a significant role in the development of cardiac allograft vasculopathy, which is one of the major causes of death after HTx. Valganciclovir (VGC) is effective for the treatment of CMV infection, but is often associated with neutropenia, especially when used with mycophenolate mophetil (MMF). We experienced an HTx recipient with positive CMV antigenemia who suffered progressive neutropenia after administration of VGC. We switched MMF to everolimus (EVL) and assay for CMV antigenemia was constantly negative even after discontinuation of VGC. In all other 14 HTx recipients who received EVL for any reason, we found that assay for CMV antigenemia remained negative throughout the period of EVL administration. Considering the prophylactic effect on CMV, EVL can not only be an alternative to rescue from comorbidity, but might also be indicated earlier especially in CMV-seronegative HTx recipients.

Topics: Adult; Antigens, Viral; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Substitution; Drug Therapy, Combination; Everolimus; Ganciclovir; Heart Transplantation; Heart-Assist Devices; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Neutropenia; Opportunistic Infections; Sirolimus; Valganciclovir

International consensus guidelines on the management of cytomegalovirus (CMV) infections in kidney transplantation recommend the use of universal prophylaxis over preemptive therapy for the highest risk kidney transplant recipients (KTR), namely donor+/recipient - CMV serostatus. However, no universal recommendations have been made for R+ KTR undergoing antithymocyte globulin (ATG) induction. In this retrospective study, we compared 1-year outcomes among 24 R+ KTR who received 3 months of valgancyclovir prophylaxis with 72 R+ KTR who were subjected to a preemptive strategy. All subjects received ATG induction. The incidence of CMV infection was significantly higher among the preemptive subjects versus the prophylaxis group (78% versus 38%, respectively; P = .0003), whereas the incidence of CMV disease was low and did not differ significantly between the cohorts (8% versus 7% respectively, P = .8). Late-onset CMV infections were only observed in the prophylaxis group (25% versus 0%, P = .0001). Finally, the rate of opportunistic infections, acute rejection episodes, and graft/patient survivals at 1 year were also similar between the two groups. In light of this study, preemptive therapy and universal prophylaxis were almost equally effective to prevent CMV infection among R+ KTR receiving ATG induction.

Topics: Acute Disease; Aged; Aged, 80 and over; Antilymphocyte Serum; Antiviral Agents; Chi-Square Distribution; Cytomegalovirus Infections; Drug Administration Schedule; Female; France; Ganciclovir; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Valganciclovir

Most cases of cytomegalovirus (CMV) colitis that develop in patients with inflammatory bowel disease (IBD) are caused by reactivation of a latent virus. Primary CMV infections are rare in adult patients. Treatment with immunosuppressive agents increases the infection risk in patients with IBD. We present a 26 year old lady with primary CMV colitis, superimposed on underlying Crohn's colitis. The diagnosis was confirmed by a viral-like prodrome, a positive CMV IgM titer, presence of low avidity IgG antibodies to CMV, high CMV DNA titers in the plasma, and immunohistological detection of CMV positive cells in her colonic mucosa. The patient responded to initial treatment with intravenous ganciclovir with a fall in plasma levels of CMV DNA, treatment was completed with oral valganciclovir until plasma CMV DNA levels became undetectable.

Topics: Adult; Antiviral Agents; Colitis; Crohn Disease; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Female; Ganciclovir; Humans; Immunocompromised Host; Immunosuppression Therapy; Immunosuppressive Agents; Opportunistic Infections; Treatment Outcome; Valganciclovir; Viral Load

Topics: Adult; Antiviral Agents; Case-Control Studies; Cytomegalovirus Infections; Follow-Up Studies; Ganciclovir; Humans; Incidence; Kidney Transplantation; Opportunistic Infections; Valganciclovir

Topics: Antiviral Agents; Cytomegalovirus Infections; Disease Management; Ganciclovir; Graft Rejection; Humans; Immune System; Lymphoproliferative Disorders; Opportunistic Infections; Organ Transplantation; Valganciclovir

Despite advances in antiviral therapies, cytomegalovirus (CMV) remains the leading opportunistic infection in the transplant population. Valganciclovir (VGC), the L-valyl ester prodrug of ganciclovir (GCV), provides an excellent oral alternative to GCV for the prevention of CMV in transplant recipients. We investigated the use of VGC for CMV prevention in high-risk renal and pancreas transplant recipients.. Patients at high risk for development of CMV disease were defined as either those who had donor positive, recipient-negative serostatus (D+/R-), or those who received antilymphocyte antibody (ALA) therapy for either rejection treatment or induction. A retrospective review was conducted of all kidney and pancreas transplants performed between August 2001 and December 2003. A total of 341 transplants were performed, of which 109 received VGC, and 88 were included in this analysis.. The overall incidence of CMV disease was 5.7% (5/88). All of the CMV episodes were in patients who were D+/R- (17.2% [5/29] versus 0% [0/59], P<0.001). Of these patients, all the episodes of CMV were in patients who received VGC prophylaxis for<100 days post transplant (29% [5/17] versus 0% [0/12], P=0.06). The overall incidence of leukopenia was 11% and thrombocytopenia was 7%, with the incidence between the D+/R- group and the ALA group being similar.. VGC is an effective agent in preventing CMV disease in kidney and pancreas transplant recipients who are at high risk for developing the disease. The optimal length of prophylaxis in D+/R- patients is still undefined, while 3 months of prophylaxis appears to be sufficient in patients who received ALA therapy.

Topics: Adult; Antibodies, Viral; Antilymphocyte Serum; Antiviral Agents; Cytomegalovirus Infections; Drug Interactions; Female; Ganciclovir; Humans; Kidney Transplantation; Leukopenia; Male; Middle Aged; Opportunistic Infections; Pancreas Transplantation; Retrospective Studies; Risk Factors; Thrombocytopenia; Valganciclovir

Topics: Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Mycoses; Opportunistic Infections; Valganciclovir