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Microorganisms Dec 2022The clinical benefits of the common off-label use of cytomegalovirus (CMV)-specific immunoglobulin (CMV-Ig) combined with antivirals in organ transplantation have not...
BACKGROUND
The clinical benefits of the common off-label use of cytomegalovirus (CMV)-specific immunoglobulin (CMV-Ig) combined with antivirals in organ transplantation have not been previously assessed. The objective was to compare the risk of CMV infection and other post-transplantation outcomes between two CMV-Ig prophylaxis regimens in lung transplant recipients; Methods: Retrospective study of 124 donor CMV positive/recipient negative (D+/R-) patients receiving preventive ganciclovir/valganciclovir for 12 months, of whom 62 received adjunctive CMV-Ig as per label indication (short regimen [SR-Ig]; i.e., 7 doses over 2.5 months) and were compared to 62 who received an extended off-label regimen (ER-Ig) consisting of 17 doses over one year after transplantation.
RESULTS
The incidence of CMV infection or disease, acute rejection, chronic lung allograft dysfunction, and survival did not differ between the two CMV-Ig schedules. Although the time to the first CMV infection after transplantation was shorter in the ER-Ig than in the SR-Ig adjunctive group (log-rank: = 0.002), the risk was independently predicted by antiviral cessation (odds ratio = 3.74; 95% confidence interval = 1.04-13.51; = 0.030), whereas the CMV-Ig schedule had no effect.
CONCLUSIONS
Extending the adjunctive CMV-Ig prophylaxis beyond the manufacturer's recommendations up to one year does not confer additional clinical benefits regarding lung post-transplantation outcomes.
PubMed: 36677327
DOI: 10.3390/microorganisms11010032 -
BMC Infectious Diseases Jan 2023Congenital cytomegalovirus (CMV) infection (cCMV) can cause sensorineural hearing loss and neurodevelopmental disabilities in children. Oral valganciclovir (VGCV)...
BACKGROUND
Congenital cytomegalovirus (CMV) infection (cCMV) can cause sensorineural hearing loss and neurodevelopmental disabilities in children. Oral valganciclovir (VGCV) therapy has been reported to improve long-term audiological and neurodevelopmental outcomes in patients with cCMV. The levels of CMV DNA in whole blood have been monitored in previous studies. However, quantitative methods using whole blood have not been standardized. Recently, the plasma viral load has been standardized and widely used in CMV-associated diseases.
METHODS
CMV viral loads in whole blood and plasma were serially measured in 24 patients with a confirmatory diagnosis of cCMV during oral VGCV therapy using an in-house real-time PCR assay. Plasma samples were assayed using the Cobas 6800 system (Roche Diagnostics) in addition to an in-house assay.
RESULTS
Plasma CMV viral loads were remarkably decreased at the end of therapy compared to before therapy. A significant correlation of CMV levels between whole blood and plasma was observed (Spearman's ρ = 0.566). The levels of CMV DNA before therapy were significantly correlated with the period of decreasing the viral loads to below the detection limit, not only in whole blood (Spearman's ρ = 0.901) but also in plasma (Spearman, ρ = 0.804). Finally, CMV viral loads between the in-house assay and commercially available standardized assay in 75 plasma samples with positive PCR results for CMV were compared; a significant correlation was observed between the results of both assays.
CONCLUSIONS
There was a significant correlation between the two assays (Spearman, ρ = 0.882), suggesting that CMV plasma viral loads measured by the standardized assay are widely used to monitor the levels of CMV DNA in patients with cCMV during oral VGCV therapy.
Topics: Child; Humans; Valganciclovir; Cytomegalovirus; Viral Load; Cytomegalovirus Infections; Real-Time Polymerase Chain Reaction; DNA, Viral
PubMed: 36658533
DOI: 10.1186/s12879-023-07995-6 -
The Pediatric Infectious Disease Journal Feb 2023The impact and outcomes of postnatal cytomegalovirus (CMV) infection are not entirely clear. We aimed to determine the associations between treatment outcomes of...
BACKGROUND
The impact and outcomes of postnatal cytomegalovirus (CMV) infection are not entirely clear. We aimed to determine the associations between treatment outcomes of postnatal CMV infection and its antiviral treatment.
METHODS
Retrospective study in a tertiary center. Infants of < 29 weeks gestational age who were tested for postnatal CMV infection were included. CMV-infected infants were compared to uninfected infants (control group). CMV-infected infants were either treated with ganciclovir and/or valganciclovir (CMVPT group) or not (CMVPNT group). Demographic, clinical, laboratory, treatment, and outcome data were collected. Primary outcomes were the length of stay, death before discharge and hearing impairment, cognitive and motor development as assessed by the Denver Developmental Screening Test II, and neurologic impairment at the corrected age of 1.5-2 years.
RESULTS
We included 103 extremely premature infants. The Median (interquartile range [IQR]) length of stay was 94 (69-112) days in control, 85 (70-102) days in CMVPNT, and 100 (88-137) days in the CMVPT group. Mortality before discharge was 6% in control, 3.8% in CMVPNT, and 3.7% in the CMVPT group. Normal hearing at follow-up was found in 30/37 infants in control (81.1%), 13/13 infants in CMVPNT (100%), and 17/20 infants in the CMVPT group (85%). Denver Developmental Screening Test II results did not differ among the three groups. Neurologic impairment was found in 21/37 infants (56.8%) in control, 9/13 infants in CMVPNT (69.2%), and 14/20 infants in CMVPT group (70%).
CONCLUSIONS
The associations between antiviral treatment of postnatal CMV infection and better treatment outcomes were nonsignificant.
Topics: Infant, Newborn; Infant; Humans; Child, Preschool; Cytomegalovirus; Retrospective Studies; Antiviral Agents; Infant, Extremely Premature; Cytomegalovirus Infections; Nervous System Diseases
PubMed: 36638404
DOI: 10.1097/INF.0000000000003737 -
Clinical and Experimental Pediatrics Sep 2023Congenital cytomegalovirus (CMV) is the most common cause of congenital infection worldwide, the most common nongenetic cause of sensorineural hearing loss in children,...
Congenital cytomegalovirus (CMV) is the most common cause of congenital infection worldwide, the most common nongenetic cause of sensorineural hearing loss in children, and a cause of neurodevelopmental disorders in the brain. Infants with symptomatic congenital CMV infection may benefit from hearing and neurodevelopmental outcomes, particularly if antiviral treatment is initiated within the first month of life. Infants with life-threatening symptoms are recommended to receive 2-6 weeks of intravenous ganciclovir and then switch to oral valganciclovir, and those without life-threatening symptoms are recommended to use oral valganciclovir during the entire 6-month period. During antiviral drug treatment, absolute neutrophil count, platelet count, blood urea nitrogen, creatinine, and liver function tests were performed to identify neutropenia, thrombocytopenia, renal failure, and liver failure. This review investigated the evidence to date of treating congenital CMV infection.
PubMed: 36596746
DOI: 10.3345/cep.2022.01032 -
Frontiers in Pediatrics 2022Cytomegalovirus (CMV) is one of the most frequent opportunistic infections in kidney transplant (KT) recipients and is a risk factor for patient and graft survival after...
BACKGROUND
Cytomegalovirus (CMV) is one of the most frequent opportunistic infections in kidney transplant (KT) recipients and is a risk factor for patient and graft survival after KT. Center-to-center variation, optimal prevention and treatment strategies in pediatric KT are currently unknown. This survey aimed to assess current CMV prevention and treatment strategies used among French pediatric KT centers.
METHODS
A web-based survey was sent to all 13 French pediatric kidney transplantation centers.
RESULTS
Twelve (92%) centers responded to the survey. All centers used prophylaxis for the donor-positive/recipient-negative (D+/R-) group. For R + patients, 54% used prophylaxis, 37% used a pre-emptive strategy. In the low-risk group, D-/R-, 50% used a pre-emptive approach and 50% had no specific prevention strategy. The antiviral used by all centers for prophylaxis was valganciclovir (VGCV). The duration of prophylaxis varied from 3 to 7 months and the duration of viral load monitoring varied from 6 months to indefinitely. No center used a hybrid/sequential approach. For the treatment of CMV DNAemia, VGCV or intravenous GCV were used. Therapeutic drug monitoring of VGCV was performed in 5 centers (42%). Five centers reported drug resistance. Eight centers (67%) administered VGCV during the treatment of acute graft rejection.
CONCLUSIONS
There is uniformity in CMV management in some areas among pediatric KT centers in France but not in others which remain diverse and are not up to date with current guidelines, suggesting unnecessary variation which could be reduced with better evidence to inform practice.
PubMed: 36589153
DOI: 10.3389/fped.2022.1057352 -
Infectious Diseases and Therapy Feb 2023Cytomegalovirus (CMV) infection can have both direct and indirect effects after solid-organ transplantation, with a significant impact on transplant outcomes. Prevention... (Review)
Review
Cytomegalovirus (CMV) infection can have both direct and indirect effects after solid-organ transplantation, with a significant impact on transplant outcomes. Prevention strategies decrease the risk of CMV disease, although CMV still occurs in up to 50% of high-risk patients. Ganciclovir (GCV) and valganciclovir (VGCV) are the main drugs currently used for preventing and treating CMV. Emerging data suggest that letermovir is as effective as VGCV with fewer hematological side effects. Refractory and resistant CMV also still occur in solid-organ-transplant patients. Maribavir has been shown to be effective and have less toxicity in the treatment of refractory and resistant CMV. In this review paper, we discuss prevention strategies, refractory and resistant CMV, and drug-related side effects and their impact, as well as optimal use of novel anti-CMV therapies.
PubMed: 36583845
DOI: 10.1007/s40121-022-00746-1 -
Indian Journal of Nephrology 2022A 45-year-old gentleman underwent kidney transplantation in March 2010. He remained apparently healthy for the next 10 years when he developed anorexia and weight loss....
A 45-year-old gentleman underwent kidney transplantation in March 2010. He remained apparently healthy for the next 10 years when he developed anorexia and weight loss. Diagnostic workup revealed cytomegalovirus (CMV) pneumonia. While viremia resolved within 3 weeks of initiation of valganciclovir, he developed progressive breathlessness and hypoxia on exertion. Imaging of thorax revealed central peri-bronchovascular consolidation and fine reticulations with peripheral sparing. Computed tomography (CT)-guided percutaneous lung biopsy revealed organizing intra-alveolar exudates, suggestive of organizing pneumonia, with no evidence of active infection on biopsy as well as bronchoalveolar lavage (BAL) cytology. This atypical pattern of central distribution of opacities is not typical of organizing pneumonia where peripheral subpleural distribution is more common. Patient responded dramatically following escalation of steroids, with complete resolution of infiltrates on follow-up imaging.
PubMed: 36568596
DOI: 10.4103/ijn.ijn_254_21 -
Actas Dermo-sifiliograficas Oct 2023
Virus Reactivation With Eosinophilia and Systemic Symptoms: An Imitator of Immune Reconstitution Inflammatory Syndrome With an Excellent Clinical Response to Valganciclovir.
Topics: Humans; Valganciclovir; Immune Reconstitution Inflammatory Syndrome; Eosinophilia; Drug Hypersensitivity Syndrome; Virus Activation
PubMed: 36567028
DOI: 10.1016/j.ad.2022.04.022 -
Microorganisms Nov 2022The efficacy of pre-emptive therapy in the prevention of cytomegalovirus (CMV) disease and the potential association of CMV infection with the occurrence of chronic lung...
The efficacy of pre-emptive therapy in the prevention of cytomegalovirus (CMV) disease and the potential association of CMV infection with the occurrence of chronic lung allograft dysfunction (CLAD) was evaluated in 129 lung transplant recipients receiving pre-emptive therapy based on pp65-antigenemia or CMV-DNA in the blood and in the bronchoalveolar lavage. Seventy-one (55%) patients received pre-emptive ganciclovir/valganciclovir (GCV/VGCV) for CMV infection for a median of 28 (9-191) days. Possible CMV disease occurred in six (5%) patients and was healed after the GCV/VGCV therapy. The cumulative incidence of CLAD was 38% and 54% at 5 and 10 years. Acute rejection and CMV load in the blood (but not in the lung) were independent predictors of the occurrence of CLAD. Pre-emptive therapy is highly effective in preventing CMV disease in lung recipients and does not induce a superior incidence of CLAD compared to what reported for other cohorts of patients who received an extended antiviral prophylaxis.
PubMed: 36557592
DOI: 10.3390/microorganisms10122339 -
Tropical Medicine and Infectious Disease Dec 2022Human cytomegalovirus (HCMV) is ubiquitous worldwide and elicits global health problems. The diseases associated with HCMV are a serious threat to humans, especially for... (Review)
Review
Human cytomegalovirus (HCMV) is ubiquitous worldwide and elicits global health problems. The diseases associated with HCMV are a serious threat to humans, especially for the sick, infant, elderly and immunocompromised/immunodeficient individuals. Although traditional antiviral drugs (e.g., ganciclovir, valganciclovir, cidofovir, foscarnet) can be used to treat or prevent acute HCMV infections, their efficacy is limited because of toxicity, resistance issues, side effects and other problems. Fortunately, novel drugs (e.g., letermovir and maribavir) with less toxicity and drug/cross-resistance have been approved and put on the market in recent years. The nucleic acid-based gene-targeting approaches including the external guide sequences (EGSs)-RNase, the clustered regularly interspaced short palindromic repeats (CRISPRs)/CRISPRs-associated protein 9 (Cas9) system and transcription activator-like effector nucleases (TALENs) have been investigated to remove both lytic and latent CMV in vitro and/or in vivo. Cell therapy including the adoptive T cell therapy (ACT) and immunotherapy have been tried against drug-resistant and recurrent HCMV in patients receiving hematopoietic stem cell transplantation (HSCT) or solid organ transplant (SOT), and they have also been used to treat glioblastoma (GBM) associated with HCMV infections. These newly developed antiviral strategies are expected to yield fruitful results and make a significant contribution to the treatment of HCMV infections. Despite this progress, the nucleic acid-based gene-targeting approaches are still under study for basic research, and cell therapy is adopted in a small study population size or only successful in case reports. Additionally, no current drugs have been approved to be indicated for latent infections. Therefore, the next strategy is to develop antiviral strategies to elevate efficacy against acute and/or latent infections and overcome challenges such as toxicity, resistance issues, and side effects. In this review, we would explore the challenges, recent advances and perspectives in the treatment of HCMV infections. Furthermore, the suitable therapeutic strategies as well as the possibility for compassionate use would be evaluated.
PubMed: 36548694
DOI: 10.3390/tropicalmed7120439