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Survey of Ophthalmology 2022Cytomegalovirus (CMV) anterior uveitis is the most common form of ocular manifestation of CMV in immunocompetent individuals. The difficulty in diagnosing CMV anterior... (Meta-Analysis)
Meta-Analysis Review
Cytomegalovirus (CMV) anterior uveitis is the most common form of ocular manifestation of CMV in immunocompetent individuals. The difficulty in diagnosing CMV anterior uveitis may delay adequate treatment and affect outcomes. We sought to review systemically the overall clinical characteristics and compare treatment outcomes in CMV anterior uveitis and endotheliitis. A literature search was performed, and studies describing clinical characteristics, treatment regimens, and outcomes that included more than 5 treated eyes were included. In these 23 studies, acute CMV anterior uveitis commonly presented with high intraocular pressure (95.31%, 95% CI 90.45-98.60) and mild anterior chamber inflammation (cells >2+ = 3.18%, 95% CI 0.21-0.54). About two-thirds of CMV endotheliitis cases presented with high intraocular pressure and coin-shaped corneal lesions. Acute CMV anterior uveitis showed good clinical response to topical 0.15% ganciclovir (GCV) gel or oral valganciclovir (VGCV) (90%, 95% CI 74-100% and 95%, 95% CI 88-100%, respectively). For chronic CMV anterior uveitis, both topical GCV and oral VGCV yielded comparable results. Topical 0.5-2% GCV or a combination of topical and oral VGCV for CMV endotheliitis both resulted in good clinical response. Recurrence of inflammation was common after cessation of maintenance therapy. Overall, topical GCV resulted in an optimal outcome for CMV anterior uveitis. Escalated concentration and frequency of usage are needed for chronic CMV anterior uveitis and endotheliitis. Adequate induction and maintenance phases of anti-CMV treatment seem necessary to prevent recurrences.
Topics: Antiviral Agents; Aqueous Humor; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Eye Infections, Viral; Ganciclovir; Glaucoma; Humans; Inflammation; Treatment Outcome; Uveitis, Anterior; Valganciclovir
PubMed: 34954093
DOI: 10.1016/j.survophthal.2021.12.006 -
Transplant International : Official... Dec 2021Cytomegalovirus (CMV) infection is common in kidney transplantation (KT). Antiviral-agents are used as universal prophylaxis. Our purpose aimed to compare and rank... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of conventional antiviral agents in preventive strategies for cytomegalovirus infection after kidney transplantation: a systematic review and network meta-analysis.
Cytomegalovirus (CMV) infection is common in kidney transplantation (KT). Antiviral-agents are used as universal prophylaxis. Our purpose aimed to compare and rank efficacy and safety. MEDLINE, Embase, SCOPUS, and CENTRAL were used from inception to September 2020 regardless language restriction. We included randomized clinical trials (RCTs) comparing the CMV infection/disease prophylaxis among antiviral-agents in adult KT recipients. Of 24 eligible RCTs, prophylactic valganciclovir (VGC) could significantly lower the overall CMV infection and disease risks than placebo with pooled risk differences (RDs) [95% confidence interval (CI)] of -0.36 (-0.54, -0.18) and -0.28 (-0.48, -0.08), respectively. Valacyclovir (VAC) and ganciclovir (GC) significantly decreased risks with the corresponding RDs of -0.25 (-0.32, -0.19) and -0.30 (-0.37, -0.22) for CMV infection and -0.26 (-0.40, -0.12) and -0.22 (-0.31, -0.12) for CMV disease. For subgroup analysis by seropositive-donor and seronegative-recipient (D+/R-), VGC and GC significantly lowered the risk of CMV infection/disease with RDs of -0.42 (-0.84, -0.01) and -0.35 (-0.60, -0.12). For pre-emptive strategies, GC lowered the incidence of CMV disease significantly with pooled RDs of -0.33 (-0.47, -0.19). VGC may be the best in prophylaxis of CMV infection/disease follow by GC. VAC might be an alternative where VGC and GC are not available.
Topics: Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Network Meta-Analysis
PubMed: 34580930
DOI: 10.1111/tri.14122 -
Microorganisms Jun 2021Congenital cytomegalovirus (cCMV) infection is the most frequent mother-to-child transmitted infection worldwide and a prevalent cause of neonatal disease and long-term... (Review)
Review
BACKGROUND
Congenital cytomegalovirus (cCMV) infection is the most frequent mother-to-child transmitted infection worldwide and a prevalent cause of neonatal disease and long-term morbidity. The kidney is a target organ for CMV, which replicates in renal tubules and is excreted in large quantities in urine for years in children with cCMV infection. Nonetheless, kidney disease has rarely been reported in cCMV-infected patients.
OBJECTIVE
We aimed to describe the available data on renal involvement in patients with cCMV infection at the pathologic, functional, anatomical, and/or clinical levels.
METHODS
A systematic search was performed in the MEDLINE/PubMed, SCOPUS, and Cochrane databases. Studies describing any renal involvement in fetuses or neonates aged ≤3 weeks at diagnosis of microbiologically confirmed cCMV infection were eligible.
RESULTS
Twenty-four articles were included, with a very low level of evidence. Pathologic findings in autopsy studies universally described CMV typical inclusion bodies in tubular cells. No functional studies were identified. cCMV infection was not associated with an increased risk of kidney malformations. Congenital nephrotic syndrome was the most common clinical condition associated with cCMV, but a causal relationship cannot be established.
CONCLUSIONS
Typical pathological features of cCMV infection are very common in renal tissue, but they do not seem to entail significant consequences at the anatomical or clinical levels.
PubMed: 34203932
DOI: 10.3390/microorganisms9061304 -
Clinical Pharmacokinetics Jun 2021Ganciclovir (GCV) and valganciclovir (VGCV) are the first-line agents used to prevent and treat cytomegalovirus (CMV) infection in allogeneic haematopoietic stem cell...
A Systematic Review of the Clinical Pharmacokinetics, Pharmacodynamics and Toxicodynamics of Ganciclovir/Valganciclovir in Allogeneic Haematopoietic Stem Cell Transplant Patients.
BACKGROUND
Ganciclovir (GCV) and valganciclovir (VGCV) are the first-line agents used to prevent and treat cytomegalovirus (CMV) infection in allogeneic haematopoietic stem cell transplant (alloHCT) patients.
OBJECTIVE
The aim of this work was to describe available data for the clinical pharmacokinetics, pharmacodynamics and toxicodynamics of GCV and VGCV and the potential of a therapeutic drug monitoring strategy to improve outcomes in the alloHCT population.
METHODS
We systematically reviewed the pharmacokinetics (dose-exposure), pharmacodynamics (exposure-efficacy) and toxicodynamics (exposure-toxicity) of GCV and VGCV in alloHCT patients with CMV infection. Studies including alloHCT patients treated for CMV infection reporting the pharmacokinetics, pharmacodynamics and toxicodynamics of GCV or VGCV were searched for using the PUBMED and EMBASE databases from 1946 to 2019. Only studies involving participants > 12 years of age and available in the English language were included.
RESULTS
A total of 179 patients were included in the 14 studies that met the inclusion criteria, of which 6 examined GCV pharmacokinetics only, while 8 also examined GCV pharmacodynamics and toxicodynamics. Reported pharmacokinetic parameters showed considerable interpatient variability and were different from other populations, such as solid organ transplant and human immunodeficiency virus-infected patients. Only one study found a correlation between neutropenia and elevated peak and trough GCV concentrations, with no other significant pharmacodynamic and toxicodynamic relationships identified. While therapeutic drug monitoring of GCV is performed in some institutions, no association between GCV therapeutic drug monitoring and clinical outcomes was identified.
CONCLUSION
Further studies of the pharmacokinetics, pharmacodynamics and toxicodynamics of GCV/VGCV in alloHCT patients are required to identify a more robust therapeutic range and to subsequently quantify the potential value of therapeutic drug monitoring of GCV/VGCV in the alloHCT population.
Topics: Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Valganciclovir
PubMed: 33515202
DOI: 10.1007/s40262-020-00982-z -
Frontiers in Immunology 2020Defining the optimal dosage of the immunosuppressive or duration of anti-infective agents is a challenge in solid organ transplant (SOT) recipients. We aimed to... (Meta-Analysis)
Meta-Analysis
Defining the optimal dosage of the immunosuppressive or duration of anti-infective agents is a challenge in solid organ transplant (SOT) recipients. We aimed to systematically review the literature regarding the use of T cell mediated immune functional assays (IFAs) for adjustment of the immunosuppressive or anti-infective agents in SOT recipients. We systematically searched PubMed, Scopus, EMBASE, Web of Science (WOS), Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov to find human interventional studies or study protocols that used either in-house or commercially available IFAs for adjustment of the immunosuppressive or anti-infective agents in SOT recipients. We included six clinical trials and six study protocols. Four out of the six clinical trials used interferon-γ release assays for cytomegalovirus (IGRA-CMV), and five out of the six registered study protocols planned to use IGRA-CMV for adjustment of anti-CMV antiviral (Valganciclovir) prophylaxis or preemptive therapy in SOT recipients. Primary or secondary anti-CMV prophylaxes were discontinued in SOT recipients who had positive IGRA-CMV results without an increase in the rate of CMV infection or reactivation. Among other IFAs, one clinical trial used interferon-γ release assays for tuberculosis (IGRA-TB), and one study used ImmuKnow for adjustment of the duration and dosage of isoniazid and tacrolimus, respectively. Our systematic review supports a promising role for the IGRA-CMVs for adjustment of the duration of anti-CMV antiviral prophylaxis in SOT recipients. There are limited data to support the use of IFAs other than IGRA-CMVs for adjustment of immunosuppressive or anti-infective agents. Further multicenter randomized clinical trials using IFAs other than IGRA-CMVs may help in personalized immunosuppressive or prophylactic anti-infective therapy in SOT recipients.
Topics: Animals; Anti-Infective Agents; Clinical Decision-Making; Disease Management; Humans; Immunoassay; Immunosuppressive Agents; Infection Control; Infections; Organ Transplantation; T-Lymphocytes; Treatment Outcome
PubMed: 33178194
DOI: 10.3389/fimmu.2020.567715 -
Transplant Infectious Disease : An... Apr 2021Kidney transplant recipients (KTRs) have increased risk for cytomegalovirus (CMV) infection/disease given the necessity of drug-induced immunosuppression. A... (Review)
Review
Kidney transplant recipients (KTRs) have increased risk for cytomegalovirus (CMV) infection/disease given the necessity of drug-induced immunosuppression. A comprehensive review of published literature reporting real-world data on prevention strategies utilized and associated CMV burden outcomes is limited. Such data could help inform future clinical practice and identify unmet needs in CMV management. We conducted a systematic review of observational studies published in Medline or EMBASE from January 2008 to November 2018 to identify current real-world CMV management approaches, CMV infection/disease risk factors, and outcomes associated with CMV infection. Descriptive statistics and pooled quantitative analyses were conducted. From 1608 records screened, 86 citations, including 69 803 adult KTR, were included. Prophylaxis and preemptive therapy (PET) were predominant approaches among D+/R- and R + CMV serostatus transplants, respectively. Valganciclovir and ganciclovir were frequently utilized across CMV risk strata. Despite prevention approaches, approximately one-fourth of KTR developed CMV infection. Age and D+/R- CMV serostatus were consistent risk factors for CMV infection/disease. CMV infection/disease was associated with increased mortality and graft loss. CMV was similarly associated with acute rejection (AR) risk, but with high heterogeneity among studies. Limited data were available on CMV and opportunistic infections (OIs) risk. CMV remains a significant issue. New strategies may be needed to optimize CMV management.
Topics: Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Risk Factors; Transplant Recipients; Valganciclovir
PubMed: 33012092
DOI: 10.1111/tid.13483 -
Zeitschrift Fur Geburtshilfe Und... Apr 2020The number of diseases covered by universal neonatal screening in Germany has risen steadily from 1 (phenylketonuria) in 1968 to 17 (with hearing impairment and...
INTRODUCTION
The number of diseases covered by universal neonatal screening in Germany has risen steadily from 1 (phenylketonuria) in 1968 to 17 (with hearing impairment and congenital hip dysplasia) in 2018. Treatment, however, of disorders diagnosed by screening may harm children, as failed neuroblastoma screening has shown. There are several pilot studies to detect congenital cytomegalovirus (CMV) infection but no consensus as to the treatment of the infants identified.
METHODOLOGY
Systematic search for studies investigating therapy of congenital CMV infection, using PubMed and the WHO International Clinical Trials Registry Platform (ICTRP).
RESULTS
We found only one controlled trial that randomized infants with symptomatic congenital CMV infection (involving the central nervous system) to treatment (intravenous ganciclovir for 6 weeks) or no treatment. Treatment was associated with significantly less hearing deterioration. A second trial comparing 6 weeks vs. 6 months of treatment with valganciclovir, an oral prodrug of ganciclovir, found no benefit for hearing but modestly improved developmental outcomes associated with 6 months of treatment. In contrast, an open-label registry reported benefits for infants with congenital CMV infection and isolated hearing who received valganciclovir for 12 months, with hearing improvement in 2/3 of cases after a median follow-up of 4½ years.
CONCLUSIONS
Antiviral treatment of neonates with congenital CMV infection and few symptoms including isolated hearing loss remains controversial. A generally accepted therapy, however, is pivotal before introducing universal or targeted screening for congenital CMV infection.
Topics: Antiviral Agents; Child; Cytomegalovirus Infections; Ganciclovir; Germany; Hearing Loss, Sensorineural; Humans; Infant; Infant, Newborn; Neonatal Screening; Treatment Outcome
PubMed: 31426118
DOI: 10.1055/a-0966-9915 -
Pediatric Transplantation Sep 2019CMV disease continues to stand as a significant threat to the longevity of renal transplants in children. More pediatric recipients are CMV-negative with CMV-positive... (Meta-Analysis)
Meta-Analysis
CMV disease continues to stand as a significant threat to the longevity of renal transplants in children. More pediatric recipients are CMV-negative with CMV-positive donor serologies resulting in a HR mismatch. The length of prophylaxis with GCV or VGCV required to optimally prevent recurrence of CMVDNAemia remains unknown. This study is a meta-analysis comparing GCV/VGCV prophylaxis regimens provided for <6 months, from 6 to <12 months, and ≥12 months after transplant in order to prevent CMVDNAemia. The search conducted involved PubMed, EMBASE, ISI Web of Science, and Cochrane Central Register from inception through December 2017. Search terms Kidney Transplantation, CMV, GCV, and VGCV provided 204 studies for abstract review. Studies excluded were those which did not itemize pediatric data separately, single case reports, and duplicate studies. Pooled analysis of five retrospective studies and one prospective study identified that there is no statistically significant difference in the incidence of CMV DNAemia when comparing <6 months of prophylaxis and >12 months of prophylaxis (23% and 15%, respectively, P = 0.23). Regardless of the length of prophylaxis, there was no statistical difference in the incidence of CMV DNAemia in the HR patients (6 to <12 months vs <6 months, P = 0.62; 6 to <12 months vs ≥12 months, P = 0.78; ≥12 months vs <6 months, P = 0.83). This study identifies no optimal length of prophylaxis for HR mismatch pediatric renal transplant patients as many develop CMV DNAemia.
Topics: Adolescent; Antiviral Agents; Child; Cytomegalovirus Infections; Female; Ganciclovir; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Kidney Transplantation; Leukopenia; Male; Risk Assessment; Transplant Recipients; Valganciclovir
PubMed: 31210393
DOI: 10.1111/petr.13514 -
Reviews in Medical Virology Mar 2019Human cytomegalovirus (CMV) represents the most common infection among recipients of solid organ transplants (SOTs). Previous meta-analysis showed 0.8% of SOT recipients...
Human cytomegalovirus (CMV) represents the most common infection among recipients of solid organ transplants (SOTs). Previous meta-analysis showed 0.8% of SOT recipients developed CMV disease whilst receiving valganciclovir (ValGCV) prophylaxis. However, the clinical utility of monitoring ganciclovir (GCV) blood concentrations is unclear. We systematically reviewed the association between GCV concentrations during prophylaxis and the incidence of CMV. MEDLINE and EMBASE databases were searched for studies between 1946 and 2018, where GCV pharmacokinetics and incidence of CMV viraemia or disease in SOT were available. Research designs included randomised trials, comparative, prospective cohort, retrospective, or case report studies. Only human adult studies were included, with English language restriction. The 11 studies that met the eligibility criteria included 610 participants receiving GCV or ValGCV prophylaxis. Quality assessment showed 2/4 randomised trials, 4/6 cohort studies, and 1/1 case report were of high quality. Despite dose adjustments for renal impairment, mean GCV exposures for patients were heterogeneous and ranged between 28 and 53.7 μg·h/mL across three randomised trials. The incidence of CMV infection and disease ranged from 0% to 50% and 0% to 3.1%, respectively, with follow up between 3 to 9 months. One study showed statistical power in determining relationship, where GCV exposure at 40 to 50 μg·h/mL in high-risk SOT recipients was associated with a reduced risk of viraemia. Clinical monitoring for GCV exposure can be applied to high-risk SOT recipients during ValGCV prophylaxis; however, further studies are needed to determine the utility of monitoring in all SOT recipients.
Topics: Adolescent; Adult; Aged; Antiviral Agents; Base Composition; Chemoprevention; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Immunocompromised Host; Incidence; Male; Middle Aged; Organ Transplantation; Prospective Studies; Retrospective Studies; Transplant Recipients; Treatment Outcome; Viremia; Young Adult
PubMed: 30556615
DOI: 10.1002/rmv.2023 -
Transplantation Proceedings Oct 2018Valganciclovir is widely used to prevent post-transplant cytomegalovirus (CMV) infection in kidney transplant patients. However, the currently used dose remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Valganciclovir is widely used to prevent post-transplant cytomegalovirus (CMV) infection in kidney transplant patients. However, the currently used dose remains controversial because the continuous use of this drug decreases kidney function and can induce leukopenia.
OBJECTIVE
The purpose of this study was to measure the appropriate dose of valganciclovir required to prevent CMV infection.
METHODS
A systematic review and meta-analysis were performed by using a random effects model. The Cochrane Central Register, MEDLINE, EMBASE, and PubMed databases were searched up to April 15, 2017. We conducted analysis on low-dose (450 mg) and standard-dose (900 mg) valganciclovir groups.
RESULTS
After completion of the research, the analysis revealed that the glomerular filtration rate, graft loss, tacrolimus level, antibody-mediated rejection, and fungal and Candida infection rates did not differ between the 2 groups. However, the incidence of CMV tended to decrease in the low-dose group (0.584 [95% confidence interval [CI], 0.352-0.967]; P = .036). The biopsy-proven rejection rate decreased by 0.427 times in the low-dose group compared with the standard-dose group (95% CI, 0.274-0.667; P = .002). Furthermore, the incidence of leukopenia decreased by 0.371 times in the low-dose group compared with the standard-dose group (95% CI, 0.264-0.523; P = .001).
CONCLUSIONS
The 450-mg dose of valganciclovir effectively prevented post-transplantation CMV infection and decreased drug-induced side effects such as leukopenia. In the future, the lower dose of valganciclovir should be considered to prevent CMV infection and enhance cost-effectiveness.
Topics: Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Female; Humans; Incidence; Kidney Transplantation; Male; Middle Aged; Valganciclovir
PubMed: 29871773
DOI: 10.1016/j.transproceed.2018.01.023