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Le Infezioni in Medicina 2023cytomegalovirus (CMV) retinitis, cerebral and ocular toxoplasmosis are common infections in patients with acquired immunodeficiency syndrome (AIDS). Material and...
BACKGROUND
cytomegalovirus (CMV) retinitis, cerebral and ocular toxoplasmosis are common infections in patients with acquired immunodeficiency syndrome (AIDS). Material and methods: this is a case of a 46-year-old female with previous Kaposi's sarcoma, diagnosed with an HIV infection two weeks prior to hospitalization. Blood test at diagnosis showed a CD4+ count of 77 cell/μL and HIV-RNA 3.758.745 copies/mL. Therapy with bictegravir/emtricitabine/tenofovir alafenamide fumarate was started and clinical, viroimmunological and microbiological investigations were performed.
RESULTS
the patient went to our hospital for the onset of left occipito-parietal headache and blurred vision. Brain CT and MRI were performed which did not show focal lesions or vascular alterations. Syphilis serology was negative, serology showed positive IgG and negative IgM, serum CMV-DNA was 31.184 IU/mL. Eye fundus evidenced intraretinal hemorrhages, fluorescein angiography and computed optical tomography documented cottony exudates, retinal hemorrhages and vitreous involvement. Therapy with valganciclovir was initiated for suspicion of CMV retinitis. About a month later, the patient reported blurred vision for which she was re-admitted. Ocular fundus showed a cottony lesion near the macula. Molecular test on vitreous body was positive for , while on cerebrospinal fluid it was negative; in addition, an MRI of the brain with contrast medium was performed which showed an area of altered hyperintense signal compatible with a diagnosis of uveitis and neurotoxoplasmosis. Therapy with pyrimethamine and clindamycin (allergy for sulfonamide reported by the patient) was started. Allergy counseling was performed with the execution of allergy tests (patch test) with negative result; therefore the administration of clindamycin was replaced with sulfadiazine. A month following the start of anti-toxoplasma therapy, there was a clinical and radiological improvement.
CONCLUSIONS
despite progressive developments in the management of PLWH, in this case two different kind of opportunistic infection are found in a late-presenter patient. In particular, two aspects can be highlighted. The first one is that, in the setting of an highly impaired immune system, clinical presentation can be deceptive and more than one opportunistic infection can be observed together in the same patient. The second aspect is that after starting antiretroviral therapy, a rapid improvement of viro-immunologic parameters has been documented, probably leading to an immune reconstitution inflammatory syndrome (IRIS).
PubMed: 37701378
DOI: 10.53854/liim-3103-15 -
Retinal Cases & Brief Reports Mar 2024To determine whether maribavir is effective at treating ganciclovir-resistant cytomegalovirus retinitis.
PURPOSE
To determine whether maribavir is effective at treating ganciclovir-resistant cytomegalovirus retinitis.
METHODS
Retrospective case report of a lung-transplant patient with bilateral cytomegalovirus retinitis documented with serum and aqueous humor studies and color fundus photographs.
RESULTS
A 72-year-old lung-transplant patient with active ganciclovir-resistant cytomegalovirus was treated with intravitreal foscarnet therapy in one eye. Retinitis developed in the contralateral eye and was managed with systemic maribavir alone. Active retinitis regressed in both the eye treated with intravitreal foscarnet and the uninjected eye.
CONCLUSION
This patient's results suggest that systemic maribavir is an effective treatment for treatment-resistant cytomegalovirus retinitis.
Topics: Humans; Aged; Cytomegalovirus Retinitis; Valganciclovir; Foscarnet; Retrospective Studies; Ganciclovir; Antiviral Agents; Dichlororibofuranosylbenzimidazole
PubMed: 36730596
DOI: 10.1097/ICB.0000000000001372 -
Eye (London, England) Jan 2024To present current practice patterns in the diagnosis and management of Cytomegalovirus anterior uveitis (CMV AU) by uveitis experts worldwide.
AIMS
To present current practice patterns in the diagnosis and management of Cytomegalovirus anterior uveitis (CMV AU) by uveitis experts worldwide.
METHODS
A two-round modified Delphi survey with masking of the study team was performed. Based on experience and expertise, 100 international uveitis specialists from 21 countries were invited to participate in the survey. Variation in the diagnostic approaches and preferred management of CMV AU was captured using an online survey platform.
RESULTS
Seventy-five experts completed both surveys. Fifty-five of the 75 experts (73.3%) would always perform diagnostic aqueous tap in suspected CMV AU cases. Consensus was achieved for starting topical antiviral treatment (85% of experts). About half of the experts (48%) would only commence systemic antiviral treatment for severe, prolonged, or atypical presentation. The preferred specific route was ganciclovir gel 0.15% for topical treatment (selected by 70% of experts) and oral valganciclovir for systemic treatment (78% of experts). The majority of experts (77%) would commence treatment with topical corticosteroid four times daily for one to two weeks along with antiviral coverage, with subsequent adjustment depending on the clinical response. Prednisolone acetate 1% was the drug of choice (opted by 70% of experts). Long-term maintenance treatment (up to 12 months) can be considered for chronic course of inflammation (88% of experts) and those with at least 2 episodes of CMV AU within a year (75-88% of experts).
CONCLUSIONS
Preferred management practices for CMV AU vary widely. Further research is necessary to refine diagnosis and management and provide higher-level evidence.
Topics: Humans; Cytomegalovirus; Cytomegalovirus Infections; Aqueous Humor; Ganciclovir; Antiviral Agents; Uveitis, Anterior
PubMed: 37419958
DOI: 10.1038/s41433-023-02631-8 -
Retinal Cases & Brief Reports Jul 2024To report a case of unilateral cytomegalovirus (CMV) panuveitis with occlusive vasculitis after injection of intravitreal dexamethasone implant in a patient with type 2... (Observational Study)
Observational Study
PURPOSE
To report a case of unilateral cytomegalovirus (CMV) panuveitis with occlusive vasculitis after injection of intravitreal dexamethasone implant in a patient with type 2 diabetes mellitus.
METHODS
Observational case report.
RESULTS
A 60-year-old immunocompetent man with well-controlled type 2 diabetes mellitus was treated with intravitreal dexamethasone implant for recurrent uveitis that was responsive to steroids. Three months after implantation, the patient develops panuveitis with occlusive vasculitis. Anterior chamber tap confirms diagnosis of cytomegalovirus retinitis. Intravitreal foscarnet and oral valganciclovir led to quiescent disease.
CONCLUSIONS
Patients treated with local immunosuppressants should be monitored carefully to assess treatment response and complications, even in the absence of frank immunodeficiency. Quantitative viral PCR can be an effective way to monitor treatment response to antiviral therapy.
Topics: Humans; Male; Dexamethasone; Middle Aged; Panuveitis; Drug Implants; Intravitreal Injections; Glucocorticoids; Cytomegalovirus Retinitis; Eye Infections, Viral; Cytomegalovirus Infections; Diabetes Mellitus, Type 2
PubMed: 36735929
DOI: 10.1097/ICB.0000000000001407 -
Transplantation and Cellular Therapy Aug 2023Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Limited data are available from...
Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Limited data are available from developing countries regarding the frequency of CMV infection and treatment outcomes. We enrolled 230 consecutive patients undergoing allogeneic HSCT for various hematologic disorders at the Armed Forces Bone Marrow Transplant Center/National Institute of Blood And Marrow Transplant between February 2017 and December 202. CMV reactivation post-HSCT was monitored weekly starting at day +30 and continuing until day +100, and preemptive antiviral therapy was administered to prevent CMV disease in all HSCT recipients with ≥2000 CMV copies/mL. The median age of the study cohort was 9.5 years (range, .6 to 53 years), and the male:female ratio was 2.4:1. The most frequent indication for HSCT was beta thalassemia major (36.1%), followed by aplastic anemia (23.9%). Malignant disorders constituted 20% of all the patients. Pretransplantation CMV seropositivity was 99.1% for the recipients and 99.5% for the donors. CMV infection was seen in 66.1% of the patients, and the median time to CMV DNAemia was 36 days (range, 12 to 95 days). Preemptive antiviral therapy was administered to 140 patients with a CMV viral load ≥2000 copies/mL (61%). In multivariate analysis, patient age >12 years, steroid administration, and use of mycophenolate mofetil with or without post-transplantation cyclophosphamide was associated with the greatest probability of CMV reactivation. Overall survival was 97.4% in patients without CMV reactivation, compared to 80.3% in those with CMV reactivation (P = .001). Event-free survival was 78.7% in the total study cohort, including 89.7% for patients without CMV reactivation and 73% for patients with CMV reactivation (P = .003). Our study is the first from this region to explore the frequency of CMV seropositivity and CMV infection, risk factors for CMV reactivation, and outcomes of antiviral therapy in HSCT recipients.
Topics: Adolescent; Adult; Child; Female; Humans; Male; Middle Aged; Young Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Hematopoietic Stem Cell Transplantation; Transplantation, Homologous; Infant; Child, Preschool
PubMed: 37164292
DOI: 10.1016/j.jtct.2023.04.023 -
International Journal of Molecular... Jul 2023Female and male glial fibrillary acidic protein-thymidine kinase (GFAP-TK) transgenic rats were made ethanol dependent via a six-week chronic intermittent ethanol vapor...
Female and male glial fibrillary acidic protein-thymidine kinase (GFAP-TK) transgenic rats were made ethanol dependent via a six-week chronic intermittent ethanol vapor (CIE) and ethanol drinking (ED) procedure. During the last week of CIE, a subset of male and female TK rats was fed valcyte to ablate dividing progenitor cells and continued the diet until the end of this study. Following week six, all CIE rats experienced two weeks of forced abstinence from CIE-ED, after which they experienced relapse to drinking, extinction, and reinstatement of ethanol seeking sessions. CIE increased ED in female and male rats, with females having higher ethanol consumption during CIE and relapse sessions compared with males. In both sexes, valcyte reduced the levels of Ki-67-labeled progenitor cells in the subgranular zone of the dentate gyrus and did not alter the levels in the medial prefrontal cortex (mPFC). Valcyte increased ED during relapse, increased lever responses during extinction and, interestingly, enhanced latency to extinguish ethanol-seeking behaviors in males. Valcyte reduced the reinstatement of ethanol-seeking behaviors triggered by ethanol cues in females and males. Reduced seeking by valcyte was associated with the normalization of cytokines and chemokines in plasma isolated from trunk blood, indicating a role for progenitor cells in peripheral inflammatory responses. Reduced seeking by valcyte was associated with increases in tight junction protein claudin-5 and oligodendrogenesis in the dentate gyrus and reduction in microglial activity in the dentate gyrus and mPFC in females and males, demonstrating a role for progenitor cells in the dentate gyrus in dependence-induced endothelial and microglial dysfunction. These data suggest that progenitor cells born during withdrawal and abstinence from CIE in the dentate gyrus are aberrant and could play a role in strengthening ethanol memories triggered by ethanol cues via central and peripheral immune responses.
Topics: Alcoholism; Stem Cells; Male; Female; Animals; Rats; Ethanol; Drug-Seeking Behavior; Behavior, Animal; Aging; Valganciclovir; Sex Characteristics; Humans; Rats, Transgenic
PubMed: 37569609
DOI: 10.3390/ijms241512233 -
The Journal of Surgical Research Jul 2024Cytomegalovirus (CMV) infection is associated with a poor prognosis after lung transplantation, and donor and recipient CMV serostatus is a risk factor for reactivation....
INTRODUCTION
Cytomegalovirus (CMV) infection is associated with a poor prognosis after lung transplantation, and donor and recipient CMV serostatus is a risk factor for reactivation. CMV prophylaxis is commonly administered in the first year following transplantation to reduce CMV infection; however, the risk factors for long-term reactivation remain unclear. We investigated the timing and risk factors of CMV infection after prophylactic administration.
METHODS
This study was a retrospective review of the institutional lung transplantation database from June 2014 to June 2022. Data on patient characteristics, pretransplantation laboratory values, postoperative outcomes, and CMV infection were collected. Donor CMV-IgG-positive and recipient CMV-IgG-negative groups were defined as the CMV mismatch group.
RESULTS
During the study period, 257 patients underwent lung transplantation and received a prophylactic dose of valganciclovir hydrochloride for up to 1 y. CMV infection was detected in 69 patients (26.8%): 40 of 203 (19.7%) in the non-CMV mismatch group and 29 of 54 (53.7%) in the CMV mismatch group (P < 0.001). CMV infection after prophylaxis occurred at a median of 425 and 455 d in the CMV mismatch and non-CMV mismatch groups, respectively (P = 0.07). Multivariate logistic regression analysis revealed that preoperative albumin level (odds ratio [OR] = 0.39, P = 0.04), CMV mismatch (OR = 15.7, P < 0.001), and donor age (OR = 1.05, P = 0.009) were significantly associated with CMV infection.
CONCLUSIONS
CMV mismatch may have increased the risk of CMV infection after lung transplantation, which decreased after prophylaxis. In addition to CMV mismatch, low preoperative albumin level and donor age were independent predictors of CMV infection.
Topics: Humans; Cytomegalovirus Infections; Male; Female; Retrospective Studies; Middle Aged; Lung Transplantation; Adult; Risk Factors; Antiviral Agents; Recurrence; Valganciclovir; Aged; Cytomegalovirus; Postoperative Complications
PubMed: 38754251
DOI: 10.1016/j.jss.2024.04.012 -
Transplant Infectious Disease : An... Apr 2024The antiviral letermovir has been increasingly used as off-label cytomegalovirus prophylaxis in solid organ transplant recipients. Observational studies have reported...
BACKGROUND
The antiviral letermovir has been increasingly used as off-label cytomegalovirus prophylaxis in solid organ transplant recipients. Observational studies have reported notable increases in tacrolimus (FK) exposure following letermovir; however, whether a significant interaction occurs in the setting of existing moderate-to-strong CYP3A4 inhibition is unknown. Therefore, the purpose of this study was to evaluate FK trough changes before and after letermovir among lung transplant recipients receiving azole antifungal prophylaxis.
METHODS
This retrospective cohort study included lung transplant recipients newly initiated on letermovir between 2019-2022 following valganciclovir intolerance. Tacrolimus doses and concentrations were collected up to 30 days before and after the letermovir start date. No pre-emptive FK dose adjustments occurred prior to letermovir initiation. Patients admitted to the hospital or lacking an appropriately timed trough in the pre- or post-period were excluded.
RESULTS
A total of 78 lung transplant recipients receiving FK (1.5 mg median total daily dose) and itraconazole (56.4%), isavuconazole (25.6%) or posaconazole (17.9%) prophylaxis were included. Letermovir was started at a median of 8.4 months post-transplant. The pre-/post-letermovir median FK trough was 9.6/9.0 ng/mL (p = .151), median dose-corrected trough was 4.2/4.7 ng/mL/mg (+11.9%, p = .032), and median weight-based dose-corrected trough was 362/326 [ng/mL]/[mg/kg/day] (-9.9%, p = .036). There was no significant difference in the proportion of patients within their goal trough range before and after letermovir initiation (62% vs. 72%, p = .229).
CONCLUSION
Empiric FK dose adjustments do not appear warranted before letermovir initiation in lung transplant recipients receiving antifungal prophylaxis with moderate-to-strong CYP3A4 inhibitors.
Topics: Humans; Antifungal Agents; Tacrolimus; Azoles; Transplant Recipients; Retrospective Studies; Lung; Antiviral Agents; Acetates; Quinazolines
PubMed: 38488776
DOI: 10.1111/tid.14267 -
Journal of Pharmacy Practice Jun 2024Cytomegalovirus (CMV) infection after abdominal organ transplantation is associated with increased morbidity and mortality. The use of valganciclovir for CMV...
Cytomegalovirus (CMV) infection after abdominal organ transplantation is associated with increased morbidity and mortality. The use of valganciclovir for CMV prophylaxis is limited by drug-induced myelosuppression and potential emergence of resistance. Letermovir is approved for primary CMV prophylaxis in CMV seropositive allogeneic hematopoietic cell transplant recipients. However, it is increasingly used off-label for prophylaxis in solid organ transplant (SOT) recipients. Based on pharmacy records, we examined retrospectively the use of letermovir for CMV prophylaxis in abdominal transplant recipients initiated on therapy at our center from January 1, 2018 through October 15, 2020. Data were summarized using descriptive statistics. Twelve episodes of letermovir prophylaxis occurred in ten patients. Four patients received primary and 6 patients received secondary prophylaxis during the study period, with 1 patient receiving letermovir secondary prophylaxis on 3 separate occasions. All patients receiving letermovir for primary prophylaxis had successful outcomes. However, letermovir secondary prophylaxis was unsuccessful in 5 of the 8 episodes (62.5%) due to breakthrough CMV DNAemia and/or disease. Only 1 patient discontinued therapy due to adverse effects. Although letermovir was generally well tolerated, the high rate of failure when used as secondary prophylaxis was noteworthy. Additional controlled clinical trials assessing the safety and efficacy of letermovir prophylaxis in SOT recipients are warranted.
Topics: Humans; Cytomegalovirus Infections; Antiviral Agents; Male; Middle Aged; Female; Retrospective Studies; Quinazolines; Aged; Adult; Acetates; Organ Transplantation; Cytomegalovirus; Secondary Prevention
PubMed: 37280011
DOI: 10.1177/08971900231176430 -
Journal of the Formosan Medical... May 2024Kidney transplant recipients have an increased risk of cytomegalovirus (CMV) infection and disease. A strategy for mitigating the risk of CMV infection in kidney... (Review)
Review
Kidney transplant recipients have an increased risk of cytomegalovirus (CMV) infection and disease. A strategy for mitigating the risk of CMV infection in kidney transplant recipients has not yet been established in Taiwan. The Transplantation Society of Taiwan aimed to develop a consensus by expert opinion on the prevention and management of CMV infection. Based on the results of Consensus Conference, we suggested low-dose valganciclovir prophylaxis (450 mg once daily) for kidney transplant recipients. The prophylaxis duration was ≥6 months for high-risk (D+/R-) patients and 3 months for moderate-risk (R+) patients. Even for low-risk (D-/R-) patients, prophylaxis for at least 3 months is recommended because of the high seroprevalence of CMV in Taiwan. CMV prophylaxis was suggested after anti-thymocyte globulin treatment but not after methylprednisolone pulse therapy. Routine surveillance after prophylaxis, secondary prophylaxis after CMV disease treatment, and mTOR inhibitors for primary CMV prophylaxis were not recommended. Letermovir and marabavir are emerging CMV agents used for prophylaxis and refractory CMV disease. CMV immunoglobulins have been used to treat refractory CMV disease in Taiwan. We hope this consensus will help professionals manage patients with CMV in Taiwan to improve the quality of care.
PubMed: 38777672
DOI: 10.1016/j.jfma.2024.05.009