Resistant Cytomegalovirus Infection After Renal Transplantation: Literature Review

Cintra-Cabrera, M.; Suárez-Benjumea, Alejandro; Bernal-Blanco, G.; González-Roncero, F.M.; Toapanta, Néstor; Suñer-Poblet, M.; Pérez-Valdivia, M.Á.; Fernández-Cuenca, Felipe; Gentil-Govantes, M.A.; Rocha, José Luis

doi:10.1016/j.transproceed.2017.09.058

Cited by 9 publications

(9 citation statements)

References 4 publications

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“…Viral resistance to ganciclovir poses a major issue clinically, as patients who later develop CMV disease due to resistant CMV have poorer clinical outcomes [21, 22]. Additionally, the treatment of CMV infections in these patients is problematic [19, 21, 23]. Presently, recommended alternative therapies include foscarnet and a reduction in immunosuppression, although no controlled trials have definitively confirmed this [3, 19].…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Failure of Primary (Val)ganciclovir Prophylaxis Against Cytomegalovirus Infection and Disease in Solid Organ Transplant Recipients

Khurana

Lodding

Mocroft³

et al. 2019

Open Forum Infectious Diseases

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Background Rates and risk factors for cytomegalovirus (CMV) prophylaxis breakthrough and discontinuation were investigated, given uncertainty regarding optimal dosing for CMV primary (val)ganciclovir prophylaxis after solid organ transplantation (SOT). Methods Recipients transplanted from 2012 to 2016 and initiated on primary prophylaxis were followed until 90 days post-transplantation. A (val)ganciclovir prophylaxis score for each patient per day was calculated during the follow-up time (FUT; score of 100 corresponding to manufacturers’ recommended dose for a given estimated glomerular filtration rate [eGFR]). Cox models were used to estimate hazard ratios (HRs), adjusted for relevant risk factors. Results Of 585 SOTs (311 kidney, 117 liver, 106 lung, 51 heart) included, 38/585 (6.5%) experienced prophylaxis breakthrough and 35/585 (6.0%) discontinued prophylaxis for other reasons. CMV IgG donor+/receipient- mismatch (adjusted HR [aHR], 5.37; 95% confidence interval [CI], 2.63 to 10.98; P < 0.001) and increasing % FUT with a prophylaxis score <90 (aHR, 1.16; 95% CI, 1.04 to 1.29; P = .01 per 10% longer FUT w/ score <90) were associated with an increased risk of breakthrough. Lung recipients were at a significantly increased risk of premature prophylaxis discontinuation (aHR, 20.2 vs kidney; 95% CI, 3.34 to 121.9; P = .001), mainly due to liver or myelotoxicity. Conclusions Recipients of eGFR-adjusted prophylaxis doses below those recommended by manufacturers were at an increased risk of prophylaxis breakthrough, emphasizing the importance of accurate dose adjustment according to the latest eGFR and the need for novel, less toxic agents.

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Section: Discussionmentioning

confidence: 99%

Risk Factors for Failure of Primary (Val)ganciclovir Prophylaxis Against Cytomegalovirus Infection and Disease in Solid Organ Transplant Recipients

Khurana

Lodding

Mocroft³

et al. 2019

Open Forum Infectious Diseases

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“…Our data also set a basis to design a pharmacokinetic model in a higher group of patients with different serum drug determinations per patient needed to obtain more accurately the AUC and other PK/PD parameters for GCV exposure [41]. Further studies must be performed to confirm these results and to conclusively establish if VGCV/GCV TDM could be useful to improve outcomes and minimize drug-related toxicity and the emergence of CMV resistance in specific populations, like renal transplant and HSCT recipients [17,42].…”

Section: Discussionmentioning

confidence: 98%

Valganciclovir—Ganciclovir Use and Systematic Therapeutic Drug Monitoring. An Invitation to Antiviral Stewardship

et al. 2021

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Valganciclovir (VGCV) and ganciclovir (GCV) doses must be adjusted according to indication, renal function and weight. No specific therapeutic exposure values have been established. We aimed to evaluate the adequacy of VGCV/GCV doses, to assess the interpatient variability in GCV serum levels, to identify predictive factors for this variability and to assess the clinical impact. This is a prospective study at a tertiary institution including hospitalized patients receiving VGCV/GCV prophylaxis or treatment. Adequacy of the antiviral dose was defined according to cytomegalovirus guidelines. Serum levels were determined using High-Performance Liquid Chromatography. Blood samples were drawn at least 3 days after antiviral initiation. Outcome was considered favorable if there was no evidence of cytomegalovirus infection during prophylaxis or when a clinical and microbiological resolution was attained within 21 days of treatment and no need for drug discontinuation due to toxicity. Seventy consecutive patients [74.3% male/median age: 59.2 years] were included. VGCV was used in 25 patients (35.7%) and GCV in 45 (64.3%). VGCV/GCV initial dosage was deemed adequate in 47/70 cases (67.1%), lower than recommended in 7/70 (10%) and higher in 16/70 (22.9%). Large inter-individual variability of serum levels was observed, with median trough levels of 2.3 mg/L and median peak levels of 7.8 mg/L. Inadequate dosing of VGCV/GCV and peak levels lower than 8.37 or greater than 11.86 mg/L were related to poor outcome. Further studies must be performed to confirm these results and to conclusively establish if VGCV/GCV therapeutic drug monitoring could be useful to improve outcomes in specific clinical situations.

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“…Drug-resistant or refractory CMV disease occasionally responds to an increased dose of ganciclovir. In cases of genotypic resistance of CMV to ganciclovir, it is necessary to introduce combined treatment with ganciclovir and foscarnet (half or standard doses) or treat with foscarnet only [44].…”

Section: Treatment Of CMV Diseasementioning

confidence: 99%

Viral Infections after Kidney Transplantation: CMV and BK

Večerić-Haler¹,

Kojc²

2019

Perioperative Care for Organ Transplant Recipient

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Opportunistic infections commonly occur during the first 6 months after kidney transplant, including cytomegalovirus (CMV) and polyomaviruses. Viral pathogens such as CMV and polyomaviruses, JC or BK virus (BKV), are able to replicate in the kidney and/or cause systemic disease, and symptomatic infection with these agents can be associated with significant morbidity and mortality in immunocompromised host. While BK virus usually replicates in kidney transplant causing BK virus nephropathy (BKN) with characteristic decoy cells in the urine, CMV infection more often leads to systemic infection involving the gastrointestinal tract (GIT), lungs, or liver and can only sporadically be detected in renal transplant. In both cases, the disease is most often due to reactivation of a latent virus. Prevention and early treatment of posttransplant infection are therefore crucial with kidney transplant recipients. Since BKV viruria and viremia can be seen without renal injury and viral nephropathy, a diagnosis of BKN must be confirmed by renal biopsy. To date, preemptive treatment is the best strategy for CMV infection, while no available standard therapy, except for reduction of immunosuppression, is available for BKV infection.

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Resistant Cytomegalovirus Infection After Renal Transplantation: Literature Review

Cited by 9 publications

References 4 publications

Risk Factors for Failure of Primary (Val)ganciclovir Prophylaxis Against Cytomegalovirus Infection and Disease in Solid Organ Transplant Recipients

Risk Factors for Failure of Primary (Val)ganciclovir Prophylaxis Against Cytomegalovirus Infection and Disease in Solid Organ Transplant Recipients

Valganciclovir—Ganciclovir Use and Systematic Therapeutic Drug Monitoring. An Invitation to Antiviral Stewardship

Viral Infections after Kidney Transplantation: CMV and BK

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