High-Dose Acyclovir for Cytomegalovirus Prophylaxis in Seropositive Abdominal Transplant Recipients

2017 ◽  
Vol 52 (1) ◽  
pp. 5-10 ◽  
Author(s):  
Margaret R. Jorgenson ◽  
Jillian L. Descourouez ◽  
Glen E. Leverson ◽  
Erin K. McCreary ◽  
Michael R. Lucey ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Invasive Disease ◽  
High Dose ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Composite Failure ◽  
Significant Difference ◽  
Low Incidence ◽  
Ganciclovir Resistance ◽  
Long Term Impact

Background: Following abdominal solid organ transplant (aSOT), valganciclovir (VGC) is recommended for cytomegalovirus (CMV) prophylaxis. This agent is associated with efficacy concerns, toxicity, and emergence of ganciclovir resistance. Objective: To evaluate the incidence of high-dose acyclovir (HD-A) prophylaxis failure in seropositive aSOT recipients (R+). Methods: This was a retrospective, single-center study of R+ transplanted without lymphocyte-depleting induction between January 1, 2000, and June 30, 2013, discharged with 3 months of HD-A prophylaxis (800 mg 4 times daily). The primary outcome was incidence of prophylaxis failure. Secondary outcomes were incidence of biopsy-proven tissue-invasive disease and prophylaxis failure for each allograft subgroup. Results: A total of 1525 patients met inclusion criteria: 944 renal (RTX), 108 simultaneous pancreas-kidneys (SPK), 462 liver (LTX), and 11 pancreas (PTX) transplant recipients. The composite rate of HD-A prophylaxis failure was 7%; incidence of tissue-invasive disease was 0.4%. Failure rates were 4.5%, 6.1%, 11%, and 20% in the RTX, SPK, LTX, and PTX populations, respectively; tissue-invasive disease rates were 0.2%, 0%, 0.7%, and 10%. Failure occurred more frequently in the LTX and PTX populations ( P < 0.0001, HR = 2.6; P = 0.04 HR = 4.4). Incidence of tissue-invasive disease was minimal and not different in the RTX, LTX and SPK populations ( P = 0.34). When evaluating recipients of seronegative allografts (D−), the composite failure rate was 3.4% with no significant difference between allograft subgroups ( P = 0.45). Conclusion: HD-A may be a reasonable prophylaxis alternative for D−/R+ recipients, in the absence of lymphocyte-depleting induction, if low incidence viremia is tolerable. Future studies are needed to determine the long-term impact of CMV viremia in the setting of this prophylaxis approach.

Impact of High-Dose Acyclovir Cytomegalovirus Prophylaxis Failure in Abdominal Solid Organ Transplant Recipients

2018 ◽  
Vol 38 (7) ◽  
pp. 694-700 ◽  
Author(s):  
Magdalena Siodlak ◽  
Margaret R. Jorgenson ◽  
Jillian L. Descourouez ◽  
Glen E. Leverson ◽  
Didier A. Mandelbrot ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Solid Organ Transplant ◽  
High Dose ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Organ Transplant Recipients ◽  
Solid Organ Transplant Recipients

Fosfomycin tromethamine for the Treatment of Cystitis in Abdominal Solid Organ Transplant Recipients With Renal Dysfunction

2017 ◽  
Vol 51 (9) ◽  
pp. 751-756 ◽  
Author(s):  
Luiza Kerstenetzky ◽  
Margaret R. Jorgenson ◽  
Jillian L. Descourouez ◽  
Glen Leverson ◽  
Warren E. Rose ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Dysfunction ◽  
Normal Renal Function ◽  
Treatment Success ◽  
Multivariable Analysis ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Significant Difference

Background: Urinary tract infection (UTI) after abdominal solid organ transplantation (SOT) is associated with significant morbidity and mortality. Fosfomycin tromethamine (FOS), a uroselective antibiotic, is FDA approved for uncomplicated UTIs in women and is used off-label for complicated UTIs and prostatitis in men. Literature supporting the use of FOS in the SOT population is limited, and efficacy is questioned in the setting of renal dysfunction. Objective: To evaluate the success of FOS for the treatment of cystitis in SOT patients with renal dysfunction. Methods: This was a single-center, retrospective study using medical records. SOT recipients receiving at least 1 dose of FOS for treatment of cystitis between January 1, 2009, and April 30, 2015, were included. Treatment outcomes were analyzed with respect to renal function. Results: A total of 76 courses of FOS were identified in 64 patients. The renal dysfunction arm (creatinine clearance [CrCl] < 40 mL/min) included 33 patients with 39 FOS courses; the normal renal function arm (CrCl ≥ 40 mL/min) included 31 patients with 37 FOS courses. Mean CrCl was 23.3 ± 9.7 mL/min for the renal-dysfunction group and 65 ± 29.3 mL/min for the normal renal function group ( P < 0.01). No significant difference in treatment success was noted between CrCl <40 mL/min and CrCl ≥40 mL/min (31 [80%] vs 34 [92%], P = 0.12) in a unilateral analysis. After adjusting for confounders in a multivariable analysis, there was no difference in the risk of failure between CrCl <40 mL/min and CrCl ≥40 mL/min groups ( P = 0.70). Conclusion: FOS appears to be successful for the treatment of cystitis in SOT recipients in the setting of renal dysfunction.

scholarly journals A Randomized Trial of High-dose Influenza Vaccine in Adult Solid-Organ Transplant Recipients

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S734-S734
Author(s):  
Yoichiro Natori ◽  
Atul Humar ◽  
Mika Shiotsuka ◽  
Jaclyn Slomovic ◽  
Katja Hoschler ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Geometric Mean ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Vaccine Group ◽  
High Dose ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Organ Transplant Recipients ◽  
Solid Organ Transplant Recipients

Abstract Background The annual influenza vaccine is recommended for solid-organ transplant recipients (SOTR) although studies have shown suboptimal immunogenicity. Influenza vaccine containing higher dose antigen may lead to greater immunogenicity in this population. Method We conducted a randomized, observer-blind trial comparing the safety and immunogenicity of high dose (HD; FluzoneHD, Sanofi) vs. standard dose (SD; Fluviral, GSK) influenza vaccine in adult SOTR. Patients were randomized 1:1 to receive the 2016–2017 influenza vaccine. Preimmunization and 4-week postimmunization sera underwent strain-specific hemagglutination inhibition assay for the three vaccine strains and an additional B strain not included in the vaccine. Result We randomized 172 patients and 161 (84 HD; 77 SD) were eligible for analysis. Median age was 57 years (range 18–86) and time from transplant was 38 (range 3–1402) months. Types of transplant were kidney 67 (39.0%), liver 38 (22.1%), lung 25 (14.5%), heart 23 (13.3%), and combined 19 (11.0%). Seroconversion to at least one of the three vaccine antigens (primary outcome) was present in 78.6% vs. 55.8% in HD vs. SD vaccine, respectively (P &lt; 0.001). Seroconversion to A/H1N1, A/H3N2, and B strains were 40.5% vs. 20.5%, 57.1% vs. 32.5%, and 58.3% vs. 41.6% in HD vs. SD vaccine (P = 0.006, 0.002, 0.028, respectively). Postimmunization geometric mean titers of A/H1N1, A/H3N2, and B strains were significantly higher in the HD group &#x2028;(P = 0.007, 0.002, 0.033). Independent factors associated with seroconversion to at least one vaccine strain were the use of HD vaccine and being on mycophenolate doses less than 2 g daily (P = 0.003, 0.013, respectively). Seroconversion rate to the B strain not included in the trivalent study vaccine was also higher in the HD vaccine group (33.3% vs. 14.1%, P = 0.004). Local and systemic adverse events were similar for the two vaccines. Biopsy-proven rejection was seen in 3.4% vs. 1.2% in HD vs. SD groups, respectively (P = 0.62). Two patients in the SD vaccine group and one in the HD group developed influenza infection during the follow-up. Conclusion High-dose vaccine demonstrated significantly better immunogenicity than SD vaccine in adult transplant recipients and may be the preferred influenza vaccine for this population. Disclosures D. Kumar, Sanofi: Speaker’s Bureau, Speaker honorarium. Pfizer: Speaker’s Bureau, Speaker honorarium. GSK: Grant Investigator, Grant recipient.

Use of High-Dose Ganciclovir for the Treatment of Cytomegalovirus Replication in Solid Organ Transplant Patients With Ganciclovir Resistance-Inducing Mutations

2013 ◽  
Vol 95 (8) ◽  
pp. 1015-1020 ◽  
Author(s):  
Irene Gracia-Ahufinger ◽  
Juan Gutiérrez-Aroca ◽  
Elisa Cordero ◽  
Elisa Vidal ◽  
Sara Cantisán ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Solid Organ Transplant ◽  
High Dose ◽  
Solid Organ ◽  
Transplant Patients ◽  
Ganciclovir Resistance

scholarly journals Evaluation of the therapeutic regimen in COVID-19 in transplant patients: where do immunomodulatory and antivirals stand?

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Mojtaba Shafiekhani ◽  
Farbod Shahabinezhad ◽  
Tahmoores Niknam ◽  
Seyed Ahmad Tara ◽  
Elham Haem ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Organ Transplant Recipients ◽  
Transplant Patients ◽  
Clinical Complications ◽  
Hospitalization Period ◽  
Significant Difference ◽  
Immunocompromised Status ◽  
Immunomodulatory Drug

Abstract Background The management of COVID-19 in organ transplant recipients is among the most imperative, yet less discussed, issues based on their immunocompromised status along with their vast post-transplant medication regimens. No conclusive study has been published to evaluate proper anti-viral and immunomodulator medications effect in treating COVID-19 patients to this date. Method This retrospective study was conducted in Shiraz Transplant Hospital, Iran from March 2020 to May 2021 and included COVID-19 diagnosed patients based on SARS-CoV-2 RT-PCR positive test who had been hospitalized for at least 48 h before enrolling in the study. Clinical and demographic information of patients, along with their treatment course and the medication used were evaluated and analyzed using multiple regression analysis. Results A total of 245 patients with a mean age of 49.59 years were included with a mortality rate of 8.16%. The administration of Remdesivir as an anti-viral drug (P value < 0.001) and Tocilizumab as an immunomodulator drug (P value < 0.001) could reduce the hospitalization period in the hospital and the intensive care unit, as well as the mortality rates significantly. Meanwhile, the patients treated with Lopinavir/Ritonavir experienced a lower chance of survival (OR < 1, P value = 0.04). No significant difference was observed between various therapeutic regimens in clinical complications such as bacterial coinfections, cardiovascular and gastrointestinal adverse reactions, and liver or kidney dysfunctions. Conclusion The administration of Remdesivir as an anti-viral and Tocilizumab as an immunomodulatory drug in solid-organ transplant recipients could be promising treatments of choice to manage COVID-19.

scholarly journals A Double-Blind, Randomized Trial of High-Dose vs Standard-Dose Influenza Vaccine in Adult Solid-Organ Transplant Recipients

2017 ◽  
Vol 66 (11) ◽  
pp. 1698-1704 ◽  
Author(s):  
Yoichiro Natori ◽  
Mika Shiotsuka ◽  
Jaclyn Slomovic ◽  
Katja Hoschler ◽  
Victor Ferreira ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Randomized Trial ◽  
Standard Dose ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
High Dose ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Double Blind ◽  
Solid Organ Transplant Recipients

scholarly journals Late-onset cytomegalovirus pneumonitis successfully treated by cytomegalovirus immunoglobulin in heart transplant patient with renal failure

2021 ◽  
Vol 9 ◽  
pp. 2050313X2198949
Author(s):  
Sandra Jaksic Jurinjak ◽  
Vanja Hulak ◽  
Mario Udovicic
Keyword(s):  
Renal Failure ◽  
Transplant Patient ◽  
Late Onset ◽  
Organ Transplant ◽  
Treatment Strategies ◽  
Invasive Disease ◽  
Young Female ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Solid Organ Transplant Recipients

Cytomegalovirus infection is one of the most serious pathogens affecting solid organ transplant recipients. Cytomegalovirus has been identified as a risk factor for graft rejection, cardiac allograft vasculopathy and is associated with increased morbidity and mortality. Viral clearance is not achieved in all patients despite standard antiviral therapy; therefore, there is great interest in prevention and treatment strategies, as use of specific cytomegalovirus immunoglobulin, to avoid progression to organ involvement. Dose regimen of specific cytomegalovirus immunoglobulin is not well studied, especially in cytomegalovirus disease. We present the case of late onset of tissue invasive disease, pneumonitis, in young female patient after heart transplantation with acute renal failure, successfully treated with frequent intermittent cytomegalovirus immunoglobulin followed by renal dosed ganciclovir.

#76: Epidemiology of Cytomegalovirus (CMV) in Pediatric Solid-Organ Transplant Recipients (SOTR) at Texas Children’s Hospital (TCH)

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S3-S4
Author(s):  
K Valencia Deray ◽  
K Hosek ◽  
E Moulton ◽  
F Munoz ◽  
G Demmler-Harrison ◽  
...  
Keyword(s):  
High Risk ◽  
Organ Transplant ◽  
Invasive Disease ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Kidney Recipients ◽  
Cmv Disease ◽  
Cmv Dnaemia ◽  
Cmv Status

Abstract Background Despite the widespread use of prevention strategies, CMV remains a common opportunistic infection in SOTR. Contemporary data regarding CMV in pediatric SOTR are limited. We sought to determine the frequency of and risk factors for CMV infection and disease in a large single-center cohort of pediatric SOTR. Methods A retrospective cohort study of patients &lt;22 years of age who received lung, heart, liver, kidney, or multi-organ transplants at TCH between 2010 and 2018 was completed. Universal CMV prophylaxis was used based on risk status (Figure 1). The primary outcome was quantifiable CMV DNAemia. Associations with CMV DNAemia were measured using Fisher exact, Kruskal–Wallis, and multivariate logistic regression. Survival analysis and time to CMV infection were assessed using Kaplan–Meier plots. Results Among 788 SOTR, 132 (17%) had quantifiable CMV DNAemia; this included 20/105 (19%) lung, 69/290 (24%) liver, 28/178 (16%) heart, 2/15 (13%) multi-organ, and 13/200 (7%) kidney recipients. Fifty-one (6%) SOTR had CMV DNAemia while on antiviral prophylaxis. Post-prophylaxis, 69 (9%) SOTR had CMV reactivation and 12 (2%) had primary infection. The median time to quantifiable DNAemia for patients that developed CMV was 290 days post-transplant for lung, 162 for liver, 186 for heart, and 294 for kidney (P &lt; 0.01), reflecting differences in prophylaxis strategies. High-risk CMV status (D+/R– for heart, liver, kidney, and D+ and/or R+ for lung) was associated with CMV DNAemia (P &lt; 0.01). Type of organ transplanted also showed an association with CMV DNAemia (P = 0.02) with liver transplant recipients more being more likely to have a positive CMV PCR. DNAemia was not associated with age at transplantation, type of organ, or the use of induction immunosuppression. There was no difference in survival during the study follow-up period (1–9 yr) for SOTR with vs. without DNAemia (P = 0.48). Overall, 22/788 (3%) SOTR had CMV disease, 3 (3%) lung, 4 (2%) heart, 8 (3%) liver, 1 (6%) multi-organ, and 6 (3%) kidney recipients. Twenty had CMV syndrome and 2 had tissue invasive disease. Median (range) maximum viral loads were 27700 IU/mL (233-3912694) for SOTR with vs. 900 IU/mL (26-112000) for SOTR without CMV disease (P &lt; 0.01). Conclusion This large contemporary cohort of pediatric SOTR on universal prophylaxis demonstrates low overall rates of CMV DNAemia and CMV disease. High-risk CMV status remains associated with CMV DNAemia, suggesting that further interventions targeting this group may be warranted.

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