scholarly journals 1233. Serious Toxicities During Antimicrobial Therapy for Disseminated Nocardia Infection in Solid Organ Transplant Recipients

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S706-S706
Author(s):  
Christopher Saling ◽  
Sabirah N Kasule ◽  
Holenarasipur R Vikram
Keyword(s):  
Adverse Events ◽  
Antimicrobial Therapy ◽  
Transplant Patient ◽  
Brain Mri ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Perinephric Abscess ◽  
First Case

Abstract Background Management of disseminated Nocardia (NC) infection in transplant recipients requires prolonged antimicrobial therapy. Treatment can be particularly challenging if NC is resistant to standard agents. Drug toxicities can further limit options. We present a series of transplant patients with multi-drug resistant, disseminated NC infection complicated by serious adverse reactions to sequential antimicrobials. Methods This is a prospective review monitoring response to treatment of disseminated NC as well as adverse events to therapies. Results The first case is a 66-year old heart transplant patient who presented with fever and cough. Investigations revealed N. otitidiscaviarum lung lesion and multiple brain abscesses. Trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid were started empirically. NC was fully susceptible to linezolid only, and intermediate to quinolones and tobramycin. Linezolid was switched to ciprofloxacin due to ongoing cytopenia, and dose of TMP-SMX was reduced due to renal insufficiency. Repeat brain MRI showed enlarging abscesses; regimen was changed to linezolid and moxifloxacin. Severe peripheral neuropathy led to linezolid discontinuation and initiation of high-dose doxycycline plus moxifloxacin. One year into therapy, he presented with a large aortic dissection. His long-term quinolone therapy was felt to be contributory. He underwent aortic stent placement and remains on doxycycline monotherapy. The second case is a 74-year old female renal transplant patient who presented with fevers. A perinephric abscess was found which grew N. farcinica resistant to floroquinolones and clarithromycin, and intermediate to doxycycline. Further imaging also revealed pulmonary and brain involvement. TMP-SMX was started but soon switched to linezolid due to acute kidney injury. One month later she presented with severe thrombocytopenia and subdural hematoma thought to be secondary to linezolid. She died despite surgery. Conclusion This series illustrates challenges encountered in the treatment of disseminated NC infection in transplant recipients. Multidrug resistant NC coupled with serious toxicities of therapies often severely limits treatment options. Counseling patients and closely monitoring for adverse events is essential. Disclosures All Authors: No reported disclosures

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

First Case of Platelet-Type Von Willebrand Disease (PT-VWD) Associated with Type 2B Von Willebrand Disease (2B VWD)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5313-5313
Author(s):  
Marie Dreyfus ◽  
Celine Desconclois ◽  
Corinne Guitton ◽  
Marie-Jeanne Baas ◽  
Helene Mandard ◽  
...  
Keyword(s):  
Platelet Count ◽  
Von Willebrand Disease ◽  
Biological Study ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
First Case ◽  
Platelet Receptor ◽  
Biological Phenotype ◽  
Neonatal Thrombocytopenia ◽  
Von Willebrand

Abstract Abstract 5313 Introduction VWD 2B and PT-VWD are rare diseases, due to mutations inducing a gain of function respectively of von Willebrand factor (VWF) and of its platelet receptor, Glycoprotein (GP)1bα Case history We report here the case of a young girl, born with an extensive purpura and a severe thrombocytopenia: platelet count: 16G/L. There was no associated biological nor clinical abnormality. A high dose of 1g/kg of immunoglobulin G infused on day 1 was unsuccessful, and a HPA-1a (−) platelet concentrate infusion led to a partial and transient increase of the platelet count up to 60G/L. Thrombocytopenia then resolved spontaneously. Biological study showed no sign of materno-fetal allo- or auto-immunity, parents were not consanguineous. The diagnosis of type 2B VWD was performed when she was 5 months old: VWF:RCo < 13 IU/dl, VWF:Ag 60 IU/dl, positive ristocetin induced platelet aggregation (RIPA) at a low ristocetin concentration (0.5 mg/ml). RIPA mixing studies were unconclusive. The same biological abnormalities were found in the father, whereas the mother had normal hemostasis tests. The biological phenotype also included a study of the multimeric VWF structure, showing a marked decrease in percentage of VWF high and intermediate molecular multimers. Genetic analysis performed on VWF gene showed the heterozygous p.Pro1266Leu missense mutation in the VWF A1 domain. This mutation ( o ) is only slightly deleterious, and induces usually a mild disease, without thrombocytopenia, even in stress situations, with normal VWF multimeric distribution; therefore, it could not explain the biological phenotype severity in this family. GPIBA was then analysed, and a candidate point mutation p.Met239Ile was evidenced. This mutation had not been described yet, but p.Met255Val had already been found in diagnosed cases of PT-VWD. Conclusion This case underlines the utmost importance to characterize precisely neonatal thrombocytopenia mechanism. Furthermore, it points out the difficulties to performing PT-VWD diagnosis, which incidence is most probably underestimated. In our case, it was the systematic and extensive biological workout performed in this case of isolated neonatal thrombocytopenia, without any obvious cause, which led to the diagnosis of a PT-VWD, inducing a severe biological phenotype, associated with type 2B VWD characterized by a mild expression. It is, to our knowledge, the first case described to date of such a morbid association. Disclosures: No relevant conflicts of interest to declare.

Impact of Pharmacogenetic Determinants of Tacrolimus and Mycophenolate on Adverse Events in Renal Transplant Patients

2021 ◽  
Vol 22 ◽  
Author(s):  
Kalluri Thishya ◽  
Boddupally Sreenu ◽  
Shree Bhushan Raju ◽  
Vijay Kutala
Keyword(s):  
Renal Transplant ◽  
Adverse Events ◽  
Metabolic Pathways ◽  
Early Stage ◽  
Maintenance Phase ◽  
Solid Organ ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Post Transplantation ◽  
Increased Risk

Background: Graft acceptance against immunity is one of themajor challenges in solid organ transplant. Immunosuppressive medications have effectively improved the post-transplantation outcome; however it has its own limitations. Genetic polymorphisms in drug-metabolizing enzymes have been identified as the potential targets in developing a pharmacogenetic strategy, to individualize drug dose and also in preventing the adverse events. Objective: The rationale of the study was to explore polymorphisms in tacrolimus and mycophenolate metabolic pathways that influence the adverse clinical outcomes in renal transplant recipients. Methods: A total of 255 renal transplant recipients were analyzed for the pharmacogenetic determinants of tacrolimus (CYP3A5*3, ABCB1 1236 T>C, ABCB1 2677 G>A/T, ABCB1 3435 T>C) and mycophenolate (UGT1A8*3, UGT1A9, IMPDH I, IMPDH II c.787C>T , ABCC2 -24 C>T and c.3972C>T) using Sanger sequencing. Results: Acute rejection (AR) was observed in 5.88% of the transplant recipients, whereas, acute tubular necrosis (ATNs) was observed in 7.45% of the patients, within early stage of the maintenance phase. Infections, such as urinary tract infection (UTI) and cytomegalovirus (CMV) infection were observed in 11.37% and 12.16% of the patients. The AUC of mycophenolate was significantly higher in patients with increased risk for infections. ABCC2 -24 C>T, c.3972C>T polymorphisms and ABCB1 3435 C-allele, were associated with reduced risk for infections. ABCC2 rs3740066 was associated with 2.06-fold all-cause mortality risk. CYP3A5 AG- and UGT1A9-440 CC-genotypes showed increased risk, and ABCC 3972C>T, CC-genotype showed protection against adverse events. Conclusion: Genetic variants in tacrolimus and mycophenolate metabolic pathways were found to influence the morbidity and mortality in renal transplant recipients.

A second administration of glucarpidase in a different cycle of high-dose methotrexate: Is it safe and effective in adults?

2020 ◽  
pp. 107815522094646 ◽  
Author(s):  
Amalia Domingo-González ◽  
Santiago Osorio ◽  
Elena Landete ◽  
Silvia Monsalvo ◽  
Jose L. Díez-Martín
Keyword(s):  
Renal Function ◽  
Case Report ◽  
Adverse Events ◽  
Kidney Injury ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
First Case ◽  
Methotrexate Concentration ◽  
Unknown Area

Introduction Methotrexate intoxication following high-dose methotrexate-induced acute kidney injury is a life-threatening complication. Glucarpidase can quickly reduce extracellular methotrexate to safe levels, but the effectiveness and safety of its use in different episodes of nephrotoxicity remain an unknown area. Case Report A 30-year-old male diagnosed with acute lymphoblastic T-cell lymphoma received methotrexate 5 g/m2 intravenous (IV) as part of the first consolidation cycle. On Consolidation 3, he restarted methotrexate at a dose of 3 g/m2 IV showing slow methotrexate elimination, associated myelosuppression, and hepatic toxicity. Glucarpidase was administered (total dose of 2000 International Units (IU)). No adverse events were observed, and his renal function returned to normal. One hundred and six days later, he was diagnosed with leptomeningeal and cerebellar relapse and treatment with methotrexate 3,5 g/m2 IV day 1 and cytosine arabinoside (Ara-C) 2 g/m2 IV twice per day days 1, 3, and 5 was started. At 36 h from methotrexate infusion, serum creatinine increased up to 1.89 mg/dL and methotrexate concentration was 100 µmol/L. Management and Outcome: Ara-C was suspended, and a second administration of glucarpidase (2000 IU) was dispensed. No adverse events were noticed, methotrexate levels decreased and renal function progressively improved, recovering completely three weeks later. Discussion The effectiveness and safety of the use of glucarpidase in different episodes of nephrotoxicity remain an unknown area, and the rate and consequences of antiglucarpidase antibody formation remain poorly understood. This case report is, to our knowledge, the first case of a second administration of glucarpidase in a different cycle of high-dose methotrexate in an adult patient.

scholarly journals Rapid Reversal of Complete Binocular Blindness With High-Dose Corticosteroids and Lumbar Drain in a Solid Organ Transplant Recipient With Cryptococcal Meningitis and Immune Reconstitution Syndrome: First Case Study and Literature Review

2018 ◽  
Vol 5 (2) ◽  
Author(s):  
Zoe Weiss ◽  
Nihaal Mehta ◽  
Su Nandar Aung ◽  
Michael Migliori ◽  
Dimitrios Farmakiotis
Keyword(s):  
Transplant Recipient ◽  
Cryptococcal Meningitis ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Organ Transplant Recipient ◽  
High Dose ◽  
Solid Organ Transplant Recipient ◽  
Solid Organ ◽  
Lumbar Drain ◽  
First Case

Abstract Blindness is a rare, devastating, usually permanent complication of cryptococcal meningitis (CM). We present the first case of complete vision loss in a solid organ transplant recipient with CM treated with placement of a lumbar drain who had a dramatic visual recovery that started after 3 doses of high-dose steroids.

scholarly journals COVID-19 in solid organ transplant recipients: initial report from national multicenter observational study «ROKKOR-recipient»

2020 ◽  
Vol 22 (3) ◽  
pp. 8-17
Author(s):  
S. V. Gautier ◽  
A. O. Shevchenko ◽  
O. M. Tsirulnikova ◽  
S. M. Khomyakov ◽  
O. N. Kotenko ◽  
...  
Keyword(s):  
Adverse Events ◽  
Observational Study ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Initial Report ◽  
Organ Transplant Recipients ◽  
Multicenter Observational Study ◽  
Solid Organ Transplant Recipients

We herein present our initial report from «ROKKOR-recipient», a national multicenter observational study. The prevalence, risk factors, clinical manifestations and outcomes of the novel coronavirus disease 2019 (COVID-19) in solid organ transplant recipients receiving immunosuppressive therapy were investigated. The study enrolled 251 COVID-19 patients (220 kidney recipients, 7 liver recipients, 1 liver-kidney recipient, and 23 heart recipients). The subjects came from 20 regions in Russia. The symptoms, clinical presentation, imaging and lab test results, therapy and outcomes of COVID-19 were described. It was established that solid organ transplant recipients with COVID-19 have a higher risk of developing adverse events. Predictors of adverse events include associated cardiovascular diseases, pulmonary diseases, diabetes, and kidney failure. Symptoms of the disease include dyspnea, rash and catarrhal signs, as well as initial low blood oxygen saturation (SpO2 <92%), leukocytosis (white blood cell count >10 × 109/L), elevated creatinine levels (>130 μmol/L) and a marked decrease in glomerular filtration rate, requiring hemodialysis. Performing organ transplant surgery in COVID-19 does not increase the risk of adverse events but could save the lives of waitlisted terminally ill patients.

scholarly journals An Unusual Presentation of Cryptococcal Infection in a Post Renal Transplant Patient: A Case Report

2021 ◽  
Vol 6 (4) ◽  
Author(s):  
Nishanthi WAAGN ◽  
Shiyam A
Keyword(s):  
Renal Transplant Patient ◽  
Transplant Patient ◽  
Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Mortality And Morbidity ◽  
Cryptococcal Infection ◽  
Solid Organ Transplant Recipients ◽  
Bird Feces ◽  
Significant Mortality

Background: Cryptococcus neoformans is opportunistic yeast commonly found in soil contaminated by bird feces throughout the world. Cryptococcosis is a severe fungal infection in a with a high mortality rate among solid organ transplant recipients. The infection usually involves the lungs, central nervous system, skin, bones, and the urinary tract. Cryptococcosis continues to cause significant mortality and morbidity in immunocompromised patients.

Approaches to The Treatment of Hyperlipidemia in the Solid Organ Transplant Recipient

1995 ◽  
Vol 29 (9) ◽  
pp. 879-891 ◽  
Author(s):  
Julienne K Kirk ◽  
Robert E Dupuis
Keyword(s):  
Transplant Recipient ◽  
Transplant Patient ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Hmg Coa Reductase ◽  
Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase

Objective: To review the literature investigating increased lipid concentrations in transplant recipients and the use of lipid-lowering agents in this population. Data Sources: Relevant articles were identified from a MEDLINE search using the terms transplantation, hyperlipidemia, immunosuppression, and therapy including diet, gemfibrozil, bile acid sequestrants, nicotinic acid, probucol, and hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Selected literature, including controlled studies, was used in this review. Study Selection: Articles published since 1970 pertaining to hyperlipidemia in solid organ transplant recipients. Emphasis was placed on clinical trials that investigated approaches to the treatment of hyperlipidemia in transplant recipients. Data Extraction: Original articles and reviews were obtained to select material pertinent to the objectives. Data Synthesis: Descriptions of lipid concentrations in the transplant patient and treatment approaches used, including potential complications, were reviewed. Conclusions: Hyperlipidemia is an important risk factor for coronary heart disease in the solid organ transplant patient. Treatment alternatives include diet modification and, in most cases, pharmacologic intervention that should be based on the type of hyperlipidemia. The HMG-CoA reductase inhibitors are effective agents in the treatment of hyperlipidemia in the transplant recipient and generally are used as single therapy in low dosages to minimize the risk of myositis or rhabdomyolysis.

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