scholarly journals Tedizolid vs Linezolid for the Treatment of Nontuberculous Mycobacteria Infections in Solid Organ Transplant Recipients

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Yi Kee Poon ◽  
Ricardo M La Hoz ◽  
Linda S Hynan ◽  
James Sanders ◽  
Marguerite L Monogue
Keyword(s):  
Adverse Drug Events ◽  
Nontuberculous Mycobacteria ◽  
Treatment Options ◽  
Safety Data ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Intrinsic Resistance ◽  
Safety Benefit

Abstract Background Treatment options for nontuberculous mycobacteria (NTM) infections are limited by the pathogen’s intrinsic resistance profile and toxicities. Tedizolid and linezolid display in vitro activity against NTM species. However, safety data and treatment outcomes are limited in the solid organ transplant (SOT) population. Methods This was a single-center retrospective cohort study of adult SOT recipients receiving linezolid or tedizolid for an NTM infection from January 1, 2010, to August 31, 2019. The primary outcome compared the hematologic safety profiles of tedizolid vs linezolid. We also described nonhematological adverse drug events (ADEs) and therapy discontinuation rates. In an exploratory analysis, we assessed symptomatic microbiologic and clinical outcomes in those receiving tedizolid or linezolid for at least 4 weeks. Results Twenty-four patients were included (15 tedizolid, 9 linezolid). No differences were identified comparing the effects of tedizolid vs linezolid on platelet counts, absolute neutrophil counts (ANCs), and hemoglobin over 7 weeks using mixed-effects analysis of variance models. ANC was significantly decreased in both groups after 7 weeks of therapy (P = .04). Approximately 20% of patients in each arm discontinued therapy due to an ADE. Seven of 12 (58%) and 2 of 3 (67%) patients were cured or clinically cured with tedizolid- and linezolid-containing regimens, respectively. Conclusions This study suggests no significant safety benefit of tedizolid over linezolid for the treatment of NTM infections in SOT recipients. Tedizolid or linezolid-containing regimens demonstrated a potential benefit in symptomatic and microbiologic improvement. Larger cohorts are needed to further delineate the comparative role of linezolid and tedizolid for the treatment of NTM infections in SOT recipients.

scholarly journals Invasive infections with Purpureocillium lilacinum: clinical characteristics and outcome of 101 cases from FungiScope® and the literature

2021 ◽  
Author(s):  
Rosanne Sprute ◽  
Jon Salmanton-García ◽  
Ertan Sal ◽  
Xhorxha Malaj ◽  
Zdeněk Ráčil ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Organ Transplant ◽  
Solid Organ ◽  
Intrinsic Resistance ◽  
Breakthrough Infection ◽  
Purpureocillium Lilacinum ◽  
Invasive Infections ◽  
Oncological Diseases ◽  
Overall Mortality

Abstract Objectives To provide a basis for clinical management decisions in Purpureocillium lilacinum infection. Methods Unpublished cases of invasive P. lilacinum infection from the FungiScope® registry and all cases reported in the literature were analysed. Results We identified 101 cases with invasive P. lilacinum infection. Main predisposing factors were haematological and oncological diseases in 31 cases (30.7%), steroid treatment in 27 cases (26.7%), solid organ transplant in 26 cases (25.7%), and diabetes mellitus in 19 cases (18.8%). The most prevalent infection sites were skin (n = 37/101, 36.6%) and lungs (n = 26/101, 25.7%). Dissemination occurred in 22 cases (21.8%). Pain and fever were the most frequent symptoms (n = 40/101, 39.6% and n = 34/101, 33.7%, respectively). Diagnosis was established by culture in 98 cases (97.0%). P. lilacinum caused breakthrough infection in 10 patients (9.9%). Clinical isolates were frequently resistant to amphotericin B, whereas posaconazole and voriconazole showed good in vitro activity. Susceptibility to echinocandins varied considerably. Systemic antifungal treatment was administered in 90 patients (89.1%). Frequently employed antifungals were voriconazole in 51 (56.7%) and itraconazole in 26 patients (28.9%). Amphotericin B treatment was significantly associated with high mortality rates (n = 13/33, 39.4%, P = <0.001). Overall mortality was 21.8% (n = 22/101) and death was attributed to P. lilacinum infection in 45.5% (n = 10/22). Conclusions P. lilacinum mainly presents as soft-tissue, pulmonary or disseminated infection in immunocompromised patients. Owing to intrinsic resistance, accurate species identification and susceptibility testing are vital. Outcome is better in patients treated with triazoles compared with amphotericin B formulations.

scholarly journals 1096. Linezolid versus Tedizolid for the Treatment of Nontuberculous Mycobacteria in Solid Organ Transplant Recipients: An Assessment of Safety

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S577-S578
Author(s):  
Yi Kee Poon ◽  
Ricardo M La Hoz ◽  
James Sanders ◽  
Linda S Hynan ◽  
Marguerite Monogue
Keyword(s):  
Nontuberculous Mycobacteria ◽  
Organ Transplant ◽  
Drug Regimen ◽  
Solid Organ Transplant ◽  
Mixed Effects ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Duration Of Therapy ◽  
Anova Model ◽  
Solid Organ Transplant Recipients

Abstract Background Treatment options for nontuberculous mycobacteria (NTM) infections are limited by the long-term tolerability of antimicrobials. The oxazolidinones, linezolid and tedizolid, display in vitro activity against many NTM species and demonstrate excellent oral bioavailability. This study compares the hematologic safety profile of linezolid versus tedizolid for the treatment of NTM in solid organ transplant (SOT) recipients. Methods This retrospective cohort study included adult SOT recipients who received linezolid or tedizolid as part of a multi-drug regimen to treat NTM between January 1, 2010 to August 31, 2019. The primary endpoint was the hematologic effects of linezolid versus tedizolid from therapy initiation to week seven. This time frame was chosen based on the median duration of therapy. A mixed-effects ANOVA model was used to assess the effects of linezolid and tedizolid on platelet counts (PLT), absolute neutrophil counts (ANC), and hemoglobin (Hgb) across time. Subjects were treated as a random effect. The secondary analysis described the proportion of adverse effects and discontinuation. Results Twenty-four patients were included in the analysis (9 linezolid, 15 tedizolid). Mycobacterium abscessus abscessus was the most common isolate, and pulmonary was the most common site of infection (Table 1). The median duration of therapy was 24 days (range 3 to 164 days) and 48 days (range 11 to 571 days) for linezolid and tedizolid, respectively. All patients in the linezolid group received 600 mg daily or less for the majority of treatment duration. In the mixed-effects ANOVA, the ANC decreased in both groups after seven weeks of therapy (p=0.04). Otherwise, no significant effects for week, treatment group, or interaction between week and treatment group were found (Figure 1). Thrombocytopenia and neutropenia were common in both groups, and around one-fifth of patients in each group discontinued the medication due to adverse effects (Table 2). Table 1. Baseline characteristics of solid organ transplant recipients who received linezolid or tedizolid as part of a multi-drug regimen to treat nontuberculous mycobacteria infections between January 1, 2010 to August 31, 2019 at UT Southwestern Medical Center. Table 2. Adverse drug events and discontinuation of therapy over seven weeks of therapy. Figure 1. Effects of linezolid versus tedizolid during the initial seven weeks of therapy using a mixed-effects ANOVA model, (a) platelet counts, (b) absolute neutrophil counts, and (c) hemoglobin. Conclusion Non-significant statistical differences were found comparing the effects of linezolid versus tedizolid for PLT, ANC, and Hgb using mixed-effects ANOVA models. Larger cohort studies are required to compare the hematologic adverse effect profile of the oxazolidinones for the treatment of NTM infections in SOT recipients. Disclosures All Authors: No reported disclosures

scholarly journals Use of Letermovir as Salvage Therapy for Drug-Resistant Cytomegalovirus Retinitis

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
Nicholas Turner ◽  
Andrew Strand ◽  
Dilraj S. Grewal ◽  
Gary Cox ◽  
Sana Arif ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Adverse Drug Events ◽  
Treatment Options ◽  
Organ Transplant ◽  
Virologic Suppression ◽  
Solid Organ ◽  
Drug Resistant ◽  
Transplant Recipients ◽  
Solid Organ Transplant Recipients ◽  
Cmv Prophylaxis

ABSTRACT Treatment options for drug-resistant cytomegalovirus (CMV) are limited. Letermovir is a novel antiviral recently approved for CMV prophylaxis following hematopoietic cell transplantation, but its efficacy in other settings is unknown. We recently used letermovir for salvage treatment in four solid organ transplant recipients with ganciclovir-resistant CMV retinitis. All patients improved clinically without known adverse drug events. However, three patients failed to maintain virologic suppression, including two patients who developed genotypically confirmed resistance to letermovir while on therapy.

scholarly journals Surgical-site mucormycosis infection in a solid-organ transplant recipient and a concise review of the literature

2019 ◽  
Vol 12 (12) ◽  
pp. e229687 ◽  
Author(s):  
Husham Haque ◽  
Scott Nettboy ◽  
Sunil Kumar
Keyword(s):  
Treatment Options ◽  
Organ Transplant ◽  
Alcoholic Cirrhosis ◽  
Solid Organ Transplant ◽  
Organ Transplant Recipient ◽  
Solid Organ Transplant Recipient ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Organ Transplant Recipients ◽  
Solid Organ Transplant Recipients

Surgical-site mucormycosis infections in solid-organ transplant recipients are rare conditions, with only 15 previously reported cases. We describe a case of a 49-year-old man who received a liver transplant due to alcoholic cirrhosis. On postoperative day 14, necrosis was noticed at the surgical site. After mucormycosis was diagnosed, monotherapy with amphotericin was started along with surgical debridements. Due to continued clinical deterioration, triple antifungal therapy was started with amphotericin, micafungin and posaconazole. Treatment with a granulocyte-macrophage colony-stimulating factor was also started. Despite therapy, the patient expired on postoperative day 31. We review the risk factors for mucormycosis infection in solid-organ transplant recipients as well as evidence for current treatment options. We also review the 15 previously reported cases of surgical-site mucormycosis infections in solid-organ transplant recipients, including time to infection, infecting organisms, mortality and treatments.

Third Party Donor Derived EBV Specific T Cells for the Treatment of Refractory EBV-Related Malignancies in Immunodeficient Recipients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 577-577
Author(s):  
Susan E. Prockop ◽  
Ekaterina Doubrovina ◽  
Juliet N Barker ◽  
Karim Baroudy ◽  
Farid Boulad ◽  
...  
Keyword(s):  
T Cells ◽  
Organ Transplant ◽  
Organ Donor ◽  
Primary Immunodeficiency Disease ◽  
Solid Organ Transplant ◽  
Third Party ◽  
Solid Organ ◽  
Hla Alleles ◽  
Immunodeficiency Disease

Abstract Abstract 577 Adoptive immunotherapy is an effective strategy for the treatment of EBV+ lymphoproliferative diseases (EBV-LPD) arising after an allogeneic hematopoietic stem cell (HSCT) or solid organ transplant (SOT). This approach is, however, often limited by an inability to generate donor derived in vitro expanded EBV-specific cytotoxic T-lymphocyte (EBV-CTL) lines in a timely manner and/or the fact that EBV CTL lines derived from HLA non-identical donors may be restricted by non-shared HLA alleles. To date, we have treated 25 consecutive patients with an EBV LPD (N=20) or EBV Leiomyosarcoma (LMS) (N=5) with in vitro expanded EBV-CTLs derived from a donor other than the patient or their transplant (HSCT or SOT) donor. EBV CTLS were selected from a bank of 345 lines generated under GMP conditions from normal HSCT donors. Each donor was specifically consented for use of their T cells in patients other than their designated transplant recipient. Patients were recipients of unmodified (n=4), T cell depleted (n=5) or unrelated cord blood (n=5) HSCT, a solid organ transplant (n=6), a combined SOT and HSCT (n=1), or were non-transplanted patients with a primary immunodeficiency disease (n=4). EBV disease in transplanted patients was of host origin in 5 of 10 evaluable HSCT recipients, in 3 of 4 evaluable solid organ recipients, and in the one patient who underwent a combined HSCT/solid organ transplant. Third party EBV-CTLs were selected on the basis of HLA matching at a minimum of 2/8 recipient alleles. Where possible EBV-CTLs were selected that were restricted through HLA alleles present on the EBV+ tumor. HLA restriction was evaluated in vitro in 20 EBV-CTL donor lines. The restriction was at a single HLA allele (n=12), at two alleles (n=6) and at >than two alleles (n=2). Patients received infusions of 3rd party EBV-CTLs after failing a median of 2 prior therapies including rituximab in all but one case of EBV LPD. Four patients failed prior infusions with EBV-CTLs which were autologous (n=1), derived from their original HSCT (n=2) or from their solid organ donor (n=1). In two patients who progressed after treatment with EBV CTLs generated from their HSCT or organ donor, it was demonstrated that the donor derived EBV CTLs were restricted by a non-shared HLA allele. Patients received a median of 5 infusions most at 1×106 EBV-CTL/kg/infusion. Four patients received EBV-CTLs from >1 3rd party donor. Nine patients achieved a completed response. Nine patients died of progressive disease, 6 shortly after the first infusion (17–29 days). Two patients with LMS achieved long term stable disease (46 and 8 months); 5 achieved partial remissions which have been sustained in 4 (11- 68 months), and 1 patient progressed after 10 months in a partial remission. Response to EBV CTL therapy did not correlate with the degree of HLA matching between donor and recipient or donor and tumor. Radiographic and clinical responses correlated with detectable increases in the frequency of CTL precursors in the blood. However durable EBV CTL engraftment was not seen. One patient developed mild skin GvHD after infusion with 3rd party EBV-CTLs, but tolerated subsequent infusion of EBV-CTLs from an alternate 3rd party donor. Although no SOT recipient developed anti-HLA antibodies, one developed and episode of steroid responsive renal transplant rejection more than 6 months after infusion of EBV CTLs without evidence of donor (by STR analysis) in biopsied tissue. This study demonstrates a high response rate among patients with otherwise refractory EBV malignancy treated with EBV specific 3rd party CTLs restricted by HLA alleles shared by the tumor. Treatment failures correlated with the use of EBV CTLs restricted by HLA alleles not shared by the tumor. In addition two patients with a primary immunodeficiency disease who were unable to mount an endogenous EBV T cell response had transient but not durable responses to 3rd party cells. EBV CTLs can be effective when selected based on restriction to shared alleles despite significant HLA disparity. The bank of EBV specific T cells can provide an immediate source of HLA partially matched appropriately restricted T cells for adoptive immunotherapy to treat EBV associated malignancy. This enables treatment early in the course of disease and the use of EBV-CTL lines previously prepared and characterized in terms of HLA restriction. This is anticipated to maximize the response rate. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Paradoxical effects of heme arginate on survival of myocutaneous flaps

2014 ◽  
Vol 306 (1) ◽  
pp. R10-R22 ◽  
Author(s):  
Marie-Claire Edmunds ◽  
Alicja Czopek ◽  
Stephen J. Wigmore ◽  
David C. Kluth
Keyword(s):  
Clinical Outcome ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Epidermal Keratinocytes ◽  
Heme Oxygenase 1 ◽  
Solid Organ ◽  
Heme Arginate

Ischemia reperfusion injury (IRI) contributes to partial flap and solid organ transplant failure. Heme-oxygenase 1 (HO-1) is an inducible, cytoprotective enzyme which protects against IRI in solid organ transplant models. Heme arginate (HA), a HO-1 inducer, is a promising, translatable, preconditioning agent. This study investigated the effects of preconditioning with HA on the clinical outcome of a myocutaneous IRI model. Forty male Lewis rats were randomized to intravenously receive 1) Control-NaCl, 2) HA, 3) HA and tin mesoporphyrin (SnMP), a HO-1 inhibitor; and 4) SnMP alone. Twenty-four hours later, an in situ transverse rectus abdominis myocutaneous flap was performed under isoflurane anesthesia. Viability of flaps was measured clinically and by laser-Doppler perfusion scanning. In vitro work on human epidermal keratinocytes (HEKa) assessed the effects of HA, SnMP, and the iron chelator desferrioxamine on 1) cytotoxicity, 2) intracellular reactive oxygen species (ROS) concentration, and 3) ROS-mediated DNA damage. In contrast to our hypothesis, HA preconditioning produced over 30% more flap necrosis at 48 h compared with controls ( P = 0.02). HA-containing treatments produced significantly worse flap perfusion at all postoperative time points. In vitro work showed that HA is cytotoxic to keratinocytes. This cytotoxicity was independent of HO-1 and was mediated by the generation of ROS by free heme. In contrast to solid organ data, pharmacological preconditioning with HA significantly worsened clinical outcome, thus indicating that this is not a viable approach in free flap research.

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