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In 2023, the EBMT Practice harmonization and Guidelines Committee partnered with the EBMT Infection Diseases Working Party (IDWP) to undertake the task of delivering best practice recommendations, aiming to harmonize by expert consensus, the already existing definitions and future epidemiological and clinical studies among centers of the EBMT network. To attain this objective, a group of experts in the field was convened. The workgroup identified and discussed some critical aspects in definitions of community-acquired respiratory viruses (CARV) and adenovirus (ADV) infections in recipient of hematopoietic cell transplant (HCT). The methodology involved literature review and expert consensus. For CARV, expert consensus focused on defining infection severity, infection duration, and establishing criteria for lower respiratory tract disease (LRTD). For ADV, the expert consensus focused on surveillance methods and the definitions of ADV infection, certainty levels of disease, response to treatment, and attributable mortality. This consensus workshop provided indications to EBMT community aimed at facilitating data collection and consistency in the EBMT registry for respiratory viral infectious complications.
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Among immunocompromised hosts, leukemia patients, and hematopoietic cell transplant recipients are particularly vulnerable, facing challenges in balancing coronavirus disease 2019 (COVID-19) management with their underlying conditions. In this How I Treat article, we discuss how we approach severe acute respiratory syndrome coronavirus 2 infections in daily clinical practice, considering the existing body of literature and for topics where the available data are not sufficient to provide adequate guidance, we provide our opinion based on our clinical expertise and experience. Diagnostic approaches include nasopharyngeal swabs for polymerase chain reaction testing and chest computed tomography scans for symptomatic patients at risk of disease progression. Preventive measures involve strict infection control protocols and prioritizing vaccination for both patients and their families. Decisions regarding chemotherapy or hematopoietic cell transplantation in leukemia patients with COVID-19 require careful consideration of factors such as COVID-19 severity and treatment urgency. Treatment protocols include early initiation of antiviral therapy, with nirmatrelvir/ritonavir or remdesivir. For cases of prolonged viral shedding, distinguishing between viable and non-viable viruses remains challenging but is crucial for determining contagiousness and guiding management decisions. Overall, individualized approaches considering immune status, clinical presentation, and viral kinetics are essential for effectively managing COVID-19 in leukemia patients.
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Monofosfato de Adenosina , Alanina , Antivirais , COVID-19 , Transplante de Células-Tronco Hematopoéticas , Hospedeiro Imunocomprometido , Leucemia , SARS-CoV-2 , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , COVID-19/complicações , Antivirais/uso terapêutico , Leucemia/complicações , Leucemia/terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Tratamento Farmacológico da COVID-19 , Ritonavir/uso terapêutico , Transplantados , Lopinavir/uso terapêutico , Eliminação de Partículas Virais , Combinação de MedicamentosRESUMO
Despite the significant progress made, CMV infection is one of the most frequent infectious complications in transplant recipients. CMV infections that become refractory or resistant (R/R) to the available antiviral drugs constitute a clinical challenge and are associated with increased morbidity and mortality. Novel anti-CMV therapies have been recently developed and introduced in clinical practice, which may improve the treatment of these infections. In this review, we summarize the treatment options for R/R CMV infections in adult hematopoietic cell transplant and solid organ transplant recipients, with a special focus on newly available antiviral agents with anti-CMV activity, including maribavir and letermovir.
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Antivirais , Infecções por Citomegalovirus , Citomegalovirus , Farmacorresistência Viral , Transplantados , Humanos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/etiologia , Antivirais/uso terapêutico , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/fisiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Órgãos/efeitos adversos , Acetatos , Diclororribofuranosilbenzimidazol/análogos & derivados , QuinazolinasRESUMO
The incidence of breakthrough mold infections (bIMI) has been increasing, due to routine administration of broad-spectrum antifungal prophylaxis and an increasing pool of high-risk patient populations, with fungi more challenging to treat, resulting in a sustained high mortality, despite progress in diagnostic and therapeutic options. Pharmacokinetics of antifungal drugs, fungal, and host, including genetic, factors play a role in the emergence of bIMI. Suggested therapeutic approaches have included change of antifungal class treatment, with amphotericin-B products predominating as first-line empirical treatment and switching from one broad-spectrum azole to another remaining the most frequently used treatment modalities. Future perspectives include determining individual susceptibility to IMI to tailor prophylaxis and treatment strategies, improved diagnostic tests, and the introduction of new antifungal agents that may reduce morbidity and mortality caused by bIMI.
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Antifúngicos , Infecções Fúngicas Invasivas , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/prevenção & controle , Infecções Fúngicas Invasivas/diagnóstico , Antifúngicos/uso terapêutico , Fungos/efeitos dos fármacos , Incidência , Farmacorresistência FúngicaRESUMO
PURPOSE OF REVIEW: Discuss the recent evidence on cytomegalovirus (CMV) serology in allogeneic hematopoeic cell transplant (HCT) recipients. RECENT FINDINGS: Whereas the role CMV-specific cellular mediated immunity has recently emerged as an important factor of CMV DNAemia posttransplant, the value of CMV serology has remained unchanged through decades, associated with donor selection and posttransplant prophylactic and monitoring strategies. In this review, we describe and discuss the emerging reports on the association between the magnitude of pretransplant CMV immunoglobulin G (IgG) titer and the posttransplant incidence of CMV DNAemia, as CMV IgG titer could become an additional tool in CMV risk assessment in the future. SUMMARY: Pretransplant recipient CMV serology may have significant implications in posttransplant CMV reactivation in allogeneic HCT recipients.
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Anticorpos Antivirais , Infecções por Citomegalovirus , Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Transplante Homólogo , Humanos , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Citomegalovirus/imunologia , Transplante Homólogo/efeitos adversos , Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Testes Sorológicos/métodos , DNA Viral/sangueRESUMO
This case involves a 53-year-old female with concurrent acute myeloid leukemia (AML) and multiple myeloma. She underwent cytarabine and daunorubicin (7+3) induction chemotherapy followed by cytarabine (HiDAC) consolidation, with an early AML relapse requiring azacitidine and venetoclax therapy. She achieved complete remission and incomplete count recovery. Following fludarabine, melphalan, and thymoglobulin induction chemotherapy, she underwent an allogeneic stem cell transplant with failure to engraft, requiring autologous stem cell rescue, buffy coat, and granulocyte transfusions, eventually presenting with a diffuse skin rash consistent with Steven-Johnson syndrome and toxic epidermal necrolysis, persistent neutropenic fevers and positive blood cultures.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Mieloma Múltiplo , Humanos , Pessoa de Meia-Idade , Feminino , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicações , Mieloma Múltiplo/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Homólogo/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/uso terapêutico , Citarabina/administração & dosagem , Quimioterapia de InduçãoRESUMO
Fat crystallization is one of the predominant factors influencing the structure and properties of fat-containing emulsions. In the present study, the role of emulsifiers on fat crystallization dynamics within droplet multiphase systems was evaluated via single-droplet analysis, taking advantage of the non-destructive properties of confocal Raman microscopy. Palm oil droplets dispersed in water were used as a model system, due to palm oil's well-known crystallization properties. Emulsion droplets of the same size were generated using two different emulsifiers (Whey Protein Isolate and Tween 60), at various concentrations. Fast and slow cooling treatments were applied to affect fat crystallisation and network formation as well as droplet morphology, and crystallization dynamics. Raman imaging analysis demonstrated that the chemical structure and concentration of the emulsifier significantly influenced both crystal nucleation within the droplets, as well as the spatial distribution and morphology of the fat crystal network. Additionally, analysis of the spectra of the crystallized phase provided essential information regarding the impact of the emulsifiers on the microstructure, degree of structural order, and structural arrangements of the fat crystal networks. Furthermore, by performing single droplet analysis during cooling it was possible to observe shape distortions in Tween 60 stabilized droplets, as a consequence of the formation of a three-dimensional network of fat crystals that strongly interacted with the interface. On the other hand, the droplets retained their shape when whey proteins were absorbed at the interface. Confocal Raman microscopy, in combination with polarized light microscopy, is, therefore, a well-suited tool for in situ, single-droplet analysis of emulsified oil systems, providing essential information about emulsified fat crystallization dynamics, contributing to better understanding and designing products with enhanced structure and function.
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Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multicenter 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in 8 cases (13%). Twelve-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotic usage (adjusted odds ratio [aOR], 4.74; P = .03) and history of pneumonia (aOR, 48.7; P = .01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; P = .01), systemic antibiotic usage (aOR, 5.03; P = .04), and antimold prophylaxis (aOR, 11.9; P = .02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ratio [aHR], 86.9; P < .001), intensive care unit stay (aHR, 3.67; P = .02), disseminated IA (aHR, 8.98; P < .001), and dialysis (aHR, 2.93; P = .001) were identified as independent risk factors associated with 12-week all-cause mortality, while recent receipt of tacrolimus (aHR, 0.11; P = .001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted antimold prophylactic and appropriate treatment strategies against IA.
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Valganciclovir (VGC) is administered as prophylaxis to kidney transplant recipients (KTR) CMV donor (D)+/recipient (R)- and CMV R+ after thymoglobulin-induction (R+/TG). Although VGC dose adjustments based on renal function are recommended, there is paucity of real-life data on VGC dosing and associations with clinical outcomes. This is a retrospective Swiss Transplant Cohort Study-embedded observational study, including all adult D+/R- and R+/TG KTR between 2010 and 2020, who received prophylaxis with VGC. The primary objective was to describe the proportion of inappropriately (under- or over-) dosed VGC week-entries. Secondary objectives included breakthrough clinically significant CMV infection (csCMVi) and potential associations between breakthrough-csCMVi and cytopenias with VGC dosing. Among 178 KTR, 131 (73.6%) patients had ≥2 week-entries for the longitudinal data of interest and were included in the outcome analysis, with 1,032 VGC dose week-entries. Overall, 460/1,032 (44.6%) were appropriately dosed, while 234/1,032 (22.7%) and 338/1,032 (32.8%) were under- and over-dosed, respectively. Nineteen (14.5%) patients had a breakthrough-csCMVi, without any associations identified with VCG dosing (p = 0.44). Unlike other cytopenias, a significant association between VGC overdosing and lymphopenia (OR 5.27, 95% CI 1.71-16.22, p = 0.004) was shown. VGC prophylaxis in KTR is frequently inappropriately dosed, albeit without meaningful clinical associations, neither in terms of efficacy nor safety.
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Antivirais , Infecções por Citomegalovirus , Transplante de Rim , Valganciclovir , Humanos , Valganciclovir/administração & dosagem , Valganciclovir/uso terapêutico , Transplante de Rim/efeitos adversos , Masculino , Infecções por Citomegalovirus/prevenção & controle , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Adulto , Idoso , Rim/efeitos dos fármacos , TransplantadosRESUMO
Background: Limited data exist on when and how to stop antifungal treatment (AFT) in patients with invasive mold infections (IMIs) who are immunocompromised. Methods: This retrospective multicenter study included adult patients with acute myelogenous leukemia and proven/probable IMI (1 January 2010-31 December 2022) in 3 university hospitals. The primary objective was to describe AFT duration and adaptation. Secondary objectives were to investigate the reasons for AFT adjustments and prolongation. Results: In total 71 patients with 73 IMIs were identified; 51 (71.8%) had an allogeneic hematopoietic cell transplant. Most infections were invasive aspergillosis (IA; 49/71, 69%), followed by mucormycosis (12, 16.9%) and other (12, 16.9%); there were 2 mixed infections. Median treatment duration was 227 days (IQR, 115.5-348.5). There was no difference in AFT duration between patients with IA and non-IA IMI (P = .85) or by center (P = .92). Treatment was longer in patients with an allogeneic hematopoietic cell transplant vs not (P = .004). Sixteen patients (22.5%) had no therapy modifications. In 55 patients (77.5%), a median 2 changes (IQR, 1-3; range, 1-8) were observed. There were 182 reasons leading to 165 changes, associated with clinical efficacy (82/182, 44.5%), toxicity (47, 25.8%), and logistical reasons (22, 12.1%); no reason was documented in 32 changes (18.8%). AFT was continued beyond days 90 and 180 in 59 (83%) and 39 (54.9%) patients, respectively, mostly due to persistence of immunosuppression. Conclusions: AFT in patients with acute myelogenous leukemia and IMI is longer than that recommended by guidelines and is frequently associated with treatment adjustments due to variable reasons. More data and better guidance are required to optimize AFT duration and secondary prophylaxis administration according to immunosuppression.
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This analysis of 116 isavuconazole therapy courses shows that hepatic test disturbances (HTDs) were relatively frequent (29% of cases) but rarely led to treatment interruption (5%). Importantly, patients with baseline HTDs, including those attributed to a first-line triazole, did not exhibit a higher risk of subsequent HTD under isavuconazole therapy.
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Background: Infectious diseases (IDs) are highly relevant after solid organ transplantation in terms of morbidity and mortality, being among the most common causes of death. Patients undergoing kidney retransplantation (re-K-Tx) have been already receiving immunosuppressive therapy over a prolonged period, potentially facilitating subsequent infections. Comparing ID events after re-K-Tx and first kidney transplantation (f-K-Tx) can delineate patterns and risks of ID events associated with prolonged immunosuppression. Methods: We included adult patients with records on f-K-Tx and re-K-Tx in the Swiss Transplant Cohort Study. We analyzed ID events after f-K-Tx and re-K-Tx within the same patients and compared infection rates, causative pathogens, and infection sites. Recurrent time-to-event analyses were performed for comparison of infection rates. Results: A total of 59 patients with a median age of 47 years (range, 18-73) were included. Overall, 312 ID events in 52 patients occurred. In multivariable recurrent event modeling, the rate of ID events was significantly lower after re-K-Tx (hazard ratio, 0.70; P = .02). More bacterial (68.9% vs 60.4%) and fungal (4.0% vs 1.1%) infections were observed after f-K-Tx but fewer viral infections (27.0% vs 38.5%) as compared with re-K-Tx (P = .11). After f-K-Tx, urinary and gastrointestinal tract infections were more frequent; after re-K-Tx, respiratory tract and surgical site infections were more frequent (P < .001). Conclusions: ID events were less frequent after re-K-Tx. Affected sites differed significantly after f-K-Tx vs re-K-Tx.
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Background: Enterobacterales are often responsible for urinary tract infection (UTI) in kidney transplant recipients. Among these, Escherichia coli or Klebsiella species producing extended-spectrum beta-lactamase (ESBL) are emerging. However, there are only scarce data on frequency and impact of ESBL-UTI on transplant outcomes. Methods: We investigated frequency and impact of first-year UTI events with ESBL Escherichia coli and/or Klebsiella species in a prospective multicenter cohort consisting of 1,482 kidney transplants performed between 2012 and 2017, focusing only on 389 kidney transplants having at least one UTI with Escherichia coli and/or Klebsiella species. The cohort had a median follow-up of four years. Results: In total, 139/825 (17%) first-year UTI events in 69/389 (18%) transplant recipients were caused by ESBL-producing strains. Both UTI phenotypes and proportion among all UTI events over time were not different compared with UTI caused by non-ESBL-producing strains. However, hospitalizations in UTI with ESBL-producing strains were more often observed (39% versus 26%, p = 0.04). Transplant recipients with first-year UTI events with an ESBL-producing strain had more frequently recurrent UTI (33% versus 18%, p = 0.02) but there was no significant difference in one-year kidney function as well as longer-term graft and patient survival between patients with and without ESBL-UTI. Conclusion: First-year UTI events with ESBL-producing Escherichia coli and/or Klebsiella species are associated with a higher need for hospitalization but do neither impact allograft function nor allograft and patient survival.
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PURPOSE OF REVIEW: Bacteria are the leading cause of infections in solid organ transplant (SOT) recipients, significantly impacting patient outcome. Recently detailed and comprehensive epidemiological data have been published. RECENT FINDING: This literature review aims to provide an overview of bacterial infections affecting different types of SOT recipients, emphasizing underlying risk factors and pathophysiological mechanisms. SUMMARY: Lung transplantation connects two microbiotas: one derived from the donor's lower respiratory tract with one from the recipient's upper respiratory tract. Similarly, liver transplantation involves a connection to the digestive tract and its microbiota through the bile ducts. For heart transplant recipients, specific factors are related to the management strategies for end-stage heart failure based with different circulatory support tools. Kidney and kidney-pancreas transplant recipients commonly experience asymptomatic bacteriuria, but recent studies have suggested the absence of benefice of routine treatment. Bloodstream infections (BSI) are frequent and affect all SOT recipients. Nonorgan-related risk factors as age, comorbidity index score, and leukopenia contribute to BSI development. Bacterial opportunistic infections have become rare in the presence of efficient prophylaxis. Understanding the epidemiology, risk factors, and pathophysiology of bacterial infections in SOT recipients is crucial for effective management and improved patient outcomes.
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Infecções Bacterianas , Transplante de Fígado , Transplante de Pulmão , Transplante de Órgãos , Humanos , Transplante de Órgãos/efeitos adversos , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/epidemiologia , Fatores de Risco , TransplantadosRESUMO
BACKGROUND: The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. METHODS: In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus. RESULTS: Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, -0.1; 95% confidence interval [CI], -13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, -26.0 days; 95%, CI, -41.1 to -10.8 days; P < .001). CONCLUSIONS: Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection. CLINICAL TRIALS REGISTRATION: NCT02538172.
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Infecções por Citomegalovirus , Transplante de Órgãos , Humanos , Citomegalovirus , Antivirais/uso terapêutico , Monitorização Imunológica , Infecções por Citomegalovirus/diagnóstico , Transplantados , Transplante de Órgãos/efeitos adversos , Ganciclovir/uso terapêuticoRESUMO
BACKGROUND: Allogeneic hematopoietic cell transplant recipients (allo-HCTRs) with positive cytomegalovirus (CMV) serology may have false-positive results due to blood product transfusion-associated passive immunity. METHODS: This single-center cohort study included allo-HCTRs with negative baseline (at malignancy diagnosis) CMV serology and indeterminate/low-positive (CMV IgG titer, ≥0.6-<50 U/mL) pretransplant CMV serology with negative pretransplant plasma CMV DNAemia. The CMV status of those patients was reclassified from R+ to R- (CMVR- reclassification group). We compared those patients to allo-HCTRs with negative (CMV IgG titer <0.6 U/mL) pretransplant CMV IgG (CMVR- group). We describe the number and type of patients whose pretransplant CMV status was reclassified from indeterminate/positive to negative. We reviewed all plasma CMV DNAemia tests performed during the first 6 months posttransplant in both groups to assess the safety of this approach. RESULTS: Among 246 (84.5%) of 291 transplanted patients identified as CMVR+ pretransplant, 60 (24.4%) were reclassified from CMV serology indeterminate (N:10)/low-positive (N:50) to R-. Only 1 of 60 patients (1.67%) in the CMVR- reclassification group versus 3 of 44 (6.8%; P = .30) in the CMVR- group developed CMV DNAemia during the follow-up period. There were no significant differences in the number of CMV DNAemia tests performed, CMV DNAemia range, and time posttransplant between the 2 groups. CONCLUSIONS: One of 4 allo-HCT CMVR+ may be falsely flagged as R+, with significant impact on donor selection and prophylaxis administration. A 2-step approach including CMV serology testing at hematologic malignancy diagnosis in allo-HCT candidates and careful review of pretransplant CMV IgG titers may help correctly classify CMV serology status.
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Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Humanos , Citomegalovirus , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplantados , Estudos de Coortes , Transplante Homólogo/efeitos adversos , Anticorpos Antivirais/uso terapêutico , Imunoglobulina G , Estudos RetrospectivosAssuntos
Clostridioides difficile , Infecções por Clostridium , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Retrospectivos , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/etiologia , Infecções por Clostridium/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Fatores de Risco , Recidiva , Antibacterianos/uso terapêuticoRESUMO
Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort of SOTRs with PJP admitted to 20 transplant centers in Canada, the United States, Europe, and Australia, was examined for whether AGT was associated with a lower rate of all-cause intensive care unit (ICU) admission, 90-day death, or a composite outcome (ICU admission or death). Of 172 SOTRs with PJP (median [IQR] age: 60 (51.5-67.0) years; 58 female [33.7%]), the ICU admission and death rates were 43.4%, and 20.8%, respectively. AGT was not associated with a reduced risk of ICU admission (adjusted odds ratio [aOR] [95% CI]: 0.49 [0.21-1.12]), death (aOR [95% CI]: 0.80 [0.30-2.17]), or the composite outcome (aOR [95% CI]: 0.97 [0.71-1.31]) in the propensity score-adjusted analysis. AGT was not significantly associated with at least 1 unit of the respiratory portion of the Sequential Organ Failure Assessment score improvement by day 5 (12/37 [32.4%] vs 39/111 [35.1%]; P = .78). We did not observe significant associations between AGT and ICU admission or death in SOTRs with PJP. Our findings should prompt a reevaluation of routine AGT administration in posttransplant PJP treatment and highlight the need for interventional studies.
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Transplante de Órgãos , Pneumocystis carinii , Pneumonia por Pneumocystis , Feminino , Humanos , Pessoa de Meia-Idade , Europa (Continente) , Glucocorticoides/uso terapêutico , Transplante de Órgãos/efeitos adversos , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/etiologia , Estudos Retrospectivos , Transplantados , Masculino , IdosoRESUMO
BACKGROUND: The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population. METHODS: Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least 1 vaccine strain at 28 days postvaccination. Secondary outcomes included polymerase chain reaction-confirmed influenza and vaccine reactogenicity. RESULTS: A total of 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n = 198; MF59-adjuvanted, n = 205; high-dose, n = 195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs standard vaccine, 0.20; 97.5% confidence interval [CI], .12-1); P < .001; difference in high-dose vs standard vaccine, 0.24 [95% CI, .16-1]; P < .001; difference in MF59-adjuvanted vs standard vaccine, 0.17 [97.5% CI, .08-1]; P < .001). Influenza occurred in 6% of the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild. CONCLUSIONS: In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov NCT03699839.
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Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Transplante de Órgãos , Adulto , Humanos , Influenza Humana/prevenção & controle , Suíça , Anticorpos Antivirais , Polissorbatos/efeitos adversos , Esqualeno/efeitos adversos , Adjuvantes Imunológicos , Testes de Inibição da Hemaglutinação , Transplante de Órgãos/efeitos adversosRESUMO
Surgical site infections (SSIs) are common health care-associated infections. SSIs after kidney transplantation (K-Tx) can endanger patient and allograft survival. Multicenter studies on this early posttransplant complication are scarce. We analyzed consecutive adult K-Tx recipients enrolled in the Swiss Transplant Cohort Study who received a K-Tx between May 2008 and September 2020. All data were prospectively collected with the exception of the categorization of SSI which was performed retrospectively according to the Centers for Disease Control and Prevention criteria. A total of 58 out of 3059 (1.9%) K-Tx recipients were affected by SSIs. Deep incisional (15, 25.9%) and organ/space infections (34, 58.6%) predominated. In the majority of SSIs (52, 89.6%), bacteria were detected, most frequently Escherichia coli (15, 28.9%), Enterococcus spp. (14, 26.9%), and coagulase-negative staphylococci (13, 25.0%). A BMI ≥25 kg/m2 (multivariable OR 2.16, 95% CI 1.07-4.34, P = .023) and delayed graft function (multivariable OR 2.88, 95% CI 1.56-5.34, P = .001) were independent risk factors for SSI. In Cox proportional hazard models, SSI was independently associated with graft loss (multivariable HR 3.75, 95% CI 1.35-10.38, P = .011). In conclusion, SSI was a rare complication after K-Tx. BMI ≥25 kg/m2 and delayed graft function were independent risk factors. SSIs were independently associated with graft loss.