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1.
Int J Infect Dis ; : 107163, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969329

RESUMO

OBJECTIVES: Patients with haematologic malignancies (HM) COVID-19 have more severe disease, with increased risk of mortality. Therefore, this study aimed to evaluate the effect of SARS-CoV-2 RNAemia and the specific humoral immune responses on the clinical outcomes of patients with HM and COVID-19. METHODS: Interferon-α/γ (IFN-α/IFN-γ) serum levels, neutralizing antibodies (NAb), and RNAemia at COVID-19 diagnosis, and persistent RNAemia during the follow-up were evaluated. RESULTS: Overall, 63 (58.9%) out of 107 patients had RNAemia, which was persistent in 26 (41.3%) patients. RNAemia at diagnosis and persistent RNAemia were associated with the need for high-flow nasal oxygen therapy during admission. Persistent RNAemia, age >70 years, and CURB-65 score ≥2 in patients with pneumonia were associated with increased 90-day mortality (p = 0.009, p = 0.030, and p = 0.001, respectively). The 90-day overall survival was lower (p = 0.006) in patients with persistent RNAemia. In addition, dexamethasone administration was associated with a COVID-19 episode with persistent RNAemia. CONCLUSIONS: Our results suggest that in patients with HM, RNAemia at the time of COVID-19 diagnosis and during the follow-up can be used to stratify patients with HM according to their clinical evolution and to guide clinical decisions tailored to the specific needs of each patient.

2.
Transplantation ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773846

RESUMO

BACKGROUND: Isavuconazole (ISA) and voriconazole (VORI) are recommended as the first-line treatment for invasive aspergillosis (IA). Despite theoretical advantages of ISA, both triazole agents have not been compared in solid organ transplant recipients. METHODS: We performed a post hoc analysis of 2 retrospective multicenter cohorts of solid organ transplant recipients with invasive fungal disease (the SOTIS [Solid Organ Transplantation and ISavuconazole] and DiasperSOT [DIagnosis of ASPERgillosis in Solid Organ Transplantation] studies). We selected adult patients with proven/probable IA that were treated for ≥48 h with ISA (n = 57) or VORI (n = 77) as first-line therapy, either in monotherapy or combination regimen. The primary outcome was the rate of clinical response at 12 wk from the initiation of therapy. Secondary outcomes comprised 12-wk all-cause and IA-attributable mortality and the rates of treatment-emergent adverse events and premature treatment discontinuation. RESULTS: Both groups were comparable in their demographics and major clinical and treatment-related variables. There were no differences in the rate of 12-wk clinical response between the ISA and VORI groups (59.6% versus 59.7%, respectively; odds ratio [OR], 0.99; 95% confidence interval [CI], 0.49-2.00). This result was confirmed after propensity score adjustment (OR, 0.81; 95% CI, 0.32-2.05) and matching (OR, 0.79; 95% CI, 0.31-2.04). All-cause and IA-attributable mortality were also similar. Patients in the ISA group were less likely to experience treatment-emergent adverse events (17.5% versus 37.7%; P = 0.011) and premature treatment discontinuation (8.8% versus 23.4%; P = 0.027). CONCLUSIONS: Front-line treatment with ISA for posttransplant IA led to similar clinical outcomes than VORI, with better tolerability and higher treatment completion.

3.
Heliyon ; 10(6): e27601, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38545219

RESUMO

Despite the increasingly widespread clinical impact of adenovirus (HAdV) infections in healthy individuals and the associated high morbidity in immunosuppressed patients, particularly among the paediatric population, a specific treatment for this virus has yet to be developed. In this study, we report the anti-HAdV activity of sub-micromolar concentrations of four heteroleptic (C^S)-cycloaurated complexes bearing a single thiophosphinamide [Au(dpta)Cl2, Au(dpta)(mrdtc), and Au(dpta)(dedtc)] or thiophosphonamide [Au(bpta)(dedtc)] chelating ligand and a dithiocarbamate moiety. In addition to their low cytotoxicity, the findings of mechanistic assays revealed that these molecules have antiviral activity by targeting stages of the viral replication cycle subsequent to DNA replication. Additionally, all four compounds showed a significant inhibition of human cytomegalovirus (HCMV) DNA replication, thereby providing evidence for potential broad-spectrum antiviral activity.

4.
Int J Antimicrob Agents ; 63(5): 107116, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38401774

RESUMO

Human adenovirus (HAdV) and cytomegalovirus (HCMV) cause high morbidity and mortality in patients undergoing solid organ transplantation (SOT) and haematopoietic stem cell transplantation (HSCT). Immunosuppressors are used universally to prevent graft-vs-host disease in HSCT and graft rejection in SOT. The long-term use of these drugs is associated with a high risk of infection, but there is also evidence of their specific interference with viral infection. This study evaluated the antiviral activity of immunosuppressors commonly used in clinical practice in SOT and HSCT recipients in vitro to determine whether their use could be associated with reduced risk of HAdV and HCMV infection. Cyclophosphamide, tacrolimus, cyclosporine, mycophenolic acid, methotrexate, everolimus and sirolimus presented antiviral activity, with 50% inhibitory concentration (IC50) values at low micromolar and sub-micromolar concentrations. Mycophenolic acid and methotrexate showed the greatest antiviral effects against HAdV (IC50=0.05 µM and 0.3 µM, respectively) and HCMV (IC50=10.8 µM and 0.02 µM, respectively). The combination of tacrolimus and mycophenolic acid showed strong synergistic antiviral activity against both viruses, with combinatory indexes (CI50) of 0.02 and 0.25, respectively. Additionally, mycophenolic acid plus cyclosporine, and mycophenolic acid plus everolimus/sirolimus showed synergistic antiviral activity against HAdV (CI50=0.05 and 0.09, respectively), while methotrexate plus cyclosporine showed synergistic antiviral activity against HCMV (CI50=0.29). These results, showing antiviral activity in vitro against both HAdV and HCMV, at concentrations below the human Cmax values, may be relevant for the selection of specific immunosuppressant therapies in patients at risk of HAdV and HCMV infections.


Assuntos
Adenovírus Humanos , Antivirais , Citomegalovirus , Imunossupressores , Humanos , Imunossupressores/farmacologia , Antivirais/farmacologia , Adenovírus Humanos/efeitos dos fármacos , Citomegalovirus/efeitos dos fármacos , Sinergismo Farmacológico , Concentração Inibidora 50 , Ácido Micofenólico/farmacologia , Tacrolimo/farmacologia , Ciclosporina/farmacologia , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/prevenção & controle
5.
Antibiotics (Basel) ; 13(2)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38391502

RESUMO

Different factors, including antimicrobial resistance, may diminish the effectiveness of antibiotic therapy, challenging the management of post-transplant urinary tract infection (UTI). The association of acidic urine pH with microbiological and clinical outcomes was evaluated after fosfomycin or ciprofloxacin therapy in 184 kidney transplant recipients (KTRs) with UTI episodes by Escherichia coli (N = 115) and Klebsiella pneumoniae (N = 69). Initial urine pH, antimicrobial therapy, and clinical and microbiological outcomes, and one- and six-month follow-up were assessed. Fosfomycin was prescribed in 88 (76.5%) E. coli and 46 (66.7%) K. pneumoniae UTI episodes in the total cohort. When the urine pH ≤ 6, fosfomycin was prescribed in 60 (52.2%) E. coli and 29 (42.0%) K. pneumoniae. Initial urine pH ≤ 6 in E. coli UTI was associated with symptomatic episodes (8/60 vs. 0/55, p = 0.04) at one-month follow-up, with a similar trend in those patients receiving fosfomycin (7/47 vs. 0/41, p = 0.09). Acidic urine pH was not associated with microbiological or clinical cure in K. pneumoniae UTI. At pH 5, the ciprofloxacin MIC90 increased from 8 to >8 mg/L in E. coli and from 4 to >8 mg/L in K. pneumoniae. At pH 5, the fosfomycin MIC90 decreased from 8 to 4 mg/L in E. coli and from 512 to 128 mg/L in K. pneumoniae. Acidic urine is not associated with the microbiological efficacy of fosfomycin and ciprofloxacin in KTRs with UTI, but it is associated with symptomatic UTI episodes at one-month follow-up in E. coli episodes.

6.
Clin Infect Dis ; 78(1): 48-56, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-37584344

RESUMO

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.


Assuntos
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 adversos
7.
Emerg Microbes Infect ; 13(1): 2292068, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38054302

RESUMO

Current clinical guidelines support the concomitant administration of seasonal influenza vaccines and COVID-19 mRNA boosters vaccine. Whether dual vaccination may impact vaccine immunogenicity due to an interference between influenza or SARS-CoV-2 antigens is unknown. We aimed to understand the impact of mRNA COVID-19 vaccines administered concomitantly on the immune response to influenza vaccines. For this, 128 volunteers were vaccinated during the 22-23 influenza season. Three groups of vaccination were assembled: FLU vaccine only (46, 35%) versus volunteers that received the mRNA bivalent COVID-19 vaccines concomitantly to seasonal influenza vaccines, FluCOVID vaccine in the same arm (42, 33%) or different arm (40, 31%), respectively. Sera and whole blood were obtained the day of vaccination, +7, and +28 days after for antibody and T cells response quantification. As expected, side effects were increased in individuals who received the FluCOVID vaccine as compared to FLU vaccine only based on the known reactogenicity of mRNA vaccines. In general, antibody levels were high at 4 weeks post-vaccination and differences were found only for the H3N2 virus when administered in different arms compared to the other groups at day 28 post-vaccination. Additionally, our data showed that subjects that received the FluCOVID vaccine in different arm tended to have better antibody induction than those receiving FLU vaccines for H3N2 virus in the absence of pre-existing immunity. Furthermore, no notable differences in the influenza-specific cellular immune response were found for any of the vaccination groups. Our data supports the concomitant administration of seasonal influenza and mRNA COVID-19 vaccines.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacinas contra Influenza , Influenza Humana , Humanos , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vírus da Influenza A Subtipo H3N2 , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Vacinas de mRNA , Estações do Ano , Vacinação
9.
Aten. prim. (Barc., Ed. impr.) ; 55(6): 102629, Jun. 2023. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-221631

RESUMO

The influenza virus has accompanied humans since time immemorial, in the form of annual epidemics and occasional pandemics. It is a respiratory infection with multiple repercussions on people's lives at an individual and social level, as well as representing a significant burden on the health system. This Consensus Document arises from the collaboration of various Spanish scientific societies involved in influenza virus infection. The conclusions drawn are based on the highest quality evidence available in the scientific literature and, failing that, on the opinion of the experts convened. The Consensus Document addresses the clinical, microbiological, therapeutic, and preventive aspects (with respect to the prevention of transmission and in relation to vaccination) of influenza, for both adult and pediatric populations. This Consensus Document aims to help facilitate the clinical, microbiological, and preventive approach to influenza virus infection and, consequently, to reduce its important consequences on the morbidity and mortality of the population.(AU)


El virus de la gripe ha acompañado al ser humano desde tiempo inmemorial, en forma de epidemias anuales y pandemias ocasionales. Se trata de una infección respiratoria con múltiples repercusiones sobre la vida de las personas a nivel individual y social, así como una importante sobrecarga para el sistema sanitario. El presente documento de consenso surge de la colaboración de diversas sociedades científicas españolas implicadas en la atención de la infección por virus de la gripe. Las conclusiones extraídas se han fundamentado en las evidencias de mayor calidad disponibles en la literatura científica y, en su defecto, en la opinión de los expertos convocados. En el documento de consenso se abordan los aspectos clínicos, microbiológicos, terapéuticos y preventivos (respecto de la prevención de la transmisión y con relación a la vacunación) de la gripe, tanto para población pediátrica como para adultos. Este documento de consenso pretende ayudar a facilitar el abordaje clínico, microbiológico y preventivo de la infección por virus de la gripe y, consecuentemente, a disminuir sus importantes consecuencias sobre la morbimortalidad de la población.(AU)


Assuntos
Humanos , Influenza Humana/diagnóstico , Influenza Humana/tratamento farmacológico , Vacinas contra Influenza , Vacinação , Influenza Humana/prevenção & controle , Consenso , Conferências de Consenso como Assunto , Espanha , Infecções Respiratórias
10.
Aten Primaria ; 55(6): 102629, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37119776

RESUMO

The influenza virus has accompanied humans since time immemorial, in the form of annual epidemics and occasional pandemics. It is a respiratory infection with multiple repercussions on people's lives at an individual and social level, as well as representing a significant burden on the health system. This Consensus Document arises from the collaboration of various Spanish scientific societies involved in influenza virus infection. The conclusions drawn are based on the highest quality evidence available in the scientific literature and, failing that, on the opinion of the experts convened. The Consensus Document addresses the clinical, microbiological, therapeutic, and preventive aspects (with respect to the prevention of transmission and in relation to vaccination) of influenza, for both adult and pediatric populations. This Consensus Document aims to help facilitate the clinical, microbiological, and preventive approach to influenza virus infection and, consequently, to reduce its important consequences on the morbidity and mortality of the population.


Assuntos
Doenças Transmissíveis , Influenza Humana , Orthomyxoviridae , Adulto , Criança , Humanos , Influenza Humana/diagnóstico , Influenza Humana/prevenção & controle , Saúde Pública , Medicina Comunitária , Vacinologia
11.
An. pediatr. (2003. Ed. impr.) ; 98(3): 213-227, mar. 2023. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-216881

RESUMO

El virus de la gripe ha acompañado al ser humano desde tiempo inmemorial, en forma de epidemias anuales y pandemias ocasionales. Se trata de una infección respiratoria con múltiples repercusiones sobre la vida de las personas a nivel individual y social y supone una importante sobrecarga para el sistema sanitario. El presente documento de consenso surge de la colaboración de diversas sociedades científicas españolas implicadas en la atención de la infección por el virus de la gripe. Las conclusiones extraídas se han fundamentado en las evidencias de mayor calidad disponibles en la literatura científica y, en su defecto, en la opinión de los expertos convocados. En el documento de consenso se abordan los aspectos clínicos, microbiológicos, terapéuticos y preventivos (respecto de la prevención de la transmisión y en relación con la vacunación) de la gripe, tanto en población pediátrica como en adultos. Este documento de consenso aspira a contribuir a facilitar el abordaje clínico, microbiológico y preventivo de la infección por el virus de la gripe y, consecuentemente, a disminuir sus importantes consecuencias sobre la morbimortalidad de la población. (AU)


The influenza virus has accompanied humans since time immemorial, in the form of annual epidemics and occasional pandemics. It is a respiratory infection with multiple repercussions on people's lives at an individual and social level, as well as representing a significant burden on the health system. This Consensus Document arises from the collaboration of various Spanish scientific societies involved in influenza virus infection. The conclusions drawn are based on the highest quality evidence available in the scientific literature and, failing that, on the opinion of the experts convened. The Consensus Document addresses the clinical, microbiological, therapeutic, and preventive aspects (with respect to the prevention of transmission and in relation to vaccination) of influenza, for both adult and pediatric populations. This Consensus Document aims to help facilitate the clinical, microbiological, and preventive approach to influenza virus infection and, consequently, to reduce its important consequences on the morbidity and mortality of the population. (AU)


Assuntos
Humanos , Antibioticoprofilaxia , Influenza Humana/diagnóstico , Influenza Humana/tratamento farmacológico , Espanha , Sociedades
12.
An Pediatr (Engl Ed) ; 98(3): 213-227, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36813618

RESUMO

The influenza virus has accompanied humans since time immemorial, in the form of annual epidemics and occasional pandemics. It is a respiratory infection with multiple repercussions on people's lives at an individual and social level, as well as representing a significant burden on the health system. This Consensus Document arises from the collaboration of various Spanish scientific societies involved in influenza virus infection. The conclusions drawn are based on the highest quality evidence available in the scientific literature and, failing that, on the opinion of the experts convened. The Consensus Document addresses the clinical, microbiological, therapeutic, and preventive aspects (with respect to the prevention of transmission and in relation to vaccination) of influenza, for both adult and pediatric populations. This Consensus Document aims to help facilitate the clinical, microbiological, and preventive approach to influenza virus infection and, consequently, to reduce its important consequences on the morbidity and mortality of the population.


Assuntos
Doenças Transmissíveis , Influenza Humana , Orthomyxoviridae , Criança , Adulto , Humanos , Influenza Humana/diagnóstico , Influenza Humana/prevenção & controle , Saúde Pública , Medicina Comunitária , Vacinologia
13.
Enferm Infecc Microbiol Clin (Engl Ed) ; 41(2): 111-122, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36759049

RESUMO

The influenza virus has accompanied humans since time immemorial, in the form of annual epidemics and occasional pandemics. It is a respiratory infection with multiple repercussions on people's lives at an individual and social level, as well as representing a significant burden on the health system. This Consensus Document arises from the collaboration of various Spanish scientific societies involved in influenza virus infection. The conclusions drawn are based on the highest quality evidence available in the scientific literature and, failing that, on the opinion of the experts convened. The Consensus Document addresses the clinical, microbiological, therapeutic, and preventive aspects (with respect to the prevention of transmission and in relation to vaccination) of influenza, for both adult and pediatric populations. This Consensus Document aims to help facilitate the clinical, microbiological, and preventive approach to influenza virus infection and, consequently, to reduce its important consequences on the morbidity and mortality of the population.


Assuntos
Doenças Transmissíveis , Influenza Humana , Orthomyxoviridae , Adulto , Criança , Humanos , Influenza Humana/diagnóstico , Influenza Humana/prevenção & controle , Influenza Humana/tratamento farmacológico , Saúde Pública , Medicina Comunitária , Vacinologia
14.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 41(2): 111-122, Feb. 2023. graf, tab
Artigo em Inglês | IBECS | ID: ibc-215781

RESUMO

The influenza virus has accompanied humans since time immemorial, in the form of annual epidemics and occasional pandemics. It is a respiratory infection with multiple repercussions on people's lives at an individual and social level, as well as representing a significant burden on the health system. This Consensus Document arises from the collaboration of various Spanish scientific societies involved in influenza virus infection. The conclusions drawn are based on the highest quality evidence available in the scientific literature and, failing that, on the opinion of the experts convened. The Consensus Document addresses the clinical, microbiological, therapeutic, and preventive aspects (with respect to the prevention of transmission and in relation to vaccination) of influenza, for both adult and pediatric populations. This Consensus Document aims to help facilitate the clinical, microbiological, and preventive approach to influenza virus infection and, consequently, to reduce its important consequences on the morbidity and mortality of the population.(AU)


El virus de la gripe ha acompañado al ser humano desde tiempo inmemorial, en forma de epidemias anuales y pandemias ocasionales. Se trata de una infección respiratoria con múltiples repercusiones sobre la vida de las personas a nivel individual y social, así como una importante sobrecarga para el sistema sanitario. El presente documento de consenso surge de la colaboración de diversas sociedades científicas españolas implicadas en la atención de la infección por virus de la gripe. Las conclusiones extraídas se han fundamentado en las evidencias de mayor calidad disponibles en la literatura científica y, en su defecto, en la opinión de los expertos convocados. En el documento de consenso se abordan los aspectos clínicos, microbiológicos, terapéuticos y preventivos (respecto de la prevención de la transmisión y en relación con la vacunación) de la gripe, tanto para población pediátrica como para adultos. Este documento de consenso pretende ayudar a facilitar el abordaje clínico, microbiológico y preventivo de la infección por virus de la gripe y, consecuentemente, a disminuir sus importantes consecuencias sobre la morbimortalidad de la población.(AU)


Assuntos
Humanos , Vírus da Influenza A , Influenza Humana , Diagnóstico , Terapêutica , Prevenção de Doenças , Vacinas contra Influenza , Doenças Transmissíveis , Espanha , Consenso
16.
Artigo em Inglês | MEDLINE | ID: mdl-33558295

RESUMO

Current guidelines recommend against systematic screening or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of post-transplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range [IQR]: 1.1 - 10.5). Most episodes (96.4% [132/137]) were caused by gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended-spectrum ß-lactamase-producing Enterobacterales [20.4%] and carbapenem-resistant GNB [2.9%]). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval [95%CI]: 31.9 - 48.9) for the whole cohort and 42.3% (95%CI: 31.2 - 54.0) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio [OR]: 2.42; 95%CI: 1.11 - 5.29; P-value = 0.027) and use of fosfomycin as salvage therapy (OR: 8.31; 95%CI: 1.67 - 41.35; P-value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse event were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens.

18.
Transplantation ; 107(3): 762-773, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36367924

RESUMO

BACKGROUND: Isavuconazole has theoretical advantages over other mold-active triazoles for the treatment of invasive aspergillosis and mucormycosis after solid organ transplantation (SOT). The available clinical experience, nevertheless, is scarce. METHODS: We performed a retrospective study including all adult SOT recipients with proven or probable invasive mold disease (IMD) that received isavuconazole for ≥24 h as first-line or salvage therapy at 10 Spanish centers between September 2017 and November 2021. The primary efficacy outcome was clinical response (complete or partial resolution of attributable symptoms and findings) by weeks 6 and 12. Safety outcomes included the rates of treatment-emergent adverse events and premature isavuconazole discontinuation. RESULTS: We included 81 SOT recipients that received isavuconazole for a median of 58.0 days because of invasive aspergillosis (n = 71) or mucormycosis (n = 10). Isavuconazole was used as first-line (72.8%) or salvage therapy due because of previous treatment-emergent toxicity (11.1%) or refractory IMD (7.4%). Combination therapy was common (37.0%), mainly with an echinocandin or liposomal amphotericin B. Clinical response by weeks 6 and 12 was achieved in 53.1% and 54.3% of patients, respectively, and was more likely when isavuconazole was administered as first-line single-agent therapy. At least 1 treatment-emergent adverse event occurred in 17.3% of patients, and 6.2% required premature discontinuation. Daily tacrolimus dose was reduced in two-thirds of patients by a median of 50.0%, although tacrolimus levels remained stable throughout the first month of therapy. CONCLUSIONS: Isavuconazole is a safe therapeutic option for IMD in SOT recipients, with efficacy comparable to other patient groups.


Assuntos
Aspergilose , Infecções Fúngicas Invasivas , Mucormicose , Transplante de Órgãos , Adulto , Humanos , Antifúngicos/efeitos adversos , Mucormicose/tratamento farmacológico , Estudos Retrospectivos , Tacrolimo/uso terapêutico , Fungos , Triazóis , Aspergilose/tratamento farmacológico , Nitrilas , Infecções Fúngicas Invasivas/tratamento farmacológico , Transplante de Órgãos/efeitos adversos , Transplantados
19.
Front Pharmacol ; 14: 1293296, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38273842

RESUMO

Regardless of the clinical impact of human adenovirus (HAdV) infections in the healthy population and its high morbidity in immunosuppressed patients, a specific treatment is still not yet available. In this study, we screened the CM1407 COST Action's chemical library, comprising 1,233 natural products to identify compounds that restrict HAdV infection. Among them, we identified rotenolone, a compound that significantly inhibited HAdV infection. Next, we selected four isoflavonoid-type compounds (e.g., rotenone, deguelin, millettone, and tephrosin), namely rotenoids, structurally related to rotenolone in order to evaluate and characterized in vitro their antiviral activities against HAdV and human cytomegalovirus (HCMV). Their IC50 values for HAdV ranged from 0.0039 µM for rotenone to 0.07 µM for tephrosin, with selective indices ranging from 164.1 for rotenone to 2,429.3 for deguelin. In addition, the inhibition of HCMV replication ranged from 50% to 92.1% at twice the IC50 concentrations obtained in the plaque assay for each compound against HAdV. Our results indicated that the mechanisms of action of rotenolone, deguelin, and tephrosin involve the late stages of the HAdV replication cycle. However, the antiviral mechanism of action of rotenone appears to involve the alteration of the microtubular polymerization, which prevents HAdV particles from reaching the nuclear membrane of the cell. These isoflavonoid-type compounds exert high antiviral activity against HAdV at nanomolar concentrations, and can be considered strong hit candidates for the development of a new class of broad-spectrum antiviral drugs.

20.
J Infect Dis ; 226(9): 1528-1536, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35993155

RESUMO

BACKGROUND: This study describes the genotypic and phenotypic characterization of novel human cytomegalovirus (HCMV) genetic variants of a cohort of 94 clinically resistant HCMV patients. METHODS AND RESULTS: Antiviral-resistant mutations were detected in the UL97, UL54, and UL56 target genes of 25 of 94 (26.6%) patients. The genotype-phenotype correlation study resolved the status of 5 uncharacterized UL54 deoxyribonucleic acid polymerase (G441S, A543V, F460S, R512C, A928T) and 2 UL56 terminase (F345L, P800L) mutations found in clinical isolates. A928T conferred high, triple resistance to ganciclovir, foscarnet, and cidofovir, and A543V had 10-fold reduced susceptibility to cidofovir. Viral growth assays showed G441S, A543V, F345L, and P800L impaired viral growth capacities compared with wild-type AD169 HCMV. Three-dimensional modeling predicted A543V and A928T phenotypes but not R512C, reinforcing the need for individual characterization of mutations by recombinant phenotyping. CONCLUSIONS: Extending mutation databases is crucial to optimize treatments and to improve the assessment of patients with resistant/refractory HCMV infection.


Assuntos
Infecções por Citomegalovirus , DNA Polimerase Dirigida por DNA , Humanos , Cidofovir/uso terapêutico , DNA Polimerase Dirigida por DNA/genética , Proteínas Virais/genética , Farmacorresistência Viral/genética , Ganciclovir/uso terapêutico , Citomegalovirus/genética , Antivirais/uso terapêutico , Fenótipo , Mutação
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