RESUMO
OBJECTIVES: Fungal bloodstream infection (fBSI) following pediatric liver transplantation presents a significant challenge; however, there remains a paucity of guidance regarding antifungal prophylaxis in this population. This study aimed to evaluate the effectiveness of universal antifungal prophylaxis and propose a desirable strategy. METHODS: We enrolled 604 pediatric patients who underwent liver transplantation between 2020 and 2023, including 242 patients with empirical prophylaxis and 362 patients with universal prophylaxis. Univariate and multivariate logistic regression analyses were performed to identify independent factors for fBSI. RESULTS: Eight (2.2%) pediatric recipients in the universal prophylaxis group and 13 (5.4%) in the empirical group developed fBSI (P = 0.038). Universal prophylaxis was a protective factor (P = 0.044), while high-volume intraoperative plasma transfusion and deceased donor liver transplantation were independent risk factors for fBSI (P = 0.035 and 0.008, respectively). Universal antifungal strategy showed an increased overall survival trend after liver transplantation although without significant statistical difference (P = 0.217). Patients with fBSI had poorer survival than those without fBSI (P <0.001). CONCLUSIONS: Universal prophylaxis strategy for fBSI in pediatrics after liver transplantation is desirable as it could markedly decrease the occurrence of fBSI. Pediatric patients with deceased donors and high-volume intraoperative transfusion should be paid more attention to preventing fBSI.
Assuntos
Antifúngicos , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Feminino , Antifúngicos/uso terapêutico , Antifúngicos/administração & dosagem , Estudos Retrospectivos , Criança , Pré-Escolar , Lactente , Fatores de Risco , Adolescente , Fungemia/prevenção & controle , Fungemia/microbiologia , TransplantadosRESUMO
OBJECTIVE: Studies evaluating the incidence, source, and preventability of hospital-onset bacteremia and fungemia (HOB), defined as any positive blood culture obtained after 3 calendar days of hospital admission, are lacking in low- and middle-income countries (LMICs). DESIGN, SETTING, AND PARTICIPANTS: All consecutive blood cultures performed for 6 months during 2020-2021 in 2 hospitals in India were reviewed to assess HOB and National Healthcare Safety Network (NHSN) reportable central-line-associated bloodstream infection (CLABSI) events. Medical records of a convenience sample of 300 consecutive HOB events were retrospectively reviewed to determine source and preventability. Univariate and multivariable logistic regression analyses were performed to identify factors associated with HOB preventability. RESULTS: Among 6,733 blood cultures obtained from 3,558 hospitalized patients, there were 409 and 59 unique HOB and NHSN-reportable CLABSI events, respectively. CLABSIs accounted for 59 (14%) of 409 HOB events. There was a moderate but non-significant correlation (r = 0.51; P = .070) between HOB and CLABSI rates. Among 300 reviewed HOB cases, CLABSIs were identified as source in only 38 (13%). Although 157 (52%) of all 300 HOB cases were potentially preventable, CLABSIs accounted for only 22 (14%) of these 157 preventable HOB events. In multivariable analysis, neutropenia, and sepsis as an indication for blood culture were associated with decreased odds of HOB preventability, whereas hospital stay ≥7 days and presence of a urinary catheter were associated with increased likelihood of preventability. CONCLUSIONS: HOB may have utility as a healthcare-associated infection metric in LMIC settings because it captures preventable bloodstream infections beyond NHSN-reportable CLABSIs.
Assuntos
Bacteriemia , Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Infecção Hospitalar , Fungemia , Sepse , Humanos , Fungemia/epidemiologia , Fungemia/prevenção & controle , Infecções Relacionadas a Cateter/epidemiologia , Estudos Retrospectivos , Bacteriemia/epidemiologia , Bacteriemia/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Hospitais , Sepse/epidemiologiaRESUMO
OBJECTIVE: To assess preventability of hospital-onset bacteremia and fungemia (HOB), we developed and evaluated a structured rating guide accounting for intrinsic patient and extrinsic healthcare-related risks. DESIGN: HOB preventability rating guide was compared against a reference standard expert panel. PARTICIPANTS: A 10-member panel of clinical experts was assembled as the standard of preventability assessment, and 2 physician reviewers applied the rating guide for comparison. METHODS: The expert panel independently rated 82 hypothetical HOB scenarios using a 6-point Likert scale collapsed into 3 categories: preventable, uncertain, or not preventable. Consensus was defined as concurrence on the same category among ≥70% experts. Scenarios without consensus were deliberated and followed by a second round of rating.Two reviewers independently applied the rating guide to adjudicate the same 82 scenarios in 2 rounds, with interim revisions. Interrater reliability was evaluated using the κ (kappa) statistic. RESULTS: Expert panel consensus criteria were met for 52 scenarios (63%) after 2 rounds.After 2 rounds, guide-based rating matched expert panel consensus in 40 of 52 (77%) and 39 of 52 (75%) cases for reviewers 1 and 2, respectively. Agreement rates between the 2 reviewers were 84% overall (κ, 0.76; 95% confidence interval [CI], 0.64-0.88]) and 87% (κ, 0.79; 95% CI, 0.65-0.94) for the 52 scenarios with expert consensus. CONCLUSIONS: Preventability ratings of HOB scenarios by 2 reviewers using a rating guide matched expert consensus in most cases with moderately high interreviewer reliability. Although diversity of expert opinions and uncertainty of preventability merit further exploration, this is a step toward standardized assessment of HOB preventability.
Assuntos
Bacteriemia , Fungemia , Médicos , Humanos , Fungemia/diagnóstico , Fungemia/prevenção & controle , Reprodutibilidade dos Testes , Hospitais , Bacteriemia/diagnóstico , Bacteriemia/prevenção & controleRESUMO
BACKGROUND: Bloodstream infection is an untoward effect of probiotic administration described by case reports and a cited reason to avoid using in the critically ill. The incidence rate of bloodstream infection in a population administered probiotics remains unknown. METHODS: A retrospective observational analysis of incident Saccharomyces cerevisiae fungemia in a population of hospitalised patients administered Saccharomyces boulardii for primary prevention of hospital-onset Clostridioides difficile infection. Adult patients admitted to an inpatient medical unit for 48-h or more between January 1, 2016 and December 31, 2019 are included. Facility medication administration records and microbiology records were evaluated for S boulardii probiotic administration and incidence of S cerevisiae positive blood cultures. Microbiologic identification methods were unable to distinguish S cerevisiae from S boulardii. RESULTS: Administration of S boulardii probiotic occurred in 16,404 of 46,729 patients analysed. S cerevisiae fungemia was identified in 18 probiotic recipients (0.11%). The observed incidence of fungemia attributable to S boulardii administration is 1.70 cases per 10,000 patient-days. Central-line days numbered 52,949 yielding an incidence of 0.26 cases of S cerevisiae per 1,000 central-line days. Intensive care unit admission was significantly associated with an increase in the risk of S cerevisiae (OR 6.55, CI 2.28-18.87), incidence rate of 0.47 cases per 1,000 patient-days. CONCLUSION: The risk of bloodstream infection as a result of S boulardii probiotic use appears restricted to S boulardii recipients. The risk for probiotic-related bloodstream infection does not appear greater than the risk of any hospital-acquired bloodstream infection both inside and outside of the intensive care unit.
Assuntos
Infecção Hospitalar , Fungemia , Probióticos , Saccharomyces boulardii , Saccharomyces cerevisiae/patogenicidade , Adulto , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Fungemia/epidemiologia , Fungemia/prevenção & controle , Humanos , Incidência , Probióticos/efeitos adversos , Estudos RetrospectivosRESUMO
Evidence to inform the management of systemic fungal infections in the setting of a cardiac implantable electronic devices (CIED), such as a permanent pacemaker or implantable cardioverter-defibrillator, is scant and limited to case reports and series. The available literature suggests high morbidity and mortality. To better characterize the shared experience of these cases and their outcomes, we performed a systematic review. We investigated all published reports of systemic fungal infections-fungemia and fungal vegetative disease-in the context of CIED, drawing from PubMed, EMBASE, and the Cochrane database of systematic reviews, inclusive of patients who received treatment between January 2000 and May 2020. Exclusion criteria included presence of ventricular assist device and concurrent bacteremia, bacterial endocarditis, bacterial vegetative infection, or viremia. Among 6261 screened articles, 48 cases from 41 individual studies were identified. Candida and Aspergillus species were the most commonly isolated fungi. There was significant heterogeneity in antifungal medication selection and duration. CIED extraction-either transvenous or surgical-was associated with increased survival to hospital discharge (92%) and clinical recovery at latest follow-up (81%), compared to cases where CIED extraction was deferred (56% and 40%, respectively). Importantly, there were no prospective data, and the data were limited to individual case reports and one small case series. In summary, CIED extraction is associated with improved fungal clearance and patient survival. Reported antifungal regimens are heterogeneous and nonuniform. Prospective studies are needed to verify these results and define optimal antifungal regimens.
Assuntos
Desfibriladores Implantáveis , Fungemia/microbiologia , Fungemia/prevenção & controle , Marca-Passo Artificial , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/prevenção & controle , Humanos , Fatores de RiscoAssuntos
Anfotericina B/administração & dosagem , Dermatomicoses/patologia , Infecções por HIV/imunologia , Hospedeiro Imunocomprometido/imunologia , Recém-Nascido de muito Baixo Peso , Umbigo/patologia , Fármacos Anti-HIV/administração & dosagem , Cesárea/métodos , Desbridamento/métodos , Dermatomicoses/imunologia , Dermatomicoses/terapia , Quimioterapia Combinada , Fungemia/prevenção & controle , Idade Gestacional , Infecções por HIV/congênito , Humanos , Lactente , Recém-Nascido Prematuro , Infusões Intravenosas , Masculino , Necrose/microbiologia , Necrose/terapia , Prognóstico , Medição de Risco , Resultado do Tratamento , Veias UmbilicaisRESUMO
BACKGROUND: We applied an in vitro model to evaluate the efficacy of a heparinized 40% ethanol-based lock solution in a wide variety of clinical isolates causing C-RBSI. METHODS: A total of 100 clinical strains were collected retrospectively from the blood of patients with C-RBSI. The reduction in biomass and metabolic activity of biofilms was measured using the crystal violet (CV) assay and XTT assay, respectively. Regrowth inhibition (RI) was measured within 24 hours and 72 hours of ethanol lock therapy. Percentage reduction of ≥ 85% in RI was considered to be successful. RESULTS: Ethanol lock was more effective in reducing metabolic activity than in reducing biomass (83% vs. 50%, respectively). Percentages of RI diminished as regrowth was prolonged (57% for 24 hours and 17% for 72 hours of regrowth). No statistically significant intraspecies differences were found in biofilm reduction or in RI (p>0.05). CONCLUSIONS: The use of heparinized 40% ethanol lock solution for 72 hours significantly reduced biomass and metabolic activity in clinical isolates from patients with C-RBSI. However, as biofilm has an important regrowth rate, 40% ethanol solution was not able to fully eradicate biofilm in vitro.
Assuntos
Anti-Infecciosos/administração & dosagem , Biofilmes/efeitos dos fármacos , Infecções Relacionadas a Cateter/prevenção & controle , Bacteriemia/microbiologia , Bacteriemia/prevenção & controle , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Biomassa , Infecções Relacionadas a Cateter/microbiologia , Etanol/administração & dosagem , Fungemia/microbiologia , Fungemia/prevenção & controle , Fungos/efeitos dos fármacos , Fungos/metabolismo , Heparina/administração & dosagem , Humanos , Técnicas In Vitro , Modelos Biológicos , SoluçõesRESUMO
OBJECTIVE: To ascertain opinions regarding etiology and preventability of hospital-onset bacteremia and fungemia (HOB) and perspectives on HOB as a potential outcome measure reflecting quality of infection prevention and hospital care. DESIGN: Cross-sectional survey. PARTICIPANTS: Hospital epidemiologists and infection preventionist members of the Society for Healthcare Epidemiology of America (SHEA) Research Network. METHODS: A web-based, multiple-choice survey was administered via the SHEA Research Network to 133 hospitals. RESULTS: A total of 89 surveys were completed (67% response rate). Overall, 60% of respondents defined HOB as a positive blood culture on or after hospital day 3. Central line-associated bloodstream infections and intra-abdominal infections were perceived as the most frequent etiologies. Moreover, 61% thought that most HOB events are preventable, and 54% viewed HOB as a measure reflecting a hospital's quality of care. Also, 29% of respondents' hospitals already collect HOB data for internal purposes. Given a choice to publicly report central-line-associated bloodstream infections (CLABSIs) and/or HOB, 57% favored reporting either HOB alone (22%) or in addition to CLABSI (35%) and 34% favored CLABSI alone. CONCLUSIONS: Among the majority of SHEA Research Network respondents, HOB is perceived as preventable, reflective of quality of care, and potentially acceptable as a publicly reported quality metric. Further studies on HOB are needed, including validation as a quality measure, assessment of risk adjustment, and formation of evidence-based bundles and toolkits to facilitate measurement and improvement of HOB rates.
Assuntos
Bacteriemia/psicologia , Infecção Hospitalar/psicologia , Epidemiologistas/psicologia , Fungemia/psicologia , Profissionais Controladores de Infecções/psicologia , Bacteriemia/prevenção & controle , Infecção Hospitalar/microbiologia , Estudos Transversais , Fungemia/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Hospitais , Humanos , Qualidade da Assistência à Saúde , Inquéritos e QuestionáriosRESUMO
Hospital-onset bacteremia and fungemia (HOB), a potential measure of healthcare-associated infections, was evaluated in a pilot study among 60 patients across 3 hospitals. Two-thirds of all HOB events and half of nonskin commensal HOB events were judged as potentially preventable. Follow-up studies are needed to further develop this measure.
Assuntos
Bacteriemia/prevenção & controle , Infecção Hospitalar/prevenção & controle , Fungemia/prevenção & controle , Feminino , Hospitais , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto , Medicina PreventivaRESUMO
Few cases of cryptococcal infection following umbilical cord blood transplantation (UCBT) have been reported. We report a case, where cryptococcal infection occurred soon after rapidly reducing the dose of tacrolimus in a UCBT recipient who received micafungin prophylaxis during the early phase of transplantation. The etiology of cryptococcal infection following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including UCBT, might be associated with rapid dose-reduction of calcineurin inhibitors, such as tacrolimus during early phase of allo-HSCT. To our knowledge, this is the first English-language report to describe in detail a case of cryptococcal meningitis with fungemia during early phase of UCBT.
Assuntos
Inibidores de Calcineurina/administração & dosagem , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Fungemia/microbiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Meningite Criptocócica/microbiologia , Tacrolimo/administração & dosagem , Antibioticoprofilaxia/métodos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/isolamento & purificação , Relação Dose-Resposta a Droga , Fungemia/prevenção & controle , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Meningite Criptocócica/prevenção & controle , Micafungina/farmacologia , Micafungina/uso terapêutico , Pessoa de Meia-Idade , Transplante Homólogo/efeitos adversosAssuntos
Antibioticoprofilaxia/métodos , Fungemia/diagnóstico , Leucemia Mieloide Aguda/imunologia , Trichosporon/isolamento & purificação , Tricosporonose/diagnóstico , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Biópsia , Evolução Fatal , Feminino , Fungemia/tratamento farmacológico , Fungemia/microbiologia , Fungemia/prevenção & controle , Humanos , Hospedeiro Imunocomprometido , Itraconazol/uso terapêutico , Pessoa de Meia-Idade , Pele/microbiologia , Pele/patologia , Falha de Tratamento , Tricosporonose/tratamento farmacológico , Tricosporonose/microbiologia , Tricosporonose/prevenção & controleRESUMO
Candidemia is a major cause of healthcare-associated infections. We describe a large outbreak of Candida krusei bloodstream infections among infants in Gauteng Province, South Africa, during a 4-month period; a series of candidemia and bacteremia outbreaks in the neonatal unit followed. We detected cases by using enhanced laboratory surveillance and audited hospital wards by environmental sampling and epidemiologic studies. During July-October 2014, among 589 patients, 48 unique cases of C. krusei candidemia occurred (8.2% incidence). Risk factors for candidemia on multivariable analyses were necrotizing enterocolitis, birthweight <1,500 g, receipt of parenteral nutrition, and receipt of blood transfusion. Despite initial interventions, outbreaks of bloodstream infection caused by C. krusei, rarer fungal species, and bacterial pathogens continued in the neonatal unit through July 29, 2016. Multiple factors contributed to these outbreaks; the most functional response is to fortify infection prevention and control.
Assuntos
Bacteriemia/epidemiologia , Infecção Hospitalar , Surtos de Doenças , Fungemia/epidemiologia , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/microbiologia , Bacteriemia/microbiologia , Bacteriemia/prevenção & controle , Criança , Feminino , Fungemia/microbiologia , Fungemia/prevenção & controle , História do Século XXI , Humanos , Recém-Nascido , Masculino , Vigilância em Saúde Pública , Fatores de Risco , África do Sul/epidemiologiaRESUMO
OBJECTIVE: To perform a cost-effectiveness analysis of skin antiseptic solutions (chlorhexidine-alcohol (CHG) versus povidone iodine-alcohol solution (PVI)) for the prevention of intravascular-catheter-related bloodstream infections (CRBSI) in intensive care unit (ICU) in France based on an open-label, multicentre, randomised, controlled trial (CLEAN). DESIGN: A 100-day time semi-markovian model was performed to be fitted to longitudinal individual patient data from CLEAN database. This model includes eight health states and probabilistic sensitivity analyses on cost and effectiveness were performed. Costs of intensive care unit stay are based on a French multicentre study and the cost-effectiveness criterion is the cost per patient with catheter-related bloodstream infection avoided. PATIENTS: 2,349 patients (age≥18 years) were analyzed to compare the 1-time CHG group (CHG-T1, 588 patients), the 4-time CHG group (CHG-T4, 580 patients), the 1-time PVI group (PVI-T1, 587 patients), and the 4-time PVI group (PVI-T4, 594 patients). INTERVENTION: 2% chlorhexidine-70% isopropyl alcohol (chlorhexidine-alcohol) compared to 5% povidone iodine-69% ethanol (povidone iodine-alcohol). RESULTS: The mean cost per alive, discharged or dead patient was of 23,798 (95% confidence interval: 20,584; 34,331), 21,822 (18,635; 29,701), 24,874 (21,011; 31,678), and 24,201 (20,507; 29,136) for CHG-T1, CHG-T4, PVI-T1, and PVI-T4, respectively. The mean number of patients with CRBSI per 1000 patients was of 3.49 (0.42; 12.57), 6.82 (1.86; 17.38), 26.04 (14.64; 42.58), and 23.05 (12.32; 39.09) for CHG-T1, CHG-T4, PVI-T1, and PVI-T4, respectively. In comparison to the 1-time PVI solution, the 1-time CHG solution avoids 22.55 CRBSI /1,000 patients, and saves 1,076 per patient. This saving is not statistically significant at a 0.05 level because of the overlap of 95% confidence intervals for mean costs per patient in each group. Conversely, the difference in effectiveness between the CHG-T1 solution and the PVI-T1 solution is statistically significant. CONCLUSIONS: The CHG-T1 solution is more effective at the same cost than the PVI-T1 solution. CHG-T1, CHG-T4 and PVI-T4 solutions are statistically comparable for cost and effectiveness. This study is based on the data from the RCT from 11 French intensive care units registered with www.clinicaltrials.gov (NCT01629550).
Assuntos
Álcoois/uso terapêutico , Bacteriemia/prevenção & controle , Infecções Relacionadas a Cateter/prevenção & controle , Clorexidina/uso terapêutico , Análise Custo-Benefício/métodos , Fungemia/prevenção & controle , Povidona-Iodo/uso terapêutico , 2-Propanol/economia , 2-Propanol/uso terapêutico , Álcoois/economia , Bacteriemia/economia , Infecções Relacionadas a Cateter/economia , Clorexidina/economia , Etanol/economia , Etanol/uso terapêutico , Feminino , França , Fungemia/economia , Humanos , Unidades de Terapia Intensiva , Tempo de Internação/economia , Masculino , Modelos Econômicos , Povidona-Iodo/economia , Resultado do TratamentoRESUMO
Among emerging non-albicans Candida species, Candida parapsilosis is of particular concern as a cause of nosocomial bloodstream infections in neonatal and intensive care unit patients. While fluconazole and echinocandins are considered effective treatments for such infections, recent reports of fluconazole and echinocandin resistance in C. parapsilosis indicate a growing problem. The present study describes a novel mechanism of antifungal resistance in this organism affecting susceptibility to azole and echinocandin antifungals in a clinical isolate obtained from a patient with prosthetic valve endocarditis. Transcriptome analysis indicated differential expression of several genes in the resistant isolate, including upregulation of ergosterol biosynthesis pathway genes ERG2, ERG5, ERG6, ERG11, ERG24, ERG25, and UPC2 Whole-genome sequencing revealed that the resistant isolate possessed an ERG3 mutation resulting in a G111R amino acid substitution. Sterol profiles indicated a reduction in sterol desaturase activity as a result of this mutation. Replacement of both mutant alleles in the resistant isolate with the susceptible isolate's allele restored wild-type susceptibility to all azoles and echinocandins tested. Disruption of ERG3 in the susceptible and resistant isolates resulted in a loss of sterol desaturase activity, high-level azole resistance, and an echinocandin-intermediate to -resistant phenotype. While disruption of ERG3 in C. albicans resulted in azole resistance, echinocandin MICs, while elevated, remained within the susceptible range. This work demonstrates that the G111R substitution in Erg3 is wholly responsible for the altered azole and echinocandin susceptibilities observed in this C. parapsilosis isolate and is the first report of an ERG3 mutation influencing susceptibility to the echinocandins.
Assuntos
Antifúngicos/farmacologia , Azóis/farmacologia , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/genética , Equinocandinas/farmacologia , Oxirredutases/genética , Azóis/metabolismo , Candida parapsilosis/isolamento & purificação , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Infecção Hospitalar/prevenção & controle , Farmacorresistência Fúngica Múltipla/genética , Equinocandinas/metabolismo , Ergosterol/biossíntese , Ergosterol/genética , Fungemia/tratamento farmacológico , Fungemia/microbiologia , Fungemia/prevenção & controle , Dosagem de Genes/genética , Genoma Fúngico/genética , Humanos , Testes de Sensibilidade Microbiana , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
The pathogen safety of blood/plasma-derived products has historically been a subject of significant concern to the medical community. Measures such as donor selection and blood screening have contributed to increase the safety of these products, but pathogen transmission does still occur. Reasons for this include lack of sensitivity/specificity of current screening methods, lack of reliable screening tests for some pathogens (e.g. prions) and the fact that many potentially harmful infectious agents are not routinely screened for. Methods for the purification/inactivation of blood/plasma-derived products have been developed in order to further reduce the residual risk, but low concentrations of pathogens do not necessarily imply a low level of risk for the patient and so the overall challenge of minimising risk remains. This review aims to discuss the variable level of pathogenic risk and describes the current screening methods used to prevent/detect the presence of pathogens in blood/plasma-derived products.
Assuntos
Bacteriemia/prevenção & controle , Patógenos Transmitidos pelo Sangue/isolamento & purificação , Fungemia/prevenção & controle , Parasitemia/prevenção & controle , Viremia/prevenção & controle , Bacteriemia/etiologia , Bacteriemia/transmissão , Transtornos da Coagulação Sanguínea/terapia , Transfusão de Componentes Sanguíneos/efeitos adversos , Doadores de Sangue/ética , Cromatografia por Troca Iônica/instrumentação , Cromatografia por Troca Iônica/métodos , Fungemia/etiologia , Fungemia/transmissão , HIV-1/isolamento & purificação , Hepacivirus/isolamento & purificação , Vírus da Hepatite B/isolamento & purificação , Humanos , Parasitemia/etiologia , Parasitemia/transmissão , Risco , Ultrafiltração/instrumentação , Viremia/etiologia , Viremia/transmissãoRESUMO
Antifungal prophylaxis may be required in high-risk patients undergoing liver transplantation and for that reason we aimed to verify its role and its related impact on the graft. From January 2006 throughout 2012, 250 liver transplants were evaluated and 54 patients identified as being at higher risk were randomly selected to undergo the following schedule: 28 patients received liposomal amphotericin B and 26 received caspofungin. We evaluated, throughout 12 months, renal and liver function tests, bacterial and fungal infection episodes, and intensive care unit (ICU) stay, as well as the Th1 and Th2 cytokine network. Differences were analyzed according to non-parametric tests (two-tailed p values). Neither of the groups showed episodes of invasive fungal infection during the 12 months follow-up; however, patients receiving prophylaxis with liposomal amphotericin B had reduced episodes of bacterial infections coupled with an improved immune system response compared with those receiving caspofungin. Finally, a reduced stay in the ICU was also observed. In conclusion, even if the results of liposomal amphotericin B and caspofungin prophylaxis strategies did not differ in terms of invasive fungal infection rate, patients receiving prophylaxis with liposomal amphotericin B had a reduced ICU stay and an improved Th2 status, as well as a reduced number of post-transplant bacterial infections. Further studies are required to better address and evaluate these findings.
Assuntos
Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Quimioprevenção/métodos , Equinocandinas/administração & dosagem , Fungemia/prevenção & controle , Transplante de Fígado , Adulto , Idoso , Caspofungina , Feminino , Seguimentos , Humanos , Hospedeiro Imunocomprometido , Tempo de Internação , Lipopeptídeos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Resultado do TratamentoRESUMO
BACKGROUND: Antifungal prophylaxis with a new oral tablet formulation of posaconazole may be beneficial to patients at high risk for invasive fungal disease. A two-part (Phase 1B/3) study evaluated posaconazole tablet pharmacokinetics (PK) and safety. METHODS: Patients with neutropenia following chemotherapy for haematological malignancy or recipients of allogeneic HSCT receiving prophylaxis or treatment for graft-versus-host disease received 300 mg posaconazole (as tablets) once daily (twice daily on day 1) for up to 28 days without regard to food intake. Weekly trough PK sampling was performed during therapy, and a subset of patients had sampling on days 1 and 8. Cmin-evaluable subjects received ≥6 days of dosing, and were compliant with specified sampling timepoints. Steady-state PK parameters, safety, clinical failure and survival to day 65 were assessed. ClinicalTrials.gov, NCT01777763; EU Clinical Trials Register, EUDRA-CT 2008-006684-36. RESULTS: Two hundred and ten patients received 300 mg posaconazole (as tablets) once daily. Among Cmin-evaluable subjects (nâ=â186), steady-state mean Cmin was 1720 ng/mL (rangeâ=â210-9140). Steady-state Cmin was ≥700 ng/mL in 90% of subjects with 5% (10 of 186) <500 ng/mL and 5% (10 of 186) 500-700 ng/mL. Six (3%) patients had steady-state Cmin ≥3750 ng/mL. One patient (<1%) had an invasive fungal infection. The most common treatment-related adverse events were nausea (11%) and diarrhoea (8%). There was no increase in adverse event frequency with higher posaconazole exposure. CONCLUSIONS: In patients at high risk for invasive fungal disease, 300 mg posaconazole (as tablets) once daily was well tolerated and demonstrated a safety profile similar to that reported for posaconazole oral suspension: most patients (99%) achieved steady-state pCavg exposures >500 ng/mL and only one patient (<1%) had a pCavg <500 ng/mL.
Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Quimioprevenção/métodos , Fungemia/prevenção & controle , Comprimidos/administração & dosagem , Triazóis/administração & dosagem , Triazóis/farmacocinética , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/efeitos adversos , Quimioprevenção/efeitos adversos , Feminino , Neoplasias Hematológicas/complicações , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Plasma/química , Análise de Sobrevida , Comprimidos/efeitos adversos , Triazóis/efeitos adversos , Adulto JovemRESUMO
Bloodstream infection due to Rhodotorula glutinis is extremely rare and mostly associated with underlying immunosuppression or cancer. Vascular access devices provide the necessary surfaces for biofilm formation and are currently responsible for a significant percentage of human infections. In this work, we describe a rare case of central venous catheter-related Rhodotorula glutinis fungemia in a female patient with acute myelogenous leukemia in remission. The timely removal of central venous catheter was an essential element for overcoming this CVC-related Rhodotorula fungemia.
Assuntos
Cateteres Venosos Centrais/efeitos adversos , Cateteres Venosos Centrais/microbiologia , Fungemia/etiologia , Fungemia/microbiologia , Rhodotorula/patogenicidade , Remoção de Dispositivo , Feminino , Fungemia/prevenção & controle , Humanos , Hospedeiro Imunocomprometido , Leucemia Mieloide Aguda , Pessoa de Meia-Idade , Rhodotorula/isolamento & purificaçãoRESUMO
Coccidioidomycosis, or valley fever, is a growing health concern endemic to the southwestern United States. Safer, more effective, and more easily administered drugs are needed especially for severe, chronic, or unresponsive infections. The novel fungal CYP51 inhibitor VT-1161 demonstrated in vitro antifungal activity, with MIC50 and MIC90 values of 1 and 2 µg/ml, respectively, against 52 Coccidioides clinical isolates. In the initial animal study, oral doses of 10 and 50 mg/kg VT-1161 significantly reduced fungal burdens and increased survival time in a lethal respiratory model in comparison with treatment with a placebo (P < 0.001). Oral doses of 25 and 50 mg/kg VT-1161 were similarly efficacious in the murine central nervous system (CNS) model compared to placebo treatment (P < 0.001). All comparisons with the positive-control drug, fluconazole at 50 mg/kg per day, demonstrated either statistical equivalence or superiority of VT-1161. VT-1161 treatment also prevented dissemination of infection from the original inoculation site to a greater extent than fluconazole. Many of these in vivo results can be explained by the long half-life of VT-1161 leading to sustained high plasma levels. Thus, the efficacy and pharmacokinetics of VT-1161 are attractive characteristics for long-term treatment of this serious fungal infection.
Assuntos
Inibidores de 14-alfa Desmetilase/farmacologia , Antifúngicos/farmacologia , Coccidioides/efeitos dos fármacos , Coccidioidomicose/tratamento farmacológico , Fluconazol/farmacologia , Fungemia/prevenção & controle , Piridinas/farmacologia , Tetrazóis/farmacologia , Inibidores de 14-alfa Desmetilase/sangue , Inibidores de 14-alfa Desmetilase/farmacocinética , Animais , Antifúngicos/sangue , Antifúngicos/farmacocinética , Coccidioides/enzimologia , Coccidioides/crescimento & desenvolvimento , Coccidioidomicose/microbiologia , Coccidioidomicose/mortalidade , Coccidioidomicose/patologia , Modelos Animais de Doenças , Feminino , Fluconazol/sangue , Fluconazol/farmacocinética , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fungemia/microbiologia , Fungemia/mortalidade , Fungemia/patologia , Meia-Vida , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Piridinas/sangue , Piridinas/farmacocinética , Esterol 14-Desmetilase/genética , Esterol 14-Desmetilase/metabolismo , Análise de Sobrevida , Tetrazóis/sangue , Tetrazóis/farmacocinética , Resultado do TratamentoRESUMO
Invasive aspergillosis (IA) is a major cause of morbidity and mortality in immunocompromised adults and children, the number of which has been continuously increasing in the last decades. The purpose of our review was to provide epidemiological, clinical, and biological data and antifungal treatment options in the pediatric population. Several biological assays (galactomannan enzyme immunoassay, ß-D-glucan, detection of Aspergillus spp. DNA) have proven useful adjuncts for the diagnosis of IA in adult studies. However, data on these assays in children is limited by small sample sizes and sometimes conflicting results concerning their sensitivity/specificity. Pediatric treatment recommendations are mainly extrapolated from results of clinical trials performed in adults. It is thus necessary to develop new antifungal formulations specifically adapted to the pediatric population and to evaluate their pharmacokinetic/pharmacodynamic profile, their safety, and their effectiveness in infants and children.