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BACKGROUND: Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates. OBJECTIVES: Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality. METHODS: This multicentre retrospective cohort study (January 2014-December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses. RESULTS: The study included 215 patients, mostly male (nâ=â158, 73%) with HIV infection (nâ=â187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (nâ=â19, 90%), acute kidney injury (nâ=â96, 59%), hypokalaemia (nâ=â73, 55%) and infusion reactions (nâ=â44, 20%) during treatment. CONCLUSIONS: We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis.
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PURPOSE: Data on the real-life use of amphotericin B lipid complex (ABLC) compared with other available formulations are limited. This study aimed to evaluate the effectiveness, tolerability, and safety of different amphotericin B (AMB) intravenously administered in the context of hospital practice for the treatment of invasive fungal infections (IFI) and to provide new insights into the profile of ABLC. METHODS: This is a multicenter, retrospective, observational study conducted at 10 tertiary Brazilian hospitals. Patients first exposed to any formulation of AMB for treating endemic and opportunistic IFI who had received at least 2 intravenous doses were screened. Retrospective data (from January 2014 to December 2019) were extracted from the patients' medical records. Clinical parameters were examined pre- and post-treatment to determine effectiveness; acute infusion-related side effects (IRSE) and drug interruption to determine tolerability; and adverse events, toxicity, and treatment interruption were stated to analyze safety. FINDINGS: Overall, 1879 medical records of patients were identified. The median (interquartile rate) duration of treatment was 14 (7-21) days. The overall success rate (95% confidence interval [CI]) was 65% (95% CI 60-65). ABLC proved to be effective among AMB formulations with 59% (95% CI 55.6-62.5) within complete response. This was significantly higher in patients who received the drug for a longer period, ≥4 weeks compared to <1 week treatment (P < 0.001). IRSE was observed in 446 (23.7%) patients. Eight cases (1.4%) of severe IRSE in pediatrics and 14 (1.1%) in adults resulted in treatment discontinuation. Regarding safety, 637 (33.9%) patients presented some alteration in creatinine levels during AMB exposure, and 89 (4.74%) had to interrupt or discontinue the drug within the first 14 days of therapy because of renal dysfunction. Overall mortality was 34%. IMPLICATIONS: ABLC is an effective formulation for the treatment of invasive fungal infections, with few adverse events leading to drug discontinuation or lethal outcomes. Furthermore, this real-life study confirmed the comparative safety of AMB lipid formulations versus AMB deoxycholate.
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Anfotericina B , Antifúngicos , Infecciones Fúngicas Invasoras , Humanos , Estudios Retrospectivos , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Anfotericina B/efectos adversos , Anfotericina B/administración & dosificación , Anfotericina B/uso terapéutico , Masculino , Femenino , Antifúngicos/efectos adversos , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Anciano , Brasil , Adolescente , Adulto JovenRESUMEN
A incidência de infecções fúngicas invasivas tem aumentado, como consequência do contingente cada vez maior de pacientes com imunossupressão. O tratamento de infecções fúngicas com anfotericina B (AmB) está associado a efeitos adversos importantes, como nefrotoxicidade e toxicidade hematológica. Nesta revisão buscou-se abordar os estudos sobre AmB nas diferentes formulações, focando em suas características farmacológicas e toxicidade. Formulações lipídicas de AmB estão associadas a um risco menor de nefrotoxicidade, entretanto ainda há controvérsia sobre diferenças entre as duas formulações lipídicas de AmB disponíveis. Diferenças em relação ao perfil imunomodulatório e ligação a lipoproteínas podem explicar parte das diferenças clínicas existentes entre as formulações de AmB. A maioria dos estudos clínicos que avaliou a nefrotoxicidade associada à AmB em diferentes formulações não utilizou critérios validados para classificação do dano renal, o que dificulta sua comparação. A toxicidade hematológica relacionada ao uso de AmB é um fenômeno descrito desde os primórdios do seu uso clínico, entretanto poucos dados existem sobre sua frequência, fatores de risco e impacto nos desfechos clínicos. Dados precisos, e adequados ao contexto local, sobre a toxicidade de AmB nas suas diferentes formulações são necessários para uma adequada avaliação dos aspectos de farmacoeconomia e custo-efetividade...
Invasive fungal infections have emerged in recent years, as a consequence of increasing numbers of immunosuppressed patients. Treatment of these conditions with amphotericin B (AmB) has been associated with important side effects, such as nephrotoxicity and hematological toxicity. In this review we aimed to assess studies about different formulations of AmB, focusing on pharmacological properties and toxicity. Lipid formulations of AmB have been linked to a lower risk of nephrotoxicity; however, there is still controversy about differences between the two available lipid formulations. Differences in immunomodulatory profile and lipoprotein binding could partly explain clinical inequalities among AmB formulations. Most clinical trials that evaluated AmB-associated nephrotoxicity did not use validated criteria for renal injury classification, impairing comparability. Hematological toxicity associated with AmB treatments is an occurrence described since the beginning of its clinical use; nevertheless, few data exist about its frequency, risk factors, and clinical impact. Clear and more precise information, derived from local studies, is needed to an adequate evaluation about pharmacoeconomic aspects of AmB treatment and cost-effectiveness of lipid formulations...
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Humanos , Anfotericina B/efectos adversos , Anfotericina B/toxicidad , Análisis Químico de la Sangre , Enfermedades Renales/inducido químicamenteRESUMEN
Enterobactérias produtoras de carbapenemase do tipo Klebsiella pneumoniae (KPC) são cada vez mais identificadas em pacientes hospitalizados, porém pouco se conhece sobre o perfil e o prognóstico dos pacientes colonizados por elas. Este estudo objetiva avaliar o perfil epidemiológico e a mortalidade total intra-hospitalar dos pacientes colonizados por KPC em um centro de referência. Métodos: Estudo de coorte retrospectivo em adultos colonizados por KPC em internação clínica de novembro/2012 a março/2013 no Hospital Nossa Senhora da Conceição, Porto Alegre (RS). Foram definidos como colonizados pacientes com exame de rastreio (swab) positivo para bactérias produtoras de KPC durante a internação. Resultados: Foram incluídos 75 pacientes, sendo 40 homens, com mediana de 52 anos. O tempo desde o início da internação até a positivação do swab apresentou uma mediana e amplitude interquartil de 18 (9-33) dias, com período de internação de 36 (24-56) dias. Foi identificado uso de cateter central em 93%, sondagem vesical de demora 88%, sondagem nasogástrica/nasoentérica 87%, ventilação mecânica 81% e hemodiálise 40%. Dois terços dos pacientes apresentaram pelo menos um evento infeccioso após a colonização. O escore de Charlson (OR 1,53 por cada ponto; IC95% 1,25-1,97) e diálise prévia (OR 4,35; IC95% 1,39-15,37) foram preditores independentes de mortalidade. Óbito ocorreu em 56% dos pacientes (n=42). Conclusão: Pacientes colonizados por KPC apresentam mortalidade total intra-hospitalar elevada. Comorbidades prévias à colonização foram associadas com mortalidade. O presente estudo não permite definir qual o papel da colonização no desfecho clínico dos pacientes...
Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae have been increasingly identified in hospitalized patients, but little is known about the profile and prognosis of patients colonized by these bacteria. This study aims to assess the epidemiological profile and overall in-hospital mortality of patients colonized by KPC in a reference center. Methods: This is a retrospective cohort study in adult patients colonized by KPC and admitted to clinical units of Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil, between November/2012 and March/2013. Those patients with screening culture test positive for KPC-producing bacteria during hospitalization were defined as colonized. Results: Seventy-five patients were included, 40 of which were males, and the median age was 52 years. The median and interquartile range of time from onset of hospitalization until colonization was 18 [9-33] days, with a median hospital stay of 36 (24-56) days. Considering the other risk factors for colonization, there was a high prevalence in the use of central access catheter (93%), indwelling catheter (88%), nasogastric/enteral tube (87%), mechanical ventilation (81%), and need for hemodialysis (40%). Two thirds of patients had at least one infectious event after colonization. Charlson score (OR 1.53 for each point; 95%CI1.25-1.97) and previous dialysis (OR 4.35; 95%CI1.39-15.37) were independent predictors for mortality. In hospital mortality was 56%. Conclusion: Patients colonized by KPC have high in-hospital overall mortality. Comorbidities were associated with mortality. This study does not enable to define the role of colonization in defining patients clinical outcomes...
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Humanos , Pacientes Internos , Infecciones por Klebsiella , Klebsiella pneumoniaeRESUMEN
INTRODUÇÃO: A disseminação de Klebsiella pneumoniae carbapenemase (KPC) no Brasil e a recente detecção de bactérias produtoras de New Delhi metalo-β-lactamase (NDM-1) em hospital terciário do sul do Brasil indicam a necessidade da avaliação da presença destas enzimas em enterobactérias resistentes a carbapenêmicos (ERC).OBJETIVO: Avaliar prevalência de carbapenemases nas ERC em quatro hospitais terciários de Porto Alegre, por meio de PCR multiplex em tempo real. MÉTODOS: Estudo descritivo, período de abril a dezembro de 2013. Isolados bacterianos de pacientes internados foram identificados pelo sistema automatizado VITEK 2, com realização do teste de suscetibilidade aos antimicrobianos. Amostras com isolados de ERC foram encaminhadas ao laboratório de referência para análise por PCR em tempo real para identificação de carbapenemases. RESULTADOS: Total de 701 isolados. As ERC predominantes foram K. pneumoniae (47% das amostras positivas) e Enterobacter cloacae (18%). As carbapenemases mais frequentes foram KPC (48%), OXA-48-like (3%) e NDM (2%). Em 47% das amostras não foi identificado o mecanismo de resistência. Isolados originados de culturas de vigilância foram associados com maior positividade para carbapenemases do que isolados de amostras clínicas (p<0,0001). Isolados de ERC pertencentes ao grupo Proteae (Proteus spp., Morganella spp., Providencia spp.) foram associados a menor positividade para carbapenemase do que isolados de outras ERC (p<0,0001). CONCLUSÃO: KPC foi a carbapenemase mais frequentemente detectada. A circulação de uma enzima OXA-48-like foi demonstrada, um achado novo e preocupante. O achado da carbapenemase NDM também é preocupante devido ao seu potencial de disseminação. Esses dados e outros estudos poderão contribuir para um entendimento maior da epidemiologia das ERC.
BACKGROUND: The spread of Klebsiella pneumoniae carbapenemase (KPC) in Brazil and the recent detection of bacteria producing New Delhi metallo-β-lactamase (NDM-1) in a tertiary care hospital in Porto Alegre indicate the need to evaluate the presence of these enzymes in carbapenem-resistant Enterobacteriaceae (CRE). AIM: To evaluate the prevalence of carbapenemases in CRE in four tertiary care hospitals in Porto Alegre using multiplex real-time PCR.METHODS: Descriptive study from April to December 2013. Bacterial isolates from hospitalized patients were identified by VITEK 2 automated system, with antimicrobial susceptibility testing. Samples with CRE isolates were sent to the reference laboratory for analysis using real-time PCR for identification of carbapenemases. RESULTS: Total of 701 isolates. The predominant CRE were K. pneumoniae (46% of positive samples) and Enterobacter cloacae (18%). The most frequent carbapenemases were KPC (48%), OXA-48-like (3%), and NDM-1 (2%). In 47% of the samples no carbapenemase was identified. Isolates originated from surveillance cultures were associated with higher positivity for carbapenemases than isolates from clinical samples (p<0.0001). CRE isolates belonging to the Proteae group (Proteus spp., Morganella spp., Providencia spp.) were associated with less positivity for carbapanemase than isolates of other CRE (p<0.0001). CONCLUSION: KPC was the most frequently detected carbapenemase. The movement of an OXA-48-like enzyme was demonstrated, a novel and worrisome finding. The finding of carbapenemase NDM is also worrisome due to its dissemination potential. These data and further studies may contribute to a better understanding of the epidemiology of CRE.