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1.
BMC Infect Dis ; 20(1): 827, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176724

RESUMO

BACKGROUND: Candida auris is a new pathogen called "superbug fungus" which caused panic worldwide. There are no large-scale epidemiology studies by now, therefore a systematic review and meta-analysis was undertaken to determine the epidemic situation, drug resistance patterns and mortality of C. auris. METHODS: We systematically searched studies on the clinical report of Candida auris in Pubmed, Embase and Cochrane databases until October 6, 2019. A standardized form was used for data collection, and then statics was performed with STATA11.0. RESULTS: It showed that more than 4733 cases of C. auris were reported in over 33 countries, with more cases in South Africa, United States of America, India, Spain, United Kingdom, South Korea, Colombia and Pakistan. C. auirs exhibited a decrease in case count after 2016. Clade I and III were the most prevalent clades with more cases reported and wider geographical distribution. Blood stream infection was observed in 32% of the cases, which varied depending on the clades. Resistance to fluconazole, amphotericin B, caspofungin, micafungin and anidulafungin in C. auris were 91, 12, 12.1, 0.8 and 1.1%. The overall mortality of C. auris infection was 39%. Furthermore, subgroup analyses showed that mortality was higher in bloodstream infections (45%), and lower in Europe (20%). CONCLUSIONS: Over 4000 cases of C. auris were reported in at least 33 countries, which showed high resistance to fluconazole, moderate resistance to amphotericin B and caspofungin, high sensitivity to micafungin and anidulafungin. The crude mortality for BSI of C. auris was 45% which was similar to some drug-resistant bacteria previously reported. In conclusion, C. auris displayed similar characteristics to some drug resistance organisms. This study depicts several issues of C. auris that are most concerned, and is of great significance for the clinical management.


Assuntos
Candida/efeitos dos fármacos , Candidíase/epidemiologia , Candidíase/mortalidade , Anfotericina B/uso terapêutico , Anidulafungina/uso terapêutico , Antifúngicos/uso terapêutico , Candida/classificação , Candida/genética , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Caspofungina/uso terapêutico , Farmacorresistência Fúngica Múltipla/efeitos dos fármacos , Fluconazol/uso terapêutico , Humanos , Micafungina/uso terapêutico , Prevalência
2.
J Med Microbiol ; 69(6): 844-849, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32459615

RESUMO

Introduction. Signal transducer and activator of transcription 3 (STAT3) deficiency is a rare primary immunodeficiency associated with increased susceptibility to bacterial and fungal infections, notably pulmonary aspergillosis.Aim. We describe the emergence of azole-resistant Aspergillus fumigatus infections in STAT3-deficient patients.Methodology. During a retrospective study of 13 pulmonary aspergillosis cases in STAT3-deficient patients conducted in France, we identified patients infected with azole-resistant A. fumigatus isolates.Results. Two out of the 13 STAT3-deficient patients with aspergillosis had azole-resistant A. fumigatus infection, indicating an unexpectedly high prevalence of resistance. The first patient with STAT3 deficiency presented several flares of allergic bronchopulmonary aspergillosis-like episodes. He was chronically infected with two azole-resistant A. fumigatus isolates (TR34/L98). Despite prolonged antifungal treatment, including caspofungin and amphotericin B, the patient was not able to clear the azole-resistant A. fumigatus. The second patient had chronic cavitary pulmonary aspergillosis (CCPA). The A. fumigatus isolate was initially azole susceptible but harboured three F46Y, M172V and E427K point mutations. Despite prolonged antifungal therapies, lesions worsened and the isolate became resistant to all azoles. Surgery and caspofungin treatments were then required to cure CCPA. Resistance was probably acquired from the environment (TR34/L98) in the first case whereas resistance developed under antifungal treatments in the second case. These infections required long-term antifungal treatments and surgery.Conclusions. The emergence of azole-resistant A. fumigatus infections in STAT3-deficiency dramatically impacts both curative and prophylactic antifungal strategies. Physicians following patients with primary immune-deficiencies should be aware of this emerging problem as it complicates management of the patient.


Assuntos
Antifúngicos/uso terapêutico , Aspergillus fumigatus/efeitos dos fármacos , Azóis/uso terapêutico , Farmacorresistência Fúngica/efeitos dos fármacos , Aspergilose Pulmonar/tratamento farmacológico , Aspergilose Pulmonar/genética , Fator de Transcrição STAT3/deficiência , Adulto , Anfotericina B/uso terapêutico , Caspofungina/uso terapêutico , Criança , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/genética , Doenças Transmissíveis/microbiologia , Farmacorresistência Fúngica/genética , França , Proteínas Fúngicas/genética , Genótipo , Humanos , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Adulto Jovem
4.
Int J Infect Dis ; 92: 123-126, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31935536

RESUMO

BACKGROUND: Candida haemulonii is an emergent, multi-resistant opportunistic pathogenic yeast that like Candida auris, can be misidentified when conventional diagnostic methods are used. Timely molecular identification using DNA sequence analysis variation in the internal transcriber spacer region, ITS1-ITS4 and the 28S ribosomal DNA gene (28S rDNA), and in vitro antifungal susceptibility assessment can lead to rapid therapeutic success. CASE REPORT: A case of Candida haemulonii candidiasis suffered by a male paediatric patient attended at Federico Gómez Children's Hospital of México City in September 2016 is reported. The isolate was yielded from peripheral blood and central catheter blood specimens. From in vitro antifungal susceptibility data, caspofungin was administered to the patient, who showed clear improvements at the end of antimicrobial administration, and the removal of the central venous catheter. Using a molecular phylogenetic approach, we identified the clinical isolate as C. haemulonii. The clinical isolate has been named as Candida haemulonii ENCB-87 from now on. C. haemulonii ENCB-87 grew well between the temperatures, 28 °C and 35 °C but not at 37 °C in YPD culture medium. The clinical isolate was susceptible to caspofungin, which resulted in therapeutic success for the patient. CONCLUSIONS: C. haemulonii is an emergent, opportunistic pathogen, closely related to C. auris, therefore, the timely and accurate identification and antifungal susceptibility assessments are paramount in generating a robust epidemiology of this emerging Candida species.


Assuntos
Candida/isolamento & purificação , Candidíase/etiologia , Infecções Relacionadas a Cateter/microbiologia , Hospitais Pediátricos , Antifúngicos/uso terapêutico , Candida/classificação , Candidíase/tratamento farmacológico , Caspofungina/uso terapêutico , DNA Fúngico , DNA Ribossômico , Humanos , Lactente , Masculino , México , Testes de Sensibilidade Microbiana , Tipagem Molecular , Filogenia , Análise de Sequência de DNA
5.
Int J Antimicrob Agents ; 55(3): 105901, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31954831

RESUMO

Antifungal combination is an interesting approach for the treatment of several fungal infections but there is currently little evidence to support combined therapy in Candida auris infections. The antibacterial colistin has recently been shown to interact synergistically with antifungals against Candida spp., including azole-resistant isolates. The current study evaluated the in vitro interaction between colistin and either caspofungin or micafungin against 15 C. auris isolates by a checkerboard methodology based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) reference method. Results were analysed by two approaches: calculation of the fractional inhibitory concentration index (FICI) and response surface analysis based on the Bliss model. The minimum inhibitory concentration (MIC) range (geometric mean [Gmean]) of caspofungin and micafungin was 0.25 to 1 µg/mL (0.691 µg/mL) and 0.03 to 0.125 µg/mL (0.114 µg/mL), respectively. No activity was observed for colistin alone with MIC of >64 µg/mL for all the isolates. When colistin was combined with caspofungin, synergistic interactions were observed for all strains with FICI values of 0.08 to 0.14. In contrast, indifferent interactions were observed for the combination of colistin with micafungin with FICI values of 0.51 to 1.01. Synergy was also demonstrated using the Bliss model against all isolates for the colistin-caspofungin combination and in 60% of isolates for the colistin-micafungin combination. Antagonism was not observed for any combination.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Colistina/farmacologia , Equinocandinas/farmacologia , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Caspofungina/farmacologia , Caspofungina/uso terapêutico , Colistina/uso terapêutico , Sinergismo Farmacológico , Equinocandinas/uso terapêutico , Humanos , Micafungina/farmacologia , Micafungina/uso terapêutico
6.
Int J Infect Dis ; 93: 15-21, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31982622

RESUMO

BACKGROUND: Candidemia is a major cause of mortality in the intensive care unit (ICU). According to the Infectious Diseases Society of America (IDSA), an echinocandin is recommended as initial therapy and fluconazole as an alternative. In a context of echinocandin resistance development, the question arising is whether azoles are a suitable alternative to echinocandins for the treatment of candidemia in critically ill patients. METHODS: A 3-year (2015-2017) retrospective multicentric cohort study was conducted. Adult patients with a diagnosis of candidemia during the ICU stay and treated with echinocandins or azoles were included. Demographic, clinical data, mycological data, and antifungal treatments were collected. Kaplan-Meier survival analysis, univariate analysis, and a multivariate logistic regression analysis using a propensity score with the inverse probability of treatment weighting method were performed. FINDINGS: Seventy-nine patients (n = 79) were analyzed. Treatment success, as well as survival on day 90 (Kaplan-Meier survival analysis, log rank test, p = 0.542), were comparable between patients who received echinocandins (caspofungin (n = 47)) or azoles (fluconazole (n = 29) or voriconazole (n = 3)). A multivariable analysis demonstrated that higher SOFA score on the day of candidemia diagnosis and absence of adequate Candida source control were independently associated with a greater risk of 90-day mortality, whereas azoles treatment was not associated with an excess 90-day mortality. INTERPRETATION: This study confirms that the use of azoles recommended for candidemia, mostly fluconazole, as a first-line therapy is a reasonable alternative to caspofungin for ICU patients in our institution. This needs to be included in local guidelines through antifungal stewardship programs.


Assuntos
Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Caspofungina/uso terapêutico , Fluconazol/uso terapêutico , Unidades de Terapia Intensiva , Idoso , Candidemia/microbiologia , Candidemia/mortalidade , Estudos de Coortes , Estado Terminal , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento , Voriconazol/uso terapêutico
7.
Ophthalmology ; 127(5): 582-588, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31892423

RESUMO

PURPOSE: To evaluate the cost-effectiveness of supplementing hypothermic cold storage media (CSM) with antifungal therapy. DESIGN: Cost-effectiveness analysis (CEA). PARTICIPANT: Base case of a patient with Fuch's endothelial dystrophy undergoing a first eye keratoplasty. METHODS: Cost-effective analysis of the base case with corneal tissue stored in CSM or CSM supplemented with antifungal therapy over a 16-year time horizon. Multiple clinical scenarios were considered, including endothelial keratoplasty (EK) and penetrating keratoplasty (PK); amphotericin B, voriconazole, caspofungin, and combination therapy; and third-party payer and societal perspectives. The incidences were derived from PubMed literature searches and average wholesale prices of medications; all costs were discounted 3% per annum and adjusted for inflation to 2019 US dollars. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs). RESULTS: In the reference case, a corneal endothelial graft stored in amphotericin B-supplemented CSM was the most cost-effective approach from a third-party payer and societal perspective. Probability sensitivity analysis (PSA) of the societal model for the EK was robust, with 93.5% being below an arbitrary willingness-to-pay threshold (WTP) of $20 000 per fungal infection averted. Voriconazole, caspofungin, and combination antifungals were less cost-effective than amphotericin B. The main factors influencing the CEA were the incidences of postkeratoplasty fungal infections, potential increases in graft failures, and antifungal costs. For grafts intended for PKs, antifungal supplementation was less cost-effective than for EKs. CONCLUSIONS: Antifungal supplementation with amphotericin B for EK grafts was the most cost-effective approach of the studied antifungals; however, the CEA was sensitive to potential changes in graft failure rates, underlining the importance of long-term safety studies. For full-thickness corneal grafts, antifungal supplementation was less cost-effective.


Assuntos
Antifúngicos/economia , Córnea , Análise Custo-Benefício , Criopreservação/economia , Distrofia Endotelial de Fuchs/economia , Soluções para Preservação de Órgãos/economia , Idoso , Anfotericina B/economia , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Caspofungina/economia , Caspofungina/uso terapêutico , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/economia , Combinação de Medicamentos , Custos de Medicamentos , Infecções Oculares Fúngicas/prevenção & controle , Distrofia Endotelial de Fuchs/cirurgia , Pesquisa sobre Serviços de Saúde , Humanos , Ceratoplastia Penetrante/economia , Masculino , Soluções para Preservação de Órgãos/química , Complicações Pós-Operatórias/prevenção & controle , Voriconazol/economia , Voriconazol/uso terapêutico
8.
World Neurosurg ; 135: 335-338, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31525477

RESUMO

BACKGROUND: Candida auris is an emerging superbug which was recently discovered and has spread widely across the world. With a steady rise in incidence involving multisystems, this presents a unique challenge to caregivers. CASE DESCRIPTION: A 50-year-old man with sickle cell disease, diabetes mellitus, and multiple surgeries presented with progressive low back pain radiating to bilateral limbs and intact neurology. Radiologic and laboratory investigations suggested spondylodiscitis with epidural collection, which was operated with posterior decompression and stabilization. The tissue analysis was reported as C. auris, which was accordingly treated with caspofungin. Magnetic resonance imaging at 4 months showed resolution of infection with return of inflammatory markers to normal. CONCLUSIONS: C. auris appears to be an emerging superbug, which is hospital-acquired. All practitioners must be aware of its existence and presentation. Given the low incidence, high mortality, and no clear guidelines of management so far, formulation of any such strategies is complicated. Further studies and research are needed for this superbug.


Assuntos
Antifúngicos/uso terapêutico , Candidíase/terapia , Caspofungina/uso terapêutico , Discite/terapia , Discotomia , Fusão Vertebral , Anemia Falciforme/epidemiologia , Candida , Candidíase/epidemiologia , Candidíase Invasiva , Comorbidade , Desbridamento , Descompressão Cirúrgica , Diabetes Mellitus/epidemiologia , Discite/epidemiologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Omã
10.
JAMA ; 322(17): 1673-1681, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31688884

RESUMO

Importance: Children, adolescents, and young adults with acute myeloid leukemia are at high risk of life-threatening invasive fungal disease with both yeasts and molds. Objective: To compare the efficacy of caspofungin vs fluconazole prophylaxis against proven or probable invasive fungal disease and invasive aspergillosis during neutropenia following acute myeloid leukemia chemotherapy. Design, Setting, and Participants: This multicenter, randomized, open-label, clinical trial enrolled patients aged 3 months to 30 years with newly diagnosed de novo, relapsed, or secondary acute myeloid leukemia being treated at 115 US and Canadian institutions (April 2011-November 2016; last follow-up June 30, 2018). Interventions: Participants were randomly assigned during the first chemotherapy cycle to prophylaxis with caspofungin (n = 257) or fluconazole (n = 260). Prophylaxis was administered during the neutropenic period following each chemotherapy cycle. Main Outcomes and Measures: The primary outcome was proven or probable invasive fungal disease as adjudicated by blinded central review. Secondary outcomes were invasive aspergillosis, empirical antifungal therapy, and overall survival. Results: The second interim efficacy analysis and an unplanned futility analysis based on 394 patients appeared to have suggested futility, so the study was closed to accrual. Among the 517 participants who were randomized (median age, 9 years [range, 0-26 years]; 44% female), 508 (98%) completed the trial. The 23 proven or probable invasive fungal disease events (6 caspofungin vs 17 fluconazole) included 14 molds, 7 yeasts, and 2 fungi not further categorized. The 5-month cumulative incidence of proven or probable invasive fungal disease was 3.1% (95% CI, 1.3%-7.0%) in the caspofungin group vs 7.2% (95% CI, 4.4%-11.8%) in the fluconazole group (overall P = .03 by log-rank test) and for cumulative incidence of proven or probable invasive aspergillosis was 0.5% (95% CI, 0.1%-3.5%) with caspofungin vs 3.1% (95% CI, 1.4%-6.9%) with fluconazole (overall P = .046 by log-rank test). No statistically significant differences in empirical antifungal therapy (71.9% caspofungin vs 69.5% fluconazole, overall P = .78 by log-rank test) or 2-year overall survival (68.8% caspofungin vs 70.8% fluconazole, overall P = .66 by log-rank test) were observed. The most common toxicities were hypokalemia (22 caspofungin vs 13 fluconazole), respiratory failure (6 caspofungin vs 9 fluconazole), and elevated alanine transaminase (4 caspofungin vs 8 fluconazole). Conclusions and Relevance: Among children, adolescents, and young adults with acute myeloid leukemia, prophylaxis with caspofungin compared with fluconazole resulted in significantly lower incidence of invasive fungal disease. The findings suggest that caspofungin may be considered for prophylaxis against invasive fungal disease, although study interpretation is limited by early termination due to an unplanned interim analysis that appeared to have suggested futility. Trial Registration: ClinicalTrials.gov Identifier: NCT01307579.


Assuntos
Antifúngicos/uso terapêutico , Caspofungina/uso terapêutico , Fluconazol/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Micoses/prevenção & controle , Adolescente , Adulto , Antifúngicos/efeitos adversos , Aspergilose/epidemiologia , Aspergilose/prevenção & controle , Caspofungina/efeitos adversos , Criança , Pré-Escolar , Término Precoce de Ensaios Clínicos , Feminino , Fluconazol/efeitos adversos , Humanos , Lactente , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/complicações , Masculino , Neutropenia/complicações , Adulto Jovem
11.
Am J Case Rep ; 20: 1526-1529, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31619662

RESUMO

BACKGROUND Spontaneous fungal peritonitis (SFP) is a life-threatening infection which occurs more commonly in patients with liver failure. SFP is not as common as spontaneous bacterial peritonitis (SBP) and has higher mortality rates due to late recognition and difficulty in differentiation between SFP and SBP. Spontaneous fungal peritonitis is extremely uncommon in patients with cardiac ascites due to a high protein content, which predisposes to a low risk of infections. CASE REPORT This report presents a rare case of spontaneous fungal peritonitis in a patient with cardiogenic ascites. To the best of our knowledge, this is the second known case of SFP occurring in a patient with cardiac cirrhosis. The patient did not respond to initiation of SBP treatment and after ascitic fluid grew Candida glabrata, the diagnosis of SFP was made. The patient's clinical status improved after initiation of intravenous caspofungin. CONCLUSIONS SFP should be a differential diagnosis in patients who have cardiac or liver cirrhosis, who are not improving with empirical antibiotic therapy for spontaneous bacterial peritonitis.


Assuntos
Ascite/complicações , Fibrose/complicações , Micoses/diagnóstico , Micoses/etiologia , Miocárdio/patologia , Peritonite/diagnóstico , Peritonite/etiologia , Antifúngicos/uso terapêutico , Candida glabrata/efeitos dos fármacos , Caspofungina/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Peritonite/tratamento farmacológico , Fatores de Tempo
12.
Euro Surveill ; 24(37)2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31530343

RESUMO

We recently isolated Candida auris from a blood culture and cutaneous swabs of a patient in her mid-70s. Our routine phenotypic methods failed to identify the microorganism, but it was identified by molecular tests and MALDI-TOF MS analysis. Our report, the first from Italy, further underlines the geographically wide distribution of C. auris and the need to confirm species identification of any suspicious colony as soon as possible to stop its spread.


Assuntos
Candida/isolamento & purificação , Candidíase/diagnóstico , Febre/etiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Doenças Vasculares/complicações , Idoso , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida/genética , Candidíase/tratamento farmacológico , Caspofungina/farmacologia , Caspofungina/uso terapêutico , Farmacorresistência Fúngica Múltipla , Feminino , Humanos , Itália , Testes de Sensibilidade Microbiana , Complicações Pós-Operatórias/virologia , Doenças Vasculares/cirurgia
13.
Acta Biochim Pol ; 66(3): 361-364, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31518088

RESUMO

PURPOSE: Candida spp. are ranked as one of the four major causative agents of fungal infections. The number of infections caused by Candida species resistant to fluconazole, which is applied as the first line drug in candidiasis treatment, increases every year. In such cases the application of echinocandin is necessary. Echinocandin susceptibility testing has become a routine laboratory practice in many countries due to the increasing frequency of clinical failures during treatment with these drugs. METHODS: We performed anidulafungin, micafungin and caspofungin susceptibility testing according to the microdilution broth method on 240 Candida isolates collected in Polish hospitals. RESULTS: We identified 12 isolates resistant to all echinocandins within 240 examined isolates. Moreover, 6 of the examined samples were identified as rare Candida species and among them we observed very high echinocandin MIC values. CONCLUSION: Our research proves that in Poland there is a problem of echinocandin resistance. Moreover, we identified two species of Candida which are rare causative agents of human infections, and there was no reported incidence of such infections in Poland until now.


Assuntos
Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Candidíase/epidemiologia , Farmacorresistência Fúngica/efeitos dos fármacos , Equinocandinas/uso terapêutico , Anidulafungina/uso terapêutico , Candida/isolamento & purificação , Candidíase/microbiologia , Caspofungina/uso terapêutico , Equinocandinas/efeitos adversos , Humanos , Micafungina/uso terapêutico , Testes de Sensibilidade Microbiana , Polônia/epidemiologia
14.
Medicine (Baltimore) ; 98(33): e16908, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415438

RESUMO

RATIONALE: Fungal infectious disease does not usually occur in low-risk patients. Clinicians tend to ignore the role of fungi in the fevers of low-risk patients. If there is not timely control of fungal infections and associated fever, the disease will continue to worsen, resulting in physical dysfunction or death. PATIENT CONCERNS: Recurrent fever continued for 1 month in a young adult. DIAGNOSES AND INTERVENTIONS: Non-albicans Candida (NAC) species probably was the main pathogen in this case based on the resolution of fever after capsofungin administration. OUTCOMES: The fever and the associated indicators, including white blood cell count, C-reaction protein, erythrocyte sedimentation rate, and BDG levels, showed improvement quickly. The patient left the hospital successfully after 18 days of caspofungin treatment. There was no recurrent fever at a follow-up of 1 year. LESSONS: Clinicians should be aware that the incidence of fungal infection is increasing in low-risk patients. The BDG assay is still an effective tool used to diagnose invasive fungal diseases. Caspofungin is an effective drug for the treatment of some unknown fungal infections.


Assuntos
Antifúngicos/uso terapêutico , Candidíase/diagnóstico , Candidíase/tratamento farmacológico , Caspofungina/uso terapêutico , Adulto , Feminino , Febre de Causa Desconhecida/diagnóstico , Humanos
15.
Indian J Med Microbiol ; 37(1): 109-112, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424020

RESUMO

Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in paediatric leukaemias. Antifungal combinations to treat these patients are being explored. Fourteen children with leukaemias and IFIs were treated with a combination of antifungal agents at our centre. The first antifungal was amphotericin-B in 13 children and voriconazole in one child. In view of no improvement and clinical deterioration, in nine patients, voriconazole was added as the second antifungal agent and in four, it was caspofungin. All patients completed 4-6 weeks of antifungal therapy. The overall mortality attributable to IFI for the cohort was 4/14 (28%).


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Caspofungina/uso terapêutico , Infecções Fúngicas Invasivas/tratamento farmacológico , Voriconazol/uso terapêutico , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Fungos/efeitos dos fármacos , Humanos , Leucemia/microbiologia , Masculino , Estudos Retrospectivos
16.
Infez Med ; 27(2): 155-158, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31205038

RESUMO

In order to compare the effectiveness of liposomal amphotericin B (LAB) and caspofungin monotherapy in Candida tropicalis-induced peritonitis in an experimental mice model 56 healthy male BALB/c mice (10-12 weeks; 20-25 g) were divided into groups and C. tropicalis strains were intraperitoneally (IP) inoculated into mice groups except the control group. After the injection, three doses of LAB (0.5, 1.0, 2.0 mg/kg/day) and caspofungin (1.0, 2.0, 5.0 mg/kg/day) were administered to groups for five consecutive days, starting 48-h post-infection. The mice were then followed up for 14 days and killed by cervical dislocation. When their peritoneal fluid was examined, the difference in fungal growth between the treatment group and control group was significant (p <0.05). Evaluation of the treatment groups revealed that fungal growth decreased with increasing dose of the antifungal agent (p >0.05). There was no dose-related difference from mice which received LAB or those which received caspofungin in our experimental model. During our study, no death was detected despite the similar injection doses compared with other studies using Candida species. The results of this study suggest that C. tropicalis could have lower virulence, perhaps limited by natural immunity, and causes mortality at much higher doses.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Candida tropicalis , Candidíase Invasiva/tratamento farmacológico , Caspofungina/uso terapêutico , Peritonite/tratamento farmacológico , Anfotericina B/administração & dosagem , Animais , Antifúngicos/administração & dosagem , Candida tropicalis/efeitos dos fármacos , Candida tropicalis/crescimento & desenvolvimento , Caspofungina/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Peritonite/microbiologia , Distribuição Aleatória
17.
Infez Med ; 27(2): 159-167, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31205039

RESUMO

Invasive candidiasis is an important cause of morbidity and mortality, which primarily occurs in intensive care units. The Candida colonization index is an accepted score as an early warning tool for invasive candidiasis. This study was performed in a medical PICU with patients prone to contracting invasive candidiasis, to determine the usefulness of the Candida colonization index in forecasting invasive candidiasis in children. This prospective study including 87 patients (children 1 month to 16 years old with several illnesses and requiring ICU care) was conducted in a 22-bed medical PICU, Health Science University of Kayseri Training and Research Hospital, between January 2015 and September 2016. Those patients not on antifungal therapy, who were expected to stay more than seven days in PICU and had no history of a PICU stay within the previous two months were included in the study. In all patients, rectal, cervical, throat, axillary, perineal and nasal swab cultures, urine culture and blood culture tests were performed at admission and every week throughout their stay. Overall, 2639 swab and urine cultures (mean: 30.3) and 325 blood cultures (mean: 3.73) were obtained from 87 patients and a total of 576 grew Candida spp. In patients' swab and urine cultures C. albicans was detected in 64.5%, C. parapsilosis in 12.1%, C. glabrata in 7.5%, Saccharomyces spp in 3.0 %, C. tropicalis in 2.4%, C. krusei in 2.1% and C. kefyr in 1.2%. Three patients had C. albicans and one had C. parapsilosis growth in blood culture. Sensitivity, specificity, positive predictive value and negative predictive value for CI were found to be 33.73%, 100%, 6.7%, and 100%, respectively. Patients are at risk of fungal infection in paediatric intensive care units. Specificity and the negative predictive value of 100 % indicate that CI is a useful score to rule out the presence of invasive fungal disease. On the other hand, the low rate of sensitivity (33.3 %) and positive predictive value (6,7%) make this score less reliable in forecasting invasive candidiasis in children.


Assuntos
Candida/isolamento & purificação , Candidemia/microbiologia , Unidades de Terapia Intensiva Pediátrica , Adolescente , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Caspofungina/uso terapêutico , Criança , Pré-Escolar , Suscetibilidade a Doenças , Estudos de Viabilidade , Feminino , Fluconazol/uso terapêutico , Humanos , Lactente , Itraconazol/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Especificidade de Órgãos , Estudos Prospectivos , Sensibilidade e Especificidade , Voriconazol/uso terapêutico
18.
J Infect Chemother ; 25(10): 801-805, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31047782

RESUMO

Caspofungin (CPFG) is an echinocandin antifungal agent that inhibits the synthesis of ß-1, 3-D-glucan, a critical component of the cell wall of target fungi. Several clinical studies have confirmed the efficacy and safety of CPFG in patients with febrile neutropenia (FN); however, there are no reports available in Japanese patients with FN. Therefore, we investigated the therapeutic efficacy and pharmacokinetics of CPFG as an empirical therapy in a Japanese hospital. Twenty-four Japanese patients, who were diagnosed with FN at Gifu University Hospital from February 2014 to August 2017, were enrolled. Blood samples were collected at the end of CPFG dosing (0.5 h after the infusion) on day 1 and immediately prior to the next infusion on days 2, 3, and 4. The concentration of CPFG in plasma was measured by high-performance liquid chromatography. The efficacy was assessed by five of the component endpoints, and safety was monitored according to the Common Terminology Criteria for Adverse Events. CPFG showed an excellent effect against FN (75%, 18/24), without any serious hepatic or renal toxicity. Regarding the pharmacokinetics, the plasma concentration of CPFG was significantly correlated with body weight; although, no correlation was observed between the plasma concentration of CPFG and the other factors investigated, such as gender or laboratory results. These results suggest the high efficacy, safety, and tolerability of CPFG as an empirical antifungal therapy for Japanese patients with FN.


Assuntos
Antifúngicos/uso terapêutico , Caspofungina/uso terapêutico , Neutropenia Febril/tratamento farmacológico , Adulto , Idoso , Antifúngicos/farmacocinética , Peso Corporal , Caspofungina/farmacocinética , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Neutropenia Febril/sangue , Feminino , Humanos , Infusões Intravenosas , Japão , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Resultado do Tratamento , Adulto Jovem
19.
Medicine (Baltimore) ; 98(8): e14580, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813175

RESUMO

RATIONALE: Opportunistic infections frequently develop in immunocompromised patients, such as those with hematological malignancies, causing significant mortality. Early diagnosis of invasive fungal infections is often important and difficult due to the difficult nature of confirming infection using cytologic and histologic findings. However, we report the first case of candidal infection leading to muscle abscesses in the legs of a patient with leukemia. PATIENT CONCERNS: A 60-year-old man with acute myeloid leukemia (AML) presented with multifocal muscle abscesses of the legs. DIAGNOSES: Multifocal muscle candidiasis of the legs was confirmed by fine-needle aspiration biopsy of 2 of the calf lesions. INTERVENTIONS: After treatment with amphotericin B and flucytosine for 1 month, the patient was administered intravenous caspofungin for 3 months. OUTCOME: A CT scan of the abdomen and an MRI of the lower calves showed significant improvement. LESSONS: This case highlights that fungal infection should be considered when patients present with multiple abscesses, emphasizing the value of early biopsy to confirm diagnosis and facilitate precision treatment.


Assuntos
Antifúngicos/uso terapêutico , Antineoplásicos/efeitos adversos , Candidíase/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Doenças Musculares/microbiologia , Abscesso/etiologia , Anfotericina B/uso terapêutico , Candida tropicalis/isolamento & purificação , Candidíase/tratamento farmacológico , Candidíase/etiologia , Caspofungina/uso terapêutico , Flucitosina/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Perna (Membro)/microbiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/microbiologia , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/tratamento farmacológico , Tomografia Computadorizada por Raios X
20.
Med Oral Patol Oral Cir Bucal ; 24(2): e172-e180, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30818309

RESUMO

BACKGROUND: Candidiasis is one of the most common opportunistic oral infections that presents different acute and chronic clinical presentations with diverse diagnostic and therapeutic approaches. The present study carries out a bibliographic review on the therapeutic tools available against oral candidiasis and their usefulness in each clinical situation. MATERIAL AND METHODS: Recent studies on treatment of oral candidiasis were retrieved from PubMed and Cochrane Library. RESULTS: Nystatin and miconazole are the most commonly used topical antifungal drugs. Both antifungal drugs are very effective but need a long time of use to eradicate the infection. The pharmacological presentations of miconazole are more comfortable for patients but this drug may interact with other drugs and this fact should be assessed before use. Other topical alternatives for oral candidiasis, such as amphotericin B or clotrimazole, are not available in many countries. Oral fluconazole is effective in treating oral candidiasis that does not respond to topical treatment. Other systemic treatment alternatives, oral or intravenous, less used are itraconazole, voriconazole or posaconazole. Available novelties include echinocandins (anidulafungin, caspofungin) and isavuconazole. Echinocandins can only be used intravenously. Isavuconazole is available for oral and intravenous use. Other hopeful alternatives are new drugs, such as ibrexafungerp, or the use of antibodies, cytokines and antimicrobial peptides. CONCLUSIONS: Nystatin, miconazole, and fluconazole are very effective for treating oral candidiasis. There are systemic alternatives for treating recalcitrant infections, such as the new triazoles, echinocandins, or lipidic presentations of amphotericin B.


Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candidíase Bucal/tratamento farmacológico , Administração Intravenosa , Administração Oral , Administração Tópica , Anfotericina B/uso terapêutico , Anidulafungina/uso terapêutico , Azóis/uso terapêutico , Caspofungina/uso terapêutico , Clotrimazol/uso terapêutico , Bases de Dados Factuais , Interações Medicamentosas , Equinocandinas/uso terapêutico , Fluconazol/uso terapêutico , Humanos , Miconazol/uso terapêutico , Nitrilos/uso terapêutico , Nistatina/uso terapêutico , Piridinas/uso terapêutico , Triazóis/uso terapêutico
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