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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
J Med Microbiol ; 68(5): 770-777, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30924763

RESUMO

PURPOSE: Identification of the emerging yeast species Candida nivariensis among presumptively identified Iranian Candida glabrata isolates. METHODOLOGY: Clinical C. glabrata species complex isolates from blood (n=71; 33.3 %), urine (n=100; 46.9 %), vaginal swabs (n=20;9.4 %), BAL (n=10; 4.7 %), and sputum (n=12; 5.6 %) from Iran were investigated. Isolates were characterized by CHROMagar, multiplex PCRs, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), amplified fragment length polymorphism (AFLP) fingerprinting, internal transcribed spacer (ITS)/large subunit (LSU) rDNA and FKS1/FKS2 sequencing, and the European Committee on Antimicrobial Susceptibility Testing broth microdilution method. A comprehensive literature review was conducted and all the relevant clinical and microbiological data were collected. RESULTS: Four C. nivariensis isolates were recovered from blood samples of three subjects and were all consistently identified by nine-plex PCR, Bruker MALDI-TOF MS, and LSU and ITS rDNA sequencing. AFLP genotyping clustered the isolates into two groups. Sequencing of the FKS1 and FKS2 hotspots showed no accountable amino acid substitutions. All isolates were susceptible to amphotericin B, fluconazole, itraconazole, posaconazole, voriconazole, anidulafungin and micafungin. CONCLUSION: In total, 4 out of 213 clinical C. glabrata species complex candidemia isolates were C. nivariensis. Improvement of the BioMerieux Vitek MS database is required to accurately identify C. nivariensis and it is advised to alternatively use CHROMagar and/or PCR-based techniques. As other species within the Nakaseomyces clade may cause infection and showed high MIC values for antifungals, inclusion of their spectra into the MALDI-TOF MS database seems relevant. Due to developing resistance to fluconazole and insufficient efficacy of caspofungin, the combination of catheter removal plus treatment with caspofungin, or voriconazole, or micafungin might be effective for patients.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/genética , Candidíase/sangue , Adolescente , Idoso , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Antifúngicos/uso terapêutico , Lavagem Broncoalveolar , Candida/isolamento & purificação , Candidemia/diagnóstico , Candidemia/tratamento farmacológico , Candidíase/tratamento farmacológico , Caspofungina/farmacologia , Caspofungina/uso terapêutico , DNA Intergênico , Evolução Fatal , Feminino , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Genótipo , Humanos , Irã (Geográfico) , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Vagina/microbiologia , Voriconazol/farmacologia , Voriconazol/uso terapêutico
9.
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 de Medicamentos , Equinocandinas/uso terapêutico , Fluconazol/uso terapêutico , Humanos , Miconazol/uso terapêutico , Nitrilos/uso terapêutico , Nistatina/uso terapêutico , Piridinas/uso terapêutico , Triazóis/uso terapêutico
10.
Transpl Infect Dis ; 21(3): e13066, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30859662

RESUMO

BACKGROUND: Invasive fungal disease (IFD) has a poor prognosis in children with hematological disorders after hematopoietic stem cell transplantation (HSCT). We assessed if drug combinations with different targets may improve the outcome. METHODS: Retrospective study to assess the outcome of combination antifungal therapy (CAT) for proven-probable IFD (PP-IFD) in children with hematological disorders after HSCT from January 2008 to June 2018. RESULTS: Over the 10-year period, 95 PP-IFD were diagnosed in pediatric recipients, median age of 5.6 years. Twenty-seven patients received combinations of caspofungin and voriconazole, 28 patients received combinations of caspofungin and amphotericin B, and 40 patients received combinations of voriconazole and amphotericin B. The overall response rate of PP-IFD was 77.9%, while the 100-day overall survival rates were 66.8%. Univariate analysis showed that factors that significantly affected the response to combination treatments were type of combination (P = 0.02), the stem cell source (P = 0.04), the donor type (P = 0.03), HLA-match (P = 0.03), aGVHD (P = 0.02), period of treatment (P = 0.044), use of corticosteroids (0.036), CD4:CD8 ratio (P = 0.014), and CMV viremia (P = 0.033). In addition, multivariate analysis demonstrated that only the type of combination remained a significant factor (odds ratio = 0.335, 95% confidence interval: 0.071-0.812, P = 0.042). Forty-three children suffered from mild and reversible adverse reactions, no serious side effects during treatment. CONCLUSION: A variety of factors can affect the outcome of CAT. Combination of caspofungin with voriconazole is a safe and helpful treatment option for HSCT recipients with IFD.


Assuntos
Antifúngicos/uso terapêutico , Doenças Hematológicas/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções Fúngicas Invasivas/tratamento farmacológico , Micoses/tratamento farmacológico , Adolescente , Anfotericina B/uso terapêutico , Caspofungina/uso terapêutico , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Doenças Hematológicas/microbiologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/microbiologia , Humanos , Lactente , Masculino , Micoses/etiologia , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Voriconazol/uso terapêutico
11.
J Mycol Med ; 28(4): 659-662, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30477694

RESUMO

Trichoderma species are saprophytic filamentous fungi that can be found all over the word. These fungi show increasing medical importance as opportunistic human pathogens, particularly in immunocompromised patients. Invasive infections due to Trichoderma are rare and definitive diagnosis is complex to achieve because of the lack of specific diagnosis tools. We report in this work the first proven case of invasive pulmonary infection due to T. longibrachiatum in a 69-year-old white male with hematologic malignancy. The patient was successfully treated initially with voriconazole alone followed by a combination of voriconazole and caspofungine.


Assuntos
Hospedeiro Imunocomprometido , Infecções Fúngicas Invasivas/complicações , Infecções Fúngicas Invasivas/microbiologia , Leucemia Mieloide Aguda/complicações , Pneumopatias Fúngicas/complicações , Pneumopatias Fúngicas/microbiologia , Idoso , Antifúngicos/uso terapêutico , Caspofungina/uso terapêutico , Quimioterapia Combinada , Humanos , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Leucemia Mieloide Aguda/imunologia , Pulmão/microbiologia , Pulmão/patologia , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/tratamento farmacológico , Masculino , Resultado do Tratamento , Trichoderma/isolamento & purificação , Voriconazol/uso terapêutico
12.
J Chemother ; 30(4): 233-239, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30025501

RESUMO

We determined micafungin, caspofungin and amphotericin B (AMB) minimum inhibitory concentration (MICs) and killing rates in RPMI-1640 and in RPMI-1640 with 50% serum against three Candida krusei bloodstream isolates. MIC ranges in RPMI-1640 were 0.125-0.25, 0.25 and 0.125-0.5 mg/L, in RPMI-1640 with 50% serum, MICs were 64-128-, 8- and 4-16-fold higher, respectively. In RPMI-1640 micafungin and caspofungin at 1, 4, 16 and 32 mg/L as well as AMB at 2 mg/L were fungicidal against all isolates in ≤3.96, ≤4.42 and 14.96 h, respectively. In RPMI-1640 with 50% serum, caspofungin was fungicidal for all isolates only at 32 mg/L, micafungin and AMB were fungistatic. In neutropenic mice, 5 mg/kg caspofungin and 1 mg/kg AMB were ineffective against two of the three isolates. Thus, in vivo efficacy of echinocandins and AMB is weak or absent against C. krusei. Prescribers treating C. krusei infections with echinocandins should watch out for clinical resistance and therapeutic failure.


Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candidemia/tratamento farmacológico , Caspofungina/farmacologia , Micafungina/farmacologia , Anfotericina B/uso terapêutico , Animais , Antifúngicos/uso terapêutico , Caspofungina/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Micafungina/uso terapêutico , Testes de Sensibilidade Microbiana
13.
Int J Hematol ; 108(5): 558-563, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29926359

RESUMO

We experienced a breakthrough fungal infection caused by Geotrichum capitatum during empirical therapy with caspofungin. A 68-year-old male patient with refractory acute lymphoblastic leukemia had received umbilical cord blood transplantation after two courses of induction therapy. Empirical therapy with caspofungin was initiated 5 days before transplantation. Tacrolimus was continuously infused to prevent graft-versus-host disease. A minidose of methotrexate was intravenously administered on days 1 and 3 post-transplantation, which was changed to prednisolone from day 7 due to severe mucositis. During a recurrence of fever on day 11, blood cultures were found to be positive for a yeast-like organism, which was later confirmed by mass spectrometry to be G. capitatum. The serum levels of beta-D-glucan were elevated to 747 pg/mL. Caspofungin was switched to liposomal amphotericin B; however, radiological findings revealed pulmonary, splenic, and central nervous system involvement. Progressive renal and hepatic dysfunction subsequently developed. The patient died on day 25 post-transplantation secondary to the development of hemophagocytic syndrome and respiratory failure. We emphasize that recurrent febrile episodes, prolonged neutropenia, and underlying gastrointestinal mucosal damage require extreme caution due to the possibility of breakthrough infection caused by new fungal pathogens during empirical therapy with caspofungin.


Assuntos
Antifúngicos/uso terapêutico , Caspofungina/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Geotrichum , Micoses/tratamento farmacológico , Micoses/etiologia , Idoso , Hemocultura , Evolução Fatal , Violeta Genciana , Geotrichum/efeitos dos fármacos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Microscopia , Micoses/diagnóstico , Fenazinas , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
14.
Clin Lab ; 64(5): 867-869, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29739053

RESUMO

BACKGROUND: Invasive fungal infections often occur in immunocompromised patients. Here, we report an infection case caused by Geotrichum capitatum in a severe aplastic anemia patient. METHODS: Identification of the pathogenic bacteria was done by sequencing and mass spectrometric analysis. RESULTS: The fungal infection was isolated from blood cultures. The pathogenic bacteria were identified as Geotrichum capitatum. The infection was primarily cured by voriconazole and caspofungin monotherapy. However, the effect was not obvious. Then a combination of liposomal amphotericin B and caspofungin was used. Body temperature of the patient decreased, and clinical symptoms improved. CONCLUSIONS: Sequencing and mass spectrometric analysis could have a role for Geotrichum capitatum diagnosis. Curative effect of using a single antifungal drug was unsatisfactory. Using liposome amphotericin B combined with caspofungin might obtain certain curative effect. Early diagnosis and appropriate combined therapy were necessary to improve the outcome of patients with Geotrichum capitatum infection.


Assuntos
Anemia Aplástica/complicações , Geotrichum/efeitos dos fármacos , Micoses/tratamento farmacológico , Adolescente , Anfotericina B/uso terapêutico , Anemia Aplástica/patologia , Antifúngicos/uso terapêutico , Caspofungina/uso terapêutico , Quimioterapia Combinada , Feminino , Geotrichum/fisiologia , Humanos , Micoses/complicações , Micoses/microbiologia , Índice de Gravidade de Doença , Voriconazol/uso terapêutico
15.
Am J Transplant ; 18(9): 2352-2355, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29790292

RESUMO

Invasive aspergillosis (IA) affects the lungs and disseminates mostly in patients with neutropenia and/or patients who are receiving immunosuppressive and steroid therapies. Despite progress in the diagnosis of and therapy for IA, it is still characterized by a high mortality rate. Currently, voriconazole is considered as the standard therapy for IA. Over recent years, triazole-resistant Aspergillus fumigatus isolates have emerged in the environment due to the use of fungicidal agricultural products, with the risk of developing IA related to a resistant isolate. However, resistance may also develop in patients who are undergoing long-term triazole therapy, particularly in the setting of chronic forms of pulmonary aspergillosis. Herein we describe a kidney transplant recipient who failed to respond to voriconazole therapy due to acquired resistance secondary to the appearance of a de novo mutation (Y121F) in the cyp51A gene during chronic necrotizing pulmonary aspergillosis. The infecting isolate acquired voriconazole resistance in 8 months despite plasma concentrations within the recommended range of the drug, necessitating lobectomy in association with a new antifungal strategy consisting of liposomal amphotericin and caspofungin with a good outcome over 36 months.


Assuntos
Antifúngicos/uso terapêutico , Aspergillus fumigatus/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Transplante de Rim/efeitos adversos , Voriconazol/farmacologia , Idoso , Anfotericina B/uso terapêutico , Caspofungina/uso terapêutico , Sistema Enzimático do Citocromo P-450/genética , Proteínas Fúngicas/genética , Humanos , Aspergilose Pulmonar Invasiva/etiologia , Aspergilose Pulmonar Invasiva/patologia , Masculino , Mutação , Prognóstico
16.
BMC Infect Dis ; 18(1): 194, 2018 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-29699503

RESUMO

BACKGROUND: Invasive candidiasis differs greatly between children and neonates. We aimed to investigate the different therapeutic approaches and their effects on treatment outcomes of these two groups. METHODS: Episodes of neonatal invasive candidiasis were compared with non-neonatal pediatric episodes during a 12-year cohort study. Clinical isolates were documented by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and DNA sequencing, and antifungal susceptibility testing was performed. RESULTS: A total of 342 episodes of invasive candidiasis (113 neonatal and 229 non-neonatal pediatric episodes) in 281 pediatric patients (96 neonates and 185 children) were identified. Candida albicans was the most common pathogen causing invasive candidiasis in neonates and children (47.8% vs. 44.1%). The antifungal susceptibility profiles were not significantly different between neonates and children. More neonates received amphotericin B as therapy, whereas more children received fluconazole or caspofungin. Compared with children, neonates had a significantly longer duration of fungemia, higher rates of septic shock (34.5% vs. 21.8%; P = 0.013), sepsis-attributable mortality (28.3% vs. 17.5%; P = 0.024) and in-hospital mortality (42.7% vs. 25.4%; P = 0.004) than children. Independent risk factors for treatment failure of invasive candidiasis were septic shock (odds ration [OR] 16.01; 95% confidence interval [CI] 7.64-33.56; P <  0.001), delayed removal of intravenous catheter (OR 6.78; 95% CI 2.80-17.41; P <  0.001), renal failure (OR 5.38; 95% CI 1.99-14.57; P = 0.001), and breakthrough invasive candidiasis (OR 2.99; 95% CI 1.04-8.67; P = 0.043). CONCLUSIONS: Neonatal invasive candidiasis has worse outcomes than non-neonatal pediatric candidiasis. Neonatologists and pediatricians must consider age-specific differences when developing treatment and prevention guidelines, or when interpreting studies of other age groups.


Assuntos
Antifúngicos/uso terapêutico , Candidíase Invasiva/tratamento farmacológico , Candidíase Invasiva/epidemiologia , Fungemia/microbiologia , Adolescente , Anfotericina B/uso terapêutico , Candida albicans/patogenicidade , Candidíase Invasiva/etiologia , Caspofungina/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Fluconazol/uso terapêutico , Fungemia/tratamento farmacológico , Fungemia/epidemiologia , Mortalidade Hospitalar , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Fatores de Risco , Taiwan/epidemiologia , Resultado do Tratamento
17.
Pediatr Infect Dis J ; 37(10): e251-e253, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29438132

RESUMO

Disseminated fusariosis is a fatal infection in immunocompromised hosts. However, the optimal antifungal treatment for disseminated fusariosis has not yet been established. We report a case of disseminated fusariosis after chemotherapy for acute lymphoblastic leukemia, presenting with multiple skin, lung and kidney lesions and cerebrospinal fluid invasion. The combination therapy of liposomal amphotericin B and caspofungin resolved disseminated fusariosis successfully.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Caspofungina/uso terapêutico , Fusariose/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Anfotericina B/administração & dosagem , Caspofungina/administração & dosagem , Criança , Tratamento Farmacológico , Quimioterapia Combinada , Feminino , Febre/etiologia , Fusariose/diagnóstico , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
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