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Brazilian Journal of Cardiovascular... Oct 2020Although it is the most common agent among the fungal causes of endocarditis, Candida albicans endocarditis is rare.
INTRODUCTION
Although it is the most common agent among the fungal causes of endocarditis, Candida albicans endocarditis is rare.
OBJECTIVE
To evaluate the efficacy of amphotericin B in the treatment of C. albicans endocarditis beyond a systematic review.
DATA SEARCH
Articles in English, Spanish and Portuguese, conducted in the following databases: MEDLINE, LILACS, IBECS and SciELO, in humans and published in the last 25 years.
STUDY SELECTION
Observational studies, clinical trials, and case series providing data on the amphotericin B use in patients with a C. albicans endocarditis diagnosis without age limitations.
DATA SYNTHESIS
From the initial search (n=79), 25 articles were fully evaluated, of which 19 were excluded for meeting one or more exclusion criteria, remaining five articles (two observational studies and three case series). Patients using amphotericin B demonstrated improvement in survival rates, and its main use was in association with the surgical method as well as with caspofungin association.
CONCLUSION
Literature lacks evidence to conclude about efficacy and safety of amphotericin B in the treatment of fungal endocarditis. Randomized clinical trials are necessary to provide better evidence on the subject.
Topics: Amphotericin B; Antifungal Agents; Candida albicans; Child; Cross-Sectional Studies; Endocarditis; Humans; Infant, Newborn
PubMed: 33118745
DOI: 10.21470/1678-9741-2019-0159 -
Italian Journal of Pediatrics Oct 2020To describe a case of thrombophlebitis associated with Candida infection and to analyze other published reports to define clinical characteristics, prognostic data,...
OBJECTIVE
To describe a case of thrombophlebitis associated with Candida infection and to analyze other published reports to define clinical characteristics, prognostic data, diagnostic and therapeutic strategies.
STUDY DESIGN
A computerized search was performed without language restriction using PubMed and Scopus databases. An article was considered eligible for inclusion if it reported cases with Candida thrombophlebitis. Our case was also included in the analysis.
RESULTS
A total of 16 articles reporting 27 cases of Candida thrombophlebitis were included in our review. The median age of patients was 4 years. In 10 cases there was a thrombophlebitis of peripheral veins; in the remaining cases the deep venous circle was interested. Candida albicans was the most frequently involved fungal species. The most recurrent risk factors were central venous catheter (19/28), broad spectrum antibiotics (17/28), intensive care unit (8/28), surgery (3/28), mechanical assisted ventilation (5/28), total parenteral nutrition (8/28), cancer (2/28), premature birth (6/28), cystic fibrosis (2/28). Fever was the most frequent clinical feature. All children with peripheral and deep thrombophlebitis were given antifungal therapy: amphotericin B was the most used, alone or in combination with other antifungal drugs. Heparin was most frequently used as anticoagulant therapy. Illness was fatal in two cases.
CONCLUSION
Candida thrombophlebitis is a rare but likely underdiagnosed infectious complication in pediatric critically ill patients. It is closely connected to risk factors such as central venous catheter, hospitalization in intensive care unit, prematurity, assisted ventilation, chronic inflammatory diseases. Antifungal therapy and anticoagulant drugs should be optimized for each patient and surgical resection is considered in the persistence of illness.
Topics: Amphotericin B; Anticoagulants; Antifungal Agents; Candidiasis; Child; Child, Preschool; Cross Infection; Humans; Prognosis; Risk Factors; Thrombophlebitis
PubMed: 33023609
DOI: 10.1186/s13052-020-00913-5 -
Epidemiology and Infection Jul 2020Trichosporon is a yeast-like basidiomycete, a conditional pathogenic fungus that is rare in the clinic but often causes fatal infections in immunocompromised...
Trichosporon is a yeast-like basidiomycete, a conditional pathogenic fungus that is rare in the clinic but often causes fatal infections in immunocompromised individuals. Trichosporon asahii is the most common pathogenic fungus in this genus and the occurrence of infections has dramatically increased in recent years. Here, we report a systematic literature review detailing 140 cases of T. asahii infection reported during the past 23 years. Statistical analysis shows that T. asahii infections were most frequently reported within immunodeficient or immunocompromised patients commonly with blood diseases. Antibiotic use, invasive medical equipment and chemotherapy were the leading risk factors for acquiring infection. In vitro susceptibility, clinical information and prognosis analysis showed that voriconazole is the primary drug of choice in the treatment of T. asahii infection. Combination treatment with voriconazole and amphotericin B did not show superiority over either drug alone. Finally, we found that the types of infections prevalent in China are significantly different from those in other countries. These results provide detailed information and relevant clinical treatment strategies for the diagnosis and treatment of T. asahii infection.
Topics: Animals; Global Health; Humans; Retrospective Studies; Trichosporon; Trichosporonosis
PubMed: 32703332
DOI: 10.1017/S0950268820001624 -
Frontiers in Pharmacology 2020Precision dosing for many antifungal drugs is now recommended. Saliva sampling is considered as a non-invasive alternative to plasma sampling for therapeutic drug...
Precision dosing for many antifungal drugs is now recommended. Saliva sampling is considered as a non-invasive alternative to plasma sampling for therapeutic drug monitoring (TDM). However, there are currently no clinically validated saliva models available. The aim of this study is firstly, to conduct a systematic review to evaluate the evidence supporting saliva-based TDM for azoles, echinocandins, amphotericin B, and flucytosine. The second aim is to develop a saliva population pharmacokinetic (PK) model for eligible drugs, based on the evidence. Databases were searched up to July 2019 on PubMed and Embase, and 14 studies were included in the systematic review for fluconazole, voriconazole, itraconazole, and ketoconazole. No studies were identified for isavuconazole, posaconazole, flucytosine, amphotericin B, caspofungin, micafungin, or anidulafungin. Fluconazole and voriconazole demonstrated a good saliva penetration with an average S/P ratio of 1.21 (± 0.31) for fluconazole and 0.56 (± 0.18) for voriconazole, both with strong correlation (r = 0.89-0.98). Based on the evidence for TDM and available data, population PK analysis was performed on voriconazole using Nonlinear Mixed Effects Modeling (NONMEM 7.4). 137 voriconazole plasma and saliva concentrations from 11 patients (10 adults, 1 child) were obtained from the authors of the included study. Voriconazole pharmacokinetics was best described by one-compartment PK model with first-order absorption, parameterized by clearance of 4.56 L/h (36.9% CV), volume of distribution of 60.7 L, absorption rate constant of 0.858 (fixed), and bioavailability of 0.849. Kinetics of the voriconazole distribution from plasma to saliva was identical to the plasma kinetics, but the extent of distribution was lower, modeled by a scale factor of 0.5 (4% CV). A proportional error model best accounted for the residual variability. The visual and simulation-based model diagnostics confirmed a good predictive performance of the saliva model. The developed saliva model provides a promising framework to facilitate saliva-based precision dosing of voriconazole.
PubMed: 32595511
DOI: 10.3389/fphar.2020.00894 -
The Cochrane Database of Systematic... Apr 2020Progressive disseminated histoplasmosis (PDH) is a serious fungal infection that affects people living with HIV. The best way to treat the condition is unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Progressive disseminated histoplasmosis (PDH) is a serious fungal infection that affects people living with HIV. The best way to treat the condition is unclear.
OBJECTIVES
We assessed evidence in three areas of equipoise. 1. Induction. To compare efficacy and safety of initial therapy with liposomal amphotericin B versus initial therapy with alternative antifungals. 2. Maintenance. To compare efficacy and safety of maintenance therapy with 12 months of oral antifungal treatment with shorter durations of maintenance therapy. 3. Antiretroviral therapy (ART). To compare the outcomes of early initiation versus delayed initiation of ART.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane CENTRAL; MEDLINE (PubMed); Embase (Ovid); Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and BIOSIS Previews (all three in the Web of Science); the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the ISRCTN registry, all up to 20 March 2020.
SELECTION CRITERIA
We evaluated studies assessing the use of liposomal amphotericin B and alternative antifungals for induction therapy; studies assessing the duration of antifungals for maintenance therapy; and studies assessing the timing of ART. We included randomized controlled trials (RCT), single-arm trials, prospective cohort studies, and single-arm cohort studies.
DATA COLLECTION AND ANALYSIS
Two review authors assessed eligibility and risk of bias, extracted data, and assessed certainty of evidence. We used the Cochrane 'Risk of bias' tool to assess risk of bias in randomized studies, and ROBINS-I tool to assess risk of bias in non-randomized studies. We summarized dichotomous outcomes using risk ratios (RRs), with 95% confidence intervals (CI).
MAIN RESULTS
We identified 17 individual studies. We judged eight studies to be at critical risk of bias, and removed these from the analysis. 1. Induction We found one RCT which compared liposomal amphotericin B to deoxycholate amphotericin B. Compared to deoxycholate amphotericin B, liposomal amphotericin B may have higher clinical success rates (RR 1.46, 95% CI 1.01 to 2.11; 1 study, 80 participants; low-certainty evidence). Compared to deoxycholate amphotericin B, liposomal amphotericin B has lower rates of nephrotoxicity (RR 0.25, 95% CI 0.09 to 0.67; 1 study, 77 participants; high-certainty evidence). We found very low-certainty evidence to inform comparisons between amphotericin B formulations and azoles for induction therapy. 2. Maintenance We found no eligible study that compared less than 12 months of oral antifungal treatment to 12 months or greater for maintenance therapy. For both induction and maintenance, fluconazole performed poorly in comparison to other azoles. 3. ART We found one study, in which one out of seven participants in the 'early' arm and none of the three participants in the 'late' arm died.
AUTHORS' CONCLUSIONS
Liposomal amphotericin B appears to be a better choice compared to deoxycholate amphotericin B for treating PDH in people with HIV; and fluconazole performed poorly compared to other azoles. Other treatment choices for induction, maintenance, and when to start ART have no evidence, or very low certainty evidence. PDH needs prospective comparative trials to help inform clinical decisions.
Topics: Amphotericin B; Anti-HIV Agents; Antifungal Agents; Cohort Studies; Deoxycholic Acid; Drug Administration Schedule; Fluconazole; HIV Infections; Histoplasmosis; Humans; Induction Chemotherapy; Itraconazole; Kidney; Liposomes; Maintenance Chemotherapy; Randomized Controlled Trials as Topic
PubMed: 32343003
DOI: 10.1002/14651858.CD013594 -
Journal of Infection and Chemotherapy :... Jun 2020Empirical antifungal therapy is recommended in high-risk patients who have persistent febrile neutropenia (FN) despite broad-spectrum antibiotic therapy. Based on... (Meta-Analysis)
Meta-Analysis
Echinocandins versus non-echinocandins for empirical antifungal therapy in patients with hematological disease with febrile neutropenia: A systematic review and meta-analysis.
Empirical antifungal therapy is recommended in high-risk patients who have persistent febrile neutropenia (FN) despite broad-spectrum antibiotic therapy. Based on high-quality evidence, most guidelines recommend caspofungin. The aim of this study was to clarify whether echinocandins, including micafungin, are associated with improved clinical outcomes in patients with persistent FN. We conducted a meta-analysis of randomized controlled trials (RCTs) of empirical therapy with echinocandins and non-echinocandins for FN in patients with hematological disease. The primary outcome was all-cause mortality within 7 days after completion of therapy. Secondary outcomes included treatment success, and discontinuation of therapy because of adverse events. For subgroup analysis, we compared RCTs of echinocandins with liposomal amphotericin B. Six RCTs (four that evaluated caspofungin and two that evaluated micafungin) were included in the meta-analysis. Mortality and adverse events in echinocandin-treated patients were significantly lower than in those treated with non-echinocandins [risk ratio (RR) 0.70, 95% confidence interval (CI) 0.49-0.99; RR 0.48, 95% CI 0.33-0.71, respectively]. There was no significant difference in treatment success (RR 1.09, 95% CI 0.87-1.36). Mortality and adverse events in echinocandin-treated patients were significantly lower than in those treated with liposomal amphotericin B (RR 0.68, 95% CI 0.46-0.99; RR 0.53, 95% CI 0.37-0.74, respectively). In conclusion, patients with persistent FN treated with echinocandins had decreased risk of death and adverse events. Both caspofungin and micafungin may be recommended as first-line empirical antifungal therapy in these patients. However, the small number of enrolled patients and the lack of RCTs involving pediatric patients should be considered when using micafungin.
Topics: Amphotericin B; Antifungal Agents; Echinocandins; Febrile Neutropenia; Humans; Mycoses; Randomized Controlled Trials as Topic; Treatment Outcome; Voriconazole
PubMed: 32171659
DOI: 10.1016/j.jiac.2020.01.015 -
Oman Medical Journal Jan 2020Histoplasmosis is uncommon in many parts of the world, including Bangladesh, where, in recent years, cases are increasingly reported. We sought to describe the... (Review)
Review
Histoplasmosis is uncommon in many parts of the world, including Bangladesh, where, in recent years, cases are increasingly reported. We sought to describe the sociodemographic characteristics, clinical presentation, investigations, treatment, and outcome of histoplasmosis in Bangladesh. We conducted a retrospective data review of published literature from 1962 to 2017, containing information on histoplasmosis in and/or from Bangladesh. Unpublished, well-documented histoplasmosis cases were also included. A total of 26 male patients aged 8-75 years, with a diagnosis of histoplasmosis were included; nine were farmers, seven had diabetes, one was a renal transplant recipient, and four had HIV/AIDS. Fever (n = 20), weight loss (n = 17), anemia (n = 15), lymphadenopathy (n = 9), and hepatosplenomegaly (n = 7) were common. Eleven patients had bilateral adrenal enlargement. Diagnosis was confirmed by histo/cytopathology from skin (n = 1), oropharyngeal ulcers (n = 8), lymph nodes (n = 3), adrenal glands (n = 11), paravertebral soft tissue (n = 2), and bone marrow (n = 4). Cultures of representative samples and antibodies were detected in three and two cases, respectively. Twenty-two patients had disseminated histoplasmosis and four patients had localized oropharyngeal disease. Nine patients were prescribed anti-tuberculosis drugs empirically before establishing the diagnosis of histoplasmosis. Treatment consisted of amphotericin B and itraconazole. Six patients died in hospital, 14 patients recovered with relapse in two cases, and the outcome of the other patients could not be ascertained. Histoplasmosis is thought to be endemic in Bangladesh, but few cases are reported to date, which may be due to many asymptomatic, undiagnosed, misdiagnosed, or under-reported cases. Histoplasmosis should be considered as a differential in appropriate clinical scenarios.
PubMed: 32095275
DOI: 10.5001/omj.2020.09 -
Journal of the International AIDS... Jan 2020HIV-associated cryptococcal, TB and pneumococcal meningitis are the leading causes of adult meningitis in sub-Saharan Africa (SSA). We performed a systematic review and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
HIV-associated cryptococcal, TB and pneumococcal meningitis are the leading causes of adult meningitis in sub-Saharan Africa (SSA). We performed a systematic review and meta-analysis with the primary aim of estimating mortality from major causes of adult meningitis in routine care settings, and to contrast this with outcomes from clinical trial settings.
METHODS
We searched PubMed, EMBASE and the Cochrane Library for published clinical trials (defined as randomized-controlled trials (RCTs) or investigator-managed prospective cohorts) and observational studies that evaluated outcomes of adult meningitis in SSA from 1 January 1990 through 15 September 2019. We performed random effects modelling to estimate pooled mortality, both in clinical trial and routine care settings. Outcomes were stratified as short-term (in-hospital or two weeks), medium-term (up to 10 weeks) and long-term (up to six months).
RESULTS AND DISCUSSION
Seventy-nine studies met inclusion criteria. In routine care settings, pooled short-term mortality from cryptococcal meningitis was 44% (95% confidence interval (95% CI):39% to 49%, 40 studies), which did not differ between amphotericin (either alone or with fluconazole) and fluconazole-based induction regimens, and was twofold higher than pooled mortality in clinical trials using amphotericin based treatment (21% (95% CI:17% to 25%), 17 studies). Pooled short-term mortality of TB meningitis was 46% (95% CI: 33% to 59%, 11 studies, all routine care). For pneumococcal meningitis, pooled short-term mortality was 54% in routine care settings (95% CI:44% to 64%, nine studies), with similar mortality reported in two included randomized-controlled trials. Few studies evaluated long-term outcomes.
CONCLUSIONS
Mortality rates from HIV-associated meningitis in SSA are very high under routine care conditions. Better strategies are needed to reduce mortality from HIV-associated meningitis in the region.
Topics: Adult; Africa South of the Sahara; Aged; Amphotericin B; Antifungal Agents; Female; Fluconazole; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 31957332
DOI: 10.1002/jia2.25416 -
The Brazilian Journal of Infectious... 2019Papiliotrema laurentii is one of several non-neoformans cryptococci that have rarely been associated with human infection, since it was previously considered saprophyte...
BACKGROUND
Papiliotrema laurentii is one of several non-neoformans cryptococci that have rarely been associated with human infection, since it was previously considered saprophyte and thought to be non-pathogenic to humans. Nevertheless, increasing number of reports of human infection have emerged in recent years, mostly in oncologic patients.
AIM
To report a case of a female patient with pyloric obstructive cancer with a catheter-related Papiliotrema laurentii blood stream infection and systematically review the available evidence on P. laurentii infection in humans.
METHODS
Retrieval of studies was based on Medical Subject Headings and Health Sciences Descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE (PubMed), BIREME (Biblioteca Regional de Medicina), LILACS (Latin American and Caribbean Health Sciences Literature), Cochrane Library for Systematic Reviews and Opengray.eu. There was no language or date of publication restrictions. The reference lists of the studies retrieved were searched manually.
RESULTS
The search strategy retrieved 1703 references. In the final analysis, 31 references were included, with the description of 35 cases. Every patient but one had a previous co-morbidity - 48.4 % of patients had a neoplasm. Amphotericin B was the most used treatment and only a single case of resistance to it was reported. Most patients were cured of the infection.
CONCLUSION
P. laurentii infection in humans is usually associated to neoplasia and multiple co-morbidities, and amphotericin B seems to be a reliable agent for treatment.
Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Bacteremia; Biopsy; Catheter-Related Infections; Cryptococcus; Female; Fluconazole; Humans; Piperacillin, Tazobactam Drug Combination; Stomach Neoplasms; Tomography, X-Ray Computed; Vancomycin
PubMed: 31738886
DOI: 10.1016/j.bjid.2019.10.005 -
Medical Mycology Apr 2020Cryptococcal meningitis causes 15% of AIDS-related deaths. Optimal management and clinical outcomes of pregnant women with cryptococcosis are limited to case reports, as...
Cryptococcal meningitis causes 15% of AIDS-related deaths. Optimal management and clinical outcomes of pregnant women with cryptococcosis are limited to case reports, as pregnant women are often excluded from research. Amongst pregnant women with asymptomatic cryptococcosis, no treatment guidelines exist. We prospectively identified HIV-infected women who were pregnant or recently pregnant with cryptococcosis, screened during a series of meningitis research studies in Uganda from 2012 to 2018. Among 571 women screened for cryptococcosis, 13 were pregnant, one was breastfeeding, three were within 14 days postpartum, and two had recently miscarried. Of these 19 women (3.3%), 12 had cryptococcal meningitis, six had cryptococcal antigenemia, and one had a history of cryptococcal meningitis and was receiving secondary prophylaxis. All women with meningitis received amphotericin B deoxycholate (0.7-1.0 mg/kg). Five were exposed to 200-800 mg fluconazole during pregnancy. Of these five, three delivered healthy babies with no gross physical abnormalities at birth, one succumbed to meningitis, and one outcome was unknown. Maternal meningitis survival rate at hospital discharge was 75% (9/12), and neonatal/fetal survival rate was 44% (4/9) for those mothers who survived. Miscarriages and stillbirths were common (n = 4). Of six women with cryptococcal antigenemia, two received fluconazole, one received weekly amphotericin B, and three had unknown treatment courses. All women with antigenemia survived, and none developed clinical meningitis. We report good maternal outcomes but poor fetal outcomes for cryptococcal meningitis using amphotericin B, without fluconazole in the first trimester, and weekly amphotericin B in place of fluconazole for cryptococcal antigenemia.
Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Clinical Trials as Topic; Cryptococcus neoformans; Deoxycholic Acid; Disease Management; Drug Combinations; Female; Fluconazole; HIV Infections; Humans; Meningitis, Cryptococcal; Postpartum Period; Pregnancy; Pregnancy Complications, Infectious; Prospective Studies; Uganda; Young Adult
PubMed: 31689712
DOI: 10.1093/mmy/myz084