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Peter G. Pappas - One of the best experts on this subject based on the ideXlab platform.
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Invasive Candidiasis
Nature Reviews Disease Primers, 2018Co-Authors: Peter G. Pappas, Michail S Lionakis, Maiken Cavling Arendrup, Luis Ostrosky-zeichner, Bart Jan KullbergAbstract:Candida spp. are common commensal organisms in the gut microbiota. However, breaches in the intestinal barrier, an impaired immune system, the use of broad-spectrum antibacterial agents and other interventions associated with medical progress can promote Invasive Candida spp. infections, including bloodstream infections, that are often fatal. Invasive Candidiasis is an important health-care-associated fungal infection that can be caused by several Candida spp.; the most common species is Candida albicans , but the prevalence of these organisms varies considerably depending on geographical location. The spectrum of disease of Invasive Candidiasis ranges from minimally symptomatic candidaemia to fulminant sepsis with an associated mortality exceeding 70%. Candida spp. are common commensal organisms in the skin and gut microbiota, and disruptions in the cutaneous and gastrointestinal barriers (for example, owing to gastrointestinal perforation) promote Invasive disease. A deeper understanding of specific Candida spp. virulence factors, host immune response and host susceptibility at the genetic level has led to key insights into the development of early intervention strategies and vaccine candidates. The early diagnosis of Invasive Candidiasis is challenging but key to the effective management, and the development of rapid molecular diagnostics could improve the ability to intervene rapidly and potentially reduce mortality. First-line drugs, including echinocandins and azoles, are effective, but the emergence of antifungal resistance, especially among Candida glabrata , is a matter of concern and underscores the need to administer antifungal medications in a judicious manner, avoiding overuse when possible. A newly described pathogen, Candida auris , is an emerging multidrug-resistant organism that poses a global threat.
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micafungin versus caspofungin for treatment of candidemia and other forms of Invasive Candidiasis
Clinical Infectious Diseases, 2007Co-Authors: Peter G. Pappas, Jose A. Vazquez, Robert F. Betts, Coleman Rotstein, Marcio Nucci, Deepak Talwar, Jan J De Waele, B Dupont, David Horn, Luis OstroskyzeichnerAbstract:Background. Invasive Candidiasis is an important cause of morbidity and mortality among patients with health care–associated infection. The echinocandins have potent fungicidal activity against most Candida species, but there are few data comparing the safety and efficacy of echinocandins in the treatment of Invasive Candidiasis. Methods. This was an international, randomized, double-blind trial comparing micafungin (100 mg daily) and micafungin (150 mg daily) with a standard dosage of caspofungin (70 mg followed by 50 mg daily) in adults with candidemia and other forms of Invasive Candidiasis. The primary end point was treatment success, defined as clinical and mycological success at the end of blinded intravenous therapy. Results. A total of 595 patients were randomized to one the treatment groups and received at least 1 dose of study drug. In the modified intent-to-treat population, 191 patients were assigned to the micafungin 100 mg group, 199 to the micafungin 150 mg group, and 188 to the caspofungin group. Demographic characteristics and underlying disorders were comparable across the groups. Approximately 85% of patients had candidemia; the remainder had noncandidemic Invasive Candidiasis. At the end of blinded intravenous therapy, treatment was considered successful for 76.4% of patients in the micafungin 100 mg group, 71.4% in the micafungin 150 mg group, and 72.3% in the caspofungin group. The median time to culture negativity was 2 days in the micafungin 100 mg group and the caspofungin group, compared with 3 days in the micafungin 150 mg groups. There were no significant differences in mortality, relapsing and emergent infections, or adverse events between the study arms.
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Invasive Candidiasis in the intensive care unit
Critical Care Medicine, 2006Co-Authors: Luis Ostroskyzeichner, Peter G. PappasAbstract:Objective:To review epidemiologic trends, advances in diagnosis and susceptibility testing, therapeutic options and guidelines, and management strategies for Invasive Candidiasis as relevant to the intensive care unit physician.Data Sources, Study Selection, Data Extraction, Data Synthesis:Nonstruct
Luis Ostroskyzeichner - One of the best experts on this subject based on the ideXlab platform.
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micafungin versus caspofungin for treatment of candidemia and other forms of Invasive Candidiasis
Clinical Infectious Diseases, 2007Co-Authors: Peter G. Pappas, Jose A. Vazquez, Robert F. Betts, Coleman Rotstein, Marcio Nucci, Deepak Talwar, Jan J De Waele, B Dupont, David Horn, Luis OstroskyzeichnerAbstract:Background. Invasive Candidiasis is an important cause of morbidity and mortality among patients with health care–associated infection. The echinocandins have potent fungicidal activity against most Candida species, but there are few data comparing the safety and efficacy of echinocandins in the treatment of Invasive Candidiasis. Methods. This was an international, randomized, double-blind trial comparing micafungin (100 mg daily) and micafungin (150 mg daily) with a standard dosage of caspofungin (70 mg followed by 50 mg daily) in adults with candidemia and other forms of Invasive Candidiasis. The primary end point was treatment success, defined as clinical and mycological success at the end of blinded intravenous therapy. Results. A total of 595 patients were randomized to one the treatment groups and received at least 1 dose of study drug. In the modified intent-to-treat population, 191 patients were assigned to the micafungin 100 mg group, 199 to the micafungin 150 mg group, and 188 to the caspofungin group. Demographic characteristics and underlying disorders were comparable across the groups. Approximately 85% of patients had candidemia; the remainder had noncandidemic Invasive Candidiasis. At the end of blinded intravenous therapy, treatment was considered successful for 76.4% of patients in the micafungin 100 mg group, 71.4% in the micafungin 150 mg group, and 72.3% in the caspofungin group. The median time to culture negativity was 2 days in the micafungin 100 mg group and the caspofungin group, compared with 3 days in the micafungin 150 mg groups. There were no significant differences in mortality, relapsing and emergent infections, or adverse events between the study arms.
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Invasive Candidiasis in the intensive care unit
Critical Care Medicine, 2006Co-Authors: Luis Ostroskyzeichner, Peter G. PappasAbstract:Objective:To review epidemiologic trends, advances in diagnosis and susceptibility testing, therapeutic options and guidelines, and management strategies for Invasive Candidiasis as relevant to the intensive care unit physician.Data Sources, Study Selection, Data Extraction, Data Synthesis:Nonstruct
Bart Jan Kullberg - One of the best experts on this subject based on the ideXlab platform.
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Invasive Candidiasis
Nature Reviews Disease Primers, 2018Co-Authors: Peter G. Pappas, Michail S Lionakis, Maiken Cavling Arendrup, Luis Ostrosky-zeichner, Bart Jan KullbergAbstract:Candida spp. are common commensal organisms in the gut microbiota. However, breaches in the intestinal barrier, an impaired immune system, the use of broad-spectrum antibacterial agents and other interventions associated with medical progress can promote Invasive Candida spp. infections, including bloodstream infections, that are often fatal. Invasive Candidiasis is an important health-care-associated fungal infection that can be caused by several Candida spp.; the most common species is Candida albicans , but the prevalence of these organisms varies considerably depending on geographical location. The spectrum of disease of Invasive Candidiasis ranges from minimally symptomatic candidaemia to fulminant sepsis with an associated mortality exceeding 70%. Candida spp. are common commensal organisms in the skin and gut microbiota, and disruptions in the cutaneous and gastrointestinal barriers (for example, owing to gastrointestinal perforation) promote Invasive disease. A deeper understanding of specific Candida spp. virulence factors, host immune response and host susceptibility at the genetic level has led to key insights into the development of early intervention strategies and vaccine candidates. The early diagnosis of Invasive Candidiasis is challenging but key to the effective management, and the development of rapid molecular diagnostics could improve the ability to intervene rapidly and potentially reduce mortality. First-line drugs, including echinocandins and azoles, are effective, but the emergence of antifungal resistance, especially among Candida glabrata , is a matter of concern and underscores the need to administer antifungal medications in a judicious manner, avoiding overuse when possible. A newly described pathogen, Candida auris , is an emerging multidrug-resistant organism that poses a global threat.
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Toll like receptor 1 polymorphisms and susceptibility to Invasive Candidiasis
Critical Care, 2009Co-Authors: Theo S. Plantinga, John R. Perfect, Bart Jan Kullberg, M Johnsson, B.a. Scott, E. Van De Vosse, D Velez, Jwm Van Der Meer, J. T. Van Dissel, Mihai G. NeteaAbstract:Invasive Candidiasis is a severe systemic fungal infection with Candida spp. affecting immunocompromised hosts, which is responsible for the highest mortality rate of all nosocomial infections. Although several clinical predisposing factors are known, the individual risk for developing Invasive Candidiasis varies significantly. Recognition of fungi such as Candida albicans is mediated through receptors of the innate immune system, such as Toll-like receptors (TLRs), that in turn activate innate immune system and antifungal defense.
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Voriconazole Salvage Treatment of Invasive Candidiasis
European Journal of Clinical Microbiology and Infectious Diseases, 2003Co-Authors: Luis Ostrosky-zeichner, Bart Jan Kullberg, A. M. L. Oude Lashof, John H. RexAbstract:Data on the salvage treatment of Invasive Candidiasis with voriconazole in 52 patients intolerant of other antifungal agents or with infection refractory to other antifungal agents were analyzed. Patients had received a mean of two previous antifungal agents (range, 1–4 agents), and 83% had received an azole. Manifestations of Invasive Candidiasis included candidemia (37%), disseminated disease (25%), and infection of other sites (38%). The median duration of voriconazole therapy was 60 days (range, 1–314 days). The overall rate of response was 56% (95%CI, 41–70), with the following response rates observed for individual Candida species: Candida albicans , 44% (20–70); Candida glabrata , 38% (14–68); Candida krusei , 70% (35–93); Candida tropicalis , 67% (30–93); and other Candida spp., 100% (40–100). The response rate in patients who had failed previous azole therapy was 58% (42–73). Common adverse events (~20%) included nausea and emesis, abnormal liver enzymes, and visual disturbances. Serious adverse events occurred in four patients, and nine patients died. Voriconazole has promise as a salvage agent for the treatment of Invasive Candidiasis, even in the settings of previous azole therapy and infection due to Candida krusei .
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Deeply Invasive Candidiasis
Infectious disease clinics of North America, 2002Co-Authors: Luis Ostrosky-zeichner, John H. Rex, John E. Bennett, Bart Jan KullbergAbstract:The incidence of Invasive Candidiasis is on the rise because of increasing numbers of immunocompromised hosts and more Invasive medical technology. Recovery of Candida spp from several body sites in a critically ill or immunocompromised patient should raise the question of disseminated disease. Although identification to the species level and antifungal susceptibility testing should guide therapy, at this time amphotericin B preparations are the usual initial therapy for severe life-threatening disease. Azole therapy has an expanding body of evidence that proves it is as effective as and safer than amphotericin B therapy. Some forms of Candidiasis (e.g., those with ocular, bone, or heart involvement) require a combined medical and surgical approach.
John R. Perfect - One of the best experts on this subject based on the ideXlab platform.
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Toll like receptor 1 polymorphisms and susceptibility to Invasive Candidiasis
Critical Care, 2009Co-Authors: Theo S. Plantinga, John R. Perfect, Bart Jan Kullberg, M Johnsson, B.a. Scott, E. Van De Vosse, D Velez, Jwm Van Der Meer, J. T. Van Dissel, Mihai G. NeteaAbstract:Invasive Candidiasis is a severe systemic fungal infection with Candida spp. affecting immunocompromised hosts, which is responsible for the highest mortality rate of all nosocomial infections. Although several clinical predisposing factors are known, the individual risk for developing Invasive Candidiasis varies significantly. Recognition of fungi such as Candida albicans is mediated through receptors of the innate immune system, such as Toll-like receptors (TLRs), that in turn activate innate immune system and antifungal defense.
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Caspofungin for Invasive Candidiasis at a tertiary care medical center.
The American Journal of Medicine, 2006Co-Authors: Aimee K. Zaas, Elizabeth Dodds Ashley, Barbara D. Alexander, Melissa D. Johnson, John R. PerfectAbstract:Abstract Background Caspofungin is emerging as first-line therapy for Invasive Candidiasis. Data on the use of caspofungin for treatment for Invasive Candidiasis are limited to clinical trials and case reports. We report a single-center experience with 104 consecutive courses of caspofungin for the treatment of Invasive Candidiasis to evaluate a real-world performance of this drug. Methods A retrospective chart review of patients receiving caspofungin at a tertiary care medical center was performed. Patient information and microbiologic data were abstracted from patient charts and electronic medical records. Results Of 241 patients receiving caspofungin for all indications, 122 (51%) had proven Invasive Candidiasis. There were 104 treatment courses for Candidiasis in 99 patients available for review. Bloodstream (66%) and abdominal infections (25%) were the most common sites of infection. Most infections were non- albicans (80/104, 77%; including patients infected with more than one species). Clinical cure rates at the end of therapy were 83% (57/69) for bloodstream infections and 84% (22/26) for abdominal infections. Caspofungin did not clear Candidiasis in 14 episodes (microbiologic cure rate 75%, 42/56). Conclusions The clinical use of caspofungin has been successful in the treatment of Invasive Candidiasis, even in patients with prior antifungal exposure. In this unselected review, caspofungin performed similarly as in clinical trials, and clinicians should consider caspofungin as first-line therapy for Invasive Candidiasis, particularly non- albicans species.
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global distribution and outcomes for candida species causing Invasive Candidiasis results from an international randomized double blind study of caspofungin versus amphotericin b for the treatment of Invasive Candidiasis
European Journal of Clinical Microbiology & Infectious Diseases, 2003Co-Authors: Arnaldo Lopes Colombo, Carole A. Sable, John R. Perfect, Mark J Dinubile, K Bartizal, Mary Motyl, P S Hicks, Robert J Lupinacci, Nicholas A. KartsonisAbstract:In a randomized study, caspofungin was compared with amphotericin B for the treatment of Invasive Candidiasis in a total of 239 adults from 56 sites in 20 countries. This study provided a unique opportunity to assess the frequency and outcome of Invasive Candidiasis caused by different Candida species worldwide, and the results are presented here. Efficacy was primarily assessed at the end of intravenous therapy using a modified intent-to-treat (MITT) analysis. This analysis was performed on 224 of the 239 patients enrolled in the study. Attempts were made to collect baseline Candida isolates from all patients for species identification at a central laboratory. Yeasts were identified to the species level using two commercial systems and microscopic examination. Viable baseline isolates were recovered from 210 of the 224 (94%) patients included in the MITT analysis. Candida albicans was the most frequently isolated species in all regions and was responsible for 45% of cases overall. Nevertheless, the majority of cases of infection were caused by non-albicans Candida species. In the USA and Canada, Candida glabrata was the second most commonly isolated pathogen (18%). In contrast, Candida parapsilosis and Candida tropicalis accounted for 55% of cases in Latin America. Outcomes were comparable for patients treated with caspofungin (74% overall; 64% and 80% for infections due to Candida albicans and non-albicans species) and amphotericin B (62% overall; 58% and 68% for infections due to Candida albicans and non-albicans species), and were generally similar across continents. The distribution of Candida species isolated from patients enrolled in a clinical trial may not be representative of pathogens causing Invasive Candidiasis in the general population. Nevertheless, our findings may affect the regional choice of empirical antifungal therapy for seriously ill patients with suspected or documented Invasive Candidiasis since different Candida species have varying susceptibility to conventional antifungal drugs.
Andreas Glöckner - One of the best experts on this subject based on the ideXlab platform.
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treatment and prophylaxis of Invasive Candidiasis with anidulafungin caspofungin and micafungin review of the literature
European Journal of Medical Research, 2011Co-Authors: Andreas GlöcknerAbstract:Working by a distinct cell wall-specific mechanism of action, the echinocandin class of antifungals has substantially expanded the range of available treatments for Invasive Candida infections. Anidulafungin, caspofungin and micafungin were investigated versus drugs from earlier antifungal classes in large clinical trials that demonstrated their excellent clinical and microbiological efficacy in the primary treatment of Invasive Candidiasis. Therefore, and supported by a number of favourable pharmacological characteristics, the echinocandins rapidly became established in guidelines and clinical practice as primary treatment options for moderately to severely ill patients with Invasive Candidiasis. This article reviews the relevant clinical evidence that forms the basis for the use of echinocandins in the management of Invasive Candidiasis, and discusses their current role in the context of recent guideline recommendations and treatment optimization strategies.
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Therapy of candidemia and Invasive Candidiasis according to guidelines
Mycoses, 2010Co-Authors: Andreas GlöcknerAbstract:Invasive fungal infections on the intensive care unit are predominantly caused by Candida spp., most frequently manifesting as candidemia. In spite of increasing treatment options during the last two decades, mortality of Invasive Candidiasis remains high with 20 to 50%. With the echinocandins, a new class of antifungal drugs with activity against clinically relevant Aspergillus and Candida spp. has become available since the beginning of the new millennium. The echinocandins have shown convincing efficacy in numerous multicentre, mostly double-blinded clinical trials. These trials compared current standard treatment regimens with the echinocandins anidulafungin, caspofungin, and micafungin. All trials observed non-inferiority of the new drugs against the standard treatment; in the case of anidulafungin, superiority against fluconazole was demonstrated. These results of the trials had resulted in modification of the current guidelines for the treatment of candidemia and Invasive Candidiasis. Especially in ICU patients frequently showing single- or multi-organ failure and receiving a multitude of drugs with complex interactions, echinocandins have become the treatment of first choice for candidemia.
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Treatment of Invasive Candidiasis with echinocandins
Mycoses, 2009Co-Authors: Andreas Glöckner, Angela Steinbach, Jörg J. Vehreschild, Oliver A. CornelyAbstract:Summary Blood stream infections by Candida spp. represent the majority of Invasive fungal infections in intensive care patients. The high crude mortality of Invasive Candidiasis remained essentially unchanged during the last two decades despite new treatment options that became available. The echinocandins, the latest class of antifungals introduced since 2001, exhibit potent activity against clinically relevant fungi including most Candida spp. In several randomised multicentre phase III trials, anidulafungin, caspofungin and micafungin showed convincing efficacy when compared with standard treatment regimens. In all trials, echinocandins were at least non-inferior to standard treatments. Anidulafungin was shown to be superior to fluconazole. Echinocandins have a favourable tolerability profile and exhibit a minimal potential for drug interactions since their pharmacokinetics is independent of renal and ‐ largely ‐ hepatic function. As a result of these properties, echinocandins are appropriate drugs of choice for Invasive Candidiasis in intensive care where many patients experience organ failure and receive multiple drugs with complex interactions.
