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Thomas J. Walsh - One of the best experts on this subject based on the ideXlab platform.
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Pharmacology and antifungal properties of anidulafungin, a new echinocandin.
Pharmacotherapy, 2009Co-Authors: Kristina E. Estes, Scott R. Penzak, Karim A. Calis, Thomas J. WalshAbstract:Anidulafungin is the third echinocandin antifungal agent to receive approval from the United States Food and Drug Administration. It is indicated for the treatment of Esophageal Candidiasis, candidemia, and other candidal infections. Anidulafungin is fungicidal against Candida species, including Candida glabrata and isolates resistant to azoles and polyenes. The drug's efficacy is comparable to that of fluconazole for the treatment of Esophageal Candidiasis, and it is effective in patients with invasive Candidiasis and candidemia. Anidulafungin is distinct among the echinocandins in that it undergoes slow, nonenzymatic chemical degradation. As a consequence, impairments in renal or hepatic function do not substantially alter its pharmacokinetics. In addition, anidulafungin has not demonstrated any drug-drug interactions because it is not a substrate, inhibitor, or inducer of the cytochrome P450 enzyme system. Anidulafungin is well tolerated in adults and pediatric patients, with few reported adverse drug events. The safety, tolerability, and potent fungicidal activity of anidulafungin against Candida species make it a reasonable alternative in the treatment of patients with serious candidal infections.
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a randomized double blind trial of anidulafungin versus fluconazole for the treatment of Esophageal Candidiasis
Clinical Infectious Diseases, 2004Co-Authors: David Krause, Beth P. Goldstein, Ahmed E. Simjee, Johann Viljoen, Thomas J. Walsh, Michele Wible, Christo Van Rensburg, Timothy HenkelAbstract:(See the editorial commentary by Darouiche on pages 850–2 and the article by de Wet et al. on pages 842–9)Anidulafungin is a novel antifungal agent of the echinocandin class. This randomized, double-blind, double-dummy study compared the efficacy and safety of intravenous anidulafungin to that of oral fluconazole in601 patients with endoscopically and microbiologically documented Esophageal Candidiasis. Patients receivedintravenous anidulafungin (100 mg on day 1, followed by 50 mg per day) or oral fluconazole (200 mg on day1, followed by 100 mg per day) for 7 days beyond resolution of symptoms (range, 14–21 days). At the end oftherapy, the rate of endoscopic success for anidulafungin (242 [97.2%] of 249 treated patients) was found tobe statistically noninferior to that for fluconazole (252 [98.8%] of 255 treated patients; treatment difference, 1.6%; 95% confidence interval, 4.1 to 0.8). The safety profile of anidulafungin was similar to that offluconazole; treatment-related adverse events occurred in 9.3% and 12.0% of patients, respectively. Laboratoryparameters were similar between treatment arms. Anidulafungin is as safe and effective as oral fluconazolefor the treatment of Esophageal Candidiasis, when assessed at the completion of therapy.
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A Randomized, Double-Blind Trial of Anidulafungin versus Fluconazole for the Treatment of Esophageal Candidiasis
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2004Co-Authors: David Krause, Beth P. Goldstein, Ahmed E. Simjee, Christo Van Rensburg, Johann Viljoen, Thomas J. Walsh, Michele Wible, Timothy HenkelAbstract:Anidulafungin is a novel antifungal agent of the echinocandin class. This randomized, double-blind, double-dummy study compared the efficacy and safety of intravenous anidulafungin to that of oral fluconazole in 601 patients with endoscopically and microbiologically documented Esophageal Candidiasis. Patients received intravenous anidulafungin (100 mg on day 1, followed by 50 mg per day) or oral fluconazole (200 mg on day 1, followed by 100 mg per day) for 7 days beyond resolution of symptoms (range, 14-21 days). At the end of therapy, the rate of endoscopic success for anidulafungin (242 [97.2%] of 249 treated patients) was found to be statistically noninferior to that for fluconazole (252 [98.8%] of 255 treated patients; treatment difference, -1.6%; 95% confidence interval, -4.1 to 0.8). The safety profile of anidulafungin was similar to that of fluconazole; treatment-related adverse events occurred in 9.3% and 12.0% of patients, respectively. Laboratory parameters were similar between treatment arms. Anidulafungin is as safe and effective as oral fluconazole for the treatment of Esophageal Candidiasis, when assessed at the completion of therapy.
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Esophageal Candidiasis in human immunodeficiency virus infected pediatric patients after the introduction of highly active antiretroviral therapy
Pediatric Infectious Disease Journal, 2002Co-Authors: Christine C Chiou, Andreas H Groll, Nikolaos Mavrogiorgos, Lauren V Wood, Thomas J. WalshAbstract:Objective. To investigate epidemiologic trends, clinical features and outcome of Esophageal Candidiasis in the era of highly active antiretroviral therapy in a prospectively monitored population of HIV-infected children and adolescents followed at the National Cancer Institute. Patients and methods. The records of all HIV-infected pediatric patients (n = 266) followed between 1995 and 2000 were reviewed for a history of Esophageal Candidiasis. Proven Esophageal Candidiasis was defined as clinical plus radiographic and/or endoscopic findings of Esophageal Candidiasis. Probable Esophageal Candidiasis was defined as Esophageal symptoms that responded promptly to appropriate antifungal therapy. The medical records of all patients fulfilling these criteria were reviewed for demographic, clinical and laboratory features at presentation, as well as therapeutic interventions and outcome. Results. Of the 266 patients 9 (3.4%) had 18 documented episodes of proven (n = 16) or probable (n = 2) Esophageal Candidiasis. A history of prior mucosal Candidiasis was present in 94% of all episodes. The median CD4+ count at the time of diagnosis was 7/μl (range, 0 to 550), and the median viral load was 98 000 copies/ml (range, 22 916 to 1 278 933). Concurrent oropharyngeal Candidiasis was the most common clinical presentation (72%) followed by fever (55%), odynophagia (50%) and nausea or vomiting (39%). Treatment consisted of antifungal triazoles (61%) or amphotericin B (39%). Clinical cure was achieved in 15 cases, including all patients receiving triazoles. Conclusion. Esophageal Candidiasis persists in the subgroup of patients not responding to highly active antiretroviral therapy and in that setting may present without concomitant oropharyngeal Candidiasis or typical clinical symptoms, thus underscoring the need for a high index of suspicion in children with very low CD4+ counts.
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dosage dependent antifungal efficacy of v echinocandin ly303366 against experimental fluconazole resistant oropharyngeal and Esophageal Candidiasis
Antimicrobial Agents and Chemotherapy, 2001Co-Authors: Vidmantas Petraitis, Andreas H Groll, Ruta Petraitiene, Tin Sein, Robert L Schaufele, Caron A Lyman, Andrea Francesconi, John Bacher, Stephen C Piscitelli, Thomas J. WalshAbstract:Esophageal Candidiasis is one of the most common opportunistic fungal infections in immunocompromised patients, including human immunodeficiency virus (HIV)-positive patients and those who are immunosuppressed as a result of underlying diseases or medications (2, 35). A number of agents have been used to treat Esophageal Candidiasis, including nystatin, miconazole, ketoconazole, fluconazole, itraconazole, and amphotericin B. Fluconazole is frequently selected for systemic therapy because it is well tolerated and has excellent oral bioavailability. During the past several years, however, there have been increasing reports of fluconazole-resistant oropharyngeal and Esophageal Candidiasis (OPEC) (27). The emergence of fluconazole-resistant OPEC has heightened the need for development of new antifungal compounds with novel targets. The echinocandins are semisynthetic lipopeptides with potent and broad-spectrum antifungal activity which act by inhibiting the synthesis of (1,3)-β-d-glucan, leading to cell wall damage and ultimately cell death (6, 7, 10, 16, 17). This novel mode of action and potent antifungal activity in vitro have led to the design of several new echinocandin compounds for potential clinical development. V-echinocandin (VER-002; LY303366) is a semisynthetic echinocandin B derivative (9; I. Rajman, K. Desante, B. Hatcher, J. Hemingway, R. Lachno, S. Brooks, and M. Turik, Abstr. 37th Intersci. Conf. Antimicrob. Agents Chemother, abstr. F-74, p. 158, 1997) which demonstrates potent and non-cross-resistant antifungal activity against Candida albicans, Candida tropicalis, Candida glabrata, and other non-C. albicans species (8, 13, 14, 15, 24, 26, 29). Little is known, however, about the activity of VER-002 is treatment for fluconazole-resistant OPEC. We therefore investigated the concentrations in the esophageus and saliva the safety, and the antifungal efficacy of VER-002 in an immunosuppressed rabbit model of fluconazole-resistant OPEC.
Felix Bongomin - One of the best experts on this subject based on the ideXlab platform.
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Prevalence of HIV-associated Esophageal Candidiasis in sub-Saharan Africa: a systematic review and meta-analysis
Tropical Medicine and Health, 2020Co-Authors: Ronald Olum, Joseph Baruch Baluku, Ronald Okidi, Irene Andia-biraro, Felix BongominAbstract:Background Esophageal Candidiasis (OC) is a common AIDS-defining opportunistic infection. Antiretroviral therapy (ART) reduces the occurrence of OC and other opportunistic infections among persons living with HIV (PLHIV). We sought to determine and compare the prevalence of OC in the ART and pre-ART era among PLHIV in sub-Saharan Africa (SSA). Methods We searched PubMed, Embase, Web of Science, and the African Journals Online databases to select studies in English and French reporting the prevalence of HIV-associated OC in SSA from January 1980 to June 2020. Reviews, single-case reports, and case series reporting < 10 patients were excluded. A random-effect cumulative meta-analysis was performed using STATA 16.0, and trend analysis performed using GraphPad Prism 8.0. Results Thirteen eligible studies from 9 SSA countries including a total of 113,272 patients were qualitatively synthesized, and 9 studies were included in the meta-analysis. Overall pooled prevalence of HIV-associated OC was 12% (95% confidence interval (CI): 8 to 15%, I ^2 = 98.61%, p
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prevalence of hiv associated Esophageal Candidiasis in sub saharan africa a systematic review and meta analysis
Tropical Medicine and Health, 2020Co-Authors: Ronald Olum, Joseph Baruch Baluku, Ronald Okidi, Felix Bongomin, Irene AndiabiraroAbstract:Esophageal Candidiasis (OC) is a common AIDS-defining opportunistic infection. Antiretroviral therapy (ART) reduces the occurrence of OC and other opportunistic infections among persons living with HIV (PLHIV). We sought to determine and compare the prevalence of OC in the ART and pre-ART era among PLHIV in sub-Saharan Africa (SSA). We searched PubMed, Embase, Web of Science, and the African Journals Online databases to select studies in English and French reporting the prevalence of HIV-associated OC in SSA from January 1980 to June 2020. Reviews, single-case reports, and case series reporting < 10 patients were excluded. A random-effect cumulative meta-analysis was performed using STATA 16.0, and trend analysis performed using GraphPad Prism 8.0. Thirteen eligible studies from 9 SSA countries including a total of 113,272 patients were qualitatively synthesized, and 9 studies were included in the meta-analysis. Overall pooled prevalence of HIV-associated OC was 12% (95% confidence interval (CI): 8 to 15%, I2 = 98.61%, p <. 001). The prevalence was higher in the pre-ART era compared to the ART era, but not to statistical significance (34.1% vs. 8.7%, p = 0.095). In those diagnosed by endoscopy, the prevalence was higher compared to patients diagnosed by non-endoscopic approaches, but not to statistical significance (35.1% vs. 8.4%, p = .071). The prevalence of OC significantly decreased over the study period (24 to 16%, p < .025). The prevalence of OC among PLHIV in the ART era in SSA is decreasing. However, OC remains a common problem. Active endoscopic surveillance of symptomatic patients and further empirical studies into the microbiology, optimal antifungal treatment, and impact of OC on quality of life of PLHIV in SSA are recommended.
Andreas H Groll - One of the best experts on this subject based on the ideXlab platform.
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efficacy of pld 118 a novel inhibitor of candida isoleucyl trna synthetase against experimental oropharyngeal and Esophageal Candidiasis caused by fluconazole resistant c albicans
Antimicrobial Agents and Chemotherapy, 2004Co-Authors: Andreas H Groll, Vidmantas Petraitis, Ruta Petraitiene, Tin Sein, John Bacher, Amy M Kelaher, Alia A Sarafandi, Diana MickieneAbstract:PLD-118, formerly BAY 10-8888, is a synthetic antifungal derivative of the naturally occurring beta-amino acid cispentacin. We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and Esophageal Candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits. Infection was established by fluconazole-resistant (MIC > 64 microg/ml) clinical isolates from patients with refractory Esophageal Candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P plasma pharmacokinetics across the investigated dosage range, as was evident from a dose-dependent increase in plasma clearance and a dose-dependent decrease in the area under the plasma concentration-time curve. The biochemical safety profile was similar to that of FLC. In summary, PLD-118 demonstrated dosage-dependent antifungal activity and nonlinear plasma pharmacokinetics in treatment of experimental FLC-resistant oropharyngeal and Esophageal Candidiasis.
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Esophageal Candidiasis in human immunodeficiency virus infected pediatric patients after the introduction of highly active antiretroviral therapy
Pediatric Infectious Disease Journal, 2002Co-Authors: Christine C Chiou, Andreas H Groll, Nikolaos Mavrogiorgos, Lauren V Wood, Thomas J. WalshAbstract:Objective. To investigate epidemiologic trends, clinical features and outcome of Esophageal Candidiasis in the era of highly active antiretroviral therapy in a prospectively monitored population of HIV-infected children and adolescents followed at the National Cancer Institute. Patients and methods. The records of all HIV-infected pediatric patients (n = 266) followed between 1995 and 2000 were reviewed for a history of Esophageal Candidiasis. Proven Esophageal Candidiasis was defined as clinical plus radiographic and/or endoscopic findings of Esophageal Candidiasis. Probable Esophageal Candidiasis was defined as Esophageal symptoms that responded promptly to appropriate antifungal therapy. The medical records of all patients fulfilling these criteria were reviewed for demographic, clinical and laboratory features at presentation, as well as therapeutic interventions and outcome. Results. Of the 266 patients 9 (3.4%) had 18 documented episodes of proven (n = 16) or probable (n = 2) Esophageal Candidiasis. A history of prior mucosal Candidiasis was present in 94% of all episodes. The median CD4+ count at the time of diagnosis was 7/μl (range, 0 to 550), and the median viral load was 98 000 copies/ml (range, 22 916 to 1 278 933). Concurrent oropharyngeal Candidiasis was the most common clinical presentation (72%) followed by fever (55%), odynophagia (50%) and nausea or vomiting (39%). Treatment consisted of antifungal triazoles (61%) or amphotericin B (39%). Clinical cure was achieved in 15 cases, including all patients receiving triazoles. Conclusion. Esophageal Candidiasis persists in the subgroup of patients not responding to highly active antiretroviral therapy and in that setting may present without concomitant oropharyngeal Candidiasis or typical clinical symptoms, thus underscoring the need for a high index of suspicion in children with very low CD4+ counts.
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dosage dependent antifungal efficacy of v echinocandin ly303366 against experimental fluconazole resistant oropharyngeal and Esophageal Candidiasis
Antimicrobial Agents and Chemotherapy, 2001Co-Authors: Vidmantas Petraitis, Andreas H Groll, Ruta Petraitiene, Tin Sein, Robert L Schaufele, Caron A Lyman, Andrea Francesconi, John Bacher, Stephen C Piscitelli, Thomas J. WalshAbstract:Esophageal Candidiasis is one of the most common opportunistic fungal infections in immunocompromised patients, including human immunodeficiency virus (HIV)-positive patients and those who are immunosuppressed as a result of underlying diseases or medications (2, 35). A number of agents have been used to treat Esophageal Candidiasis, including nystatin, miconazole, ketoconazole, fluconazole, itraconazole, and amphotericin B. Fluconazole is frequently selected for systemic therapy because it is well tolerated and has excellent oral bioavailability. During the past several years, however, there have been increasing reports of fluconazole-resistant oropharyngeal and Esophageal Candidiasis (OPEC) (27). The emergence of fluconazole-resistant OPEC has heightened the need for development of new antifungal compounds with novel targets. The echinocandins are semisynthetic lipopeptides with potent and broad-spectrum antifungal activity which act by inhibiting the synthesis of (1,3)-β-d-glucan, leading to cell wall damage and ultimately cell death (6, 7, 10, 16, 17). This novel mode of action and potent antifungal activity in vitro have led to the design of several new echinocandin compounds for potential clinical development. V-echinocandin (VER-002; LY303366) is a semisynthetic echinocandin B derivative (9; I. Rajman, K. Desante, B. Hatcher, J. Hemingway, R. Lachno, S. Brooks, and M. Turik, Abstr. 37th Intersci. Conf. Antimicrob. Agents Chemother, abstr. F-74, p. 158, 1997) which demonstrates potent and non-cross-resistant antifungal activity against Candida albicans, Candida tropicalis, Candida glabrata, and other non-C. albicans species (8, 13, 14, 15, 24, 26, 29). Little is known, however, about the activity of VER-002 is treatment for fluconazole-resistant OPEC. We therefore investigated the concentrations in the esophageus and saliva the safety, and the antifungal efficacy of VER-002 in an immunosuppressed rabbit model of fluconazole-resistant OPEC.
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Esophageal Candidiasis in pediatric acquired immunodeficiency syndrome clinical manifestations and risk factors
Pediatric Infectious Disease Journal, 2000Co-Authors: Christine C Chiou, Andreas H Groll, Lauren V Wood, Corina E Gonzalez, Diana Callender, David Venzon, Philip A Pizzo, Thomas J. WalshAbstract:Background, Little is known about the epidemiology and clinical features of Esophageal Candidiasis (EC) in pediatric AIDS. We therefore investigated the clinical presentation and risk factors of EC in a large prospectively monitored population of HIV-infected children at the National Cancer Institute. Patients and methods. We reviewed the records of all HIV-infected children (N = 448) followed between 1987 and 1995 for a history of Esophageal Candidiasis to characterize the epidemiology, clinical features, therapeutic interventions and outcome of Esophageal Candidiasis. To understand further the risk factors for EC in pediatric AIDS, we then performed a matched case-control analysis of 25 patients for whom control cases were available. Results. There were 51 episodes of EC documented in 36 patients with 23 male and 13 female patients (0.2 to 17 years; median CD4, count 11/ μl), representing a frequency of EC of 8.0%. Concurrent oropharyngeal Candidiasis (OPC) was the most common clinical presentation of EC (94%); other signs and symptoms included odynophagia (80%), retrosternal pain (57%), fever (29%), nausea/vomiting (24%), drooling (12%), dehydration (12%), hoarseness (6%) and upper gastrointestinal bleeding (6%). The causative organism documented in 36 episodes (18 from OPC, 17 from endoscopic biopsy and 1 from autopsy) was Candida albicans in all cases. Patients received treatment for EC with amphotericin B (63%), fluconazole (29%), ketoconazole (4%) or itraconazole (1%). A clinical response was documented in all 45 evaluable episodes. In 6 other cases, EC was a final event without contributing to the cause of death. By a conditional logistic regression model for matched data, the best predictor of EC was the presence of prior OPC (P < 0.0001), followed by CD4 count and CD4 percentage (P = 0.0002) and use of antibacterial antibiotics (P = 0.0013). The risks associated with low CD4 count were independent of that of prior OPC. Conclusion. EC in pediatric AIDS is a debilitating infection, which develops in the setting of prior OPC, low CD4 counts and previous antibiotics.
Jose A. Vazquez - One of the best experts on this subject based on the ideXlab platform.
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Anidulafungin: an evidence-based review of its use in invasive fungal infections
Core evidence, 2008Co-Authors: Susan L. Davis, Jose A. VazquezAbstract:INTRODUCTION Anidulafungin is a new echinocandin antifungal agent with indications for use in Esophageal Candidiasis and candidemia. The mortality and morbidity associated with fungal infections in healthcare facilities necessitates the development of new treatment options for these diseases. AIMS This review assesses the pharmacology and evidence for the use of anidulafungin in the treatment of serious fungal infections. EVIDENCE REVIEW There is substantial evidence that anidulafungin is a potent antifungal agent with activity against a broad range of fungal species. Likewise, evidence supports that anidulafungin is a well-tolerated antifungal agent. Clinical studies provide sufficient evidence for regulatory approval for Esophageal Candidiasis and candidemia, and limited evidence suggests that anidulafungin may be superior to fluconazole for candidemia and invasive Candidiasis. The introduction of anidulafungin into clinical practice adds a third option for therapy in the echinocandin class. Research into its efficacy in other fungal infections is ongoing, and further studies into the impact of anidulafungin on economic outcomes will be beneficial. PLACE IN THERAPY Current evidence supports the use of anidulafungin in the management of candidemia, Esophageal Candidiasis, and invasive Candidiasis, as demonstrated by the successful results in large multicenter clinical trials.
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a phase 2 open label study of the safety and efficacy of intravenous anidulafungin as a treatment for azole refractory mucosal Candidiasis
Journal of Acquired Immune Deficiency Syndromes, 2008Co-Authors: Jose A. Vazquez, Beth P. Goldstein, Annette C Reboli, Jennifer Schranz, Kay Clark, Carl J FichtenbaumAbstract:Background: Azole-refractory mucosal Candidiasis is a debilitating disease frequently seen in patients who are immunosuppressed as a result of HIV, malignancy, posttransplant immunosuppressive therapy, persistent neutropenia, steroid use, or diabetes. Anidulafungin has potent activity against a broad spectrum of Candida species, including strains resistant to azoles and amphotericin B. We performed an open-label, noncomparative study to examine efficacy and safety of anidulafungin in patients with azole-refractory oropharyngeal and Esophageal Candidiasis. Methods: Patients enrolled met diagnostic criteria for azole-refractory mucosal Candidiasis. They received intravenous anidulafungin 100 mg on day 1 followed by daily 50-mg doses on day 2 through day 14 or for a maximum of 21 days. Primary efficacy variables were clinical response (for oropharyngeal Candidiasis) and endoscopic and clinical response (for Esophageal Candidiasis) at the end of therapy. Results: Nineteen patients were enrolled; 89% had advanced HIV infection. Clinical success was observed in 95% of patients at end of therapy, and endoscopic success was observed in 92% of patients with Esophageal Candidiasis. At follow-up, clinical success was maintained in 47% of patients. The most common adverse event, experienced by 4 patients, was nausea and/or vomiting. Conclusions: Anidulafungin was well tolerated and efficacious in the treatment of patients with azole-refractory Esophageal and oropharyngeal Candidiasis.
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role of posaconazole in the management of oropharyngeal and Esophageal Candidiasis
Therapeutics and Clinical Risk Management, 2007Co-Authors: Jose A. VazquezAbstract:Mucocutaneous Candidiasis (MC) is one of the first signs of human immunodeficiency virus (HIV) infection. Over 90% of patients with AIDS will eventually develop oropharyngeal Candidiasis (OPC) at some time during their illness, and an additional 10% will develop Esophageal Candidiasis (EC). Although numerous antifungal agents are available, azoles, both topical (clotrimazole) and systemic (fluconazole, itraconazole), have replaced older topical antifungals (gentian violet and nystatin) in the management of MC in these patients. The systemic azoles, itraconazole and fluconazole, are generally safe and effective agents in HIV-infected patients with MC. A concern in these patients is the clinical relapse, which appears to be dependent on degree of immunosuppression and is more common following clotrimazole and ketoconazole than with fluconazole or itraconazole. Posaconazole is a new extended-spectrum triazole recently approved for the management of OPC. In vitro, posaconazole possesses potent activity against numerous Candida species, including strains that are resistant to fluconazole. Recent clinical trials demonstrate that posaconazole is as efficacious as fluconazole in producing a successful clinical response in HIV-infected patients with OPC/EC. In addition, posaconazole was safe and more effective in sustaining clinical success after treatment was discontinued. Posaconazole appears to be an effective alternative in the management of MC in this difficult- to-treat population.
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safety and efficacy of posaconazole in the long term treatment of azole refractory oropharyngeal and Esophageal Candidiasis in patients with hiv infection
Hiv Clinical Trials, 2007Co-Authors: Jose A. Vazquez, Daniel J Skiest, H Tissotdupont, J L Lennox, Navdeep Boparai, Randi IsaacsAbstract:Purpose: To evaluate safety and efficacy of long-term posaconazole in HIV-infected patients with azole-refractory oropharyngeal Candidiasis and/or Esophageal Candidiasis. Method: In this noncompara...
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posaconazole for the treatment of azole refractory oropharyngeal and Esophageal Candidiasis in subjects with hiv infection
Clinical Infectious Diseases, 2007Co-Authors: Jose A. Vazquez, Daniel J Skiest, Navdeep Boparai, Gregory M Anstead, John R Graybill, Jacques Reynes, Douglas J Ward, Roberta S Hare, Randi IsaacsAbstract:Background. We evaluated the efficacy and safety of oral posaconazole for human immunodeficiency virus (HIV)‐infected subjects with oropharyngeal Candidiasis (OPC) and/or Esophageal Candidiasis (EC) who were clinically refractory to treatment with oral fluconazole or itraconazole. Methods. Subjects with confirmed OPC or EC who did not improve after receiving standard courses of fluconazole or itraconazole treatment were eligible for study enrollment. Subjects received either oral posaconazole (400 mg twice daily) for 3 days followed by oral posaconazole (400 mg once daily) for 25 days (regimen A; 103 patients) or oral posaconazole (400 mg twice daily) for 28 days (regimen B; 96 patients). The primary end point was cure or improvement after 28 days. Primary efficacy analyses were performed on the subset of treated subjects with refractory disease (e.g., baseline culture positive for fluconazole- or itraconazole-resistant Candida species or persistent or progressive clinical signs or symptoms consistent with treatment failure). Results. Of the modified intent-to-treat population, 132 (75%) of 176 subjects achieved a clinical response to posaconazole treatment. Clinical response rates were similar between regimen A recipients (75.3%) and regimen B recipients (74.7%). Clinical responses occurred in 67 (73%) of 92 subjects with baseline isolates resistant to fluconazole, 49 (74%) of 66 subjects with baseline isolates resistant to itraconazole, and 42 (74%) of 57 subjects with isolates resistant to both. Clinical response was achieved in 32 (74.4%) of 43 subjects with endoscopically documented EC. The most common treatment-related adverse events were diarrhea (11%), neutropenia (7%), flatulence (6%), and nausea (6%). Eight subjects (4%) discontinued therapy as a result of a treatment-related adverse event. Conclusions. Posaconazole offers a safe and effective treatment option for HIV-infected subjects with azolerefractory OPC and/or EC. In patients with HIV infection, oropharyngeal Candidiasis (OPC) and Esophageal Candidiasis (EC) can be recurrent and debilitating [1‐3]. Fluconazole and itraconazole treatments are usually effective against these forms of mucosal Candidiasis (MC), have a favorable safety profile, and permit oral administration [2, 4]. Refractory MC has been reported in 4%‐5% of HIV
Timothy Henkel - One of the best experts on this subject based on the ideXlab platform.
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a randomized double blind trial of anidulafungin versus fluconazole for the treatment of Esophageal Candidiasis
Clinical Infectious Diseases, 2004Co-Authors: David Krause, Beth P. Goldstein, Ahmed E. Simjee, Johann Viljoen, Thomas J. Walsh, Michele Wible, Christo Van Rensburg, Timothy HenkelAbstract:(See the editorial commentary by Darouiche on pages 850–2 and the article by de Wet et al. on pages 842–9)Anidulafungin is a novel antifungal agent of the echinocandin class. This randomized, double-blind, double-dummy study compared the efficacy and safety of intravenous anidulafungin to that of oral fluconazole in601 patients with endoscopically and microbiologically documented Esophageal Candidiasis. Patients receivedintravenous anidulafungin (100 mg on day 1, followed by 50 mg per day) or oral fluconazole (200 mg on day1, followed by 100 mg per day) for 7 days beyond resolution of symptoms (range, 14–21 days). At the end oftherapy, the rate of endoscopic success for anidulafungin (242 [97.2%] of 249 treated patients) was found tobe statistically noninferior to that for fluconazole (252 [98.8%] of 255 treated patients; treatment difference, 1.6%; 95% confidence interval, 4.1 to 0.8). The safety profile of anidulafungin was similar to that offluconazole; treatment-related adverse events occurred in 9.3% and 12.0% of patients, respectively. Laboratoryparameters were similar between treatment arms. Anidulafungin is as safe and effective as oral fluconazolefor the treatment of Esophageal Candidiasis, when assessed at the completion of therapy.
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A Randomized, Double-Blind Trial of Anidulafungin versus Fluconazole for the Treatment of Esophageal Candidiasis
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2004Co-Authors: David Krause, Beth P. Goldstein, Ahmed E. Simjee, Christo Van Rensburg, Johann Viljoen, Thomas J. Walsh, Michele Wible, Timothy HenkelAbstract:Anidulafungin is a novel antifungal agent of the echinocandin class. This randomized, double-blind, double-dummy study compared the efficacy and safety of intravenous anidulafungin to that of oral fluconazole in 601 patients with endoscopically and microbiologically documented Esophageal Candidiasis. Patients received intravenous anidulafungin (100 mg on day 1, followed by 50 mg per day) or oral fluconazole (200 mg on day 1, followed by 100 mg per day) for 7 days beyond resolution of symptoms (range, 14-21 days). At the end of therapy, the rate of endoscopic success for anidulafungin (242 [97.2%] of 249 treated patients) was found to be statistically noninferior to that for fluconazole (252 [98.8%] of 255 treated patients; treatment difference, -1.6%; 95% confidence interval, -4.1 to 0.8). The safety profile of anidulafungin was similar to that of fluconazole; treatment-related adverse events occurred in 9.3% and 12.0% of patients, respectively. Laboratory parameters were similar between treatment arms. Anidulafungin is as safe and effective as oral fluconazole for the treatment of Esophageal Candidiasis, when assessed at the completion of therapy.