The Experts below are selected from a list of 10350 Experts worldwide ranked by ideXlab platform

John R Graybill - One of the best experts on this subject based on the ideXlab platform.

  • Evaluation of aminocandin and Caspofungin against Candida glabrata including isolates with reduced Caspofungin susceptibility
    Journal of Antimicrobial Chemotherapy, 2008
    Co-Authors: Gabriela E. Brzankalski, Laura K Najvar, Rosie Bocanegra, Nathan P. Wiederhold, Annette W. Fothergill, Michael G. Rinaldi, Thomas F. Pattterson, John R Graybill
    Abstract:

    Background: Aminocandin is an investigational echinocandin with excellent activity against Candida species, including Candida albicans and Candida tropicalis. However, few data are available for this agent versus Candida glabrata. We compared the in vitro potency and in vivo efficacy of aminocandin and Caspofungin against clinical isolates of C. glabrata including those with reduced Caspofungin susceptibility (MIC > 2 mg/L). Methods: In vitro activity was assessed using microdilution broth susceptibility testing. Three isolates, one with a low and two with elevated Caspofungin MICs, were chosen and mice were infected with C. glabrata followed by a single dose of aminocandin or Caspofungin (0.5‐100 mg/kg), or daily doses of Caspofungin (0.07‐14.3 mg/kg) begun 1 day after inoculation. Reduction in fungal burden, assessed in kidney tissue on day 8 post-inoculation, was the marker of antifungal response. Results: Aminocandin was more potent than Caspofungin against each isolate with reduced Caspofungin susceptibility. Mice infected with the Caspofungin-susceptible isolate had significant decreases in tissue burden with low doses of either drug. Higher single doses of aminocandin (� 10 mg/kg) were required to reduce fungal burden against the two isolates with elevated Caspofungin MICs. Single dose administration of Caspofungin was ineffective against one of these isolates, and higher daily doses were required to reduce fungal burden. Conclusions: These studies suggest that aminocandin has the potential for extended interval dosing in the treatment of C. glabrata infections caused by susceptible isolates. However, higher doses may be required against isolates with reduced Caspofungin susceptibility.

  • in vivo efficacy of anidulafungin and Caspofungin against candida glabrata and association with in vitro potency in the presence of sera
    Antimicrobial Agents and Chemotherapy, 2007
    Co-Authors: Laura K Najvar, Rosie Bocanegra, Nathan P. Wiederhold, Destiny Molina, Marcos Olivo, John R Graybill
    Abstract:

    In vitro studies have demonstrated that anidulafungin has greater potency than Caspofungin against Candida glabrata. However, data from in vivo studies demonstrating that it has superior efficacy are lacking. The objective of this study was to compare the activities of anidulafungin and Caspofungin against C. glabrata in a murine model of disseminated candidiasis. Two clinical C. glabrata isolates were used, including one with reduced Caspofungin susceptibility. MICs were determined by broth microdilution in the presence and absence of sera. For the animal studies, mice were immunosuppressed with 5-fluorouracil one day prior to intravenous inoculation. Treatment with anidulafungin and Caspofungin (0, 0.5, 1, 5, and 10 mg/kg of body weight per day) was begun 24 h later and was continued through day 7 postinoculation. The CFU were enumerated from kidney tissue. According to the standard microdilution methodology, anidulafungin had superior in vitro activity. However, this enhanced potency was attenuated by the addition of mouse and human sera. Caspofungin reduced the kidney fungal burden at lower doses compared to that achieved with anidulafungin in mice infected with the isolate with the lower MIC. Against the strain with the elevated Caspofungin MIC, both anidulafungin and Caspofungin were effective in reducing the kidney fungal burden at the higher doses studied. Despite the greater in vitro activity of anidulafungin in the absence of sera, both echinocandins were similarly effective in reducing the fungal burden in kidney tissue. The superior in vitro activity of anidulafungin did not confer enhanced in vivo efficacy against C. glabrata.

  • In vitro pharmacodynamics of anidulafungin and Caspofungin against Candida glabrata isolates, including strains with decreased Caspofungin susceptibility.
    Antimicrobial Agents and Chemotherapy, 2006
    Co-Authors: Jason M. Cota, Laura K Najvar, John R Graybill, Michael F. Carden, David S. Burgess, Nathan P. Wiederhold
    Abstract:

    The activities of anidulafungin and Caspofungin against Candida glabrata were evaluated. MICs, 50% inhibitory concentrations (IC 50 values), and IC 90 values for anidulafungin were lower than those for Caspofungin for 16 of 18 strains tested. Anidulafungin has potent in vitro activity against C. glabrata that is maintained against isolates with elevated Caspofungin MICs.

  • Caspofungin resistance in candida albicans correlating clinical outcome with laboratory susceptibility testing of three isogenic isolates serially obtained from a patient with progressive candida esophagitis
    Antimicrobial Agents and Chemotherapy, 2004
    Co-Authors: Steve Hernandez, Jose L Lopezribot, Laura K Najvar, Dora I Mccarthy, Rosie Bocanegra, John R Graybill
    Abstract:

    A patient with azole-refractory thrush-esophagitis responded initially to Caspofungin, but the treatment eventually failed. In a murine model, Caspofungin was effective against two early isolates for which the MICs of Caspofungin were low, but it was less effective against a late isolate for which the MIC of Caspofungin was greater. We concluded that there is a correlation between in vivo failure and rising in vitro Caspofungin MICs.

  • Addition of Caspofungin to Fluconazole Does Not Improve Outcome in Murine Candidiasis
    Antimicrobial Agents and Chemotherapy, 2003
    Co-Authors: John R Graybill, Steve Hernandez, Laura K Najvar, Rosie Bocanegra, Robert A. Larsen
    Abstract:

    Caspofungin is a potent antifungal inhibiting glucan synthesis in Candida species. However, Caspofungin is not 100% curative in candidiasis. Therefore, we evaluated combinations of fluconazole with Caspofungin for murine candidemia. We could not show any benefit of combined therapy over individual antifungal drugs.

Daniel J Diekema - One of the best experts on this subject based on the ideXlab platform.

  • multicenter comparison of the vitek 2 antifungal susceptibility test with the clsi broth microdilution reference method for testing Caspofungin micafungin and posaconazole against candida spp
    Journal of Clinical Microbiology, 2011
    Co-Authors: Jess F Peterson, Michael G. Rinaldi, Daniel J Diekema, Michael A Pfaller, Katherine M Riebe, Nathan A Ledeboer
    Abstract:

    ABSTRACT The performance of the automated Vitek 2 (bioMerieux, Inc., Marcy l9Etoile, France) antifungal susceptibility system was compared to that of broth microdilution (BMD) for the determination of MICs of various antifungal drugs. A total of 112 challenge strains and 755 clinical isolates of Candida spp. were tested against Caspofungin and micafungin. An additional 452 clinical isolates of Candida albicans were tested against posaconazole. Reference BMD MIC endpoints were established after 24 h of incubation for Caspofungin and micafungin and after 48 h of incubation for posaconazole. Essential agreements (EAs) between the Vitek 2 and BMD methods for Caspofungin and micafungin were 99.5% and 98.6%, respectively. EA between the Vitek 2 and BMD methods was 95.6% for posaconazole. The overall categorical agreements (CAs) between the Vitek 2 system and BMD were 99.8% for Caspofungin, 98.2% for micafungin, and 98.1% for posaconazole. The Vitek 2 system reliably determined Caspofungin and micafungin MICs among Candida spp. and posaconazole MICs among C. albicans isolates and demonstrated excellent quantitative and qualitative agreement with the reference BMD method.

  • in vitro susceptibilities of candida spp to Caspofungin four years of global surveillance
    Journal of Clinical Microbiology, 2006
    Co-Authors: Michael A Pfaller, S A Messer, R J Hollis, L. Boyken, S. Tendolkar, Daniel J Diekema
    Abstract:

    Caspofungin is being used increasingly as therapy for invasive candidiasis. Prospective sentinel surveillance for emergence of in vitro resistance to Caspofungin among invasive Candida spp. isolates is indicated. We determined the in vitro activity of Caspofungin against 8,197 invasive (bloodstream or sterile-site) unique patient isolates of Candida collected from 91 medical centers worldwide from 1 January 2001 to 31 December 2004. We performed antifungal susceptibility testing according to the Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) M27-A2 method and used a 24-h prominent inhibition endpoint for determination of the MIC. Of 8,197 invasive Candida spp. isolates, species distribution was as follows: 54% Candida albicans, 14% C. glabrata, 14% C. parapsilosis, 11% C. tropicalis, 3% C. krusei, and 4% other Candida spp. Overall, Caspofungin was very active against Candida (MIC50/MIC90, 0.03/0.25 μg/ml; 98.2% were inhibited at a MIC of ≤0.5 μg/ml and 99.7% were inhibited at a MIC of ≤1 μg/ml). Results by species (expressed as MIC50/MIC90 and the percentage inhibited at ≤1 μg/ml) were as follows: C. albicans, 0.03/0.06, 99.9; C. glabrata, 0.03/0.06, 99.9; C. parapsilosis, 0.5/0.5, 99.0; C. tropicalis, 0.03/0.06, 99.7; C. krusei, 0.12/0.5, 99.0; and C. guilliermondii, 0.5/1, 94.4. Of the 25 isolates with Caspofungin MICs of >1 μg/ml, 12 isolates were C. parapsilosis, 6 isolates were C. guilliermondii, 2 isolates were C. rugosa, and 1 isolate each was C. albicans, C. glabrata, C. krusei, C. lusitaniae, and C. tropicalis. There was no significant change in Caspofungin activity over the 4-year study period. Likewise, there was no difference in activity by geographic region. Caspofungin has excellent in vitro activity against invasive clinical isolates of Candida from centers worldwide. Our prospective sentinel surveillance reveals no evidence of emerging Caspofungin resistance among invasive clinical isolates of Candida.

  • In Vitro Susceptibilities of Candida spp. to Caspofungin: Four Years of Global Surveillance
    Journal of Clinical Microbiology, 2006
    Co-Authors: Michael A Pfaller, L. Boyken, Richard J. Hollis, Shawn A. Messer, S. Tendolkar, Daniel J Diekema
    Abstract:

    Caspofungin is the first of three new echinocandin antifungal agents to become available for the treatment of invasive mycoses (3, 7, 11, 17, 19, 21, 22, 26, 28). Like other echinocandins, Caspofungin acts via inhibition of 1,3-β-d-glucan synthase, an enzyme necessary for the formation of the essential cell wall component of Candida and other important fungal pathogens (3). First introduced in 2001, Caspofungin is now approved for the treatment of candidemia and other forms of invasive candidiasis, treatment of invasive aspergillosis in patients refractory to or intolerant of other licensed antifungal agents, and empirical antifungal therapy of febrile neutropenia (1, 13, 14, 27). The potent, broad-spectrum fungicidal activity of Caspofungin against Candida spp. has led to extensive use of this agent for the treatment of all forms of serious candidal infections over the past 4 years (9, 12, 17, 25). Thus far, clinical experience with Caspofungin and invasive candidiasis has been good (9, 14, 17). However, recent reports describing the emergence of Caspofungin resistance during treatment of esophagitis (6) and endocarditis (15) raise concerns about the potential emergence of Caspofungin-resistant Candida species. Specific mutations in the FKS1 genes (which encode essential components of the glucan synthase complex) have been found to confer resistance to echinocandins among Candida spp. (10, 20). Ongoing surveillance of the activity of Caspofungin and other echinocandins will be important as these agents are used more broadly worldwide. The optimization of in vitro susceptibility testing of Caspofungin against Candida spp. has been a difficult process (2). A recent multicenter (17-laboratory) study by Odds and colleagues (18) indicated that the optimal method for testing Caspofungin against Candida spp. included the Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) broth microdilution method with RPMI 1640 broth, incubation for no longer than 24 h, and an MIC endpoint criterion of prominent reduction in growth (MIC-2, defined as ≥50% inhibition relative to control growth) (16, 18). These testing conditions not only provided excellent reproducibility of results within and between laboratories but were also sufficient to differentiate isolates with “normal” or “wild-type” susceptibilities from glucan synthesis mutant strains with decreased susceptibilities to Caspofungin. These results were further validated by a subsequent study using a large (3,322-isolate) international collection of Candida spp. (23). The latter isolate collection represented bloodstream infection isolates of Candida spp. collected from >100 medical centers prior to the introduction of Caspofungin (1992 to 2000); thus, the MIC distribution profile may be considered to represent the “wild-type” distribution for Caspofungin and Candida (8). In the present study, we have employed the optimal testing conditions, as described by Odds et al. (18) and Pfaller et al. (23), to examine the temporal and geographic trends in the susceptibility of Candida spp. to Caspofungin since the clinical availability of the drug. An international collection of 8,197 isolates of Candida spp. obtained from 91 medical centers between 2001 and 2004 was tested in a central laboratory, and the MIC results were compared to the previously defined “wild-type” MIC distribution.

  • activities of Caspofungin itraconazole posaconazole ravuconazole voriconazole and amphotericin b against 448 recent clinical isolates of filamentous fungi
    Journal of Clinical Microbiology, 2003
    Co-Authors: Daniel J Diekema, S A Messer, R J Hollis, Rn Jones, M A Pfaller
    Abstract:

    We examined the in vitro activity of Caspofungin, posaconazole, voriconazole, ravuconazole, itraconazole, and amphotericin B against 448 recent clinical mold isolates. The endpoint for reading Caspofungin was the minimum effective concentration (MEC). Among the triazoles, posaconazole was most active, inhibiting 95% of isolates at ≤1 μg/ml, followed by ravuconazole (91%), voriconazole (90%), and itraconazole (79%). Caspofungin and amphotericin B inhibited 93% and 89% of isolates at ≤1 μg/ml, respectively, with Caspofungin demonstrating an MEC 90 of 0.12 μg/ml. All three new triazoles and Caspofungin inhibited >95% of Aspergillus spp. at ≤1 μg/ml compared to 83% for itraconazole and 91% for amphotericin B. Amphotericin B inhibited only 38% of Aspergillus terreus isolates at ≤1 μg/ml, whereas the three new triazoles and Caspofungin inhibited all A. terreus at ≤0.5 μg/ml. The new triazoles and Caspofungin have excellent in vitro activity against a very large collection of recent clinical isolates of Aspergillus spp., and some in vitro activity against selected other filamentous fungi.

  • in vitro activities of Caspofungin compared with those of fluconazole and itraconazole against 3 959 clinical isolates of candida spp including 157 fluconazole resistant isolates
    Antimicrobial Agents and Chemotherapy, 2003
    Co-Authors: Michael A Pfaller, Daniel J Diekema, S A Messer, R J Hollis, Rn Jones
    Abstract:

    Caspofungin is an echinocandin antifungal agent with broad-spectrum activity against Candida and Aspergillus spp. The in vitro activities of Caspofungin against 3,959 isolates of Candida spp. obtained from over 95 different medical centers worldwide were compared with those of fluconazole and itraconazole. The MICs of the antifungal drugs were determined by broth microdilution tests performed according to the NCCLS method using RPMI 1640 as the test medium. Caspofungin was very active against Candida spp. (MIC at which 90% of the isolates were inhibited [MIC 90 ], 1 μg/ml; 96% of MICs were ≤2 μg/ml). Candida albicans , C. dubliniensis , C. tropicalis , and C. glabrata were the most susceptible species of Candida (MIC 90 , 0.25 to 0.5 μg/ml), and C. guilliermondii was the least susceptible (MIC 90 , >8 μg/ml). Caspofungin was very active against Candida spp., exhibiting high-level resistance to fluconazole and itraconazole (99% of MICs were ≤1 μg/ml). These results provide further evidence for the spectrum and potency of Caspofungin activity against a large and geographically diverse collection of clinically important isolates of Candida spp.

Carole A. Sable - One of the best experts on this subject based on the ideXlab platform.

  • Efficacy and safety of Caspofungin in solid organ transplant recipients.
    Transplantation Proceedings, 2007
    Co-Authors: J. Petrovic, Angela L. Ngai, Susan K. Bradshaw, A. Williams-diaz, Arlene Taylor, Carole A. Sable, S. Vuocolo, Nicholas A. Kartsonis
    Abstract:

    Efficacy and safety data for the echinocandins in solid organ transplant (SOT) recipients are limited. We reviewed data from three clinical trials that enrolled SOT patients receiving Caspofungin therapy for an invasive fungal infection (IFI). Caspofungin was administered at doses ranging from 50 to 100 mg/day. Efficacy was assessed in all patients at the end of Caspofungin therapy (EOT). Adverse events (AE) and laboratory data were collected from all patients. We identified data from 22 SOT patients (aged 34-67 years) with proven invasive candidiasis (IC; 6 patients) or proven or probable invasive aspergillosis (IA; 16 patients) who received at least one dose of Caspofungin therapy. All patients with IC received Caspofungin as primary therapy. Caspofungin success against IC at EOT was 83% (5 of 6), with responses seen across Candida spp. Success by SOT type was: kidney 4 of 5 and liver 1 of 1. All 16 patients with IA (all pulmonary) received Caspofungin as salvage therapy. Caspofungin success against IA at EOT was 50% (8 of 16), with responses seen for both definite (3 of 4) and probable IA (5 of 12). Success by SOT type was: heart 2 of 2, heart/lung 0 of 2, kidney 3 of 3, liver 1 of 3, and lung 2 of 6. The outcome was not influenced by Caspofungin dose. Caspofungin, dosed for 2 to 162 (mean 36.8) days, was well tolerated. No patient had a serious drug-related adverse event or discontinued Caspofungin due to toxicity. Based on these limited data, Caspofungin appears to be an effective and well-tolerated option for the treatment of IC and IA in SOT recipients.

  • Caspofungin susceptibility testing of isolates from patients with esophageal candidiasis or invasive candidiasis relationship of mic to treatment outcome
    Antimicrobial Agents and Chemotherapy, 2005
    Co-Authors: Nicholas A. Kartsonis, Carole A. Sable, John Killar, Lori Mixson, Chaomin Hoe, Kenneth Bartizal, Mary Motyl
    Abstract:

    The Caspofungin clinical trial database offers an opportunity to assess susceptibility results for Candida pathogens obtained from patients with candidiasis and allows for correlations between efficacy outcomes and MICs. Candida isolates have been identified from patients enrolled in four studies of esophageal candidiasis and two studies of invasive candidiasis. The MICs of Caspofungin for all baseline isolates were measured at a central laboratory using NCCLS criteria (document M-27A); MICs for Caspofungin were defined as the lowest concentration inhibiting prominent growth at 24 h. MICs were then compared to clinical and microbiological outcomes across the two diseases. Susceptibility testing for Caspofungin was performed on 515 unique baseline isolates of Candida spp. obtained from patients with esophageal candidiasis. MICs for Caspofungin ranged from 0.008 to 4 g/ml; the MIC50 and MIC90 were 0.5 and 1.0 g/ml, respectively. Susceptibility testing was also performed on 231 unique baseline isolates of Candida spp. from patients with invasive candidiasis. The majority (96%) of MICs were between 0.125 and 2 g/ml, with MIC50 and MIC90 for Caspofungin being 0.5 and 2.0 g/ml, respectively. Overall, Caspofungin demonstrated potent in vitro activity against clinical isolates of Candida species. A relationship between MIC for Caspofungin and treatment outcome was not seen for patients with either esophageal candidiasis or invasive candidiasis. Patients with isolates for which the MICs were highest (>2 g/ml) had better outcomes than patients with isolates for which the MICs were lower (<1 g/ml). Additionally, no correlation between MIC and outcome was identified for specific Candida species.

  • Salvage therapy with Caspofungin for invasive aspergillosis: results from the Caspofungin compassionate use study
    Journal of Infection, 2005
    Co-Authors: Nicholas A. Kartsonis, Arlene Taylor, Alfred J. Saah, C. Joy Lipka, Carole A. Sable
    Abstract:

    Abstract Objectives . The objective was to prospectively assess the efficacy and safety of Caspofungin as salvage therapy for invasive aspergillosis in patients enrolled in the Caspofungin compassionate-use study. Methods . Forty-eight patients with invasive Aspergillus infections (36 with pulmonary infection, 12 with extrapulmonary or disseminated infection) were enrolled in this study. All patients were refractory to or intolerant of intravenous amphotericin B or a lipid amphotericin formulation(s). Efficacy was assessed at end of intravenous Caspofungin therapy based on the clinical (symptom/sign and radiographic) response. Results . Underlying diseases included hematological malignancy (69%), organ transplant (8%), and AIDS (6%). Forty-three (90%) patients were refractory to prior antifungal treatment, including 25 patients refractory to multiple agents. Sixteen (33%) were neutropenic at study entry. Following Caspofungin therapy, a favorable response was noted in 44% (20/45) of the patients, including nine (20%) and 11 (24%) patients with complete and partial responses, respectively. Caspofungin was generally well tolerated one serious drug-related adverse event was reported. Conclusions . In this study, Caspofungin was an effective alternative for patients with refractory Aspergillus infections.

  • Second-line therapy with Caspofungin for mucosal or invasive candidiasis: results from the Caspofungin compassionate-use study
    Journal of Antimicrobial Chemotherapy, 2004
    Co-Authors: Nicholas A. Kartsonis, Arlene Taylor, Alfred J. Saah, C. Joy Lipka, Carole A. Sable
    Abstract:

    Objectives: To prospectively assess the efficacy and safety of Caspofungin as second-line therapy for mucosal or invasive candidiasis in patients enrolled in the Caspofungin compassionate-use study. Materials and methods: Thirty-seven patients with mucosal or invasive candida infections (17 oesophageal, four oropharyngeal and 16 invasive candidiasis) were enrolled in the Caspofungin compassionate-use study. All patients were refractory to or intolerant of intravenous amphotericin B or lipid amphotericin formulation(s). Efficacy was assessed at the end of intravenous Caspofungin therapy based on clinical (and, where appropriate, microbiological) response. Results: HIV was the most common (91%) risk factor in patients with mucosal candidiasis; patients with invasive candidiasis commonly had acute leukaemia/lymphoma (50%) or diabetes mellitus (31%). Most patients with mucosal candidiasis (91%) and invasive candidiasis (94%) were refractory to ≥1 antifungal agent(s). A favourable response was noted in 82% (14/17) with oesophageal candidiasis, 100% (4/4) with oropharyngeal candidiasis and 87% (13/15) with invasive candidiasis. Caspofungin was generally well tolerated; one serious drug-related adverse event was reported. Conclusion: In this study, Caspofungin was an effective alternative for patients with refractory candida infections.

  • COMPARISON OF Caspofungin AND AMPHOTERICIN B FOR INVASIVE CANDIDIASIS
    New England Journal of Medicine, 2002
    Co-Authors: Jorge Mora-duarte, Carole A. Sable, Nicholas A. Kartsonis, Robert F. Betts, Coleman Rotstein, Arnaldo Lopes Colombo, Luis Thompson-moya, Juanita M Smietana, Robert J. Lupinacci, John R. Perfect
    Abstract:

    Background Caspofungin is an echinocandin agent with fungicidal activity against candida species. We performed a double-blind trial to compare Caspofungin with amphotericin B deoxycholate for the primary treatment of invasive candidiasis. Methods We enrolled patients who had clinical evidence of infection and a positive culture for candida species from blood or another site. Patients were stratified according to the severity of disease, as indicated by the Acute Physiology and Chronic Health Evaluation (APACHE II) score, and the presence or absence of neutropenia and were randomly assigned to receive either Caspofungin or amphotericin B. The study was designed to compare the efficacy of Caspofungin with that of amphotericin B in patients with invasive candidiasis and in a subgroup with candidemia. Results Of the 239 patients enrolled, 224 were included in the modified intention-to-treat analysis. Base-line characteristics, including the percentage of patients with neutropenia and the mean APACHE II score, were similar in the two treatment groups. A modified intention-to-treat analysis showed that the efficacy of Caspofungin was similar to that of amphotericin B, with successful outcomes in 73.4 percent of the patients treated with Caspofungin and in 61.7 percent of those treated with amphotericin B (difference after adjustment for APACHE II score and neutropenic status, 12.7 percentage points; 95.6 percent confidence interval, i0.7 to 26.0). An analysis of patients who met prespecified criteria for evaluation showed that Caspofungin was superior, with a favorable response in 80.7 percent of patients, as compared with 64.9 percent of those who received amphotericin B (difference, 15.4 percentage points; 95.6 percent confidence interval, 1.1 to 29.7). Caspofungin was as effective as amphotericin B in patients who had candidemia, with a favorable response in 71.7 percent and 62.8 percent of patients, respectively (difference, 10.0 percentage points; 95.0 percent confidence interval, i4.5 to 24.5). There were significantly fewer drug-related adverse events in the Caspofungin group than in the amphotericin B group. Conclusions Caspofungin is at least as effective as amphotericin B for the treatment of invasive candidiasis and, more specifically, candidemia. (N Engl J Med

Michael A Pfaller - One of the best experts on this subject based on the ideXlab platform.

  • multicenter comparison of the vitek 2 antifungal susceptibility test with the clsi broth microdilution reference method for testing Caspofungin micafungin and posaconazole against candida spp
    Journal of Clinical Microbiology, 2011
    Co-Authors: Jess F Peterson, Michael G. Rinaldi, Daniel J Diekema, Michael A Pfaller, Katherine M Riebe, Nathan A Ledeboer
    Abstract:

    ABSTRACT The performance of the automated Vitek 2 (bioMerieux, Inc., Marcy l9Etoile, France) antifungal susceptibility system was compared to that of broth microdilution (BMD) for the determination of MICs of various antifungal drugs. A total of 112 challenge strains and 755 clinical isolates of Candida spp. were tested against Caspofungin and micafungin. An additional 452 clinical isolates of Candida albicans were tested against posaconazole. Reference BMD MIC endpoints were established after 24 h of incubation for Caspofungin and micafungin and after 48 h of incubation for posaconazole. Essential agreements (EAs) between the Vitek 2 and BMD methods for Caspofungin and micafungin were 99.5% and 98.6%, respectively. EA between the Vitek 2 and BMD methods was 95.6% for posaconazole. The overall categorical agreements (CAs) between the Vitek 2 system and BMD were 99.8% for Caspofungin, 98.2% for micafungin, and 98.1% for posaconazole. The Vitek 2 system reliably determined Caspofungin and micafungin MICs among Candida spp. and posaconazole MICs among C. albicans isolates and demonstrated excellent quantitative and qualitative agreement with the reference BMD method.

  • in vitro susceptibilities of candida spp to Caspofungin four years of global surveillance
    Journal of Clinical Microbiology, 2006
    Co-Authors: Michael A Pfaller, S A Messer, R J Hollis, L. Boyken, S. Tendolkar, Daniel J Diekema
    Abstract:

    Caspofungin is being used increasingly as therapy for invasive candidiasis. Prospective sentinel surveillance for emergence of in vitro resistance to Caspofungin among invasive Candida spp. isolates is indicated. We determined the in vitro activity of Caspofungin against 8,197 invasive (bloodstream or sterile-site) unique patient isolates of Candida collected from 91 medical centers worldwide from 1 January 2001 to 31 December 2004. We performed antifungal susceptibility testing according to the Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) M27-A2 method and used a 24-h prominent inhibition endpoint for determination of the MIC. Of 8,197 invasive Candida spp. isolates, species distribution was as follows: 54% Candida albicans, 14% C. glabrata, 14% C. parapsilosis, 11% C. tropicalis, 3% C. krusei, and 4% other Candida spp. Overall, Caspofungin was very active against Candida (MIC50/MIC90, 0.03/0.25 μg/ml; 98.2% were inhibited at a MIC of ≤0.5 μg/ml and 99.7% were inhibited at a MIC of ≤1 μg/ml). Results by species (expressed as MIC50/MIC90 and the percentage inhibited at ≤1 μg/ml) were as follows: C. albicans, 0.03/0.06, 99.9; C. glabrata, 0.03/0.06, 99.9; C. parapsilosis, 0.5/0.5, 99.0; C. tropicalis, 0.03/0.06, 99.7; C. krusei, 0.12/0.5, 99.0; and C. guilliermondii, 0.5/1, 94.4. Of the 25 isolates with Caspofungin MICs of >1 μg/ml, 12 isolates were C. parapsilosis, 6 isolates were C. guilliermondii, 2 isolates were C. rugosa, and 1 isolate each was C. albicans, C. glabrata, C. krusei, C. lusitaniae, and C. tropicalis. There was no significant change in Caspofungin activity over the 4-year study period. Likewise, there was no difference in activity by geographic region. Caspofungin has excellent in vitro activity against invasive clinical isolates of Candida from centers worldwide. Our prospective sentinel surveillance reveals no evidence of emerging Caspofungin resistance among invasive clinical isolates of Candida.

  • In Vitro Susceptibilities of Candida spp. to Caspofungin: Four Years of Global Surveillance
    Journal of Clinical Microbiology, 2006
    Co-Authors: Michael A Pfaller, L. Boyken, Richard J. Hollis, Shawn A. Messer, S. Tendolkar, Daniel J Diekema
    Abstract:

    Caspofungin is the first of three new echinocandin antifungal agents to become available for the treatment of invasive mycoses (3, 7, 11, 17, 19, 21, 22, 26, 28). Like other echinocandins, Caspofungin acts via inhibition of 1,3-β-d-glucan synthase, an enzyme necessary for the formation of the essential cell wall component of Candida and other important fungal pathogens (3). First introduced in 2001, Caspofungin is now approved for the treatment of candidemia and other forms of invasive candidiasis, treatment of invasive aspergillosis in patients refractory to or intolerant of other licensed antifungal agents, and empirical antifungal therapy of febrile neutropenia (1, 13, 14, 27). The potent, broad-spectrum fungicidal activity of Caspofungin against Candida spp. has led to extensive use of this agent for the treatment of all forms of serious candidal infections over the past 4 years (9, 12, 17, 25). Thus far, clinical experience with Caspofungin and invasive candidiasis has been good (9, 14, 17). However, recent reports describing the emergence of Caspofungin resistance during treatment of esophagitis (6) and endocarditis (15) raise concerns about the potential emergence of Caspofungin-resistant Candida species. Specific mutations in the FKS1 genes (which encode essential components of the glucan synthase complex) have been found to confer resistance to echinocandins among Candida spp. (10, 20). Ongoing surveillance of the activity of Caspofungin and other echinocandins will be important as these agents are used more broadly worldwide. The optimization of in vitro susceptibility testing of Caspofungin against Candida spp. has been a difficult process (2). A recent multicenter (17-laboratory) study by Odds and colleagues (18) indicated that the optimal method for testing Caspofungin against Candida spp. included the Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) broth microdilution method with RPMI 1640 broth, incubation for no longer than 24 h, and an MIC endpoint criterion of prominent reduction in growth (MIC-2, defined as ≥50% inhibition relative to control growth) (16, 18). These testing conditions not only provided excellent reproducibility of results within and between laboratories but were also sufficient to differentiate isolates with “normal” or “wild-type” susceptibilities from glucan synthesis mutant strains with decreased susceptibilities to Caspofungin. These results were further validated by a subsequent study using a large (3,322-isolate) international collection of Candida spp. (23). The latter isolate collection represented bloodstream infection isolates of Candida spp. collected from >100 medical centers prior to the introduction of Caspofungin (1992 to 2000); thus, the MIC distribution profile may be considered to represent the “wild-type” distribution for Caspofungin and Candida (8). In the present study, we have employed the optimal testing conditions, as described by Odds et al. (18) and Pfaller et al. (23), to examine the temporal and geographic trends in the susceptibility of Candida spp. to Caspofungin since the clinical availability of the drug. An international collection of 8,197 isolates of Candida spp. obtained from 91 medical centers between 2001 and 2004 was tested in a central laboratory, and the MIC results were compared to the previously defined “wild-type” MIC distribution.

  • in vitro activities of Caspofungin compared with those of fluconazole and itraconazole against 3 959 clinical isolates of candida spp including 157 fluconazole resistant isolates
    Antimicrobial Agents and Chemotherapy, 2003
    Co-Authors: Michael A Pfaller, Daniel J Diekema, S A Messer, R J Hollis, Rn Jones
    Abstract:

    Caspofungin is an echinocandin antifungal agent with broad-spectrum activity against Candida and Aspergillus spp. The in vitro activities of Caspofungin against 3,959 isolates of Candida spp. obtained from over 95 different medical centers worldwide were compared with those of fluconazole and itraconazole. The MICs of the antifungal drugs were determined by broth microdilution tests performed according to the NCCLS method using RPMI 1640 as the test medium. Caspofungin was very active against Candida spp. (MIC at which 90% of the isolates were inhibited [MIC 90 ], 1 μg/ml; 96% of MICs were ≤2 μg/ml). Candida albicans , C. dubliniensis , C. tropicalis , and C. glabrata were the most susceptible species of Candida (MIC 90 , 0.25 to 0.5 μg/ml), and C. guilliermondii was the least susceptible (MIC 90 , >8 μg/ml). Caspofungin was very active against Candida spp., exhibiting high-level resistance to fluconazole and itraconazole (99% of MICs were ≤1 μg/ml). These results provide further evidence for the spectrum and potency of Caspofungin activity against a large and geographically diverse collection of clinically important isolates of Candida spp.

  • antifungal activities of fluconazole Caspofungin mk0991 and anidulafungin ly 303366 alone and in combination against candida spp and crytococcus neoformans via time kill methods
    Diagnostic Microbiology and Infectious Disease, 2002
    Co-Authors: Ellen E Roling, Russell E Lewis, Michael E Klepser, Ashley Wasson, Erika J Ernst, Michael A Pfaller
    Abstract:

    Abstract The activities of the echinocandins Caspofungin and anidulafungin were evaluated alone and in combination with fluconazole using time-kill methods against isolates of Candida albicans, Candida glabrata, Candida tropicalis, Candida krusei, and Cryptococcus neoformans. Antifungal concentrations tested against each isolate were 0.5 μg/mL and 20 μg/mL of fluconazole and 0.007 μg/mL and 2 μg/mL of both Caspofungin and anidulafungin. In addition, 20 μg/mL of fluconazole was tested with 2 μg/mL of Caspofungin and anidulafungin to test for additive or antagonistic activity. Finally 0.5 μg/mL of fluconazole was tested with 0.007 μg/mL of Caspofungin and anidulafungin to test for synergy. Combinations of fluconazole and Caspofungin or anidulafungin resulted in indifference. Azole-echinocandin combinations do not produce antagonistic effects; therefore, combinations of these agents may warrant future clinical evaluation.

Nicholas A. Kartsonis - One of the best experts on this subject based on the ideXlab platform.

  • a double blind comparative study of the safety and efficacy of Caspofungin versus micafungin in the treatment of candidiasis and aspergillosis
    European Journal of Clinical Microbiology & Infectious Diseases, 2013
    Co-Authors: Shigeru Kohno, Nicholas A. Kartsonis, Koichi Izumikawa, Minoru Yoshida, Yoshio Takesue, Shinichi Oka, Katsuhiko Kamei, Yoshitsugu Miyazaki, Tomoko Yoshinari, Yoshihito Niki
    Abstract:

    The safety and efficacy profile of Caspofungin and micafungin in Japanese patients with fungal infections were directly compared in this prospective, randomized, double-blind study. The proportion of patients who developed significant drug-related adverse event(s) (defined as a serious drug-related adverse event or a drug-related adverse event leading to study therapy discontinuation) was compared in 120 patients [Caspofungin 50 mg, or 50 mg following a 70-mg loading dose on Day 1 (hereinafter, 70/50 mg) group: 60 patients; micafungin 150 mg: 60 patients]. The overall response rate was primarily evaluated in the per-protocol set (PPS) population. The proportion of patients who developed significant drug-related adverse events was 5.0 % (3/60) in the Caspofungin group and 10.0 % (6/60) in the micafungin group [95 % confidence interval (CI) for the difference: −15.9 %, 5.2 %]. The favorable overall response in the PPS population for patients with esophageal candidiasis, invasive candidiasis, and chronic pulmonary aspergillosis including aspergilloma was 100.0 % (6/6), 100.0 % (3/3), and 46.7 % (14/30) in the Caspofungin group, and 83.3 % (5/6), 100.0 % (1/1), and 42.4 % (14/33) in the micafungin group, respectively. In Japanese patients with Candida or Aspergillus infections, there was no statistical difference in the safety between Caspofungin and micafungin. Consistent with other data on these two agents, the efficacy of Caspofungin and micafungin was similar.

  • Efficacy and safety of Caspofungin in solid organ transplant recipients.
    Transplantation Proceedings, 2007
    Co-Authors: J. Petrovic, Angela L. Ngai, Susan K. Bradshaw, A. Williams-diaz, Arlene Taylor, Carole A. Sable, S. Vuocolo, Nicholas A. Kartsonis
    Abstract:

    Efficacy and safety data for the echinocandins in solid organ transplant (SOT) recipients are limited. We reviewed data from three clinical trials that enrolled SOT patients receiving Caspofungin therapy for an invasive fungal infection (IFI). Caspofungin was administered at doses ranging from 50 to 100 mg/day. Efficacy was assessed in all patients at the end of Caspofungin therapy (EOT). Adverse events (AE) and laboratory data were collected from all patients. We identified data from 22 SOT patients (aged 34-67 years) with proven invasive candidiasis (IC; 6 patients) or proven or probable invasive aspergillosis (IA; 16 patients) who received at least one dose of Caspofungin therapy. All patients with IC received Caspofungin as primary therapy. Caspofungin success against IC at EOT was 83% (5 of 6), with responses seen across Candida spp. Success by SOT type was: kidney 4 of 5 and liver 1 of 1. All 16 patients with IA (all pulmonary) received Caspofungin as salvage therapy. Caspofungin success against IA at EOT was 50% (8 of 16), with responses seen for both definite (3 of 4) and probable IA (5 of 12). Success by SOT type was: heart 2 of 2, heart/lung 0 of 2, kidney 3 of 3, liver 1 of 3, and lung 2 of 6. The outcome was not influenced by Caspofungin dose. Caspofungin, dosed for 2 to 162 (mean 36.8) days, was well tolerated. No patient had a serious drug-related adverse event or discontinued Caspofungin due to toxicity. Based on these limited data, Caspofungin appears to be an effective and well-tolerated option for the treatment of IC and IA in SOT recipients.

  • Caspofungin susceptibility testing of isolates from patients with esophageal candidiasis or invasive candidiasis relationship of mic to treatment outcome
    Antimicrobial Agents and Chemotherapy, 2005
    Co-Authors: Nicholas A. Kartsonis, Carole A. Sable, John Killar, Lori Mixson, Chaomin Hoe, Kenneth Bartizal, Mary Motyl
    Abstract:

    The Caspofungin clinical trial database offers an opportunity to assess susceptibility results for Candida pathogens obtained from patients with candidiasis and allows for correlations between efficacy outcomes and MICs. Candida isolates have been identified from patients enrolled in four studies of esophageal candidiasis and two studies of invasive candidiasis. The MICs of Caspofungin for all baseline isolates were measured at a central laboratory using NCCLS criteria (document M-27A); MICs for Caspofungin were defined as the lowest concentration inhibiting prominent growth at 24 h. MICs were then compared to clinical and microbiological outcomes across the two diseases. Susceptibility testing for Caspofungin was performed on 515 unique baseline isolates of Candida spp. obtained from patients with esophageal candidiasis. MICs for Caspofungin ranged from 0.008 to 4 g/ml; the MIC50 and MIC90 were 0.5 and 1.0 g/ml, respectively. Susceptibility testing was also performed on 231 unique baseline isolates of Candida spp. from patients with invasive candidiasis. The majority (96%) of MICs were between 0.125 and 2 g/ml, with MIC50 and MIC90 for Caspofungin being 0.5 and 2.0 g/ml, respectively. Overall, Caspofungin demonstrated potent in vitro activity against clinical isolates of Candida species. A relationship between MIC for Caspofungin and treatment outcome was not seen for patients with either esophageal candidiasis or invasive candidiasis. Patients with isolates for which the MICs were highest (>2 g/ml) had better outcomes than patients with isolates for which the MICs were lower (<1 g/ml). Additionally, no correlation between MIC and outcome was identified for specific Candida species.

  • Salvage therapy with Caspofungin for invasive aspergillosis: results from the Caspofungin compassionate use study
    Journal of Infection, 2005
    Co-Authors: Nicholas A. Kartsonis, Arlene Taylor, Alfred J. Saah, C. Joy Lipka, Carole A. Sable
    Abstract:

    Abstract Objectives . The objective was to prospectively assess the efficacy and safety of Caspofungin as salvage therapy for invasive aspergillosis in patients enrolled in the Caspofungin compassionate-use study. Methods . Forty-eight patients with invasive Aspergillus infections (36 with pulmonary infection, 12 with extrapulmonary or disseminated infection) were enrolled in this study. All patients were refractory to or intolerant of intravenous amphotericin B or a lipid amphotericin formulation(s). Efficacy was assessed at end of intravenous Caspofungin therapy based on the clinical (symptom/sign and radiographic) response. Results . Underlying diseases included hematological malignancy (69%), organ transplant (8%), and AIDS (6%). Forty-three (90%) patients were refractory to prior antifungal treatment, including 25 patients refractory to multiple agents. Sixteen (33%) were neutropenic at study entry. Following Caspofungin therapy, a favorable response was noted in 44% (20/45) of the patients, including nine (20%) and 11 (24%) patients with complete and partial responses, respectively. Caspofungin was generally well tolerated one serious drug-related adverse event was reported. Conclusions . In this study, Caspofungin was an effective alternative for patients with refractory Aspergillus infections.

  • Second-line therapy with Caspofungin for mucosal or invasive candidiasis: results from the Caspofungin compassionate-use study
    Journal of Antimicrobial Chemotherapy, 2004
    Co-Authors: Nicholas A. Kartsonis, Arlene Taylor, Alfred J. Saah, C. Joy Lipka, Carole A. Sable
    Abstract:

    Objectives: To prospectively assess the efficacy and safety of Caspofungin as second-line therapy for mucosal or invasive candidiasis in patients enrolled in the Caspofungin compassionate-use study. Materials and methods: Thirty-seven patients with mucosal or invasive candida infections (17 oesophageal, four oropharyngeal and 16 invasive candidiasis) were enrolled in the Caspofungin compassionate-use study. All patients were refractory to or intolerant of intravenous amphotericin B or lipid amphotericin formulation(s). Efficacy was assessed at the end of intravenous Caspofungin therapy based on clinical (and, where appropriate, microbiological) response. Results: HIV was the most common (91%) risk factor in patients with mucosal candidiasis; patients with invasive candidiasis commonly had acute leukaemia/lymphoma (50%) or diabetes mellitus (31%). Most patients with mucosal candidiasis (91%) and invasive candidiasis (94%) were refractory to ≥1 antifungal agent(s). A favourable response was noted in 82% (14/17) with oesophageal candidiasis, 100% (4/4) with oropharyngeal candidiasis and 87% (13/15) with invasive candidiasis. Caspofungin was generally well tolerated; one serious drug-related adverse event was reported. Conclusion: In this study, Caspofungin was an effective alternative for patients with refractory candida infections.