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Michael A Pfaller - One of the best experts on this subject based on the ideXlab platform.
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activity of echinocandins and triazoles against a contemporary 2012 worldwide collection of yeast and moulds collected from invasive infections
International Journal of Antimicrobial Agents, 2014Co-Authors: Mariana Castanheira, S A Messer, Ronald N Jones, David J Farrell, Michael A PfallerAbstract:In this study, 1717 fungal clinical isolates causing invasive fungal infections were evaluated against nine antifungal agents using Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution methods. The isolates comprised 1487 Candida spp., 109 Aspergillus spp., 86 non-Candida yeasts (including 52 isolates of Cryptococcus neoformans) and 35 rare moulds obtained during 2012 from 72 hospitals worldwide. Echinocandin resistance among Candida spp. was low, and resistance rates to anidulafungin, caspofungin and micafungin varied from 0.0% to 2.8% among different species. Echinocandin-resistant Candida glabrata were shown to have fks mutations (fks2 HS1 F659Y, F659del, S663F and S663P), and fluconazole resistance was also observed in those strains. One Candida krusei and one Candida dubliniensis had L701M or S645P fks1 mutations, respectively. Candida tropicalis and C. glabrata had higher fluconazole resistance rates of 6.1% and 6.9%, respectively, compared with other Candida spp. Fluconazole-resistant C. tropicalis were collected in five countries (USA, China, Germany, Belgium and Thailand). Voriconazole was active against all Candida spp., inhibiting 91.2-99.7% of isolates using species-specific breakpoints. All agents except for the echinocandins and posaconazole were active against Cr. neoformans. Triazoles were active against other yeasts [MIC90 (Minimum inhibitory Concentration encompassing 90% of isolates tested), 2μg/mL]. The echinocandins and the mould-active triazoles were active against Aspergillus [MIC/MEC90 (Minimum Effective Concentration encompassing 90% of isolates tested) range, 0.015-2μg/mL], but the activity of these agents was limited against uncommon mould species (MIC/MEC90 range, 4μg/mL to >16μg/mL).
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in vitro activity of a new oral glucan synthase inhibitor mk 3118 tested against aspergillus spp by clsi and eucast broth microdilution methods
Antimicrobial Agents and Chemotherapy, 2013Co-Authors: Michael A Pfaller, S A Messer, Mary Motyl, Ronald N Jones, Mariana CastanheiraAbstract:ABSTRACT MK-3118, a glucan synthase inhibitor derived from enfumafungin, and comparator agents were tested against 71 Aspergillus spp., including itraconazole-resistant strains (MIC, ≥4 μg/ml), using CLSI and EUCAST reference broth microdilution methods. The CLSI 90% Minimum Effective Concentration (MEC 90 )/MIC 90 values (μg/ml) for MK-3118, amphotericin B, and caspofungin, respectively, were as follows: 0.12, 2, and 0.03 for Aspergillus flavus species complex (SC); 0.25, 2, and 0.06 for Aspergillus fumigatus SC; 0.12, 2, and 0.06 for Aspergillus terreus SC; and 0.06, 1, and 0.03 for Aspergillus niger SC. Essential agreement between the values found by CLSI and EUCAST (±2 log 2 dilution steps) was 94.3%. MK-3118 was determined to be a potent agent regardless of the in vitro method applied, with excellent activity against contemporary wild-type and itraconazole-resistant strains of Aspergillus spp.
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wild type Minimum Effective Concentration distributions and epidemiologic cutoff values for caspofungin and aspergillus spp as determined by clinical and laboratory standards institute broth microdilution methods
Diagnostic Microbiology and Infectious Disease, 2010Co-Authors: Michael A Pfaller, S A Messer, R J Hollis, Linda Boyken, J Kroeger, S Tendolkar, Daniel J DiekemaAbstract:Abstract Antifungal susceptibility testing of Aspergillus spp. against caspofungin has been standardized by the Clinical and Laboratory Standards Institute (CLSI). Recent studies have documented breakthrough infections with Aspergillus spp. for which the Minimum Effective Concentration (MEC) for caspofungin ranged from 0.25 to 8 μg/mL. We tested a collection of 1590 clinical isolates of Aspergillus spp. (188 Aspergillus flavus , 1187 Aspergillus fumigatus , 114 Aspergillus niger , 71 Aspergillus terreus , and 30 Aspergillus versicolor ) against caspofungin using the CLSI broth microdilution method. An epidemiologic cutoff value (ECV) of ≤0.06 μg/mL encompassed the wild-type (WT) MEC distribution (percentage of MECs) of A. flavus (99.5%), A. fumigatus (98.7%), A. niger (100%), and A. terreus (97.2%), and an ECV of ≤0.12 μg/mL encompassed the WT distribution of A. versicolor (96.7%). A total of 20 strains showed MECs that were outside the ECVs: 1 A. flavus (0.12 μg/mL), 16 A. fumigatus (0.12 μg/mL [13], 1 μg/mL [1], 2 μg/mL [2]), 2 A. terreus (0.12 [1] and >8 μg/mL [1]), and 1 A. versicolor (4 μg/mL). The establishment of the WT MEC distributions and ECVs for caspofungin and the major species of Aspergillus will be useful in resistance surveillance and is an important step toward the development of clinical breakpoints.
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in vitro susceptibility of clinical isolates of aspergillus spp to anidulafungin caspofungin and micafungin a head to head comparison using the clsi m38 a2 broth microdilution method
Journal of Clinical Microbiology, 2009Co-Authors: Michael A Pfaller, S A Messer, R J Hollis, J Kroeger, S Tendolkar, L Boyken, Daniel J DiekemaAbstract:We determined the in vitro activities of anidulafungin, caspofungin, and micafungin against 526 isolates of Aspergillus spp. (64 A. flavus, 391 A. fumigatus, 46 A. niger, and 25 A. terreus isolates) collected from over 60 centers worldwide from 2001 through 2007. Susceptibility testing was performed according to the CLSI M38-A2 method. All three echinocandins—anidulafungin (50% Minimum Effective Concentration [MEC50], 0.007 μg/ml; MEC90, 0.015 μg/ml), caspofungin (MEC50, 0.015 μg/ml; MEC90, 0.03 μg/ml), and micafungin (MEC50, 0.007 μg/ml; MEC90, 0.015 μg/ml)—were very active against Aspergillus spp. More than 99% of all isolates were inhibited by ≤0.06 μg/ml of all three agents.
Rioko Kinmiko Sakata - One of the best experts on this subject based on the ideXlab platform.
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Minimum Effective Concentration of bupivacaine in ultrasound guided femoral nerve block after arthroscopic knee meniscectomy a randomized double blind controlled trial
Pain Physician, 2016Co-Authors: Ed Carlos Rey Moura, Claudio Alex De Oliveira Honda, Roberto Cesar Teixeira Bringel, Plinio Da Cunha Leal, Gasper De Jesus Lopes Filho, Rioko Kinmiko SakataAbstract:BACKGROUND Adequate analgesia is important for early hospital discharge after meniscectomy. A femoral nerve block may reduce the need for systemic analgesics, with fewer side effects; however, motor block can occur. Ultrasound-guided femoral nerve block may reduce the required local anesthetic Concentration, preventing motor block. OBJECTIVE The primary objective of this study was to determine the lowest Effective analgesic Concentration of bupivacaine in 50% (EC50) and in 90% (EC90) of patients for a successful ultrasound-guided femoral nerve block in arthroscopic knee meniscectomy. STUDY DESIGN This was a prospective, randomized, double-blind, controlled trial. SETTINGS This study was conducted at Hospital Sao Domingos. METHODS A total of 52 patients undergoing arthroscopic knee meniscectomy were submitted to ultrasound-guided femoral nerve block using 22 mL bupivacaine. The bupivacaine Concentration given to a study patient was determined by the response of the previous patient (a biased-coin design up-down sequential method). If the previous patient had a negative response, the bupivacaine Concentration was increased by 0.05% for the next case. If the previous patient had a positive response, the next patient was randomized to receive the same bupivacaine Concentration (with a probability of 0.89) or to have a decrease by 0.05% (with a probability of 0.11). A successful block was defined by a numerical pain intensity scale score < 4 (0 = no pain; 10 = worst imaginable pain) in 3 different evaluations. If the pain intensity score was = 4 (moderate or severe pain) at any time, the block was considered failed. General anesthesia was induced with 30 µg/kg alfentanil and 2 mg/kg propofol, followed by propofol maintanance, plus remifentanil if needed. Postoperative analgesia supplementation was performed with dipyrone; ketoprofen and tramadol were given if needed. DATA MEASUREMENTS The following parameters were evaluated: numerical pain intensity score, duration of analgesia, supplementary analgesic dose in 24 hours, and need for intraoperative remifentanil. RESULTS The EC50 was 0.160 (95% CI: 0.150 - 0.189), and EC90 was 0.271 (95% CI: 0.196 - 0.300). There was no difference in numerical pain intensity score for the different Concentrations of bupivacaine. A successful block was achieved in 45 patients, with no difference according to bupivacaine Concentration. Time to first analgesic supplementation dose was longer for bupivacaine Concentrations = 0.3% (543.8 ± 283.8 min.), compared to 0.25% (391.3 ± 177.8 min.) and < 0.25% (302.3 ± 210.1 min.). There were no differences in supplementary analgesic dose in 24 hours nor in the use of intraoperative remifentanil according to bupivacaine Concentration. LIMITATIONS The analgesic effect was measured only during the first 2 hours. CONCLUSIONS Bupivacaine EC50 for ultrasound-guided femoral nerve block was 0.160 (95% CI: 0.150 - 0.189), and EC90 was 0.271 (95% CI: 0.196 - 0.300).
S A Messer - One of the best experts on this subject based on the ideXlab platform.
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activity of echinocandins and triazoles against a contemporary 2012 worldwide collection of yeast and moulds collected from invasive infections
International Journal of Antimicrobial Agents, 2014Co-Authors: Mariana Castanheira, S A Messer, Ronald N Jones, David J Farrell, Michael A PfallerAbstract:In this study, 1717 fungal clinical isolates causing invasive fungal infections were evaluated against nine antifungal agents using Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution methods. The isolates comprised 1487 Candida spp., 109 Aspergillus spp., 86 non-Candida yeasts (including 52 isolates of Cryptococcus neoformans) and 35 rare moulds obtained during 2012 from 72 hospitals worldwide. Echinocandin resistance among Candida spp. was low, and resistance rates to anidulafungin, caspofungin and micafungin varied from 0.0% to 2.8% among different species. Echinocandin-resistant Candida glabrata were shown to have fks mutations (fks2 HS1 F659Y, F659del, S663F and S663P), and fluconazole resistance was also observed in those strains. One Candida krusei and one Candida dubliniensis had L701M or S645P fks1 mutations, respectively. Candida tropicalis and C. glabrata had higher fluconazole resistance rates of 6.1% and 6.9%, respectively, compared with other Candida spp. Fluconazole-resistant C. tropicalis were collected in five countries (USA, China, Germany, Belgium and Thailand). Voriconazole was active against all Candida spp., inhibiting 91.2-99.7% of isolates using species-specific breakpoints. All agents except for the echinocandins and posaconazole were active against Cr. neoformans. Triazoles were active against other yeasts [MIC90 (Minimum inhibitory Concentration encompassing 90% of isolates tested), 2μg/mL]. The echinocandins and the mould-active triazoles were active against Aspergillus [MIC/MEC90 (Minimum Effective Concentration encompassing 90% of isolates tested) range, 0.015-2μg/mL], but the activity of these agents was limited against uncommon mould species (MIC/MEC90 range, 4μg/mL to >16μg/mL).
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in vitro activity of a new oral glucan synthase inhibitor mk 3118 tested against aspergillus spp by clsi and eucast broth microdilution methods
Antimicrobial Agents and Chemotherapy, 2013Co-Authors: Michael A Pfaller, S A Messer, Mary Motyl, Ronald N Jones, Mariana CastanheiraAbstract:ABSTRACT MK-3118, a glucan synthase inhibitor derived from enfumafungin, and comparator agents were tested against 71 Aspergillus spp., including itraconazole-resistant strains (MIC, ≥4 μg/ml), using CLSI and EUCAST reference broth microdilution methods. The CLSI 90% Minimum Effective Concentration (MEC 90 )/MIC 90 values (μg/ml) for MK-3118, amphotericin B, and caspofungin, respectively, were as follows: 0.12, 2, and 0.03 for Aspergillus flavus species complex (SC); 0.25, 2, and 0.06 for Aspergillus fumigatus SC; 0.12, 2, and 0.06 for Aspergillus terreus SC; and 0.06, 1, and 0.03 for Aspergillus niger SC. Essential agreement between the values found by CLSI and EUCAST (±2 log 2 dilution steps) was 94.3%. MK-3118 was determined to be a potent agent regardless of the in vitro method applied, with excellent activity against contemporary wild-type and itraconazole-resistant strains of Aspergillus spp.
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wild type Minimum Effective Concentration distributions and epidemiologic cutoff values for caspofungin and aspergillus spp as determined by clinical and laboratory standards institute broth microdilution methods
Diagnostic Microbiology and Infectious Disease, 2010Co-Authors: Michael A Pfaller, S A Messer, R J Hollis, Linda Boyken, J Kroeger, S Tendolkar, Daniel J DiekemaAbstract:Abstract Antifungal susceptibility testing of Aspergillus spp. against caspofungin has been standardized by the Clinical and Laboratory Standards Institute (CLSI). Recent studies have documented breakthrough infections with Aspergillus spp. for which the Minimum Effective Concentration (MEC) for caspofungin ranged from 0.25 to 8 μg/mL. We tested a collection of 1590 clinical isolates of Aspergillus spp. (188 Aspergillus flavus , 1187 Aspergillus fumigatus , 114 Aspergillus niger , 71 Aspergillus terreus , and 30 Aspergillus versicolor ) against caspofungin using the CLSI broth microdilution method. An epidemiologic cutoff value (ECV) of ≤0.06 μg/mL encompassed the wild-type (WT) MEC distribution (percentage of MECs) of A. flavus (99.5%), A. fumigatus (98.7%), A. niger (100%), and A. terreus (97.2%), and an ECV of ≤0.12 μg/mL encompassed the WT distribution of A. versicolor (96.7%). A total of 20 strains showed MECs that were outside the ECVs: 1 A. flavus (0.12 μg/mL), 16 A. fumigatus (0.12 μg/mL [13], 1 μg/mL [1], 2 μg/mL [2]), 2 A. terreus (0.12 [1] and >8 μg/mL [1]), and 1 A. versicolor (4 μg/mL). The establishment of the WT MEC distributions and ECVs for caspofungin and the major species of Aspergillus will be useful in resistance surveillance and is an important step toward the development of clinical breakpoints.
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in vitro susceptibility of clinical isolates of aspergillus spp to anidulafungin caspofungin and micafungin a head to head comparison using the clsi m38 a2 broth microdilution method
Journal of Clinical Microbiology, 2009Co-Authors: Michael A Pfaller, S A Messer, R J Hollis, J Kroeger, S Tendolkar, L Boyken, Daniel J DiekemaAbstract:We determined the in vitro activities of anidulafungin, caspofungin, and micafungin against 526 isolates of Aspergillus spp. (64 A. flavus, 391 A. fumigatus, 46 A. niger, and 25 A. terreus isolates) collected from over 60 centers worldwide from 2001 through 2007. Susceptibility testing was performed according to the CLSI M38-A2 method. All three echinocandins—anidulafungin (50% Minimum Effective Concentration [MEC50], 0.007 μg/ml; MEC90, 0.015 μg/ml), caspofungin (MEC50, 0.015 μg/ml; MEC90, 0.03 μg/ml), and micafungin (MEC50, 0.007 μg/ml; MEC90, 0.015 μg/ml)—were very active against Aspergillus spp. More than 99% of all isolates were inhibited by ≤0.06 μg/ml of all three agents.
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activities of caspofungin itraconazole posaconazole ravuconazole voriconazole and amphotericin b against 448 recent clinical isolates of filamentous fungi
Journal of Clinical Microbiology, 2003Co-Authors: S A Messer, R J Hollis, Rn Jones, M A PfallerAbstract: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.
Nirup B Mondal - One of the best experts on this subject based on the ideXlab platform.
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search for a potent microbicidal spermicide from the isolates of shorea robusta resin
Contraception, 2013Co-Authors: Yogesh P Bharitkar, Maitreyee Banerjee, Shrabanti Kumar, Rupankar Paira, Ravindra Meda, Ketousetu Kuotsu, Nirup B MondalAbstract:Abstract Background An alarming increase in global population is the root cause of poverty, malnutrition, sexually transmitted infections (STIs) and many other social problems. Microbicidal spermicides possessing dual function of contraception and STI protection can Effectively combat this problem, and their development is of utmost importance at present. Study Design A major metabolite isolated from Shorea robusta resin was spectroscopically characterized as asiatic acid. Spermicidal efficacy of the isolate was evaluated in vitro by a modified Sander–Cramer test. The mode of spermicidal action was assessed by (a) double fluoroprobe staining, (b) hypoosmotic swelling test and (c) scanning electron microscopy. Antimicrobial efficacy was assessed by disc diffusion and broth dilution methods using human isolates of bacteria ( Escherichia coli ATCC 25938 and Pseudomonas aeruginosa 71) and fungus ( Candida tropicalis ). Results The Minimum Effective Concentration of asiatic acid that induced instantaneous immobilization of rat spermatozoa in vitro was 125 mcg/mL. The mechanism of action involved disruption of sperm plasma membrane. The microbicidal efficacy was found to be moderate for vaginal pathogens, with no effect on normal vaginal flora. Conclusion Asiatic acid possesses appreciable spermicidal and microbicidal potential and may be explored as an Effective microbicidal spermicide.
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original research article search for a potent microbicidal spermicide from the isolates of shorea robusta resin
2013Co-Authors: Yogesh P Bharitkar, Maitreyee Banerjee, Shrabanti Kumar, Rupankar Paira, Ravindra Meda, Ketousetu Kuotsu, Nirup B MondalAbstract:Background: An alarming increase in global population is the root cause of poverty, malnutrition, sexually transmitted infections (STIs) and many other social problems. Microbicidal spermicides possessing dual function of contraception and STI protection can Effectively combat this problem, and their development is of utmost importance at present. Study Design: A major metabolite isolated from Shorea robusta resin was spectroscopically characterized as asiatic acid. Spermicidal efficacy of the isolate was evaluated in vitro by a modified Sander–Cramer test. The mode of spermicidal action was assessed by (a) double fluoroprobe staining, (b) hypoosmotic swelling test and (c) scanning electron microscopy. Antimicrobial efficacy was assessed by disc diffusion and broth dilution methods using human isolates of bacteria (Escherichia coli ATCC 25938 and Pseudomonas aeruginosa 71) and fungus (Candida tropicalis). Results: The Minimum Effective Concentration of asiatic acid that induced instantaneous immobilization of rat spermatozoa in vitro was 125 mcg/mL. The mechanism of action involved disruption of sperm plasma membrane. The microbicidal efficacy was found to be moderate for vaginal pathogens, with no effect on normal vaginal flora. Conclusion: Asiatic acid possesses appreciable spermicidal and microbicidal potential and may be explored as an Effective microbicidal spermicide.
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chenopodium album seed extract a potent sperm immobilizing agent both in vitro and in vivo
Contraception, 2007Co-Authors: Shrabanti Kumar, Smritinath Chakraborty, Shampa Biswas, Debayan Mandal, Heramba Nandan Roy, Syed N Kabir, Sukdeb Banerjee, Nirup B MondalAbstract:Abstract Purpose Aqueous decoction of Chenopodium album seeds (CAD) was assessed for its sperm-immobilizing and contraceptive efficacy in laboratory mammals. Method Spermicidal efficacy was evaluated in vitro by a modified Sander���Cramer test. The mode of spermicidal action was assessed by (a) supravital and double fluoroprobe staining of sperm, (b) hypoosmotic swelling tests and (c) transmission electron microscopy. Contraceptive efficacy was evaluated by intrauterine and vaginal application of CAD in rats and rabbits, respectively, followed by their mating and evaluation of pregnancy outcomes. Results The Minimum Effective Concentration of CAD that induced instantaneous immobilization of rat spermatozoa in vitro was 2 mg/mL. The mechanism of CAD action involved disintegration of sperm plasma membrane and dissolution of acrosomal cap causing sperm death. Fertilization of oocytes and establishment of implantation were prevented in the uterine horn that was administered with CAD, while these events occurred unhindered in the untreated contralateral side. In rabbit, intravaginal application of CAD significantly blocked the establishment of pregnancy. Conclusion CAD possesses appreciable spermicidal potential, which may be explored as an effector constituent of vaginal contraceptive.
Thomas J Walsh - One of the best experts on this subject based on the ideXlab platform.
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comparative in vitro pharmacodynamics of caspofungin micafungin and anidulafungin against germinated and nongerminated aspergillus conidia
Antimicrobial Agents and Chemotherapy, 2008Co-Authors: Charalampos Antachopoulos, Joseph Meletiadis, Tin Sein, Emmanuel Roilides, Thomas J WalshAbstract:The Concentration-dependent effects of echinocandins on the metabolic activity of Aspergillus spp. were comparatively studied by using nongerminated and germinated conidia. The susceptibilities of 11 Aspergillus fumigatus , 8 A. terreus and 8 A. flavus isolates to caspofungin, micafungin, and anidulafungin were studied by a CLSI (formerly NCCLS) M38-A broth microdilution-based method. After 48 h of incubation the Minimum Effective Concentration (MEC) was defined microscopically. Metabolic activity was assessed by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2 H -tetrazolium-5-carboxanilide assay and modeled by using the sigmoid ( E max ) or “bell-shaped” model. The median MEC values of caspofungin (0.5 to 1 μg/ml), micafungin (0.06 to 0.12 μg/ml), and anidulafungin (0.03 μg/ml) against nongerminated conidia increased by 0 to 1, 1 to 2, and 2 to 3 twofold dilutions, respectively (depending on the species), over those against germinated conidia. A similar shift to the right was demonstrated for the corresponding curves of metabolic activity. There was a significant correlation between the degrees of maximal metabolic inhibition caused by different echinocandins at both the species level (greater inhibition for A. flavus ) and the strain level ( r = 0.84 to 0.93; P A. fumigatus isolates, respectively; 5, 1, and 2 of the A. terreus isolates, respectively; and 1, 0, and 0 of the A. flavus isolates, respectively. Based on the model, 50% of the maximal paradoxical increase was detected with 4.2, 11.1, and 10.8 μg/ml of caspofungin, micafungin, and anidulafungin, respectively. All echinocandins therefore exerted comparable levels of maximal metabolic inhibition against Aspergillus spp. at Concentrations that were differentially increased for germinated versus nongerminated conidia. The paradoxical increase in metabolism occurred more frequently and at lower Concentrations with caspofungin than with micafungin and anidulafungin.
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comparative in vitro pharmacodynamics of caspofungin micafungin and anidulafungin against germinated and nongerminated aspergillus conidia
Antimicrobial Agents and Chemotherapy, 2008Co-Authors: Charalampos Antachopoulos, Joseph Meletiadis, Tin Sein, Emmanuel Roilides, Thomas J WalshAbstract:The Concentration-dependent effects of echinocandins on the metabolic activity of Aspergillus spp. were comparatively studied by using nongerminated and germinated conidia. The susceptibilities of 11 Aspergillus fumigatus, 8 A. terreus and 8 A. flavus isolates to caspofungin, micafungin, and anidulafungin were studied by a CLSI (formerly NCCLS) M38-A broth microdilution-based method. After 48 h of incubation the Minimum Effective Concentration (MEC) was defined microscopically. Metabolic activity was assessed by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay and modeled by using the sigmoid (E max) or "bell-shaped" model. The median MEC values of caspofungin (0.5 to 1 microg/ml), micafungin (0.06 to 0.12 microg/ml), and anidulafungin (0.03 microg/ml) against nongerminated conidia increased by 0 to 1, 1 to 2, and 2 to 3 twofold dilutions, respectively (depending on the species), over those against germinated conidia. A similar shift to the right was demonstrated for the corresponding curves of metabolic activity. There was a significant correlation between the degrees of maximal metabolic inhibition caused by different echinocandins at both the species level (greater inhibition for A. flavus) and the strain level (r = 0.84 to 0.93; P < 0.0001). Paradoxical increases in metabolism in the presence of higher Concentrations of caspofungin, micafungin, and anidulafungin were detected in 6, 2, and 5 of the A. fumigatus isolates, respectively; 5, 1, and 2 of the A. terreus isolates, respectively; and 1, 0, and 0 of the A. flavus isolates, respectively. Based on the model, 50% of the maximal paradoxical increase was detected with 4.2, 11.1, and 10.8 microg/ml of caspofungin, micafungin, and anidulafungin, respectively. All echinocandins therefore exerted comparable levels of maximal metabolic inhibition against Aspergillus spp. at Concentrations that were differentially increased for germinated versus nongerminated conidia. The paradoxical increase in metabolism occurred more frequently and at lower Concentrations with caspofungin than with micafungin and anidulafungin.