Amphotericin B-resistant Aspergillus flavus infection successfully treated with caspofungin, a novel antifungal agent

Koss, Tamara; Bagheri, Bita; Zeana, Cosmina; Romagnoli, Mario; Grossman, Marc E.

doi:10.1067/mjd.2002.120627

Cited by 30 publications

(17 citation statements)

References 10 publications

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“…Caspofungin has been approved by the U.S. Food and Drug Administration for use in refractory cases of invasive asper- (2,13,14,26). Importantly, direct comparisons of MIC and MEC values should not be made, since they represent different inhibition endpoints for different antifungal classes.…”

Section: Resultsmentioning

confidence: 99%

Activities of Caspofungin, Itraconazole, Posaconazole, Ravuconazole, Voriconazole, and Amphotericin B against 448 Recent Clinical Isolates of Filamentous Fungi

et al. 2003

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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 g/ml, followed by ravuconazole (91%), voriconazole (90%), and itraconazole (79%). Caspofungin and amphotericin B inhibited 93% and 89% of isolates at <1 g/ml, respectively, with caspofungin demonstrating an MEC 90 of 0.12 g/ml. All three new triazoles and caspofungin inhibited >95% of Aspergillus spp. at <1 g/ml compared to 83% for itraconazole and 91% for amphotericin B. Amphotericin B inhibited only 38% of Aspergillus terreus isolates at <1 g/ml, whereas the three new triazoles and caspofungin inhibited all A. terreus at <0.5 g/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.Invasive infections due to Aspergillus spp. and other filamentous fungi have emerged as prominent causes of infectious morbidity and mortality in the United States and worldwide (6,7,20). Treatment of these infections with available antifungal agents still results in an unacceptably high associated mortality (18).Two new antifungal agents recently have been introduced for treatment of invasive aspergillosis or other invasive mold infections. Voriconazole and caspofungin offer new alternatives for therapy of these difficult infections (10, 11). In addition, the investigational triazoles ravuconazole and posaconazole have been demonstrated to have in vitro potency against Aspergillus spp. and selected other filamentous fungi (8,9,24).Since the availability of these agents represents an exciting opportunity for improving the outcome of invasive infections due to filamentous fungi, their in vitro activity against contemporary clinical isolates is of great interest. We performed a 2-year, 20-center survey of filamentous fungal infections from January 2000 through December 2001. We previously reported preliminary results of the activity of new triazoles against molds collected during the first year of this survey (24). We now report final 2-year results, including the in vitro activity of caspofungin, the new triazoles, amphotericin B, and itraconazole against over 400 recent clinical isolates of filamentous fungi collected from January 2000 through December of 2001. In the process, we present the largest collection of clinical mold isolates tested against caspofungin yet reported. MATERIALS AND METHODS Organisms.A total of 448 unique clinical isolates (one per patient, duplicate patient isolates excluded) of filamentous fungi were obtained from 20 different medical centers in the United States and Canada between January 2000 and December 2001. These centers were participants in the SENTRY Antimicrobial Surveillance Program. The isolates were obta...

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Section: Resultsmentioning

confidence: 99%

Activities of Caspofungin, Itraconazole, Posaconazole, Ravuconazole, Voriconazole, and Amphotericin B against 448 Recent Clinical Isolates of Filamentous Fungi

et al. 2003

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“…Amphotericin preparations or voriconazole would be the preferred initial therapy. Koss et al (155) described an elderly patient with acute myelogenous leukemia whose cutaneous infection with A. flavus failed to respond to amphotericin B lipid complex. Therapy was switched to caspofungin, with dramatic and sustained improvement.…”

Section: Vol 18 2005 Aspergillus Infections In Transplant Recipientmentioning

confidence: 99%

AspergillusInfections in Transplant Recipients

2005

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Aspergillus infections are occurring with an increasing frequency in transplant recipients. Notable changes in the epidemiologic characteristics of this infection have occurred; these include a change in risk factors and later onset of infection. Management of invasive aspergillosis continues to be challenging, and the mortality rate, despite the use of newer antifungal agents, remains unacceptably high. Performing molecular studies to discern new targets for antifungal activity, identifying signaling pathways that may be amenable to immunologic interventions, assessing combination regimens of antifungal agents or combining antifungal agents with modulation of the host defense mechanisms, and devising diagnostic assays that can rapidly and reliably diagnose infections represent areas for future investigations that may lead to further improvement in outcomes

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“…After dosing, the catheter was flushed with 1 ml of saline. Blood samples were collected from a central auricular artery or a marginal ear vein via venipuncture into tubes containing heparin before the dose, at 0.083, 0.25, 0.50, 1, 2, 4, 8, and 24 h after the dose, and at days 2,3,4,5,6,7,9,11,13,15,17,19,21,23,25,27, and 28 after dose administration.…”

Section: Chemicals [mentioning

confidence: 99%

“…Caspofungin has been used successfully in the clinical arena for the treatment of candidiases as well as candidemia (2,7,12,13). Caspofungin has also been shown to be efficacious in the treatment of Aspergillus infections (11,15,17) and invasive aspergillosis in patients refractory or intolerant to amphotericin B (J. Maertens, I. Raad, C. A. Sable, A. Ngai, R. Berman, T. F. Patterson, D. Denning, and T. Walsh, Abstr. 40th Intersci.…”

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confidence: 99%

Disposition of Caspofungin, a Novel Antifungal Agent, in Mice, Rats, Rabbits, and Monkeys

Sandhu

Bondiskey

et al. 2004

Antimicrob Agents Chemother

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The metabolism, excretion, and pharmacokinetics of caspofungin (Cancidas; Merck & Co., Inc.) were investigated after administration of a single intravenous dose to mice, rats, rabbits, and monkeys. Caspofungin had a low plasma clearance (0.29 to 1.05 ml/min/kg) and a long terminal elimination half-life (11.7 h to 59.7 h) in all preclinical species. The elimination kinetics of caspofungin were multiphasic and displayed an initial distribution phase followed by a dominant ␤-elimination phase. The presence of low levels of prolonged radioactivity in plasma was observed and was partially attributable to the chemical degradation product M0. Excretion studies with [ 3 H]caspofungin indicated that the hepatic and renal routes play an important role in the elimination of caspofungin, as a large percentage of the radiolabeled dose was recovered in urine and feces. Excretion of radioactivity in all species studied was slow, and low levels of radioactivity were detected in daily urine and fecal samples throughout a prolonged collection period. Although urinary profiles indicated the presence of several metabolites (M0, M1, M2, M3, M4, M5, and M6), the majority of the total radioactivity was associated with the polar metabolites M1 [4(S)-hydroxy-4-(4-hydroxyphenyl)-L-threonine] and M2 [N-acetyl-4(S)-hydroxy-4-(4-hydroxyphenyl)-L-threonine].Caspofungin was thus primarily eliminated by metabolic transformation; however, the rate of metabolism was slow. These results suggest that distribution plays a prominent role in determining the plasma pharmacokinetics and disposition of caspofungin, as very little excretion or biotransformation occurred during the early days after dose administration, a period during which concentrations in plasma fell substantially. The disposition of caspofungin in preclinical species was similar to that reported previously in humans.

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Amphotericin B-resistant Aspergillus flavus infection successfully treated with caspofungin, a novel antifungal agent

Cited by 30 publications

References 10 publications

Activities of Caspofungin, Itraconazole, Posaconazole, Ravuconazole, Voriconazole, and Amphotericin B against 448 Recent Clinical Isolates of Filamentous Fungi

Activities of Caspofungin, Itraconazole, Posaconazole, Ravuconazole, Voriconazole, and Amphotericin B against 448 Recent Clinical Isolates of Filamentous Fungi

AspergillusInfections in Transplant Recipients

Disposition of Caspofungin, a Novel Antifungal Agent, in Mice, Rats, Rabbits, and Monkeys

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