Successful treatment of Candida krusei infection with caspofungin acetate: A new antifungal agent

McGee, William T.; Tereso, Gary

doi:10.1097/01.ccm.0000063145.15336.31

Cited by 15 publications

(11 citation statements)

References 3 publications

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“…Several authors have reported breakthrough infections due to C. krusei among patients receiving fluconazole or amphotericin B (1,11,19,21,31,34,61), and Goldman et al (9) found that response rates of C. krusei infection were significantly better for patients who had received amphotericin B in doses of Ն1 mg/kg of body weight per day than for those who had received lower doses. Furthermore, amphotericin B exhibits markedly delayed killing kinetics against C. krusei compared with that against Candida albicans (4,19).…”

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confidence: 99%

“…In addition, the echinocandins have been used based on their fungicidal activity and excellent in vitro activity against C. krusei (41,42,56,57). Whereas echinocandin antifungals such as caspofungin have been used successfully to treat several different infections involving C. krusei (21,28,31,34,50), there have been recent troubling reports of caspofungin failure in the treatment of C. krusei infections (10,15,33). Notably, Hakki et al (10) reported a strain of C. krusei from a leukemic patient that displayed reduced susceptibilities to caspofungin, anidulafungin, and micafungin.…”

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Candida krusei , a Multidrug-Resistant Opportunistic Fungal Pathogen: Geographic and Temporal Trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005

Pfaller¹,

Diekema

Gibbs³

et al. 2008

J Clin Microbiol

226

140

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Candida krusei is well known as a fungal pathogen for patients with hematologic malignancies and for transplant recipients. Using the ARTEMIS Antifungal Surveillance Program database, we describe geographic and temporal trends in the isolation of C. krusei from clinical specimens and the in vitro susceptibilities of 3,448 isolates to voriconazole as determined by CLSI (formerly NCCLS) disk diffusion testing. In addition, we report the in vitro susceptibilities of bloodstream infection isolates of C. krusei to amphotericin B (304 isolates), flucytosine (254 isolates), anidulafungin (121 isolates), caspofungin (300 isolates), and micafungin (102 isolates) as determined by CLSI broth microdilution methods. Geographic differences in isolation were apparent; the highest frequency of isolation was seen for the Czech Republic (7.6%) and the lowest for Indonesia, South Korea, and Thailand (0 to 0.3%). Overall, 83% of isolates were susceptible to voriconazole, ranging from 74.8% in Latin America to 92.3% in North America. C. krusei was most commonly isolated from hematology-oncology services, where only 76.7% of isolates were susceptible to voriconazole. There was no evidence of increasing resistance of C. krusei to voriconazole from 2001 to 2005. Decreased susceptibilities to amphotericin B (MIC at which 90% of isolates were inhibited [MIC 90 ], 4 g/ml) and flucytosine (MIC 90 , 16 g/ml) were noted, whereas 100% of isolates were inhibited by <2 g/ml of anidulafungin (MIC 90 , 0.06 g/ml), micafungin (MIC 90 , 0.12 g/ml) or caspofungin (MIC 90 , 0.25 g/ml). C. krusei is an uncommon but multidrugresistant fungal pathogen. Among the systemically active antifungal agents, the echinocandins appear to be the most active against this important pathogen.

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Candida krusei , a Multidrug-Resistant Opportunistic Fungal Pathogen: Geographic and Temporal Trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005

Pfaller¹,

Diekema

Gibbs³

et al. 2008

J Clin Microbiol

226

140

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“…Caspofungin has demonstrated potent antifungal activity in vitro against Candida and Aspergillus isolates (4) and in vivo efficacy in mouse models of disseminated aspergillosis and candidiasis (1) as well as in a persistently neutropenic rabbit model of pulmonary aspergillosis (14). 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.…”

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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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“…Die mukosale Candidiasis kann bei immunsupprimierten Menschen (z.B.transplantierte und HIV-infizierte Patienten) schwer verlaufen.In den letzten Jahren ersetzten neue Triazole (Fluconazol und Itraconazol) mit verbesserten WirkungsNebenwirkungs-Profilen bisher gängige Pilzmedikamente wie Amphotericin B und Nystatin [8,23,33].…”

Section: Candidainfektion Von Haut Und Schleimhautunclassified

“…Die klinische Antwort wird meist rasch innerhalb weniger Tage erreicht und selbst bei schweren Formen oraler Candidiasis ist die Ansprechrate hoch (Fluconazol je nach Schwere und ösophagealer Beteiligung höher dosiert mit 200-400 mg täglich peroral). Itraconazol-Suspension, 100-200 mg täglich peroral verabreicht, war ähnlich wirksam wie Fluconazol mit Ansprechraten von über 90% [8,12,23,31,33]. Allerdings ist wegen der Grundkrankheiten mit T-Zellfunktionsstörungen mit Rezidiven zu rechnen, sodass je nach Situation und Grunderkrankung eine Sekundärprophy-laxe anzuschließen ist.…”

Section: Risikofaktoren Für Candidainfekteunclassified

Therapie schwerer Pilzinfektionen

Battegay¹,

Flückiger²

2003

Der Internist

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Severe fungal infections increase in numbers in the Western world. This is due to more intensive therapies against cancers leading to severe and prolonged immunosuppression. For many years treatment of severe fungal infections had to be done solely with amphothericin B desoxycholate and 5-fluorocytosine. With the advent of triazoles such as fluconazole, lipid formulations of amphotericin B and the development of echinocandines such as caspofungin also severe candidiasis and invasive aspergillosis has become treatable. In particular, caspofungin for invasive candidiasis and voriconazole for invasive aspergillosis seem at least equivalent to amphotericin B. A clear advantage is the advent of lipid formulations of amphotericin B. This regards especially side effects which are reduced with these newer formulations, i.e. nephrotoxicity. Due to the fact that prospective trials are difficult to conduct because patient populations may vary considerably (especially the underlying disease) many comparisons were not yet performed. Nevertheless, promising results indicate that certain combinations of antifungals may enhance prognosis of refractory fungal infections with a so far very serious prognosis.

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Successful treatment of Candida krusei infection with caspofungin acetate: A new antifungal agent

Abstract: Efficacy of caspofungin acetate in a patient with life-threatening Candida Krusei infection.

Cited by 15 publications

References 3 publications

Candida krusei , a Multidrug-Resistant Opportunistic Fungal Pathogen: Geographic and Temporal Trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005

Candida krusei , a Multidrug-Resistant Opportunistic Fungal Pathogen: Geographic and Temporal Trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005

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

Therapie schwerer Pilzinfektionen

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