Download PDF
Klin Padiatr 2005; 217(3): 158-168
DOI: 10.1055/s-2005-836502
Supportive Therapie

© Georg Thieme Verlag Stuttgart · New York

New Antifungal Drugs and the Pediatric Cancer Patient: Current Status of Clinical Development

Neue Antimykotika für die Pädiatrische Hämatologie/Onkologie: Stand der klinischen EntwicklungA. H. Groll1 , T. Lehrnbecher2
  • 1Department of Pediatric Hematology and Oncology, University Children's Hospital, Münster, Germany
  • 2Department of Pediatric Hematology and Oncology, University Children's Hospital, Frankfurt am Main, Germany
Further Information

Publication History

Publication Date:
27 April 2005 (online)

Also available at
    Permissions and Reprints

Abstract

Invasive mycoses are important causes for treatment related morbidity and mortality in severely immunocompromised pediatric patients with hematological malignancies or hematopoietic stem cell transplantation. The past decade has witnessed a major expansion of antifungal drug research, which has resulted in the development of the novel class of echinocandin lipopeptides (anidulafungin, micafungin, caspofungin) and a new generation of antifungal triazoles with improved pharmacological properties (posaconazole, ravuconazole, voriconazole). Whereas caspofungin and voriconazole have been licensed in the European Union, the United States, Canada and several other countries throughout the world, posaconazole, ravuconazole, anidulafungin and micafungin are under regulatory review or in advanced stages of clinical development. Caspofungin and voriconazole are increasingly prescribed in pediatric patients, although pediatric dosage finding and safety evaluations have not been completed. This article reviews the clinical pharmacology of the new antifungal agents and the status of their clinical development in immunocompromised pediatric patients.

Zusammenfassung

Invasive Pilzinfektionen sind wichtige Ursachen von Morbidität und Mortalität bei der Behandlung abwehrgeschwächter Kinder und Jugendlicher mit hämatologischen Neoplasien oder hämatopoetischer Stammzell-Transplantation. Das vergangene Jahrzehnt hat eine intensivierte Forschung auf dem Gebiet der antimykotischen Chemotherapie erlebt, die zu der Entwicklung der neuen Substanzklasse der Echinocandine (Anidulafungin, Micafungin, Caspofungin) und einer neuen Generation von antimykotischen Triazolen mit verbesserten pharmakologischen Eigenschaften (Posaconazol, Ravuconazol, Voriconazol) geführt hat. Während Caspofungin und Voriconazol in der Europäischen Union, den Vereinigten Staaten, Kanada und mehreren anderen Ländern zugelassen ist, befinden sich Posaconazol, Ravuconazol, Anidulafungin und Micafungin in Evaluation durch die Zulassungsbehörden bzw. in fortgeschrittenen Stadien der klinischen Entwicklung. Caspofungin und Voriconazole werden zunehmend bei pädiatrische Patienten eingesetzt, obwohl Dosisfindung und Prüfung von Sicherheit und Verträglichkeit in dieser Population nicht abgeschlossen sind. Die vorliegende Arbeit gibt eine Übersicht über die klinische Pharmakologie der neuen antimykotischen Substanzen und über den derzeitigen Stand ihrer klinischen Entwicklung bei abwehrgeschwächten Kindern und Jugendlichen.

Key words

antifungal agents - voriconazole - caspofungin - mycoses - cancer - children

Schlüsselwörter

Antimykotika - Voriconazol - Caspofungin - Pilzinfektionen - Krebs - Kinder

References

  • 1 Ally R, Schurmann D, Kreisel W, Carosi G, Aguirrebengoa K, Dupont B, Hodges M, Troke P, Romero A J. A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients.  Clin Infect Dis. 2001;  33 1447-1454
    CrossrefPubMedGoogle Scholar
  • 2 Andes D, Marchillo K, Stamstad T, Conklin R. In vivo pharmacokinetics and pharmacodynamics of a new triazole, voriconazole, in a murine candidiasis model.  Antimicrob Agents Chemother. 2003;  47 3165-3169
    CrossrefPubMedGoogle Scholar
  • 3 Arathoon E G, Gotuzzo E, Noriega L M, Berman R S, DiNubile M J, Sable C A. Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiases.  Antimicrob Agents Chemother. 2002;  46 451-457
    CrossrefPubMedGoogle Scholar
  • 4 Baden L R, Katz J T, Fishman J A, Koziol C, DelVecchio A, Doran M, Rubin R H. Salvage therapy with voriconazole for invasive fungal infections in patients failing or intolerant to standard antifungal therapy.  Transplantation. 2003;  76 1632-1637
    PubMedGoogle Scholar
  • 5 Balani S K, Xu X, Arison B H, Silva M V, Gries A, DeLuna F A, Cui D, Kari P H, Ly T, Hop C E, Singh R, Wallace M A, Dean D C, Lin J H, Pearson P G, Baillie T A. Metabolites of caspofungin acetate, a potent antifungal agent, in human plasma and urine.  Drug Metab Dispos. 2000;  28 1274-1278
    PubMedGoogle Scholar
  • 6 Beale M, Queiroz-Telles F, Banhegyi D. et al .Randomized, double-blind study of the safety and antifungal efficacy of ravuconazole relative to fluconazole in esophageal candidiasis. In: Abstracts of the 41th Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstract J-1621. American Society for Microbiology, Washington, DC 2001; 392
    Google Scholar
  • 7 Benjamin D K, Driscoll T, Seibel N L, Gonzalez C E, Roden M M, Dowell J A, Schranz J, Walsh T J. Safety and pharmacokinetics of anidulafungin in pediatric patients with neutropenia. In: Abstracts of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstract A-34. American Society for Microbiology, Washington, DC 2004; 8
    Google Scholar
  • 8 Boucher H W, Groll A H, Chiou C C, Walsh T J. Newer systemic antifungal agents: pharmacokinetics, safety and efficacy.  Drugs. 2004;  64 1997-2020
    PubMedGoogle Scholar
  • 9 Bowden R, Chadrasekar P, White M H, Li X, Pietrelli L, Gurwith M, Burik J A van, Laverdiere M, Safrin S, Wingard J R. A double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients.  Clin Infect Dis. 2002;  35 359-366
    CrossrefPubMedGoogle Scholar
  • 10 Bowman J C, Hicks P S, Kurtz M B, Rosen H, Schmatz D M, Liberator P A, Douglas C M. The antifungal echinocandin caspofungin acetate kills growing cells of Aspergillus fumigatus in vitro.  Antimicrob Agents Chemother. 2002;  46 3001-3012
    CrossrefPubMedGoogle Scholar
  • 11 Caspofungin package circular. Cancidas (Fachinformation). Version 11/2004. BPI, Aulendorf, Germany 2004
    Google Scholar
  • 12 Courtney R, Pai S, Laughlin M, Lim J, Batra V. Pharmacokinetics, safety, and tolerability of oral posaconazole administered in single and multiple doses in healthy adults.  Antimicrob Agents Chemother. 2003;  47 2788-2795
    CrossrefPubMedGoogle Scholar
  • 13 Dannaoui E, Meletiadis J, Mouton J W, Meis J F, Verweij P E. Eurofung Network . In vitro susceptibilities of zygomycetes to conventional and new antifungals.  J Antimicrob Chemother. 2003;  51 45-52
    CrossrefPubMedGoogle Scholar
  • 14 de Wet N, Llanos-Cuentas A, Suleiman J, Baraldi E, Krantz E F, Della Negra M, Diekmann-Berndt H. A randomized, double-blind, parallel-group, dose-response study of micafungin compared with fluconazole for the treatment of esophageal candidiasis in HIV-positive patients.  Clin Infect Dis. 2004;  39 842-849
    CrossrefPubMedGoogle Scholar
  • 15 Denning D W, Ribaud P, Milpied N, Caillot D, Herbrecht R, Thiel E, Haas A, Ruhnke M, Lode H. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis.  Clin Infect Dis. 2002;  34 563-571
    CrossrefPubMedGoogle Scholar
  • 16 Denning D W. Echinocandin antifungal drugs.  Lancet. 2003;  362 1142-1151
    CrossrefPubMedGoogle Scholar
  • 17 Ernst E J, Klepser M E, Ernst M E, Messer S A, Pfaller M A. In vitro pharmacodynamic properties of MK-0991 determined by time-kill methods.  Diagn Microbiol Infect Dis. 1999;  33 75-80
    CrossrefPubMedGoogle Scholar
  • 18 Franklin J A, McCormick J, Flynn P M. Retrospective study of the safety of caspofungin in immunocompromised pediatric patients.  Pediatr Infect Dis J. 2003;  22 747-749
    PubMedGoogle Scholar
  • 19 Grasela D M, Olsen S J, Mummaneni V, Rolan P, Christopher L, Norton J, Hadjilambris O W, Marino M R. Ravuconazole: Multiple ascending oral dose study in healthy subjects. In: Abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstract 839. American Society for Microbiology, Washington, DC 2000; 22
    Google Scholar
  • 20 Greenberg R N, Anstead G, Herbrecht R, Langston A, Marr K, Mullane K, Raad I, Schiller G, Schuster M, Burik J van, Wingard J R, Hare R, Corcoran G. Posaconazole experience in the treatment of zygomycosis. In: Abstracts of the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstract M-1757. American Society for Microbiology, Washington, DC 2003; 476
    Google Scholar
  • 21 Groll A H, Gea-Banacloche J C, Glasmacher A, Just-Nuebling G, Maschmeyer G, Walsh T J. Clinical pharmacology of antifungal compounds.  Infect Dis Clin North Am. 2003;  17 159-191
    CrossrefPubMedGoogle Scholar
  • 22 Groll A H, Piscitelli S C, Walsh T J. Clinical pharmacology of systemic antifungal agents: a comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development.  Adv Pharmacol. 1998;  44 343-500
    PubMedGoogle Scholar
  • 23 Groll A H, Ritter J, Muller F M. Prevention of fungal infections in children and adolescents with cancer.  Klin Padiatr. 2001;  213 (Suppl 1) A50-A68
    PubMedGoogle Scholar
  • 24 Groll A H, Walsh T J. Caspofungin: pharmacology, safety and therapeutic potential in superficial and invasive fungal infections.  Expert Opin Investig Drugs. 2001;  10 1545-1558
    CrossrefPubMedGoogle Scholar
  • 25 Groll A H, Walsh T J. Cell wall synthesis inhibitors. In: Dismukes WE, Pappas PG, Sobel JD (eds). Oxford Textbook of Clinical Mycology. Oxford University Press, New York, NY 2003; 88-103
    Google Scholar
  • 26 Groll A H, Walsh T J. Uncommon opportunistic fungi: new nosocomial threats.  Clin Microbiol Infect. 2001;  7 (Suppl 2) 8-24
    CrossrefPubMedGoogle Scholar
  • 27 Hachem R Y, Raad I I, Afif C M. et al .An open, non-comparative multicenter study to evaluate efficacy and safety of posaconazole (SCH 56592) in the treatment of invasive fungal infections refractory to or intolerant to standard therapy. In: Abstracts of the 40th International Conference on Antimicrobial Agents and Chemotherapy. Abstr. 1109. American Society for Microbiology, Washington, D.C. 2000; 372
    Google Scholar
  • 28 Hegener P, Troke P F, Fatkenheuer G, Diehl V, Ruhnke M. Treatment of fluconazole-resistant candidiasis with voriconazole in patients with AIDS.  AIDS. 1998;  12 2227-2228
    PubMedGoogle Scholar
  • 29 Herbrecht R, Denning D W, Patterson T F, Bennett J E, Greene R E, Oestmann J W, Kern W V, Marr K A, Ribaud P, Lortholary O, Sylvester R, Rubin R H, Wingard J R, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar P H, Hodges M R, Schlamm H T, Troke P F, de Pauw B. Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group . Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis.  N Engl J Med. 2002;  347 408-415
    CrossrefPubMedGoogle Scholar
  • 30 Hoffman H L, Ernst E J, Klepser M E. Novel triazole antifungal agents.  Expert Opin Investig Drugs. 2000;  9 593-605
    CrossrefPubMedGoogle Scholar
  • 31 Johnson L B, Kauffman C A. Voriconazole: a new triazole antifungal agent.  Clin Infect Dis. 2003;  36 630-637
    CrossrefPubMedGoogle Scholar
  • 32 Klepser M E, Malone D, Lewis R E, Ernst E J, Pfaller M A. Evaluation of voriconazole pharmacodynamics using time-kill methodology.  Antimicrob Agents Chemother. 2000;  44 1917-1920
    CrossrefPubMedGoogle Scholar
  • 33 Kolve H, Lehrnbecher T, Ehlert K, Paulussen M, Bielack S, Vormoor J, Walsh T J, Groll A H. Safety, tolerance and plasma concentrations of voriconazole in immunocompromised pediatric patients (abstract).  Clin Microbiol Infect. 2004;  10 (Suppl 3) 40-41
    PubMedGoogle Scholar
  • 34 Krause D S, Reinhardt J, Vazquez J A, Reboli A, Goldstein B P, Wible M, Henkel T. Anidulafungin Invasive Candidiasis Study Group . Phase 2, randomized, dose-ranging study evaluating the safety and efficacy of anidulafungin in invasive candidiasis and candidemia.  Antimicrob Agents Chemother. 2004;  48 2021-2024
    CrossrefPubMedGoogle Scholar
  • 35 Krause D S, Simjee A E, Rensburg C van, Viljoen J, Walsh T J, Goldstein B P, Wible M, Henkel T. A randomized, double-blind trial of anidulafungin versus fluconazole for the treatment of esophageal candidiasis.  Clin Infect Dis. 2004;  39 770-775
    CrossrefPubMedGoogle Scholar
  • 36 Krieter P, Flannery B, Musick T, Gohdes M, Martinho M, Courtney R. Disposition of posaconazole following single-dose oral administration in healthy subjects.  Antimicrob Agents Chemother. 2004;  48 3543-3551
    CrossrefPubMedGoogle Scholar
  • 37 Krishna G, Wexler D, Courtney R, Sansone A, Suh E, Shah A, Martinho M, Kantesaria B, Corcoran G. Posaconazole plasma concnetrations in pediatric patients with invasive fungal infections. In: Abstracts of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstract A-41. American Society for Microbiology, Washington, DC 2004: 10
    Google Scholar
  • 38 Kullberg B J, Pappas P, Ruhnke M, Viscoli C, Cleary J D, Rubinstein E, Church L WP, Brown J M, Rex J H, Hilton F, Oborska I, Hodges M, Schlamm H AT, Sobel J. Voriconazole compared with a strategy of amphotericin B followed by fluconazole for treatment of candidemia in nonneutropenic patients (abstract).  Clin Microbiol Infect. 2004;  10 (Suppl 3) 41
    CrossrefPubMedGoogle Scholar
  • 39 Kurtz M B, Douglas C M. Lipopeptide inhibitors of fungal glucan synthase.  J Med Vet Mycol. 1997;  35 79-86
    PubMedGoogle Scholar
  • 40 Lehrnbecher T, Attarbaschi A, Schuster F, Herzog N, Grigull L, Dworzak M, Beutel K, Laws H J, Groll A H. Caspofungin in immunocompromised pediatric patients without therapeutic alternative: a multicenter survey. Abstracts of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstr. M-1019. American Society for Microbiology, Washington, DC 2004; 414
    Google Scholar
  • 41 Lehrnbecher T, Groll A H, Chanock S J. Treatment of fungal infections in neutropenic children.  Curr Opin Pediatr. 1999;  11 47-55
    CrossrefPubMedGoogle Scholar
  • 42 Louie A, Deziel M, Liu W, Drusano M, Gumbo T, Drusano G L. AUC/MIC is the pharmacodynamic variable for caspofungin as determined in a non-neutropenic mouse model of disseminated candidiasis. In: Abstracts of the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstract A-1572. American Society for Microbiology, Washington, DC 2003; 31
    Google Scholar
  • 43 Maertens J, Raad I, Petrikkos G, Boogaerts M, Selleslag D, Petersen F B, Sable C A, Kartsonis N A, Ngai A, Taylor A, Patterson T F, Denning D W, Walsh T J. Caspofungin Salvage Aspergillosis Study Group . Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy.  Clin Infect Dis. 2004;  39 1563-1571
    CrossrefPubMedGoogle Scholar
  • 44 Manavathu E K, Cutright J L, Chandrasekar P H. Organism-dependent fungicidal activities of azoles.  Antimicrob Agents Chemother. 1998;  42 3018-3021
    PubMedGoogle Scholar
  • 45 Marr K A, Boeckh M, Carter R A, Kim H W, Corey L. Combination antifungal therapy for invasive aspergillosis.  Clin Infect Dis. 2004;  39 797-802
    CrossrefPubMedGoogle Scholar
  • 46 Mora-Duarte J, Betts R, Rotstein C, Colombo A L, Thompson-Moya L, Smietana J, Lupinacci R, Sable C, Kartsonis N, Perfect J. Caspofungin Invasive Candidiasis Study Group . Comparison of caspofungin and amphotericin B for invasive candidiasis.  N Engl J Med. 2002;  347 2020-2029
    CrossrefPubMedGoogle Scholar
  • 47 Nieto L, Northland R, Pittisuttithum P, Firnhaber C, Jacobson S, Greaves W, Plott R T, Taglietti M. Posaconazole equivalent to fluconazole in the treatment of oropharyngeal candidiasis. In: Abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstract 1108. American Society for Microbiology, Washington, DC 2000; 372
    Google Scholar
  • 48 Olsen S J, Mummaneni V, Rolan P, Norton J, Grasela D M. Ravuconazole single ascending oral dose study in healthy subjects. In: Abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstract 838. American Society for Microbiology, Washington, DC 2000; 22
    Google Scholar
  • 49 Ostrosky-Zeichner L, Oude Lashof A M, Kullberg B J, Rex J H. Voriconazole salvage treatment of invasive candidiasis.  Eur J Clin Microbiol Infect Dis. 2003;  22 651-655
    CrossrefPubMedGoogle Scholar
  • 50 Perfect J R, Marr K A, Walsh T J, Greenberg R N, DuPont B, de la Torre-Cisneros J, Just-Nubling G, Schlamm H T, Lutsar I, Espinel-Ingroff A, Johnson E. Voriconazole treatment for less-common, emerging, or refractory fungal infections.  Clin Infect Dis. 2003;  36 1122-1131
    CrossrefPubMedGoogle Scholar
  • 51 Pettengell K, Mynhardt J, Kluyts T, Lau W, Facklam D, Buell D. FK463 South African Study Group . Successful treatment of oesophageal candidiasis by micafungin: a novel systemic antifungal agent.  Aliment Pharmacol Ther. 2004;  20 475-481
    CrossrefPubMedGoogle Scholar
  • 52 Pfaller M A, Messer S A, Boyken L, Tendolkar S, Hollis R J, Diekema D J. Geographic variation in the susceptibilities of invasive isolates of Candida glabrata to seven systemically active antifungal agents: a global assessment from the ARTEMIS Antifungal Surveillance Program conducted in 2001 and 2002.  J Clin Microbiol. 2004;  42 3142-3146
    CrossrefPubMedGoogle Scholar
  • 53 Pfaller M A, Messer S A, Hollis R J, Jones R N, Diekema D J. In vitro activities of ravuconazole and voriconazole compared with those of four approved systemic antifungal agents against 6 970 clinical isolates of Candida spp.  Antimicrob Agents Chemother. 2002;  46 1723-1727
    CrossrefPubMedGoogle Scholar
  • 54 Pfaller M A, Messer S A, Hollis R J, Jones R N, Doern G V, Brandt M E, Hajjeh R A. In vitro susceptibilities of Candida bloodstream isolates to the new triazole antifungal agents BMS-207147, Sch 56592, and voriconazole.  Antimicrob Agents Chemother. 1998;  42 3242-3244
    PubMedGoogle Scholar
  • 55 Pittisuttithum P, Gaona-Flores V, Negroni R, Sanne I, Graybill J R, Bustamente A, Hare R, Hardalo C. Efficacy of posaconazole in treatment of central nervous system fungal infections: results of an open label study. In: Abstracts of the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstract M-978. American Society for Microbiology, Washington, DC 2003; 450
    Google Scholar
  • 56 Purkins L, Wood N, Ghahramani P, Greenhalgh K, Allen M J, Kleinermans D. Pharmacokinetics and safety of voriconazole following intravenous- to oral-dose escalation regimens.  Antimicrob Agents Chemother. 2002;  46 2546-2553
    CrossrefPubMedGoogle Scholar
  • 57 Purkins L, Wood N, Greenhalgh K, Allen M J, Oliver S D. Voriconazole, a novel wide-spectrum triazole: oral pharmacokinetics and safety.  Br J Clin Pharmacol. 2003;  56 (Suppl 1) 10-16
    CrossrefPubMedGoogle Scholar
  • 58 Purkins L, Wood N, Greenhalgh K, Eve M D, Oliver S D, Nichols D. The pharmacokinetics and safety of intravenous voriconazole - a novel wide-spectrum antifungal agent.  Br J Clin Pharmacol. 2003;  56 (Suppl 1) 2-9
    CrossrefPubMedGoogle Scholar
  • 59 Ratanatharathorn V, Flynn P, Burik J A van, McSweeney P, Niederwieser D, Kontoyiannis D. Micafungin in combination with systemic antifungal agents in the treatment of refractory aspergillosis in bone marrow transplant patients. Abstract 2472. American Society of Hematology, Philadelphia 2002
    Google Scholar
  • 60 Roffey S J, Cole S, Comby P, Gibson D, Jezequel S G, Nedderman A N, Smith D A, Walker D K, Wood N. The disposition of voriconazole in mouse, rat, rabbit, guinea pig, dog, and human.  Drug Metab Dispos. 2003;  31 731-741
    CrossrefPubMedGoogle Scholar
  • 61 Sable C A, Nguyen B Y, Chodakewitz J A, DiNubile M J. Safety and tolerability of caspofungin acetate in the treatment of fungal infections.  Transpl Infect Dis. 2002;  4 25-30
    CrossrefPubMedGoogle Scholar
  • 62 Schwartz S, Thiel E. Update on the treatment of cerebral aspergillosis.  Ann Hematol. 2004;  83 (Suppl 1) 42-44
    PubMedGoogle Scholar
  • 63 Seibel N, Schwarzt C, Arrieta A, Flynn P, Shad A, Albano E, Walsh T. A phase I study to determine the safety and pharmacokinetics of FK463 echinocandin in febrile neutropenic patients. In: Abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstract 18. American Society for Microbiology, Washington, DC 2000; 1
    Google Scholar
  • 64 Steinbach W J, Benjamin D K, Kontoyiannis D P, Perfect J R, Lutsar I, Marr K A, Lionakis M S, Torres H A, Jafri H, Walsh T J. Infections due to Aspergillus terreus: a multicenter retrospective analysis of 83 cases.  Clin Infect Dis. 2004;  39 192-198
    CrossrefPubMedGoogle Scholar
  • 65 Stone J, Migoya E, Li S, Deutsch P, Winchell G, Ghosh K, Miller A, Bi S, Bass A, Mistry G, Dawkins R. Safety and pharmacokinetics of higher doses of caspofungin. In: Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstract A-1389. American Society for Microbiology, Washington, DC 2002; 19
    Google Scholar
  • 66 Stone J A, Holland S D, Wickersham P J, Sterrett A, Schwartz M, Bonfiglio C, Hesney M, Winchell G A, Deutsch P J, Greenberg H, Hunt T L, Waldman S A. Single- and multiple-dose pharmacokinetics of caspofungin in healthy men.  Antimicrob Agents Chemother. 2002;  46 739-745
    CrossrefPubMedGoogle Scholar
  • 67 Stone J A, Xu X, Winchell G A, Deutsch P J, Pearson P G, Migoya E M, Mistry G C, Xi L, Miller A, Sandhu P, Singh R, deLuna F, Dilzer S C, Lasseter K C. Disposition of caspofungin: role of distribution in determining pharmacokinetics in plasma.  Antimicrob Agents Chemother. 2004;  48 815-823
    CrossrefPubMedGoogle Scholar
  • 68 Suleiman J, Della Negra M, llanos-Cuentas A, Ticona E, Rex J H, Buell D N. Open label study of micafungin in the treatment of esophageal candidiasis. In: Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstract M-892. American Society for Microbiology, Washington, DC 2002; 394
    Google Scholar
  • 69 Burik J A van, Ratanatharathorn V, Stepan D E, Miller C B, Lipton J H, Vesole D H, Bunin N, Wall D A, Hiemenz J W, Satoi Y, Lee J M, Walsh T J. National Institute of Allergy and Infectious Diseases Mycoses Study Group . Micafungin versus Fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation.  Clin Infect Dis. 2004;  39 1407-1416
    CrossrefPubMedGoogle Scholar
  • 70 Vazquez J A, Northland R, Miller S, Dickinson G, Wright G. Posaconazole compared to fluconazole for oral candidiasis in HIV-positive patients. In: Abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstract 1107. American Society for Microbiology, Washington, DC 2000; 372
    Google Scholar
  • 71 Villanueva A, Arathoon E G, Gotuzzo E, Berman R S, DiNubile M J, Sable C A. A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagitis.  Clin Infect Dis. 2001;  33 1529-1535
    CrossrefPubMedGoogle Scholar
  • 72 Villanueva A, Gotuzzo E, Arathoon E G, Noriega L M, Kartsonis N A, Lupinacci R J, Smietana J M, DiNubile M J, Sable C A. A randomized double-blind study of caspofungin versus fluconazole for the treatment of esophageal candidiasis.  Am J Med. 2002;  113 294-299
    CrossrefPubMedGoogle Scholar
  • 73 Voriconazol package circular Vfend (Fachinformation). Version 12/2003. BPI, Aulendorf, Germany 2003
    Google Scholar
  • 74 Walsh T J, Adamson P C, Seibel N L, Flynn P M, Neely M N, Miller A, Sable C A, Kartsonis M A, Stone J A. Pharmacokinetics of caspofungin in pediatric patients. In: Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstract M-896. American Society for Microbiology, Washington, DC 2002; 395
    Google Scholar
  • 75 Walsh T J, Karlsson M O, Driscoll T, Arguedas A G, Adamson P, Saez-Llorens X, Vora A J, Arrieta A C, Blumer J, Lutsar I, Milligan P, Wood N. Pharmacokinetics and safety of intravenous voriconazole in children after single- or multiple-dose administration.  Antimicrob Agents Chemother. 2004;  48 2166-2172
    CrossrefPubMedGoogle Scholar
  • 76 Walsh T J, Lutsar I, Driscoll T, Dupont B, Roden M, Ghahramani P, Hodges M, Groll A H, Perfect J R. Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children.  Pediatr Infect Dis J. 2002;  21 240-248
    CrossrefPubMedGoogle Scholar
  • 77 Walsh T J, Pappas P, Winston D J, Lazarus H M, Petersen F, Raffalli J, Yanovich S, Stiff P, Greenberg R, Donowitz G, Schuster M, Reboli A, Wingard J, Arndt C, Reinhardt J, Hadley S, Finberg R, Laverdiere M, Perfect J, Garber G, Fioritoni G, Anaissie E, Lee J. National Institute of Allergy and Infectious Diseases Mycoses Study Group . Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever.  N Engl J Med. 2002;  346 225-234
    CrossrefPubMedGoogle Scholar
  • 78 Walsh T J, Teppler H, Donowitz G R, Maertens J A, Baden L R, Dmoszynska A, Cornely O A, Bourque M R, Lupinacci R J, Sable C A, dePauw B E. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia.  N Engl J Med. 2004;  351 1391-1402
    CrossrefPubMedGoogle Scholar
  • 79 Wiederhold N P, Kontoyiannis D P, Chi J, Prince R A, Tam V H, Lewis R E. Pharmacodynamics of caspofungin in a murine model of invasive pulmonary aspergillosis: evidence of concentration-dependent activity.  J Infect Dis. 2004;  190 1464-1471
    PubMedGoogle Scholar
  • 80 Wiederhold N P, Kontoyiannis D P, Prince R A, Lewis R E. Eagle-like effect of caspofungin against Candida- and Aspergillus spp.: Association with homeostatic mechanisms of cell wall integrity. In: Abstracts of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy. Abstract M-1682. American Society for Microbiology, Washington DC 2004; 427
    Google Scholar

Andreas H. GrollM. D. 

Infectious Disease Research Program · Department of Pediatric Hematology and Oncology · University Children's Hospital

Albert-Schweitzer-Strasse 33

48129 Muenster

Germany

Phone: +49/2 51/8 35 28 01

Fax: +49/2 51/8 35 28 04

Email: grollan@mednet.uni-muenster.de

      >