Klinik für Kinder- und Jugendmedizin - Pädiatrische Hämatologie und Onkologie

Infektiologisches Forschungsprogramm

Infektionen sind häufige und zum Teil lebensbedrohliche Komplikationen in der Behandlung abwehrgeschwächter Patienten mit Krebserkrankungen und nach hämatopoetischer Stammzelltransplatation. Der Vorbeugung, Früherkennung und der optimalen Behandlung von Infektionen kommt eine wichtige Rolle zu, insbesondere im Zusammenhang mit der Entwicklung neuer Behandlungsstrategien in Onkologie und Transplantationsmedizin.
Das Ziel des 2002 etablierten Infektiologischen Forschungsprogramms ist es, die sich fortwährend wandelnde Natur von Infektionen bei Patienten mit Abwehrschwäche besser zu verstehen und die infektiologische Supportivtherapie in dieser Population zu optimieren.

Die Aktivitäten des Infektiologischen Forschungsprogrammes umfassen:

  • Entwicklung und Durchführung klinischer Studien in Kooperation mit dem Zentrum für Klinische Studien und industriellen Partnern mit Schwerpunkten auf dem Gebiet invasiver Pilzinfektionen und klinischen Studien bei pädiatrischen Patienten
  • ein kliniknahes Forschungsprogramm in den Bereichen der Epidemiologie, Pathogenese, Diagnostik, Therapie und Prophylaxe infektiöser Komplikationen sowie der Pharmakokinetik, Pharmakodynamik, Resistenzentwicklung und Arzneimittelinteraktionen antimykotischer Substanzen in Kooperation mit nationalen und internationalen Partnern und Verbünden.

Investigator-initiierte klinische Studien (AHG):

  • A Phase II study investigating the pharmacokinetics, safety and tolerance of caspofungin alone and in combination with liposomal amphotericin B in patients with allogeneic hematopoietic stem cell transplantation (multizentrisch; abgeschlossen in 2009)
  • A phase I/II dose escalation study of caspofungin in patients with invasive aspergillosis (multizentrisch in Kollaboration mit Universitätsklinikum Köln; abgeschlossen in 2010)

Offene Klinische Studien (Oktober 2010):

  • Prospective, open-label, non randomized, multicenter study to investigate the saftey and tolerability of voriconazole as primary therapy for treatment of invasive aspergillosis and molds such as Scedosporium or Fusarium species in pediatric patients (Pfizer A1501080)
  • A prospective, open-label study to assess the pharmacokinetics, safety, and efficacy of anidulafungin when used to treat childen with invasive candidiasis, including candidemia (Pfizer A8851008)
  • Klinische Prüfung der Phase Ib zur Bestimmung der Sicherheit, der Verträglichkeit, und des pharmakokinetischen Profils von Posaconazol p.o. bei abwehrgeschwächten Kindern/Jugnedlichen mit Neutropenie (Essex P03579-05)
  • Pediatric Fungal Network Invasive Fungal Infection Case Registry (Duke University, Durham, NC)

PubMed gelistete Originalarbeiten (seit 2002):

  • Walsh TJ, Driscoll T, Milligan PA, Wood ND, Schlamm H, Groll AH, Jafri H, Arrieta AC, Klein NJ, Lutsar I. Pharmacokinetics, safety, and tolerability of voriconazole in immunocompromised children. Antimicrob Agents Chemother. 2010 Oct;54(10):4116-23. Epub 2010 Jul 26.
  • Groll AH, Silling G, Young C, Schwerdtfeger R, Ostermann H, Heinz WJ, Gerss J, Kolve H, Lanvers-Kaminsky C, Vieira Pinheiro JP, Gammelin S, Cornely OA, Wuerthwein G. Randomized comparison of safety and pharmacokinetics of caspofungin, liposomal amphotericin B, and the combination of both in allogeneic hematopoietic stem cell recipients. Antimicrob Agents Chemother. 2010 Oct;54(10):4143-9. Epub 2010 Jul 26.
  • Lehrnbecher T, Frank C, Engels K, Kriener S, Groll AH, Schwabe D.  Trends in the postmortem epidemiology of invasive fungal infections at a university hospital.. J Infect. 2010 Sep;61(3):259-65. Epub 2010 Jul 31.
  • Lehrnbecher T, Attarbaschi A, Duerken M, Garbino J, Gruhn B, Kontny U, Lüer S, Phillips R, Scholz J, Wagner HJ, Wiesel T, Groll AH. Posaconazole salvage treatment in paediatric patients: a multicentre survey. Eur J Clin Microbiol Infect Dis. 2010 Aug;29(8):1043-5. Epub 2010 May 22.
  • Maertens JA, Madero L, Reilly AF, Lehrnbecher T, Groll AH, Jafri HS, Green M, Nania JJ, Bourque MR, Wise BA, Strohmaier KM, Taylor AF, Kartsonis NA, Chow JW, Arndt CA, DePauw BE, Walsh TJ; Caspofungin Pediatric Study Group.  A randomized, double-blind, multicenter study of caspofungin versus liposomal amphotericin B for empiric antifungal therapy in pediatric patients with persistent fever and neutropenia. Pediatr Infect Dis J. 2010 May;29(5):415-20.
  • Zaoutis T, Lehrnbecher T, Groll AH, Steinbach WJ, Jafri HS, Maertens J, Ngai AL, Chow JW, Taylor AF, Strohmaier KM, Bourque M, Bradshaw SK, Petrecz M, Kartsonis NA. Safety experience with caspofungin in pediatric patients. Pediatr Infect Dis J. 2009 Dec;28(12):1132-5.
  • Kolve H, Ahlke E, Fegeler W, Ritter J, Jürgens H, Groll AH. Safety, tolerance and outcome of treatment with liposomal amphotericin B in paediatric patients with cancer or undergoing haematopoietic stem cell transplantation. J Antimicrob Chemother. 2009 Aug;64(2):383-7. Epub 2009 Jun 2.
  • Masjosthusmann K, Ehlert K, Eing BR, Roth J, Koehler G, Juergens H, Fruehwald  M, Groll AH. Delay in B-lymphocyte recovery and function following rituximab for EBV-associated lymphoproliferative disease early post-allogeneic hematopoietic SCT. Bone Marrow Transplant. 2009 May;43(9):679-84.
  • Queiroz-Telles F, Berezin E, Leverger G, Freire A, van der Vyver A, Chotpitayasunondh T, Konja J, Diekmann-Berndt H, Koblinger S, Groll AH, Arrieta A; Micafungin Invasive Candidiasis Study Group. Micafungin versus liposomal amphotericin B for pediatric patients with invasive candidiasis: substudy of a randomized double-blind trial. Pediatr Infect Dis J. 2008 Sep;27(9):820-6.
  • Lehrnbecher T, Laws HJ, Boehm A, Dworzak M, Janssen G, Simon A, Groll AH. Compliance with anti-infective preventive measures: A multicentre survey among paediatric oncology patients. Eur J Cancer. 2008 Sep;44(13):1861-5. 
    Allinson K, Kolve H, Gumbinger HG, Vormoor HJ, Ehlert K, Groll AH. Secondary  antifungal prophylaxis in paediatric allogeneic haematopoietic stem cell recipients. J Antimicrob Chemother. 2008 Mar;61(3):734-42.
  • Hope WW, Mickiene D, Petraitis V, Petraitiene R, Kelaher AM, Hughes JE, Cotton MP, Bacher J, Keirns JJ, Buell D, Heresi G, Benjamin DK Jr, Groll AH, Drusano GL, Walsh TJ. The pharmacokinetics and pharmacodynamics of micafungin in  experimental hematogenous Candida meningoencephalitis: implications for echinocandin therapy in neonates. J Infect Dis. 2008 Jan 1;197(1):163-71.
  • Simon A, Lehrnbecher T, Bode U, Groll AH, Tramsen L, Wieland R, Molitor E, Fleischhack G, Laws HJ. Piperacillin-tazobactam in pediatric cancer patients younger than 25 months: a retrospective multicenter survey. Eur J Clin Microbiol  Infect Dis. 2007 Nov;26(11):801-6.
  • Lehrnbecher T, Kaiser J, Varwig D, Ritter J, Groll AH, Creutzig U, Klingebiel T, Schwabe D. Antifungal usage in children undergoing intensive treatment for acute myeloid leukemia: analysis of the multicenter clinical trial AML-BFM 93. Eur J Clin Microbiol Infect Dis. 2007 Oct;26(10):735-8.
  • Meisel R, Kuypers L, Dirksen U, Schubert R, Gruhn B, Strauss G, Beutel K, Groll AH, Duffner U, Blütters-Sawatzki R, Holter W, Feuchtinger T, Grüttner HP, Schroten H, Zielen S, Ohmann C, Laws HJ, Dilloo D; Impfung von Kindern nach allogener Stammzelltransplantation (IKAST) Study Group. Pneumococcal conjugate vaccine provides early protective antibody responses in children after related and unrelated allogeneic hematopoietic stem cell transplantation. Blood. 2007 Mar 15;109(6):2322-6.
  • Groll AH, Lyman CA, Petraitis V, Petraitiene R, Armstrong D, Mickiene D, Alfaro RM, Schaufele RL, Sein T, Bacher J, Walsh TJ. Compartmentalized intrapulmonary pharmacokinetics of amphotericin B and its lipid formulations. Antimicrob Agents Chemother. 2006 Oct;50(10):3418-23.
  • Groll AH, Attarbaschi A, Schuster FR, Herzog N, Grigull L, Dworzak MN, Beutel K, Laws HJ, Lehrnbecher T. Treatment with caspofungin in Immunocompromised paediatric patients: a multicentre survey. J Antimicrob Chemother. 2006 Mar;57(3):527-35..
  • Würthwein G, Groll AH, Hempel G, Adler-Shohet FC, Lieberman JM, Walsh TJ. Population pharmacokinetics of amphotericin B lipid complex in neonates. Antimicrob Agents Chemother. 2005 Dec;49(12):5092-8.
  • Groll AH, Mickiene D, Petraitis V, Petraitiene R, Kelaher A, Sarafandi A, Wuerthwein G, Bacher J, Walsh TJ. Compartmental pharmacokinetics and tissue distribution of the antifungal triazole ravuconazole following intravenous administration of its di-lysine phosphoester prodrug (BMS-379224) in rabbits. JAntimicrob Chemother. 2005 Nov;56(5):899-907.
  • Petraitiene R, Petraitis V, Kelaher AM, Sarafandi AA, Mickiene D, Groll AH, Sein T, Bacher J, Walsh TJ. Efficacy, plasma pharmacokinetics, and safety of icofungipen, an inhibitor of Candida isoleucyl-tRNA synthetase, in treatment of experimental disseminated candidiasis in persistently neutropenic rabbits. Antimicrob Agents Chemother. 2005 May;49(5):2084-92.
  • Petraitis V, Petraitiene R, Kelaher AM, Sarafandi AA, Sein T, Mickiene D, Bacher J, Groll AH, Walsh TJ. Efficacy of PLD-118, a novel inhibitor of candida isoleucyl-tRNA synthetase, against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant C. albicans. Antimicrob Agents Chemother. 2004 Oct;48(10):3959-67.
  • Petraitiene R, Petraitis V, Lyman CA, Groll AH, Mickiene D, Peter J, Bacher J, Roussillon K, Hemmings M, Armstrong D, Avila NA, Walsh TJ. Efficacy, safety, and plasma pharmacokinetics of escalating dosages of intravenously administered ravuconazole lysine phosphoester for treatment of experimental pulmonary aspergillosis in persistently neutropenic rabbits. Antimicrob Agents Chemother. 2004 Apr;48(4):1188-96.
  • Groll AH, Mickiene D, Petraitis V, Petraitiene R, Alfaro RM, King C, Piscitelli SC, Walsh TJ. Comparative drug disposition, urinary pharmacokinetics,  and renal effects of multilamellar liposomal nystatin and amphotericin B deoxycholate in rabbits. Antimicrob Agents Chemother. 2003 Dec;47(12):3917-25.
  • Petraitis V, Petraitiene R, Sarafandi AA, Kelaher AM, Lyman CA, Casler HE, Sein T, Groll AH, Bacher J, Avila NA, Walsh TJ. Combination therapy in treatment  of experimental pulmonary aspergillosis: synergistic interaction between an antifungal triazole and an echinocandin. J Infect Dis. 2003 Jun 15;187(12):1834-43.
  • Chiou CC, Groll AH, Mavrogiorgos N, Wood LV, Walsh TJ. Esophageal candidiasis in human immunodeficiency virus-infected pediatric patients after the introduction of highly active antiretroviral therapy. Pediatr Infect Dis J. 2002  May;21(5):388-92.
  • Groll AH, Wood L, Roden M, Mickiene D, Chiou CC, Townley E, Dad L, Piscitelli SC, Walsh TJ. Safety, pharmacokinetics, and pharmacodynamics of cyclodextrin itraconazole in pediatric patients with oropharyngeal candidiasis. Antimicrob Agents Chemother. 2002 Aug;46(8):2554-63.
  • Petraitis V, Petraitiene R, Groll AH, Roussillon K, Hemmings M, Lyman CA, Sein T, Bacher J, Bekersky I, Walsh TJ. Comparative antifungal activities and plasma pharmacokinetics of micafungin (FK463) against disseminated candidiasisand invasive pulmonary aspergillosis in persistently neutropenic rabbits. Antimicrob Agents Chemother. 2002 Jun;46(6):1857-69
  • Walsh TJ, Lutsar I, Driscoll T, Dupont B, Roden M, Ghahramani P, Hodges M, Groll AH, Perfect JR. Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children. Pediatr Infect Dis J. 2002 Mar;21(3):240-8

Weitere, in Abstractform publizierte Originalarbeiten (in Auswahl; seit 2002):

  • Pieper S, Kolve H, Gumbinger HG, Wuerthwein G, Groll AH. Therapeutic drug monitoring of voriconazole in immunocompromised pediatric patients. In In Abstracts of the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington DC, 2010: abstract M-1048, page 80
  • Mikolajewska, A, Groll AH, Cornely OA, Laas-Floerl C, Ruhnke M. Register systemischer Mykosen (ReSyMe) – experience from ICUs in Germany. Mycoses 2010; 53: 384-385
  • Jocham S, Holzinger D, Froehlich B, Groll AH.  Influenza-associated morbidity in children with cancer:  Experience at the University Children’s Hospital of Münster, Germany. ICHS Meeting 2010
  • Groll AH, Yunus S, Pieper S, Froehlich B. Azol-basierte Chemoprophylaxe invasiver Pilzinfektionen bei paediatrisch-onkologischen Patienten – ein Audit. Monatschr. Kinderheilk 2010 (submitted)
  • Cornely OA, Vehreschild JJ, Rueping MJGT, Arenz D, Schwartz S, Heusel CP, Silling G, Mahne M, Franklin J, Harnischmacher U, Wilkens A, Fraowski F, Karthaus M, Lehrnbecher T, Ullmann AJ, Hallek M, Groll AH. A Phase II Dose Escalation Study of Caspofungin for Invasive Aspergillosis. ECCMID 2010
  • Wuerthwein G, Young C, Lanvers-Kaminsky C, Silling G, Hempel G, Boos J, Groll AH. Population Pharmacokinetics of Liposomal Amphotericin B, Caspofungin and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients In Abstracts of the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington DC, 2009
  • Tragiannidis A, Fegeler W, Debus V, Rellensmann G, Mueller V, Atthanasiadou F, Juergens H, Groll AH. Candidemia in pediatric patients in a German tertiary care hospital: a 10-year study. Mycoses 2009; 52 (Suppl.1): 26-27
  • Groll AH, Tintelnot K, Wintergerst U, Jendreyko N, Schuster F, Kremens B, Attarbschi A, Schrod L, v. Loewenich F, Lehrnbecher T. Zygomycosis in pediatric patients; a report from the ECMM survey. Mycoses 2009, 52: 413-412
  • Groll AH, Mickiene D, Petraitiene R, Petraitis V, Piscitelli S, Walsh TJ. Pharmacodynamics of posaconazole in a neutropenic animal model of invasive pulmonary aspergillosis. Mycoses 2009; 52 (Suppl.1): 24-25
  • Groll AH, Edelbusch CM, Thedieck S and Novak-Goettl U. Interaction of antifungal agents with human platelet function in vitro. Mycoses 2009; 52 (Suppl.1): 21
  • Walsh TJ, Shad A, Bekersky I, Gonzalez C, Groll AH, Wood LV, Buell D, Seibel NL. Safety, Tolerability and Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Pediatric Patients.  In Abstracts of the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington DC, 2008: Abstr. A-005, page 2
  • Petrikkos GL, Skiada A, Pagano L, Zimmerli S, Dupont B, Groll AH, Aoun M, Lass-Floerl C, Bouza E, Roilides E, Meis J. Zygomycosis in Europe: A prospective, epidemiologic study of the European Council of Medical Mycology Working Group on Zygomycosis. In Abstracts of the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington DC, 2008: Abstr. M-1845, page 657
  • Groll AH, Lyman CA, Petraitis V, Petraitiene R, Mickiene D, Kelaher A, Sarafandi A, Walsh TJ. Differential intrapulmonary disposition of voriconazole and liposomal amphotericin B in noninfected rabbits. In Abstracts of the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington DC (2003): Abstract M-2056, page 474
  • Groll AH, Mickiene, Petraitiene R, Petraitis V, Sarafandi A, Kelaher A, Wuerthwein G, Walsh TJ. Plasma pharmacokinetics and tissue distribution of intravenous cyclodextrin itraconazole in noninfected rabbits. abstr. M-1508, p. 408 . In Abstracts of the 42th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington DC (2002).
  • Groll AH, Mickiene D, Petraitiene R, Petraitis V, Roussillion K, Hemmings M, Raskas S, Walsh TJ. Antifungal efficacy, pharmacokinetics, and pharmacodynamics of intravenous itraconazole against invasive pulmonary aspergillosis in persistently neutropenic rabbits. Int J Infect Dis 2002; 6 (suppl.2): 2S46-2S47
 
 
 
 

Leitung

Prof. Dr. Andreas Groll
Arzt für Kinderheilkunde und Jugendmedizin
Kinderhämatologie und –onkologie; Infektiologie
E-Mail: grollan(at)­ukmuenster(dot)­deBeteiligte Wissenschaftler (intern): Dr. Birgit Fröhlich
Dr. Kornelius Kerl
Apothekerin Hedwig Kolve (Zentralapotheke)
Dr. rer. nat. Claudia Lanvers-Kaminsky
Prof. Dr. Joachim Boos (experimentelle Onkologie)
Dr. Gerda Silling (Medizinische Klinik A)
Dr. rer. nat. Gudrun Würthwein (Zentrum für Klinische Studien)
Prof. Dr. Karsten Becker (Medizinische Mikrobiologie) Beteiligte Wissenschaftler (extern): Thomas J. Walsh, M.D. (Weill Cornell Medical College, New York): Phase-II-Studien und tierexperimentelle Studien
Prof. Thomas Lehrnbecher, M.D. (Dept. of Pediatric Hematology/Oncology, University of Frankfurt): zelluläre Immuntherapie
Michael Kresken, M.D. (Anti-infectives Intelligence GmbH, Rheinbach, Germany): In-vitro-Studien
Prof. Cornelia Lass-Floerl, M.D. (Dept. of Social Medicine and Hygiene, University of Innsbruck, Austria): In-vitro-Studien