Interventional Antimicrobial Therapy in Febrile Neutropenic Patients (PEG Study II)

  • O. A. Cornely
  • W. Hiddemann
  • H. Link
  • G. Maschmeyer
  • B. Glass
  • D. Buchheidt
  • M. Wilhelm
  • Th. Büchner
  • Th. Lipp
  • R. Haas
  • V. Heinemann
  • M. Helmerking
  • D. Adam
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 39)

Abstract

The aim of this study was to evaluate the efficacy and safety of an empiric therapy escalation scheme comprising the early institution of antifungals. The study was conducted at more than 20 German hospitals over a 5-year-period beginning in 1991. Patients with a documented infection or fever of unknown origin (FUO) were randomized to receive empiric therapy Step I: either an extended spectrum penicillin (Pen) or cephalosporin (Ceph), each in combination with an aminoglycoside (Amg).

Those patients who did not defervesce after 72 h of therapy were randomized to receive Step II: imipenem-cilastatin (Imi) and a glycopeptide (Glp) or Imi + Glp + fluconazole (Fluc) or Imi + Glp + amphotericin B (AmB) + 5-flucytosin (5FC).

After further 72 h of unsuccessful treatment patients were randomized to receive Step III: Pen + Ceph + Amg + AmB + 5FC or quinolone + Amg + AmB + 5FC.

In case of pneumonia AmB with or without 5FC was added; 1041 patients were randomised; 934 (89.7%) patients were evaluable for the intention-to-treat analysis. Underlying diseases were: 54.5% AML, 19.1% NHL, 13.6% ALL/AUL, 7.3% M.Hodgkin, 5.6% others. Initial diagnoses were 82.2% FUO, 9.1% pneumonia, 8.8% other documented infections.

FUO responded to therapy in Step I in 51.8%, in Step II in 59.1% and in Step III in 12/23 patients. The response rates as treated in Step II were 55.6% (Imi + Glp) vs 77.8% (Imi + Glp + AmB + 5FC), and 62.5% (Imi + Glp + Fluc).

The overall response including all modifications of therapy was 97.7% (FUO), 94.5% (bacteremia), 78.2% (pneumonia) and 88.8% (other documented infections); 6.5% patients died within the study period.

We conclude that the supplementation of amphotericin B after 72 h of unsuccessful empiric therapy improves the response rate in neutropenic fever of unknown origin.

Keywords

Vancomycin Cephalosporin Fluconazole Aminoglycoside Quinolone 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • O. A. Cornely
    • 1
  • W. Hiddemann
    • 2
  • H. Link
    • 3
  • G. Maschmeyer
    • 4
  • B. Glass
    • 5
  • D. Buchheidt
    • 6
  • M. Wilhelm
    • 7
  • Th. Büchner
    • 8
  • Th. Lipp
    • 9
  • R. Haas
    • 10
  • V. Heinemann
    • 11
  • M. Helmerking
    • 12
  • D. Adam
    • 13
  1. 1.Department I of Internal MedicineUniversität KölnKölnGermany
  2. 2.Department of Hematology and OncologyUniversität GöttingenGöttingenGermany
  3. 3.Department of Internal MedicineMedizinische Hochschule HannoverHannoverGermany
  4. 4.Department of Medical Oncology and Applied Molecular BiologyRobert-Rössle-KlinikGermany
  5. 5.Department II of Internal MedicineKielUniversität KielGermany
  6. 6.Department III of Internal MedicineKlinikum Mannheim der Universität HeidelbergMannheimGermany
  7. 7.Department of Internal MedicineUniversität WürzburgWürzburgGermany
  8. 8.Department of Internal MedicineUniversität MünsterMünsterGermany
  9. 9.Department I of Internal MedicineStädtisches Krankenhaus München-SchwabingMünchenGermany
  10. 10.Department of Internal Medicine VUniversität HeidelbergHeidelbergGermany
  11. 11.III. Medical Clinic, Klinikum GroßbadernUniversität MünchenMünchenGermany
  12. 12.PEG-StudienzentraleMünchenGermany
  13. 13.Children’s HospitalUniversität MünchenMünchenGermany

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