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)


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.


Unknown Origin Empiric Therapy Neutropenic Patient Febrile Episode Neutropenic Fever 
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  1. 1.
    Bodey GP, Buckley M, Sathe YS, Freireich EJ (1996) Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Int Med 64 (2): 328–40Google Scholar
  2. 2.
    Link H, Maschmeyer G, Meyer P, Hiddemann W, Stille W, Helmerking M, Adam D (1994) Interventional antimicrobial therapy in febrile neutropenic patients. Ann Hematol 69: 231–43PubMedCrossRefGoogle Scholar
  3. 3.
    Hughes WT, Pizzo PA, Wade JC, Armstrong D, Webb CD, Young LS (1992) Evaluation of new anti-infective drugs for the treatment of febrile episodes in neutropenic patients. Clin Inf Dis 15 (Suppl 1): S206–15CrossRefGoogle Scholar
  4. 4.
    Cordonnier C, Herbrecht R, Pico JL, Gardembas M, Delmer A, Delain M, Moreau P, Ladeb S, Nalet V, Rollin C, Gres JJ (1997) Cefepime/amikacin versus ceftazidime/amikacin as empirical therapy for febrile episodes in neutropenic patients: a comparative study. Clin Inf Dis 24: 41–51CrossRefGoogle Scholar
  5. 5.
    Cometta A, Zinner S, de Bock R, Calandra T, Gaya H, Klastersky J, Langenaeken J, Paesmans M, Viscoli C, Glauser MP (1995) Piperacillintazobactam plus amikacin versus cef-tazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. Antimicrob Agents Chemoth 39 (2): 445–52Google Scholar
  6. 6.
    de Pauw BE, Deresinski SC, Feld R, Lane-Allman EF, Donnelly JP (1994) Ceftazidime compared with piperacillin and tobramycin for the empir- ic treatment of fever in neutropenic patients with cancer. Ann Int Med 120: 834–44PubMedGoogle Scholar
  7. 7.
    Cornelissen JJ, de Graeff A, Verdonck LF, Branger T, Rozenberg-Arska M, Verhoef J, Dekker AW (1997) Imipenem versus gentamicin combined with either cefuroxime or cephalotin as initial therapy for febrile neutropenic patients. Antimicrob Agents Chemoth 36 (4): 801–7Google Scholar
  8. 8.
    Martino P, Micozzi A, Gentile G, Raccah R, Girmenia C, Mandelli F (1992) Piperacillin plus amikacin vs. piperacillin plus amikacin plus teicoplanin for empirical treatment of febrile episodes in neutropenic patients receiving quinolone prophylaxis. Clin Inf Dis 15: 290–4CrossRefGoogle Scholar
  9. 9.
    Bodey GP, Rolston K, Jones P, Alvarez ME, Fain-stain V, Steelhammer L (1986) Imipenem/cilastatin as secondary therapy for infections in cancer patients. J Antimicrob Chemoth 18 (Suppl E): 161–6Google Scholar
  10. 10.
    Cony-Makhoul P, Brossard G, Marit G, Pellegrin JL, Texier-Maugein J, Reiffers J. A prospective study comparing vancomycin and teicoplanin as second-line empiric therapy for infection in neutropenic patients. Br J Haematol 76 (Suppl 2 ): 35–40.Google Scholar
  11. 11.
    Maschmeyer G, Link H, Hiddemann W, Meyer P, Helmerking M, Eisenmann E, Schmitt J, Adam D (1994) Empirische antimikrobielle Therapie bei neutropenischen Patienten. Med Klinik 89 (3): 114–23Google Scholar
  12. 12.
    Bodey GP, Alvarez ME, Jones PG, Rolston KVI, Steelhammer L, Fainstain V (1986) Imipenemcilastatin as initial therapy for febrile cancer patients. Antimicrob Agents Chemoth 30 (2): 211–4Google Scholar
  13. 13.
    Boogaerts MA, Demuynck H, Mestdagh N, Verbist L, Goldstone AH, Kelsey HC, Machin S, de Pauw BE, Donnelly JP, Raemaekers JMM, Atkinson G, Williams KJ (1995) Equivalent efficacies of meropenem and ceftazidime as empiric monotherapy of febrile neutropenic patients. J Antimicrob Chemoth 36: 185–200Google Scholar
  14. 14.
    Behre GF, Link H, Maschmeyer G, Meyer P, Paaz U, Wilhelm M, Hiddemann W (1996) Meropenem monotherapy exhibits comparable efficacy to combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients. Antiinfect Drugs Chemoth 14: 34Google Scholar

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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