Pulmonary infiltrations in febrile patients with neutropenia. Risk factors and outcome under empirical antimicrobial therapy in a randomized multicenter study

Cancer. 1994 May 1;73(9):2296-304. doi: 10.1002/1097-0142(19940501)73:9<2296::aid-cncr2820730910>3.0.co;2-7.


Background: Different empirical approaches to antimicrobial treatment of lung infiltrates in patients with neutropenia were studied within a prospective, randomized multicenter trial.

Methods: Patients with neutropenia with hematologic malignancies and fever of 38.5 degrees C or higher associated with newly diagnosed lung infiltrates were randomized for an initial therapy with acylaminopenicillin plus aminoglycoside (Group A), third-generation cephalosporin plus aminoglycoside (Group B), or the double beta-lactam combination (Group C), each in combination with rifampin. Nonresponders were given empirical amphotericin B plus 5-fluorocytosine beginning on day 4, day 5, or day 6 under study.

Results: Of 295 patients entered, 91.2% were evaluable. Complete response was obtained in 61.3% with no significant difference between treatment groups. The addition of rifampin did not improve treatment results. Only 27.1% of patients achieved a complete response by antibiotic therapy without additional antifungal therapy. Fungi dominated in cases of microbiologically documented infections and were associated with a poorer outcome compared with bacterial pneumonias. The trend of leukocyte counts under study had a highly significant effect on the outcome of infection.

Conclusions: Lung infiltrates in febrile patients with neutropenia represent a high risk of treatment failure. Persistent neutropenia has a significantly adverse effect on the outcome of infection. Incorporation of systemic antifungal agents into first-line therapy, particularly in selected high-risk subgroups, might improve future treatment results. The quality of diagnostic techniques to establish the etiology of pulmonary infiltrates needs to be improved.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use*
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / therapeutic use*
  • Bacterial Infections / complications
  • Bacterial Infections / drug therapy*
  • Female
  • Fever / complications*
  • Humans
  • Leukemia / drug therapy
  • Lung Diseases / complications
  • Lung Diseases / drug therapy*
  • Lung Diseases / microbiology*
  • Lung Diseases, Fungal / complications
  • Lung Diseases, Fungal / drug therapy*
  • Lymphoma, Non-Hodgkin / drug therapy
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy
  • Neutropenia / complications*
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Antifungal Agents