Maschmeyer, G., Beinert, T., Buchheidt, D., Cornely, O. A., Einsele, H., Heinz, W., . . . Mattiuzzi, G., (2009). Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients:  guidelines of the Infectious Diseases Working Party of the German Society of Haematology and Oncology. European Journal of Cancer, 45, 2462–2472.

Patients with febrile neutropenia who developed lung infiltrates were included.

In these guidelines, prospective clinical trials involving patients with febrile neutropenia and lung infiltrates were reviewed. 

Categories of Evidence Used: 

Strength of Evidence:

• (A) Good evidence to support a recommendation for use
• (B) Moderate evidence to support a recommendation for use  
• (C) Poor evidence to support a recommendation
• (D) Moderate evidence to support a recommendation against use
• (E) Good evidence to support a recommendation against use. 

Quality of Evidence:

• (I) Evidence from ≥1 well-designed clinical trials
• (II) Evidence from  ≥1 well-designed clinical trials, without randomization; from cohort or case-controlled analytic studies (preferably from >1 center); from multiple time series; or from dramatic results from uncontrolled experiments 
• (III) Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

Search Strategy

Databases searched were not specified.

Search keywords were lung infiltrate, treatment, aspergillosis, febrile neutropenia, and infection.

Patients receiving allogeneic hematopoietic stem cell transplantations were excluded.

Using systemic antifungals that are mold-active can improve outcomes for patients with neutropenia that has been present 10 or more days and who have developed fever and lung infiltrates (BII).  The recommended pre-emptive (i.e., administration of antimicrobial agents on the basis of clinical, imaging, or laboratory findings indicative of a particular infection in patients at risk for, but without proof of, this infection) antifungal therapy is voriconazole or liposomal amphotericin B.  Much of the content in this guideline is related to diagnosing and managing infections for neutropenic patients with lung infiltrates, not preventing infection, but reducing the risk of second and subsequent infections.

Specific pre-emptive therapy with voriconazole or liposomal amphotericin B in neutropenic patients can improve outcomes (BII).  Patients with cancer who are neutropenic and have respiratory failure–related lung infiltrates have better outcomes if transferred to intensive care units for care, including mechanical ventilation (AII).

Conflicts of Interest: Georg Maschmeyer has been a consultant for Gilead Sciences, MSD, Pfizer, Essex (Schering-Plough), Novartis, and Sanofi-Aventis and has been on the Speakers’ Bureau for Gilead Sciences, MSD, Pfizer, and Cephalon.  Dieter Buchheidt receives grants and research support from Gilead Sciences, MSD, Pfizer, and Essex (Schering-Plough) and has served on the Speakers’ Bureau for Gilead Sciences, MSD, Pfizer, and Essex (Schering-Plough).  Oliver Cornely has received grants and research support from Astellas, Basilea, Gilead Schinces, MSD, Pfizer, Essex (Schering-Plough), and Cephalon and has been a consultant for Astellas, Basilea, F2G, Gilead Sciences, MSD, Pfizer, Essex (Schering-Plough), and Cephalon and has served on the Speakers’ Bureau for Gilead Sciences, MSD, Pfizer, and Cephalon.  Hermann Einsele has been a consultant for MSD.  Werner Heinz has received grants and research support from Astellas, Gilead Sciences, MSD, Pfizer, and Essex (Schering-Plough); has been a consultant for Pfizer and Essex (Schering-Plough); and has served on the Speakers’ Bureau for Gilead Sciences, MSD, Pfizer, and Essex (Schering-Plough).  Claus Peter Heussel has received research support and grants from AstraZeneca, Bayer, Bracco, General Electric, Intermun, Merck, Novartis, Pfizer, PneumRx, PulmonRx, ROX, Essex (Schering-Plough), Siemens, Roche, Wyeth, and ZLB Behring and has been a consultant for AstraZeneca, Basilea, Baxter, Bracco, Essex (Schering-Plough), Systema, Gilead Sciences, Pfizer, Perceptive, Phillips, and Siemens.  Herbert Hof has been a consultant for Gilead Sciences and MSD and has served on the Speakers’ Bureau for Gilead Sciences, MSD, Pfizer, and Essex (Schering-Plough).  Michael Kiehl has been a consultant for Gilead Sciences and Essex (Schering-Plough) and has served on the Speakers’ Bureau for Gilead Sciences, MSD, and Essex (Schering-Plough).  Gloria Mattuizzi has received research support and grants from Astellas, MGI Pharma Inc., and Novartis.

Many of the interventions discussed were aimed at minimizing invasive fungal and other infections in patients, primarily neutropenic, who presented with lung infiltrates.  The pre-emptive B-II recommendation for antifungals lacked the strength of randomized, controlled trials.  The recommendation for intensive care to improve outcomes does not really address the prevention of infection.