A Prospective, Randomized Multicenter Trial of the Empirical Addition of Antifungal Therapy for Febrile Neutropenic Cancer Patients: Results of the Paul Ehrlich Society for Chemotherapy (PEG) Multicenter Trial II

Abstract

In neutropenic cancer patients with persistent fever the combination of antibiotics with AmB/5-FC is superior to salvage antibacterial therapy alone. There is no difference in efficacy between Pip and third generation Ceph given as initial empirical therapy in combination with an AMG.

Prophylactic Application of Nebulized Liposomal Amphotericin B in Hematologic Patients with Neutropenia

“…Forthisreason,earlyantifungalinterventionswithoutclearcutevidenceofafungalinfectionarecommonpractice,becauseanundetectedanduntreatedIFImayrapidlybecome life-threatening. This strategy is also supported by a recent publication [16].Inourpatients,systemicantifungaltherapy wasfrequentlyappliedempiricallybytreatingphysiciansin ambiguoussituations.ForstudiesofIFIprophylaxisorearly intervention, stringent diagnostic workup schedules using frequent determination of serum Aspergillus antigen and high-resolutionCTscanswithdefineddiagnosticcriteriaare helpful;however,unfortunatelythesecriteriahavenotbeen definedinsuchastrictmannerinourprotocolanddiagnosticshavebeensomewhatsparserintheearliercontrolgroup. However, even in recent clinical trials with standardized diagnostics,largepatientnumberswereneededtoshowthe advantageofaprophylacticantimycoticstrategy,inthatcase oralposaconazolesolution [17].Therefore,inretrospect,the absence of a significant difference in proven and probable IFIbetweenthestudyarmandthehistoricalcontrolisnot surprising.Inaddition,theresultsmayalsobebiasedagainst a positive result of our study by a somewhat increasing empiricaluseofantifungalsinourinstitutionoverthestudy period.ThisismainlyduetotheincreasinguseofCTscans allowingearlierandmoresensitivedetectionofpulmonary infiltratesandduetotheapprovalofvoriconazolewhichis applied more generously due to fewer side effects when comparedtosystemicAmBd.…”

Diagnosis and Antimicrobial Therapy of Lung Infiltrates in Febrile Neutropenic Cancer Patients

“…Apart from broad-spectrum antibacterial treatment established for FUO [2], early coverage of filamentous fungi, predominantly Aspergillus spp., is recommended in febrile patients with severe neutropenia lasting for more than 10 days and LI [3,11]. Voriconazole (6 mg/kg every 12 h day 1, 4 mg/kg every 12 h thereafter) or liposomal amphotericin B (3 mg/kg daily) are agents of choice in this setting [14•], and liposomal amphotericin B is preferable in patients in whom mucormycosis is suspected as well as in those who have been pretreated with voriconazole or posaconazole.…”

“…Voriconazole (6 mg/kg every 12 h day 1, 4 mg/kg every 12 h thereafter) or liposomal amphotericin B (3 mg/kg daily) are agents of choice in this setting [14•], and liposomal amphotericin B is preferable in patients in whom mucormycosis is suspected as well as in those who have been pretreated with voriconazole or posaconazole. This recommendation is based on the prospective clinical trials in febrile neutropenic patients with LI [3,11], showing a significant benefit from prompt [11] as compared to delayed [3] mold-active antifungal therapy, as well as on trials in patients with proven or probable or proven, probable and possible aspergillosis [54] treated with voriconazole, and on studies on mold infections in immunosuppressed patients treated with liposomal amphotericin B [55]. The place for echinocandin antifungals in this situation remains to be defined.…”

“…The assumption that a high proportion of fungal pathogens is involved is backed up by the observation that success rates under broad-spectrum antibacterial treatment are below 30% [3], whereas prompt addition of mold-active systemic antifungals in all febrile, severely neutropenic patients with LI increases the response rate to up to 78% [11]. Beyond this, the incidence of LI in acute leukemia patients could be reduced to 0% by voriconazole prophylaxis as compared with 33% under placebo [12].…”

Infektionen als Ursache von Fieber unklarer Genese

“…Weiterfiebernde Patienten ohne Erregernachweis und Fokus sprechen zu etwa 50% auf eine geänderte empirische antibakterielle Therapie an, etwa weitere 25% auf eine empirische antimykotische Therapie [15]. Hiernach ist von einem entsprechenden Erregerspektrum auszugehen.…”