Pagano Livio, Verga Luisa, Busca Alessandro, Martino Bruno, Mitra Maria Enza, Fanci Rosa, Ballanti Stelvio, Picardi Marco, Castagnola Carlo, Cattaneo Chiara, Nadali Gianpaolo, Nosari Annamaria, Candoni Anna, Caira Morena, Salutari Prassede, Lessi Federica, Aversa Franco, Tumbarello Mario
Istituto di Ematologia, Università Cattolica del Sacro Cuore, Roma, Italy
Unità di Ematologia, Università di Milano-Bicocca, Ospedale S.Gerardo, Monza, Italy.
J Antimicrob Chemother. 2014 Nov;69(11):3142-7. doi: 10.1093/jac/dku227. Epub 2014 Jun 19.
To investigate the incidence, treatment and outcome of breakthrough invasive fungal infections (IFIs) in adult acute myeloid leukaemia (AML) patients after posaconazole prophylaxis.
From January 2010 to April 2012, all consecutive patients with newly diagnosed AML were prospectively registered at 33 participating Italian centres. All cases of IFIs occurring within 30 days after the end of the first induction chemotherapy were recorded. The strategy of antifungal treatment (empirical, pre-emptive or targeted) and the drugs used were analysed. ClinicalTrials.gov code: NCT01315925.
In total, 1192 patients with newly diagnosed AML were enrolled in the study, of whom 510 received posaconazole prophylaxis and were included in the present analysis. Of these patients, 140 (27%) needed systemic antifungal treatment. Among the 127 evaluable cases, an empirical approach was utilized in 102 patients (80%), a pre-emptive approach in 19 patients (15%) and targeted therapy in 6 patients (5%). Only five patients died of IFIs (three in the empirical group and two in the targeted group; 4%). A critical review of IFI diagnoses at 30 days demonstrated that among the patients treated empirically, ∼30% were not affected by IFIs but rather only by fever of unidentified origin. A comparison between the empirical and the pre-emptive groups showed no significant differences regarding the attributable and overall mortalities.
This study confirms that posaconazole prophylaxis reduces the incidence of breakthrough IFIs and does not modify the efficacy of subsequent systemic antifungal treatment, regardless of the approach (empirical or pre-emptive) or the antifungal drug used.
调查接受泊沙康唑预防治疗的成年急性髓系白血病（AML）患者中突破性侵袭性真菌感染（IFI）的发生率、治疗情况及转归。
2010年1月至2012年4月，所有新诊断AML的连续患者在33个参与研究的意大利中心进行前瞻性登记。记录首次诱导化疗结束后30天内发生的所有IFI病例。分析抗真菌治疗策略（经验性、抢先性或靶向性）及所用药物。ClinicalTrials.gov编号：NCT01315925。
共有1192例新诊断AML患者纳入本研究，其中510例接受泊沙康唑预防治疗并纳入本分析。这些患者中，140例（27%）需要全身抗真菌治疗。在127例可评估病例中，102例（80%）采用经验性治疗方法，19例（15%）采用抢先性治疗方法，6例（5%）采用靶向治疗。仅5例患者死于IFI（经验性治疗组3例，靶向治疗组2例；4%）。对30天时IFI诊断的严格审查表明，在接受经验性治疗的患者中，约30%未受IFI影响，而是仅受不明原因发热影响。经验性治疗组和抢先性治疗组在归因死亡率和总死亡率方面无显著差异。
本研究证实，无论采用何种方法（经验性或抢先性）或使用何种抗真菌药物，泊沙康唑预防治疗均可降低突破性IFI的发生率，且不改变后续全身抗真菌治疗的疗效。
