Risk factors for early mortality in haematological malignancy patients with pulmonary mucormycosis

Abstract

Summary Pulmonary mucormycosis (PM) is a life‐threatening opportunistic mycosis with a variable clinical evolution and few prognostic markers for outcome assessment. Several clinical risk factors for poor outcome present at the diagnosis of PM were analyzed in 75 consecutive hematology patients from 2000–2012. Significant variables (P < 0.1) were entered into a multivariate Cox‐proportional hazard regression model adjusting for baseline APACHE II to identify independent risk factors for mortality within 28 days. Twenty‐eight of 75 patients died within 4‐week follow up. A lymphocyte count < 100/mm3 at the time of diagnosis (adjusted hazard ratio 4.0, 1.7–9.4, P = 0.01) and high level of lactate dehydrogenase (AHR 3.7, 1.3–10.2, P = 0.015) were independent predictors along with APACHE II score for 28‐day mortality. A weighted risk score based on these 3 baseline variables accurately identified non‐surviving patients at 28 days (area under the receiver‐operator curve of 0.87, 0.77–0.93, P < 0.001). A risk score > 22 was associated with 8‐fold high rates of mortality (P < 0.0001) within 28 days of diagnosis and median survival of 7 days versus ≥28 days in patients with risk scores ≤22. We found that APACHE II score, severe lymphocytopenia and high LDH levels at the time of PM diagnosis were independent markers for rapid disease progression and death.

Isavuconazole: Pharmacology, Pharmacodynamics, and Current Clinical Experience with a New Triazole Antifungal Agent

“…Although Aspergillus species continue to represent most of the invasive mold infections, a gradual increase in the reported prevalence of Mucorales and other uncommon but difficult‐to‐treat molds has been reported in patients in several cancer treatment centers . Despite the availability of current antifungal therapy, the outcomes associated with IFD in these highly immunocompromised patients remain dire, most notably in patients with Mucorales, where current mortality rates may reach 80% .…”

“…Although Aspergillus species continue to represent most of the invasive mold infections, a gradual increase in the reported prevalence of Mucorales and other uncommon but difficult‐to‐treat molds has been reported in patients in several cancer treatment centers . Despite the availability of current antifungal therapy, the outcomes associated with IFD in these highly immunocompromised patients remain dire, most notably in patients with Mucorales, where current mortality rates may reach 80% . Pharmacologic treatment of invasive mucormycosis consists primarily of case series–supported use of lipid formulations of amphotericin B as well as posaconazole, although a few case reports also presented preliminarily positive results with isavuconazole in the salvage setting .…”

“…5,47 Despite the availability of current antifungal therapy, the outcomes associated with IFD in these highly immunocompromised patients remain dire, most notably in patients with Mucorales, where current mortality rates may reach 80%. [47][48][49] Pharmacologic treatment of invasive mucormycosis consists primarily of case series-supported use of lipid formulations of amphotericin B as well as posaconazole, although a few case reports also presented preliminarily positive results with isavuconazole in the salvage setting. [50][51][52][53][54] The VITAL trial (ClinicalTrials.gov registry number NCT00634049) evaluated the use of isavucona-zole for the treatment of proven or probable invasive aspergillosis in patients with renal impairment as well as IFD caused by rare molds, yeasts, or dimorphic fungi and in patients with or without renal function abnormalities.…”

ESCMID† and ECMM‡ joint clinical guidelines for the diagnosis and management of mucormycosis 2013

“…In patients with haematological malignancy mucormycosis was less common than invasive aspergillosis, but mucormycosis independently predicted death in these patients [22,23]. Lymphocytopenia has recently been identified as independently predicting death in this setting [24]. Mortality rates in patients with mucormycosis remain high and in recent reports they ranged from 24% to 49% [7,19,25,26].…”

Development of new strategies for early diagnosis of mucormycosis from bench to bedside

“…Mucormycosis is an important emerging fungal infection, associated with high morbidity and mortality. [1][2][3][4] The recent Schueler Foundation Symposium conducted in Chicago, Illinois in the United States underscored the suffering, tragedy and challenges of mucormycosis through a comprehensive series of papers on its epidemiology, pathogenesis, clinical manifestations, diagnosis and treatment. 5 The symposium underscored the need for new advances in diagnosis, treatment and prevention as the key to improving survival.…”