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Inicio Enfermedades Infecciosas y Microbiología Clínica Mortality risk factors in patients with zygomycosis: a retrospective and multice...
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Vol. 29. Núm. 4.
Páginas 263-268 (Abril 2011)
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Vol. 29. Núm. 4.
Páginas 263-268 (Abril 2011)
Original article
DOI: 10.1016/j.eimc.2010.09.008
Acceso a texto completo
Mortality risk factors in patients with zygomycosis: a retrospective and multicentre study of 25 cases
Factores de riesgo de mortalidad en pacientes con zigomicosis: un estudio retrospectivo y multicéntrico de 25 casos
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Andreu Llorentea,
Autor para correspondencia
allorente.hj23.ics@gencat.cat

Corresponding author.
, Ignacio Perez-Valerob, E. Garcíac, I. Herasd, V. Frailee, P. Garcíaf, J. Lópezg, M. Salaverth, F. Bobilloi
a Servicio de Hematología, Hospital Joan XXIII, IISPV, Tarragona, Spain
b Servicio Medicina Interna, Hospital Universitario La Paz, Madrid, Spain
c Enfermedades Infecciosas, Clínica Universitaria de Navarra, Pamplona, Navarra, Spain
d Servicio Hematología, Hospital General Universitario Morales Messeguer, Murcia, Spain
e Servicio Hematología, Hospital Universitario “Río Hortega”, Valladolid, Spain
f Servicio Hematología, Hospital Clínico San Carlos, Madrid, Spain
g Servicio Hematología, Hospital Universitario Ramón y Cajal, Madrid, Spain
h Servicio Hematología, Hospital Universitario La Fe, Valencia, Spain
i Servicio Medicina Intensiva, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
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Tablas (3)
Table 1. Demographic and clinical characteristics.
Table 2. Use of antifungals in 25 cases of definite or probable zygomycosis.
Table 3. Univariate analysis of risk factors for mortality among 25 patients with proven or probable zygomycosis.
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Abstract
Aim

To investigate mortality risk factors in patients with zygomycosis.

Patients and Methods

Retrospective case history review of patients diagnosed with proven zygomicosis in 17 centres in Spain. We compared demographics and risk factors in patients who survived, and in those who died.

Results

We identified twenty-five patients with proven zygomycosis. The primary site of infection was rhino-orbito-cerebral (28%) and disseminated (20%) or cutaneous/soft infections (20%) of the patients. Eleven patients (44%) received preemptive or empirical antifungal treatment; of these patients, 4 received liposomal amphotericin B, 1 received amphotericin B lipid complex, and 6 received other antifungals. The overall mortality rate was 72%. In the univariate analysis factors associated with an increased risk of death were the presence of a haematological malignancy (P=.03), neutropenia (P=.03) and monocytopenia (P=.008).

Conclusion

Our study supports previous research that has documented a high mortality rate among patients with invasive zygomycosis, especially among those with an underlying haematological malignancy, and the need for a rapid initiation of an effective antifungal treatment.

Keywords:
Zygomycosis
Mortality
Risk factors
Liposomal amphotericin B
Resumen
Objetivo

Investigar los factores de riesgo de mortalidad en pacientes con zigomicosis.

Pacientes & Métodos

Revisión retrospectiva de pacientes diagnosticados de zigomicosis documentada en 17 centros en España, comparando los datos demográficos y los factores de riesgo entre los pacientes que sobrevivieron y aquellos que fallecieron.

Resultados

Se identificaron 25 pacientes con zigomicosis probada. El lugar primario de la infección fue rino-órbito-cerebral (28%) e infecciones diseminadas o cutáneas / de tejidos blandos en el 20% de los pacientes cada una. Once pacientes (44%) recibieron tratamiento antifúngico anticipado o empírico; de estos pacientes, cuatro de ellos recibieron anfotericina B liposomal, un paciente recibió anfotericina B complejo lipídico y 6 pacientes recibieron otros antifúngicos. La tasa de mortalidad global fue del 72%. En el análisis univariado, los factores asociados a un mayor riesgo de muerte fueron la presencia de enfermedad hematológica maligna (p=0,03), neutropenia (p=0,03) y monocitopenia (p=0,008).

Conclusión

Los datos de nuestro estudio concuerdan con los de trabajos previos que habían documentado una elevada tasa de mortalidad en pacientes con zigomicosis invasiva, especialmente en aquellos con enfermedad hematológica maligna subyacente, y la necesidad de instaurar rápidamente un tratamiento antifúngico eficaz.

Palabras clave:
Zigomicosis
Mortalidad
Factores de riesgo
Anfotericina B
Texto completo
Introduction

Zygomycosis is a rare but devastating invasive fungal infection (IFI) caused by the agents of Zygomycetes, most commonly by those of the order Mucorales.1 Zygomycosis is becoming increasingly important among certain populations, such as recipients of haematopoietic stem cell or solid-organ transplants and among patients with haematological malignancies.1,2 In these populations, reports of zygomycosis have been increasing since the 1990s,2,3 and zygomycosis has become the third leading cause of IFI (following invasive aspergillosis and invasive candidiasis).1,4 Although it has been proposed that this increase in the frequency of zygomycosis might be due to the introduction of voriconazole, an antifungal not active against Zygomycetes, for the prophylaxis of opportunistic fungal infections,5,6 this association is not yet well-established.3

The clinical manifestations of invasive zygomycosis include tissue necrosis from invasion of blood vessels and subsequent thrombosis, and the most common clinical presentations are a rhinocerebral syndrome and pulmonary infection.1 A definitive diagnosis of zygomycosis can be difficult to reach and requires histopathological confirmation.1 The adequate management of zygomycosis requires a multifaceted approach that includes the control or reversal of the underlying risk factors (such as diabetic ketoacidosis or immunosuppression), surgical debridement, and the use of systemic antifungal therapy.1,7 Amphotericin B, particularly the liposomal formulation, is the mainstay for the treatment of this IFI.7-9 More recently, posaconazole has also been shown to be active against zygomycosis,10 with some evidence of its clinical efficacy as a salvage therapy11,12 but without the same spectrum of coverage as amphotericin B.

Zygomycosis has a poor prognosis. Despite the introduction of amphotericin B, mortality in patients with zygomycosis is high and has remained almost unchanged in the last four decades.2 According to data from the largest series of patients with zygomycosis,2 the current mortality rate is close to 40%, and it can be as high as 76% in cases of pulmonary zygomycosis.2 However, a smaller study examined 16 cases of proven zygomycosis and found an overall mortality rate of only 25%.13 These different mortality rates may be due to differences in the clinical characteristics of the cases or in their management. To better manage this serious infection, it is important to know what factors are associated with a greater risk of mortality.

Our study was aimed at investigating risk factors for mortality in a retrospective case series of patients with proven zygomycosis.

Patients and methods

We performed a retrospective review of the clinical history of all patients with zygomycosis who were seen in seventeen health centres in Spain between January 1, 2007 and June 30, 2008. Patients were included in the study only if they had no previous history of zygomycosis and had been diagnosed with proven zygomycosis according to the EORTC/MSG criteria.14

A standardised case report form was used to extract information from the medical records. Demographic information, including age and sex, and clinical data were recorded. The clinical information collected included (1) clinical outcome and, in cases of death, the relationship between this outcome and the IFI; (2) site of the infection (categorized as sinusitis, sinopulmonary, pneumonia, rhino-orbito-cerebral, disseminated, and cutaneous/soft-tissue infection); (3) underlying conditions and APACHE II at the time of diagnosis; (4) risk factors for zygomycosis within one month of the diagnosis (including type of bone marrow transplantation (BMT), graft-versus-host disease grade, use of immunosuppressive therapy, cytomegalovirus infection, diagnosis of diabetes mellitus, hyperglycaemia defined as a glucose level equal to or greater than 200g/dL, neutropenia defined as a neutrophil count equal to or lower than 500 cells/mm3, lymphopenia, monocytopenia, acidosis defined as a pH value lower than 7.35, malnutrition defined as a serum albumin level equal to or lower than 3g/dL, use of corticosteroids, use of tumour necrosis factor inhibitors, serum iron level, serum ferritin level, and use of deferoxamine therapy); (5) use of an antifungal agent within three months of the diagnosis as either prophylactic, pre-emptive, empirical, or targeted therapy; and (6) whether or not the patient underwent surgical debridement.

Demographic and clinical characteristics were described using the mean, median and standard deviation for continuous measures and the frequency and percentage for categorical variables. The demographic information and risk factors of patients who survived were compared with the information of those who died in a univariate analysis using the Student's t-test, Chi-squared test, or Fisher's exact test where appropriate. In addition, a stepwise logistic regression analysis was planned to explore variables independently associated with mortality. All statistical analyses were performed using SPSS version 15.0 (SPSS Inc, Chicago, Illinois). All analyses were two-tailed and were considered significant if P<.05.

Results

Throughout the 18-months study period, we identified twenty-five patients with proven zygomycosis. Patients were predominantly male (80%) with a median age of 46 years. The most common underlying conditions were haematological malignancies (52%) and diabetes mellitus (32%). At the time of diagnosis, nearly one third of the patients presented with rhino-orbito-cerebral infections; 20% of the patients presented with disseminated infections and 20% presented with cutaneous/soft-tissue infections. The median of the follow-up duration was 2 months (interquartile range 0.9 to 5.5) and the mean (SD) was 5.2 (7.1) months. Mean time between the beginning of the symptoms and the diagnosis, independently of patient outcome, was 8 days. In all cases, targeted antifungal treatment was started in the first 24h after a confirmatory diagnosis. Patient demographics, underlying conditions, infection locations and case history are presented in Table 1.

Table 1.

Demographic and clinical characteristics.

Characteristic  N=25 
Age, years   
Mean (SD)  47.4 (14.1) 
Median (Range)  46 (21-76) 
Sex, n (%)   
Male  20 (80) 
Female  5 (20) 
Underlying condition at the time of the infection, n (%)
Hematological malignancy  13 (52) 
Allogeneic transplant  5 (2) 
Autologous transplant  1 (4) 
Diabetes  8 (32) 
Solid organ transplantation  3 (12) 
Trauma  2 (8) 
Solid tumor  2 (8) 
Rheumatological  1 (4) 
None  1 (4) 
Location of the infection, n (%)
Rhinoorbitocerebral  7 (28) 
Disseminated  5 (20) 
Cutaneous/soft tissue  5 (20) 
Gastrointestinal  3 (12) 
Sinusitis+Rhinoorbitocerebral  2 (8) 
Other  3 (12) 
Case documentation
Histopathological assessment  11 (44) 
Culture  7 (28) 
Histopathological assessment and culture  7 (28) 

SD: standard deviation.

Eleven patients (44%) received pre-emptive or empirical antifungal treatment; of these, 4 (16%) received liposomal amphotericin B (in one case, this treatment was combined with caspofungin), 1 (4%) received amphotericin B lipid complex, and 6 (24%) received other antifungals (Table 2). These other antifungals were not effective against zygomycosis. The rationale to start empirical or pre-emptive antifungal treatment was based on clinical suspicion by the clinician in charge of the patient. One patient did not receive any antifungal treatment, and the remaining thirteen patients (52%) commenced antifungal treatment after they were diagnosed with zygomycosis. The most common antifungals, used either alone or in combination as targeted treatment, were liposomal amphotericin B (n=19, 76%), posaconazole (n=7, 28%), caspofungin (n=6, 24%), voriconazole (n=3, 12%), and amphotericin B lipid complex (n=1, 4%). Table 2 shows the antifungals received by each patient during the entire follow-up period. Seventeen patients (68%) underwent surgical debridement.

Table 2.

Use of antifungals in 25 cases of definite or probable zygomycosis.

Patients1  Type of therapya  Antifungal  Treatment Duration (Days)  Outcome  Surgery 
CASE 1  Empirical  Voriconazole  Death  No 
  Preemptive  Ambisome+Caspofungin  10     
  Targeted (1st)  Ambisome+Posaconazole     
  Targeted (2nd)  Posaconazole     
CASE 2  Targeted (1st)  Ambisome  30  Alive  Yes 
  Targeted (2nd)  Posaconazole  28     
CASE 3  Empirical  Fluconazole  31  Alive  Yes 
  Preemptive  Ambisome     
  Targeted (1st)  Ambisome  112     
  Targeted (2nd)  Posaconazole  40     
CASE 4  Prophylaxis  Fluconazole  Death  Yes 
  Preemptive  Caspofungin  13     
  Targeted (1st)  Ambisome  16     
CASE 5  Empirical  Voriconazole  Death  No 
  Empirical  Voriconazole+Caspofungin     
CASE 6  Prophylaxis  Fluconazole  Death  No 
  Preemptive (without symptoms)  Caspofungin     
  Pre-emptive  Caspofungin+Voriconazole     
CASE 7  Prophylaxis  Fluconazole  12  Death  No 
  Empirical  Caspofungin  17     
  Targeted  Caspofungin+Voriconazole     
CASE 8  Targeted  Ambisome  32  Alive  Yes 
CASE 9  Prophylaxis  Fluconazole  70  Death  Yes 
  Targeted (1st)  Abelcet     
  Targeted (2nd)  Posaconazole+Ambisome  19     
  Targeted (3rd)  Ambisome  35     
  Targeted (4th)  Posaconazole  47     
CASE 10  Targeted  Ambisome  31  Alive  Yes 
CASE 11  Prophylaxis  Itraconazole  18  Death  No 
  Empirical  Caspofungin     
  Targeted  Caspofungin+Voriconazole     
CASE 12  Targeted (1st)  Ambisome  43  Death  Yes 
  Targeted (2nd)  Posaconazole  16     
CASE 13  Targeted  Ambisome  101  Alive  Yes 
CASE 14  Targeted  Ambisome  17  Alive  Yes 
CASE 15  Pre-emptive  Fluconazole  Death  No 
  Targeted  Ambisome     
CASE 16  Prophylaxis  Fluconazole  14  Death  Yes 
  Pre-emptive  Abelcet     
  Pre-emptive  Abelcet+Caspofungin     
  Targeted (1st)  Caspofungin+Ambisome  19     
  Targeted (2nd)  Ambisome+Posaconazole  66     
  Targeted (3rd)  Ambisome  10     
CASE 17  Targeted  Ambisome  Death  Yes 
CASE 18  Pre-emptive  Ambisome  Death  No 
  Targeted  Ambisome+Posaconazole  24     
CASE 19  Prophylaxis  Fluconazole  15  Death  Yes 
  Targeted (1st)  Ambisome+Caspofungin  34     
  Targeted (2nd)  Caspofungin  79     
CASE 20  Prophylaxis  Itraconazole  13  Death  No 
  Targeted (1st)  Caspofungin     
  Targeted (2nd)  Ambisome+Caspofungin     
CASE 21  Prophylaxis  Fluconazole  94  Death  Yes 
  Targeted (1st)  Ambisome     
  Targeted (2nd)  Caspofungin+Ambisome  11     
CASE 22  Targeted (1st)  Ambisome  59  Death  Yes 
CASE 23  Empirical  Ambisome  12  Alive  Yes 
  Targeted  Ambisome+Voriconazole  12     
CASE 24  Prophylaxis  Itraconazole  41  Death  Yes 
  Targeted  Ambisome  45     

NOTE. One patient did not receive any antifungal agent.

a

Except otherwise indicated pre-emptive treatment was initiated in the presence of symptoms.

The overall mortality rate in our cohort was 72% (18 of 25 patients). Mortality was high between patients treated empirically with an ineffective drug (80%). The only case treated empirically with an active antifungal against zygomycosis survived. The mortality rate was similar between patients treated empirically (67%) and patients who received a targeted treatment (70%). Zygomycosis was the cause of death in 13 of the 18 patients who died (52%) and contributed to the death of four other patients (16%). In the univariate analysis (Table 3) the factors associated with an increased risk of death were the presence of an underlying haematological malignancy (P=.03), neutropenia (P=.03) and monocytopenia (P=.008). We did not run a multivariate analysis since the same patients had both haematological malignancies and neutropenia, and the monocytopenia variable had a zero cell count.

Table 3.

Univariate analysis of risk factors for mortality among 25 patients with proven or probable zygomycosis.

Characteristica  Survival N=Death N=18  P-value 
Age, mean (SD)  48.2 (14.2)  45.3 (14.8)  .657 
Sex      .274 
Male  7 (100)  13 (72.2)   
Female  0 (0)  5 (27.8)   
Underlying disease
Haematological malignancy  1 (14.3)  12 (66.7)  .030 
Solid tumor  1 (14.3)  1 (5.6)  .490 
Solid organ transplantation  1 (14.3)  3 (16.7)  <.999 
Other  5 (71.4)  7 (38.9)  .202 
Active haematological malignancyb  1 (100)  10 (83.3)  >.999 
APACHE II ≥ 16b  3 (75)  7 (50)  .588 
Currently admitted at the ICU  2 (28.6)  3 (16.7)  .597 
Previously admitted at the ICU  1 (14.3)  0 (0)  .280 
Bone marrow transplantation
None  7 (100)  12 (66.7)   
Autologous  0 (0)  1 (5.6)  .215 
Allogeneic  0 (0)  5 (27.8)   
GvHD gradeb
I-II  0 (0)  1 (20) 
III-IV  0 (0)  1 (20) 
Immunosuppressive therapy  2 (28.6)  11 (61.1)  .202 
Cytomegalovirus infection  1 (14.3)  2 (11.1)  >.999 
Diabetes mellitus  2 (28.6)  6 (33.3)  >.999 
Hyperglycaemia ≥200 g/dL  3 (42.9)  8 (44.4)  >.999 
Neutropenia (WBC≤500 cells/mm31 (14.3)  12 (66.7)  .030 
Neutropenia (≥10 days)b  1 (100)  10 (83.3)  >.999 
Lymphopenia  3 (42.9)  12 (66.7)  .378 
Monocytopenia  0 (0)  11 (61.1)  .008 
Acidosis (pH ≤7.35)  3 (42.9)  3 (17.6)  .307 
Malnutrition (Albumin ≤ 3 g/dL)  3 (42.9)  9 (50)  >.999 
Use of corticosteroids therapy  3 (42.9)  10 (55.6)  .673 
Use of anti-tumour necrosis factor therapy  0 (0)  1 (5.6)  >.999 
Use of deferoxamine therapy  0 (0)  0 (0) 
Sinusitis  1 (14.3)  1 (5.6)  .490 
Surgical procedures  1 (100)  10 (58.8)  .057 
Treatment with liposomal amphotericin Bb
Early treatment (≤1 day)  6 (85.7)  9 (69.2)  .613 
Delayed treatment (>1day)  1 (14.3)  4 (30.8)   
Type of infection
Hospital-acquired  2 (28.6)  10 (55.6)  .378 
Community-acquired  5 (71.4)  8 (44.4)   
Breakthrough zygomycosis  0 (0)  3 (17.6)  .530 
Prophylactic, pre-emptive or empirical treatment with liposomal amphotericin B  1 (14.3)  3 (16.7)  >.999 

GvHD: graft-versus-host-disease; ICU: intensive care unit; SD: standard deviation.

a

All data are presented as number (%) of patients except otherwise indicated.

b

Percentage of patients calculated over valid or available cases.

Discussion

In our cohort of 25 patients with proven zygomycosis the overall mortality rate was 72%. This rate is much higher than the 40% mortality rate found by Roden et al.2 in the largest review of reported zygomycosis cases over the last several decades. However, the primary sites of infection among patients in our cohort differed from those in the cases reported by Roden et al. In their review, Roden et al. found that 58% of 929 patients presented with either sinus (39%) or cutaneous (19%) infections; these locations were associated with the lowest mortality rates (46% and 31%, respectively).2 In our sample, two-thirds of the patients had rhino-orbito-cerebral, disseminated, or gastrointestinal infection; Rhoden et al. found that infections in these locations were associated with higher mortality rates (from 62% in the case of rhinocerebral infection to 85% in the case of gastrointestinal infection.2 The most common underlying disease in our study was haematological malignancy, which was present in over half of the patients. Mortality rates reported in the literature in patients with zygomycosis and underlying haematological malignancies are similar to those seen in our study.15,16 In a retrospective study of 59 patients with haematological malignancies and proven or probable zygomycosis, the overall mortality rate was 79.7%; in 41 of the cases (69.5%) the death was attributed to the IFI.15 In another review of 120 cases of zygomycosis with an underlying haematological or oncological disorder, the overall mortality rate was 61.6%; 68 of the patients (56.7%) died from either zygomycosis or a combination of zygomycosis and an additional factor.16 However, the presence of a haematological malignancy as underlying disease cannot entirely explain the high mortality observed in our study. In a recently reported survey which included 60 cases of zygomycosis, 37 (60%) of them having a haematological malignancy, Pagano et al. reported an attributable mortality rate of 32%, a rate that is substantially lower than the 52% we have found in our study.17

We identified several mortality risk factors in the univariate analysis: the presence of an underlying haematological malignancy, neutropenia, and monocytopenia. These risk factors for mortality are consistent with those reported in previous studies of patients with zygomycosis and other IFIs. As mentioned earlier, zygomycosis in patients with haematological malignancies is associated with a high mortality rate.15,16 Moreover, in a multivariate analysis of 70 patients with zygomycosis and haematological malignancies, Chamilos et al. reported that the presence of an active haematological malignancy was an independent predictor of a poorer outcome.18 Neutropenia has been associated with a higher risk of mortality in patients with haematological malignancies and other IFIs such as Fusarium sp.19 or invasive aspergillosis.20 However, in two different series of patients with haematological malignancies and zygomycosis, neutropenia was not associated with a higher risk of mortality in either univariate or multivariate analysis.15,18 One of those studies, however, found that monocytopenia was an independent risk factor for a poorer outcome18 and both studies found that neutrophil recovery was associated with a protective effect.15,18 Like Chamilos,18 we think that it is likely that monocytopenia reflects the immunosuppression state of those patients, and the neutrophil recovery reflects the reversal of the predisposing underlying condition.

In our analysis the use of amphotericin B was not identified as a protective factor; this may be due to the small study sample size. However, the use of amphotericin B has been associated with a positive outcome in patients who have zygomycosis and several underlying conditions, such as patients with underlying haematological malignancies,15,18 patients with haematological or oncological disorders16 and solid organ transplant recipients.21 In the multivariate analysis by Chamilos et al, a delay in treatment with an amphotericin-based regimen was an independent predictor of mortality (OR 8.1, 95% CI 1.7-38.2).14 Similarly, a multivariate analysis of 59 patients with zygomycosis and underlying haematological malignancies found that treatment with liposomal amphotericin B was the only factor that predicted recovery from the IFI (Relative risk 0.5, 95% CI 0.3-0.8).12 It is noteworthy that only 5 patients (20%) in our study received an amphotericin B-based treatment as a pre-emptive or empirical treatment. This fact alone could explain the high mortality rate observed in our study, and it illustrates the need for a rapid initiation of an effective antifungal treatment. Early diagnosis and treatment, including surgical debridement, reversal of underlying risk factors, and rapid initiation of an amphotericin B-based treatment, are the mainstays of management of zygomycosis.1,7 Moreover, since zygomycosis is difficult to diagnose, some authors have proposed the use of pre-emptive amphotericin B-based regimens in patients who are at high risk for zygomycosis and who are receiving other antifungal agents that have little or no activity against Zygomycetes.18 With the data obtained and according to the published literature, when a zygomycosis infection is suspected, treatment with effective in vitro antifungal drugs should be started as soon as possible.

Despite the limitations of our retrospective design and the small sample size, our study supports previous research that has documented a high mortality rate among patients with invasive zygomycosis, especially among those with an underlying haematological malignancy, and the need for a rapid initiation of an effective antifungal treatment and the correction of underlying predisposing factors.

Funding

This study was partially funded by a research grant from Gilead Sciences S.L.

Biometría Médica provided assistance in preparing the manuscript

Conflict of interest

The authors have no conflict of interest to declare.

Acknowledgments

We would like to thank following authors for taking part on this study:

Llorente A, Hospital Joan XXIII, Tarragona.

García E, Clínica Universitaria de Navarra, Navarra.

Heras I, Hospital General Universitario Morales Messeguer, Murcia.

Fraile V, Hospital Universitario “Río Hortega”, Valladolid.

García P, Hospital Clínico San Carlos, Madrid.

López J, Hospital Universitario Ramón y Cajal, Spain

Salavert M, Hospital Universitario La Fe, Valencia.

Pérez I, Hospital Universitario La Paz, Madrid.

Bobillo F, Hospital Clínico Universitario de Valladolid, Valladolid.

Cantalapiedra A, Hospital Universitario “Río Hortega”, Valladolid.

Gómez J, Hospital Central de Asturias, Oviedo.

Andreu MAJ, Hospital de Mostoles, Madrid.

Fortún J, Hospital Ramón y Cajal, Madrid.

Díaz MA, Hospital de Mérida, Badajoz.

Heredia M, Hospital Clínico Universitario de Valladolid, Valladolid.

Martín P, Complejo Hospitalario Carlos Haya, Málaga.

Martínez P, Hospital Universitario Puerto Real, Cádiz.

Sanduende Y, Hospital Montecelo, Pontevedra.

Sarriá C, Hospital Universitario La Princesa, Madrid.

Bermúdez A, Hospital Universitario Marqués de Valdecilla, Cantabria.

References
[1]
D.P. Kontoyiannis, R.E. Lewis.
Invasive zygomycosis: update on pathogenesis, clinical manifestations, and management.
Infect Dis Clin North Am., 20 (2006), pp. 581-607
[2]
M.M. Roden, T.E. Zaoutis, W.L. Buchanan, T.A. Knudsen, T.A. Sarkisova, R.L. Schaufele, et al.
Epidemiology and outcome of zygomycosis: a review of 929 reported cases.
Clin Infect Dis., 41 (2005), pp. 634-653
[3]
A. Glöckner, J.J. Vehreschild, O.A. Cornely.
Zygomycosis--current epidemiological aspects.
[4]
D. Neofytos, D. Horn, E. Anaissie, W. Steinbach, A. Olyaei, J. Fishman, et al.
Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry.
Clin Infect Dis., 48 (2009), pp. 265-273
[5]
S. Trifilio, S. Singhal, S. Williams, O. Frankfurt, L. Gordon, A. Evens, et al.
Breakthrough fungal infections after allogeneic hematopoietic stem cell transplantation in patients on prophylactic voriconazole.
Bone Marrow Transplant., 40 (2007), pp. 451-456
[6]
N. Singh, J.M. Aguado, H. Bonatti, G. Forrest, K.L. Gupta, N. Safdar, et al.
Zygomycosis in solid organ transplant recipients: a prospective, matched case-control study to assess risks for disease and outcome.
J Infect Dis., 200 (2009), pp. 1002-1011
[7]
L. Pagano, C.G. Valentini, M. Caira, L. Fianchi.
ZYGOMYCOSIS: current approaches to management of patients with haematological malignancies.
Br J Haematol., 146 (2009), pp. 597-606
[8]
G.L. Petrikkos.
Lipid formulations of amphotericin B as first-line treatment of zygomycosis.
Clin Microbiol Infect., 15 (2009 Oct), pp. 87-92
[9]
M.D. Moen, K.A. Lyseng-Williamson, L.J. Scott.
Liposomal amphotericin B: a review of its use as empirical therapy in febrile neutropenia and in the treatment of invasive fungal infections.
[10]
A.H. Groll, T.J. Walsh.
Antifungal efficacy and pharmacodynamics of posaconazole in experimental models of invasive fungal infections.
[11]
R.N. Greenberg, K. Mullane, J.A. van Burik, I. Raad, M.J. Abzug, G. Anstead, et al.
Posaconazole as salvage therapy for zygomycosis.
Antimicrob Agents Chemother., 50 (2006), pp. 126-133
[12]
J.A. van Burik, R.S. Hare, H.F. Solomon, M.L. Corrado, D.P. Kontoyiannis.
Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases.
Clin Infect Dis., 42 (2006), pp. e61-e65
[13]
C.R. Sims, L. Ostrosky-Zeichner.
Contemporary treatment and outcomes of zygomycosis in a non-oncologic tertiary care center.
Arch Med Res., 38 (2007), pp. 90-93
[14]
S. Ascioglu, J.H. Rex, B. de Pauw, J.E. Bennett, J. Bille, F. Crokaert, et al.
Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus.
Clin Infect Dis., 34 (2002), pp. 7-14
[15]
L. Pagano, M. Offidani, L. Fianchi, A. Nosari, A. Candoni, M. Piccardi, et al.
Mucormycosis in hematologic patients.
Haematologica., 89 (2004), pp. 207-214
[16]
B. Gleissner, A. Schilling, I. Anagnostopolous, I. Siehl, E. Thiel.
Improved outcome of zygomycosis in patients with hematological diseases?.
Leuk Lymphoma., 45 (2004), pp. 1351-1360
[17]
L. Pagano, C.G. Valentini, B. Posteraro, C. Girmenia, C. Ossi, A. Pan, et al.
Zygomycosis in Italy: a survey of FIMUA-ECMM (Federazione Italiana di Micopatologia Umana ed Animale and European Confederation of Medical Mycology).
J Chemother., 21 (2009), pp. 322-329
[18]
G. Chamilos, R.E. Lewis, D.P. Kontoyiannis.
Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis.
Clin Infect Dis., 47 (2008), pp. 503-509
[19]
M. Nucci, E.J. Anaissie, F. Queiroz-Telles, C.A. Martins, P. Trabasso, C. Solza, et al.
Outcome predictors of 84 patients with hematologic malignancies and Fusarium infection.
Cancer., 98 (2003), pp. 315-319
[20]
M. Mikulska, A.M. Raiola, B. Bruno, E. Furfaro, M.T. Van Lint, S. Bregante, et al.
Risk factors for invasive aspergillosis and related mortality in recipients of allogeneic SCT from alternative donors: an analysis of 306 patients.
Bone Marrow Transplant., 44 (2009), pp. 361-370
[21]
G.N. Forrest, K. Mankes.
Outcomes of invasive zygomycosis infections in renal transplant recipients.
Transpl Infect Dis., 9 (2007), pp. 161-164
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