Zigomicosis y síndrome hemofagocítico en un paciente inmunocompetente: informe de caso / Zygomycosis and hemophagocytic lymphohistiocytosis in an immunocompetent patient: a case report

Introducción: la zigomicosis es una infección fúngica poco frecuente, con alta tasa de mortalidad y de mal pronóstico. Afecta principalmente a pacientes inmunocomprometidos. La asociación con el síndrome hemofagocítico es extremadamente inusual, más aún en pacientes inmunocompetentes, con pocos ejemplos registrados en la literatura. Caso clínico: se presenta el caso de un paciente masculino inmunocompetente de 40 años con diagnóstico de mucormicosis y síndrome hemofagocítico que evoluciona desfavorablemente, con fallo multiorgánico, a pesar de los esfuerzos médicos. Conclusión: la asociación de mucormicosis con síndrome hemofagocítico en un paciente inmunocompetente es extremadamente rara; existen pocos casos informados en Latinoamérica. Debemos tener presente esta asociación, ya que requiere un tratamiento agresivo y soporte vital avanzado. (AU)

Introduction: zygomycosis is a rare fungal infection that carries with high mortality rates. This poor prognosis, rapidly progressive infection mainly affects immunocompromised patients. The association with hemophagocytic lymphohistiocytosis is extremely unusual, even more in immunocompetent patients, with few cases reported. Case: we present the case of an immunocompetent male patient who was diagnosed with zygomycosis and hemophagocytic lymphohistiocytosis. Despite medical efforts he developed multiorganic failure. Conclusion: the association of mucormycosis with hemophagocytic lymphohistiocytosis in an immunocompetent patient is exceptional with few cases reported in Latin America. We must always suspect this association considering they require aggressive treatment and advanced life support. (AU)

Epidemiological aspects and clinical outcome of patients with Rhinocerebral zygomycosis: a survey in a referral hospital in Iran.

INTRODUCTION: No comprehensive reports have been published on epidemiological status of Rhinocerebral zygomycosis infections and its outcome in our population, Hence, the current study came to address epidemiological characteristics as well as clinical outcome of patients with Rhinocerebral zygomycosis infection referred to a referral hospital in Iran. METHODS: This retrospective study was performed at the Rasoul-e-Akram hospital, an 800-bed tertiary care teaching hospital in Tehran, Iran. The pathology recorded charts were reviewed to identify all cases of Rhinocerebral zygomycosis from patients admitted between April 2007 and March 2014. A diagnosis of Rhinocerebral zygomycosis was based on histopathological assessments. RESULTS: Sixty four patients with Rhinocerebral zygomycosis were assessed. The mean age of the patients was 46.07 ± 22.59 years and 51.6% were female. Among those, 67.2% were diabetic, 26.6% were hypertensive and 29.7% had history of cancer. Different sinuses were infected in 73.4% of the patients. Out of all the patients 26.6% underwent surgical procedures and 17.2% were controlled medically. Extensive debridement was carried out in 40.6%. Neutropenia (<1500 cell/ µl) was revealed in 12.5%. In-hospital mortality rate was 35.9% and prolonged hospital stay (> 14 days) was found in 60.9%. According to the Multivariable logistic regression analysis, the main predictors of in-hospital mortality included female gender, advanced age, the presence of sinus infection, and neutropenia, while higher dosages of amphotericin administered had a protective role in preventing early mortality. In a similar Multivariate model, history of cancer could predict prolonged hospital stay, whereas using higher dose of amphotericin could lead to shortening length of hospital stay. CONCLUSION: There is no difference in demographic characteristics between our patients with Rhinocerebral zygomycosis and other nations. The presence of diabetes mellitus is closely associated with the presence of this infection. Sinus involvement is very common in those with Rhinocerebral zygomycosis leading to high mortality and morbidity. Besides female gender, advanced age, and presence of neutropenia was a major risk factor for increasing early mortality. The use of higher doses of antifungal treatment such as amphotericin can prevent both mortality and prolonged hospital stay. The cancer patients may need longer hospital stay because of needing comprehensive in-hospital treatment.

Disseminated zygomycosis caused by Cunninghamella bertholletiae in patient with hematological malignancy and review of published case reports.

Cunninghamella bertholletiae is an unusual opportunistic pathogen belonging to the class Zygomycetes, order Mucorales, and the family Cunninghamellaceae. It has been identified with increased frequency in immunocompromised patients, especially those with hematological malignancy. Clinical infection by this fungus is almost always devastating. We report a fatal case of disseminated zygomycosis due to Cunninghamella bertholletiae in an acute myeloid leukemia patient without chemotherapy. We also reviewed the cases of Cunninghamella bertholletiae infection reported in these 20 years. These cases highlight the high mortality rate and rapid progression associated with this opportunistic fungal infection in immunocompromised patients.

Surgical management of gastrointestinal basidiobolomycosis in pediatric patients.

INTRODUCTION: Gastrointestinal basidiobolomycosis (GIB) is a rare fungal disease. We reviewed our experience with this disease over the last 10 years, with special emphasis on the surgical aspects. METHODS: A retrospective chart review was conducted for pediatric patients with GIB who were managed at our institution over the last 10 years. Demographic, clinical, and follow-up data were collected, and descriptive data were generated. RESULTS: Nine patients with a median age of 7 years were managed for GIB over the study period. Six patients were managed surgically. Four had colonic and liver involvement, 1 had a left hepatic lesion, and 1 had a porta hepatic mass. One patient had multiple liver lesions and was managed medically, and 2 patients had disseminated disease and died shortly after presentation. Tissue biopsies confirmed the diagnosis, and all received antifungal treatment. Patients were followed up for a median of 6 years. All live patients are free of disease, and 4 are still on antifungal medications. CONCLUSIONS: Gastrointestinal basidiobolomycosis is an aggressive disease that requires early surgical intervention to avoid complications and hasten disease eradication. Long-term follow-up is warranted, given the significant potential for complications.

[Estimated numbers of visceral mycoses in cases of leukemia and MDS in Japan : analysis of data from the Annual of Pathological Autopsy Cases and the vital statistics published by Ministry of health, labour and welfare in Japan].

Our analysis reported here, is the first one in the world to make a nationwide-level estimate on numbers of visceral mycoses in case of leukemia and myelodysplastic syndrome (MDS)in Japan. The data on visceral mycoses in cases reported in the" Annual of the Pathological Autopsy Cases in Japan" published by the Japanese society of pathology in 2002 and 2006, and the data in the vital statics in Japan published by Ministry of health, labour and welfare were analyzed epidemiologically. The estimated numbers of visceral mycoses were 2,250 out of the estimated total death 8,976 in 2001, and 2290 out of 9,805 in 2005, respectively, in cases of leukemia and MDS in Japan. Furthermore, the estimated severe cases that we thought direct cause of death were 1,454 in 2001, and 1,464 in 2005, respectively. In the severe cases, the most causative agents were Aspergillus. The estimated numbers of Candida and Zygomycetes were interestingly almost same in the severe cases, but the lethal rate in Zygomycetes was about 60-80 % , almost twice as that in Candida. We think it is imperative to continuously survey and watch these rates towards the future.

Mortality risk factors in patients with zygomycosis: a retrospective and multicentre study of 25 cases

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 (AU)

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 wasrhino-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 (AU)

Mortality risk factors in patients with zygomycosis: a retrospective and multicentre study of 25 cases.

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.

Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007.

Zygomycosis is an important emerging fungal infection, associated with high morbidity and mortality. The Working Group on Zygomycosis of the European Confederation of Medical Mycology (ECMM) prospectively collected cases of proven and probable zygomycosis in 13 European countries occurring between 2005 and 2007. Cases were recorded by a standardized case report form, entered into an electronic database and analysed descriptively and by logistic regression analysis. During the study period, 230 cases fulfilled pre-set criteria for eligibility. The median age of the patients was 50 years (range, 1 month to 87 years); 60% were men. Underlying conditions included haematological malignancies (44%), trauma (15%), haematopoietic stem cell transplantation (9%) and diabetes mellitus (9%). The most common manifestations of zygomycosis were pulmonary (30%), rhinocerebral (27%), soft tissue (26%) and disseminated disease (15%). Diagnosis was made by both histology and culture in 108 cases (44%). Among 172 cases with cultures, Rhizopus spp. (34%), Mucor spp. (19%) and Lichtheimia (formerly Absidia) spp. (19%) were most commonly identified. Thirty-nine per cent of patients received amphotericin B formulations, 7% posaconazole and 21% received both agents; 15% of patients received no antifungal therapy. Total mortality in the entire cohort was 47%. On multivariate analysis, factors associated with survival were trauma as an underlying condition (p 0.019), treatment with amphotericin B (p 0.006) and surgery (p <0.001); factors associated with death were higher age (p 0.005) and the administration of caspofungin prior to diagnosis (p 0.011). In conclusion, zygomycosis remains a highly lethal disease. Administration of amphotericin B and surgery, where feasible, significantly improve survival.

Rhino-orbital-cerebral zygomycosis in solid organ transplant recipients.

BACKGROUND: Rhino-orbital-cerebral disease is a significant manifestation of zygomycosis in solid organ transplant (SOT) recipients. However, its characteristics and outcome are not well addressed. METHODS: SOT recipients with zygomycosis as per the European Organization for Research and Treatment in Cancer and the Mycoses Study Group criteria in a cohort study at our centers published previously and those identified with a PubMed search from the 1950s to November 2009 were studied. Patients with mycosis involving the sinuses, orbits, or central nervous system (CNS) were included. RESULTS: Patients comprised a total of 90 SOT recipients with rhino-orbital-cerebral zygomycosis, including 13 in our cohort and 77 in the literature. CNS disease occurred in 57% (51 of 90). Overall mortality was 52.3% (46 of 88), and the mortality in patients with CNS disease was 73.5% (36 of 49). In logistic regression analysis, older age (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.04-1.21, P=0.002) was associated with a higher mortality rate, whereas lipid formulations of amphotericin B compared with amphotericin B deoxycholate (OR 0.09, 95% CI 0.02-0.50, P=0.006) and surgery (OR 0.12, 95% CI 0.01-0.94, P=0.043) were independently associated with an improved survival even when controlled for CNS involvement and the era of diagnosis of disease. CONCLUSIONS: Rhino-orbital-cerebral zygomycosis, particularly CNS disease, is associated with substantial mortality rate in SOT recipients. Older age is a significant risk factor for mortality, whereas lipid formulations of amphotericin B and surgery improved outcomes.

Primary treatment of zygomycosis with liposomal amphotericin B: analysis of 28 cases.

Lipid formulations of amphotericin B are increasingly used in lieu of deoxycholate amphotericin B for primary treatment of zygomycosis, but little is known about the efficacy of the former antifungal in treating this fungal disease. We therefore undertook an analysis of a case series of all patients with zygomycosis who received L-AMB for primary antifungal therapy in five major mid-Atlantic medical centers. Among the categories of variables studied were demographics, methods of diagnosis, microbiology, sites of infection, global responses, and survival. The median patient age was 44 years and 71% were male. Immunosuppressive hematological disorders (54%) were the most common underlying condition. Pulmonary disease constituted 50% of infections, sinus infection 29%, and cutaneous disease 18%. Members of the genus Rhizopus were the most common recovered agents. Success as defined by complete or partial positive response was noted in 32% of the cases. Concomitant surgery was performed in 46% of the cases, with similar response rates (31%). Overall survival was 39%. L-AMB was effective as primary therapy in only some patients in this cohort of highly immunocompromised individuals with invasive zygomycosis underscoring the importance of host response and the need for further advances for treatment of this lethal infection.

Increasing incidence of zygomycosis (mucormycosis), France, 1997-2006.

We analyzed hospital records to provide a population-based estimate of zygomycosis incidence and trends over a 10-year period at a national level in France. Data showed an increasing incidence from 0.7/million in 1997 to 1.2/million in 2006 (p<0.001). We compared our data with those from the French Mycosis Study Group, a recently established voluntary network of French mycologists coordinated by the National Reference Center for Mycoses and Antifungals. We documented that incidence of zygomycosis increased, particularly in patients with hematologic malignancies or bone marrow transplants. The role of previous exposure to antifungal drugs lacking activity against zygomycetes could explain this increase but does not appear exclusive. Incidence also increased in the population of patients with diabetes mellitus. We conclude that observed trends reflect a genuine increase of zygomycosis cases in at-risk populations.

Invasive zygomycosis in neonates and children.

Invasive zygomycosis in neonates and children has both similarities to and differences from that in adults. We searched PubMed and individual references for English-language reports of single cases or case series of neonatal (<1 month) and paediatric (< or =18 years) zygomycosis and compared the results with published results in adults. Cases were included if they fulfilled pre-specified criteria. A total of 59 cases of neonatal zygomycosis were reported to July 2007; 157 paediatric cases were published up to 2004 and an additional 30 paediatric cases were reported more recently. Prematurity was a major underlying factor among neonatal cases. The most common manifestations of zygomycosis were gastrointestinal (54%) and cutaneous (36%). This pattern differs from the sinopulmonary and rhinocerebral patterns typical in older children and adults. Overall mortality was 64% in neonates, 56% in children and 53% in adults. A tendency for dissemination was higher in neonates than adults. Dissemination and young age (<1 year) were independent risk factors for death in children. Most patients who survived received antifungal therapy. Surgery combined with antifungal therapy was a protective factor against death. Most neonates and children who survived had received an amphotericin B formulation. Zygomycosis is a life-threatening infection in children and neonates with differing patterns of involvement in individuals of different ages. The most common management strategy in survivors involved a combination of amphotericin B and surgery.

Zygomycosis in neonates: an uncommon but life-threatening infection.

We systematically reviewed all published cases of zygomycosis, an increasingly important infection with high mortality, in neonates. We searched PubMed and individual references for English publications of single cases or case series of neonatal (0 to 1 month) zygomycosis. Cases were included if they fulfilled prespecified criteria. Fifty-nine cases were published through July 2007. Most of the infants (77%) were premature. The most common sites of zygomycosis were gastrointestinal (54%) and cutaneous (36%) diseases. This pattern differs from sinopulmonary and rhinocerebral patterns of older children. Fifty-six percent of cases were diagnosed by histology only and 44% by histology and culture. RHIZOPUS spp. were isolated from 18/25 (72%) cases. Thirty-seven percent of patients received no antifungal therapy. Thirty-two (54%) neonates underwent surgery with (39%) or without (15%) antifungal agents. Overall mortality was 64%. A higher fraction of neonates treated with amphotericin B and surgery survived than those who received no therapy (70% versus 5%). Zygomycosis is a life-threatening infection in neonates with a distinct pattern of gastrointestinal and cutaneous involvement and high mortality. Combination of amphotericin B and surgery was common management strategy in survivors.

Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis.

BACKGROUND: Zygomycosis is an emerging opportunistic mycosis among immunocompromised patients with a particularly poor prognosis. METHODS: We analyzed the impact of delaying effective amphotericin B-based therapy on outcome among 70 consecutive patients with hematologic malignancy who had zygomycosis in our institution during the period 1989-2006. We used classification and regression tree analysis to identify the mortality breakpoint between early and delayed treatment. RESULTS: Delayed amphotericin B-based therapy (i.e., initiating treatment >/=6 days after diagnosis) resulted in a 2-fold increase in mortality rate at 12 weeks after diagnosis, compared with early treatment (82.9% vs. 48.6%); this remained constant across the years of the study and was an independent predictor of poor outcome (odds ratio, 8.1; 95% confidence interval, 1.7-38.2; P = .008) in multivariate analysis. Active malignancy (P = .003) and monocytopenia (P =.01) at the time of diagnosis of infection were also independently associated with a poor outcome, whereas salvage posaconazole-based therapy (P=.01) and neutrophil recovery (P = .009) were predictive of a favorable outcome. CONCLUSIONS: Because discriminating between zygomycosis and aspergillosis in a timely fashion is difficult, the pursuit of aggressive diagnostic strategies and prompt initiation of antifungal agents with activity against Zygomycetes should be considered for patients with hematological malignancy who are at an increased risk for zygomycosis.

Comparison of lipid amphotericin B preparations in treating murine zygomycosis.

We compared the efficacies of liposomal amphotericin B (LAmB) and an amphotericin B lipid complex (ABLC) in diabetic ketoacidotic (DKA) or neutropenic mice with disseminated zygomycosis. ABLC was as effective as LAmB in neutropenic but not DKA mice. Low-dose ABLC was less effective than LAmB at reducing brain fungal burdens in both models.

[Invasive zygomycosis in patients treated for haematological malignancies]. / Invasieve zygomycose bij patiënten die worden behandeld voor een hematologische maligniteit.

A 52-year-old man underwent haematopoietic stem-cell transplant for myelodysplastic syndrome; after treatment with voriconazole for invasive aspergillosis, he was diagnosed with invasive zygomycosis caused by Rhizopus microsporus. He died despite treatment with intravenous liposomal amphotericin B and posaconazole. A 5-year-old boy with acute lymphatic leukaemia was diagnosed with invasive zygomycosis at autopsy. In a third case, a 16-year-old boy with acute myeloid leukaemia received repeated courses of empiric antifungal therapy, although the presence of an invasive fungal infection was not demonstrated. The patient died, and disseminated invasive zygomycosis caused by Rhizomucor pusillus was found at autopsy. Invasive infections by Zygomycetes are difficult to diagnose and are associated with a high mortality rate. The incidence of invasive zygomycosis appears to be increasing. Therefore, awareness of this type of invasive fungal infection is warranted. Lipid formulations ofamphotericin B remain the first choice for therapy.

[Invasive zygomycosis: notably in diabetes mellitus and iron overload]. / Invasieve zygomycose: vooral bij diabetes mellitus en ijzerstapeling.

The incidence of invasive zygomycosis, a severe and often life-threatening infection, is increasing. The most common manifestations are pulmonary infection (following anti-cancer chemotherapy or haematopoietic stem-cell transplant) and invasive rhinocerebral infection (in patients with diabetes mellitus or iron overload). Iron metabolism plays an important role in the pathogenesis of infection in these high-risk populations. Rapid diagnosis, reversal of the underlying predisposition and timely surgical debridement are the underlying principles of therapy for this disease.

Outcomes of invasive zygomycosis infections in renal transplant recipients.

Zygomycosis is an infrequent and difficult-to-treat fungal infection that is found in patients with underlying immunocompromised states. The advent of the lipid amphotericin B products has allowed for treatment with higher doses of therapy and less systemic toxicity. We reviewed the outcomes of 6 renal transplant recipients diagnosed with biopsy-proven invasive zygomycosis who received amphotericin B lipid complex (ABLC) in doses greater than 5 mg/kg between 2000 and 2004. All 6 patients had baseline diabetes mellitus, were receiving immunosuppressive agents, and subsequently underwent concomitant surgery. Three of the 6 patients that survived had undergone significant surgical debridement, reduction of their immunosuppression to minimal prednisone, and received prolonged course of ABLC at 10 mg/kg/day. All survivors lost graft function during the course of their therapy. The 3 patients who died all had delays in diagnosis of their disease and subsequent surgical and appropriate medical therapy. Therefore, in renal transplant recipients the early diagnosis of invasive zygomycosis is imperative along with early therapy with surgical debridement, reduced immunosuppression, and the use of high doses of ABLC.

Zigomicosis cutanea en un paciente de 10 años: primer caso pediátrico en Venezuela: revisión de la literatura / Cutaneous zigomycosis in a 10 year-old patient: first pediatric case in Venezuela: revision of the literature

La zinomicosis es una infección aguda causada por los hongos de la clase Zigomicetos, de la cual no existen casos publicados anteriormente en el área pediátrica en nuestro país. Estos hongos producen una angioinvasión que puede manifestarse de varias formas, siendo la forma mas frecuente la rino-órbito- cerebral. Se describe el caso de un escolar masculino de 10 años que representa politraumatismo con herida muy contaminada en muslo izquierdo. Recibe antibióticos, curas quirúrgicas y dexametasona. En el curso de 13 días presentó una fascitis necrotizante con una zona aterciopelada blanca de la cual se toma muestra, diagnosticándose hongos del tipo Zigomicetos, especie Saksenaea vasiformis. Se desatircula el miembro inferior izquierdo, se le coloca Anfotericina B liposomal y Caspofungina. El paciente falleció luego de 13 días a pesar del tratamiento. La Zigomicosis cutánea severa es una patología de alta mortalidad cuyo pronóstico dependerá de un diagnóstico precoz y un manejo médico y quirúrgico agresivo. El Posaconazol ofrece nuevas perspectivas en el tratamiento de esta enfermedad.

Zygomycosis is an acute micotic infection caused by the Zygomycetes class that has not been previously described in the pediatric area in our country. These fungi produce an angioinvasion with several clinical manifestations, of which the most frequent isthe rhino-orbito-cerebral form. This is a 10 year-old male who presents with multiple injuries and a very contaminated wound in the left thigh. The child receives antibiotics, surgical cleaning, dexametaxone and presents, during the course of 13 days, a necrotizing fasciitis with a velvety white zone from where Zygomycete, specie Saksenaea vasiformis was isolated. The left thigh and leg had to bedis articulated and liposomal Amphotericin B plus Caspofungin was prescribed. In spite of the treatment the patient died 13 days later. Cutaneous Zygomycosis is a severe pathology of high mortality which prognosis will depend on an early diagnosis and aggressive medical and surgical treatment. Posaconazole offers a new perspective in the treatment of this disease.

Epidemiology and outcome of zygomycosis: a review of 929 reported cases.

BACKGROUND: Zygomycosis is an increasingly emerging life-threatening infection. There is no single comprehensive literature review that describes the epidemiology and outcome of this disease. METHODS: We reviewed reports of zygomycosis in the English-language literature since 1885 and analyzed 929 eligible cases. We included in the database only those cases for which the underlying condition, the pattern of infection, the surgical and antifungal treatments, and survival were described. RESULTS: The mean age of patients was 38.8 years; 65% were male. The prevalence and overall mortality were 36% and 44%, respectively, for diabetes; 19% and 35%, respectively, for no underlying condition; and 17% and 66%, respectively, for malignancy. The most common types of infection were sinus (39%), pulmonary (24%), and cutaneous (19%). Dissemination developed in 23% of cases. Mortality varied with the site of infection: 96% of patients with disseminated disease died, 85% with gastrointestinal infection died, and 76% with pulmonary infection died. The majority of patients with malignancy (92 [60%] of 154) had pulmonary disease, whereas the majority of patients with diabetes (222 [66%] of 337) had sinus disease. Rhinocerebral disease was seen more frequently in patients with diabetes (145 [33%] of 337), compared with patients with malignancy (6 [4%] of 154). Hematogenous dissemination to skin was rare; however, 78 (44%) of 176 cutaneous infections were complicated by deep extension or dissemination. Survival was 3% (8 of 241 patients) for cases that were not treated, 61% (324 of 532) for cases treated with amphotericin B deoxycholate, 57% (51 of 90) for cases treated with surgery alone, and 70% (328 of 470) for cases treated with antifungal therapy and surgery. By multivariate analysis, infection due to Cunninghamella species and disseminated disease were independently associated with increased rates of death (odds ratios, 2.78 and 11.2, respectively). CONCLUSIONS: Outcome from zygomycosis varies as a function of the underlying condition, site of infection, and use of antifungal therapy.