Zygomycosis in children: a systematic review and analysis of reported cases.

BACKGROUND: Zygomycosis has emerged as an increasingly important infection with a high mortality especially in immunocompromised patients. No comprehensive analysis of pediatric zygomycosis cases has been published to date. METHODS: We used a PUBMED search for English publications of pediatric (0-18 years) zygomycosis cases and references from major books as well as single case reports or case series. Individual references were reviewed for additional cases. Data were entered into Filemaker-pro database and analyzed by logistic regression analysis. RESULTS: One hundred fifty-seven cases (64% male) were found with median age 5 years (range, 0.16-13). Underlying conditions included neutropenia (18%), prematurity (17%), diabetes mellitus (15%), ketoacidosis (10%), and no apparent underlying condition (14%). The most common patterns of zygomycosis were cutaneous (27%), gastrointestinal (21%), rhinocerebral (18%), and pulmonary (16%). Among 77 culture-confirmed cases, Rhizopus spp. (44%) and Mucor spp. (15%) were most commonly identified. Of 81 patients who were given antifungal therapy, 73% received an amphotericin B formulation only. The remaining patients received mostly amphotericin B in combination with other antifungal agents. Mortality in patients without antifungal therapy was higher than in those with therapy (88% versus 36%, P < 0.0001). Ninety-two (59%) patients underwent surgery. Cerebral, gastrointestinal, disseminated and cutaneous zygomycosis were associated with mortality rates of 100, 100, 88, and 0%, respectively. Independent risk factors for death were disseminated infection (OR: 7.18; 95% CI: 3.02-36.59) and age <1 year (OR: 3.85; 95% CI: 1.05-7.43). Antifungal therapy and particularly surgery reduced risk of death by 92% (OR: 0.07; 95% CI: 0.04-0.25) and 84% (OR: 0.16; 95% CI: 0.09-0.61), respectively. CONCLUSIONS: Zygomycosis is a life-threatening infection in children with neutropenia, diabetes mellitus, and prematurity as common predisposing factors, and there is high mortality in untreated disease, disseminated infection, and age <1 year. Amphotericin B and surgery significantly improve outcome.

Epidemiology, outcomes, and costs of invasive aspergillosis in immunocompromised children in the United States, 2000.

OBJECTIVE: Invasive aspergillosis (IA) is the most common filamentous fungal infection observed in immunocompromised patients. The incidence of invasive aspergillosis has increased significantly in recent decades in parallel with the increasing number and improved survival of immunocompromised patients. IA in adults has been well characterized; however, only a few small studies of IA in children have been reported. Therefore, the objective of this study was to describe the incidence and outcomes of children with IA. METHODS: We performed a retrospective cohort study using the 2000 Kids Inpatient Database, a national database of hospital inpatient stays during 2000. IA was defined as aspergillosis that occurred in a child with malignancy (solid tumor, leukemia, or lymphoma), hematologic/immunologic deficiency, or transplant (bone marrow or solid organ). Discharge weighting was applied to the data to obtain nationally representative estimates of disease. RESULTS: During 2000, there were an estimated 666 pediatric cases of IA among 152,231 immunocompromised children, yielding an annual incidence of 437/100,000 (0.4%) among hospitalized immunocompromised children. Children with malignancy accounted for the majority (74%) of cases of IA. The highest incidence of IA was seen in children who had undergone allogeneic bone marrow transplantation (4.5%) and those with acute myelogenous leukemia (4%). The overall in-hospital mortality of immunocompromised children with IA was 18%. Children with malignancy and IA were at higher risk for death than children with malignancy and without IA. Pediatric patients with IA had a significantly longer median length of hospital stay (16 days) than immunocompromised children without IA (3 days). The median total hospital charges for patients with IA were $49309 compared with immunocompromised children without IA ($9035). CONCLUSIONS: The impact of IA on increases in mortality, length of hospital stay, and the burden of cost in the hospital setting underscores the need for improved means of diagnosis, prevention, and treatment of IA in immunocompromised children.

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.