Patient Characteristics and Risk Factors in Invasive Mold Infections: Comparison from a Systematic Review and Database Analysis (original) (raw)
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Invasive Non-AspergillusMold Infections in Transplant Recipients, United States, 2001–2006
Emerging Infectious Diseases, 2011
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International Journal of Antimicrobial Agents, 2010
A prospective, observational, multicentre study was performed to assess the incidence, diagnosis, epidemiology and outcome of invasive mould infections (IMIs) reported to the Nationwide Austrian Aspergillus Registry. In total, 186 cases were recorded, corresponding to an annual incidence of 42 cases/1000 patients at risk or 2.36 cases/100 000 inhabitants. Patients with acute myelogenous leukaemia (34%) and lung transplant recipients (17%) are currently at highest risk for IMI, followed by a mixed population with impaired immunity (14%). In total, 34%, 30% and 36% were proven, probable and possible cases of IMI. Predominant pathogens were Aspergillus spp. (67%), followed by the zygomycetes (28%). Voriconazole was the most frequently administered agent (38%), followed by caspofungin (20%) and posaconazole (19%). Eighty patients (43%) received antifungal prophylaxis for ≥7 days, 30% of whom (24 patients) suffered from a breakthrough infection. The overall crude 12-week mortality was 34%. Multivariate analysis showed that outcome and survival did not correlate with the status of fungal disease, breakthrough infection, fungal species or age (P > 0.05). Aspergillosis remains the most commonly identified IMI amongst immunocompromised and/or immunosuppressed patients, but other moulds constitute a significant problem. Survival from IMIs appears to have improved and the main challenge is to overcome breakthrough fungal infections.
A Prospective, International Cohort Study of Invasive Mold Infections in Children
Journal of the Pediatric Infectious Diseases Society, 2014
Background. Invasive mold infections (IMIs) are a leading cause of mortality in immunocompromised children, yet there has never been an international epidemiologic investigation of pediatric IMIs. Methods. This international, prospective cohort study was performed to characterize the epidemiology, antifungal therapy, and outcomes of pediatric IMIs. Children (18 years) with proven or probable IMIs were enrolled between August 2007 and May 2011 at 22 sites. Risk factors, underlying diagnoses, and treatments were recorded. Outcomes were assessed at 12 weeks after diagnosis using European Organization for Research and Treatment of Cancer/Mycoses Study Group response criteria. Results. One hundred thirty-one pediatric patients with IMIs were enrolled; the most common IMI was invasive aspergillosis ([IA] 75%). Children with IA and those with other types of IMIs had similar underlying risk factors, except that children with IMIs caused by non-Aspergillus species were more likely to have received mold-active antifungal agents preceding diagnosis. The most commonly used antifungal classes after diagnosis were triazoles (82%) and polyenes (63%). Combination therapy was used in 53% of patients. Use of combination therapy was associated with an increased risk of adverse events (risk ratio, 1.98; 95% confidence interval, 1.06-3.68; P = .031), although there was no detectable difference in outcome. Conclusions. Although risk factors for IMIs are similar across specific subtypes, preceding antifungal therapy may be an important modifier. Combination antifungal therapy requires further study to determine its true risks and benefits.
Bone Marrow Transplantation, 2015
Risk factors for non-Aspergillus mold infection (NAMI) and the impact on transplant outcome are poorly assessed in the current era of antifungal agents. Outcomes of 124 patients receiving allogeneic hematopoietic cell transplantation (HCT) diagnosed with either mucormycosis (n = 72) or fusariosis (n = 52) between days 0 and 365 after HCT are described and compared with a control cohort (n = 11 856). Patients with NAMI had more advanced disease (mucormycois: 25%, fusariosis: 23% and controls: 18%; P = 0.004) and were more likely to have a Karnofsky performance status (KPS) o90% at HCT (mucormycosis: 42%, fusariosis: 38% and controls: 28%; P = 0.048). The 1-year survival after HCT was 22% (15-29%) for cases and was significantly inferior compared with controls (65% (64-65%); P o 0.001). Survival from infection was similarly dismal regardless of mucormycosis: 15% (8-25%) and fusariosis: 21% (11-33%). In multivariable analysis, NAMI was associated with a sixfold higher risk of death (P o 0.0001) regardless of the site or timing of infection. Risk factors for mucormycosis include preceding acute GvHD, prior Aspergillus infection and older age. For fusariosis, increased risks including receipt of cord blood, prior CMV infection and transplant before May 2002. In conclusion, NAMI occurs infrequently, is associated with high mortality and appears with similar frequency in the current antifungal era.
Transplant Infectious Disease, 2016
Objectives. Our aim was to assess the impact of positive cultures for non-Aspergillus molds on the risk of progression to invasive fungal infection (IFI), and the effect of prophylactic nebulized liposomal amphotericin B (n-LAB) on these pathogens. Methods. This was an observational study (2003-2013) including lung transplant recipients (LTR) receiving lifetime n-LAB prophylaxis, in whom non-Aspergillus molds were isolated on respiratory culture before and after transplantation (minimum 1-year follow-up). Results. We studied 412 patients, with a mean postoperative followup of 2.56 years (interquartile range 1.01-4.65). Pre-and posttransplantation respiratory samples were frequently positive for non-Aspergillus molds (11.9% and 16.9% of LTR respectively). Post transplantation, 10 (2.42%) patients developed non-Aspergillus mold infection (4 Scedosporium species, 4 Purpureocillium species, 1 Penicillium species, and 1 Scopulariopsis species); 5 (1.21%) had IFI, with 60% IFI-related mortality. Non-Aspergillus molds with intrinsic amphotericin B (AB) resistance were more commonly isolated in bronchoscopy samples than AB-variably sensitive or AB-sensitive molds (54.5% vs. 25%, P = 0.04) and were associated with a higher risk of infection (56.3% vs. 1.3%%, P < 0.01). Conclusions. In LTR undergoing n-LAB prophylaxis, pre-and posttransplantation isolation of non-Aspergillus molds is frequent, but IFI incidence (1.21%) is low. Purpureocillium is an emerging mold. AB-resistant non-Aspergillus species were found more often in bronchoscopy samples and were associated with a higher risk of infection.
Open Forum Infectious Diseases
Background Invasive aspergillosis (IA) and mucormycosis contribute to substantial mortality, especially among immunocompromised persons, including those with hematopoietic stem cell transplant (HSCT), hematologic malignancy (HM), and solid organ transplant (SOT). Methods Using International Classification of Diseases, Ninth Revision codes available in the National Inpatient Sample, a hospital discharge database, we estimated IA-related hospitalizations (IA-RH), mucormycosis-RH (M-RH), HSCT-RH, HM-RH, and SOT-RH during 2000–2013. United States census data were used to calculate overall M-RH and IA-RH rates and present trends; estimated annual numbers of HSCT-RH, HM-RH, and SOT-RH served as denominators to calculate M-RH and IA-RH rates occurring with these conditions. Weighted least-squares technique was used to test for linear trends and calculate average annual percentage change (APC). Results There were an estimated 169 110 IA-RH and 9966 M-RH during 2000–2013. Overall, IA-RH and ...
Diagnostic Microbiology and Infectious Disease, 2011
Mucormycosis has been reported to be occurring more frequently in hematopoietic stem cell transplant (HSCT) recipients in recent years. We investigated a hospital cluster of mucormycosis cases among patients with hematologic disorders. Case-patients were identified through hospital microbiology and pathology database searches and compared to randomly selected controls matched on underlying disease and hospital discharge date using conditional logistic regression. Environmental assessments, including collection of samples for fungal cultures, were performed. Of 11 case-patients, 6 (55%) had acute myelogenous leukemia and 3 (27%) were allogeneic HSCT recipients. Five casepatients (45%) died. In univariate analysis, case-patients were more likely than controls to have refractory hematologic disease (odds ratio [OR], 13.75; 95% confidence interval [CI], 1.31-689); neutropenia N14 days (OR, 11.50; 95% CI, 1.27-558) or to have received voriconazole prophylaxis (OR, 11.26; 95% CI, 1.11-infinity). A point source was not identified. Factors such as underlying disease state and antifungal prophylaxis type may identify hematology patients at highest risk for mucormycosis. Our investigation highlighted critical Abstract P-0023). ★ Financial support. Office of Workforce and Career Development, Centers for Disease Control and Prevention. ★★ Potential conflicts of interest: A.A.L. has served on advisory boards for Schering-Plough and has participated in clinical research trials sponsored by Schering-Plough and Astellas. G.M.L. has received research support from Astellas, Merck, and Pfizer; has received honoraria from Astellas, Schering-Plough, and Wyeth; and has consulted for Astellas and Merck. S.S.M. consulted for and received grant support from Pfizer and received an honorarium from Astellas, before commencing employment at the Centers for Disease Control and Prevention. All other authors: no conflict. ⁎ Corresponding autho.
Infection, 2013
Purpose We compared the risk factors, the diagnostic tools and the outcome of filamentous fungal infections (FFIs) in hematological patients (HAEs) and non-hematological patients (non-HAEs). Methods Prospective surveillance (2009-2011) of proven and probable FFIs was implemented in 23 Italian hospitals. Results Out of 232 FFIs, 113 occurred in HAEs and 119 in non-HAEs. The most frequent infection was invasive aspergillosis (76.1 % for HAEs, 56.3 % for non-HAEs), and the localization was principally pulmonary (83.2 % for HAEs, 74.8 % for non-HAEs). Neutropenia was a risk factor for 89.4 % HAEs; the main underlying condition was corticosteroid treatment (52.9 %) for non-HAEs. The distribution of proven and probable FFIs was different in the two groups: proven FFIs occurred more frequently in non-HAEs, whereas probable FFIs were correlated with the HAEs. The sensitivity of the galactomannan assay was higher for HAEs than for non-HAEs (95.3 vs. 48.1 %). The overall mortality rate was 44.2 % among the HAEs and 35.3 % among the non-HAEs. The etiology influenced the patient outcomes: mucormycosis was associated with a
Risk assessment and prognostic factors for mould-related diseases in immunocompromised patients
Journal of Antimicrobial Chemotherapy, 2011
Invasive fungal diseases are important causes of morbidity and mortality in immunocompromised patients. Patients with haematological malignancies and solid cancers, as well as those with allogeneic haematopoietic stem cell and solid organ transplants, are at high risk of developing such an infection. Many fungi can cause invasive disease, with Aspergillus spp. and Candida spp. being the prevalent fungal pathogens infecting susceptible patients. During the past few years, rare moulds (for example Zygomycetes and Fusarium spp.) have come into focus as the cause of devastating clinical disease. This review aims to analyse environmental factors and parameters related to impairment of the immune system that are thought to favour the onset of invasive mould infections. Some moulds are quite common among all categories of patients, while others appear to be limited to a given subset of patients, such as allogeneic haematopoietic stem cell or solid organ transplant recipients. In addition to an exploration of factors that predispose patients to the acquisition of an invasive mould infection, prognostic factors that help to predict the eventual outcome of these infections are identified.