Osteomyelitis due to Aspergillus spp. in patients with chronic granulomatous disease: comparison of Aspergillus nidulans and Aspergillus fumigatus

AbstractObjective: Chronic granulomatous disease (CGD) is a rare inherited disorder of NADPH oxidase in which phagocytes fail to generate reactive antimicrobial oxidants. Invasive fungal infections are an important cause of morbidity and mortality in CGD patients, with Aspergillus spp. being the most frequent fungal pathogens. We reviewed the reported cases of osteomyelitis in CGD patients due to Aspergillus nidulans and compared them with those due to Aspergillus fumigatus.Methods: Twenty-four cases of osteomyelitis due to Aspergillus spp. in 22 male CGD patients were found in MEDLINE.Results: Fourteen cases (58%) were due to Aspergillus nidulans and ten cases to Aspergillus fumigatus. No other aspergilli were reported as causes of osteomyelitis. Osteomyelitis due to Aspergillus nidulans was associated with pulmonary infection and involved ‘small bones’ more frequently than Aspergillus fumigatus osteomyelitis (p=0.032). Half of the CGD patients with Aspergillus nidulans osteomyelitis died compared with none of those with Aspergillus fumigatus osteomyelitis (p=0.019). In both Aspergillus nidulans and Aspergillus fumigatus cases, cure was achieved by prompt antifungal treatment combined with surgery and immunotherapy.Conclusion: Aspergillus nidulans causes osteomyelitis in CGD patients relatively frequently compared with Aspergillus fumigatus and may be accompanied by higher mortality. This contrasts with the low frequency with which Aspergillus nidulans causes osteomyelitis in patients with other types of immunodeficiency

Central nervous system aspergillosis in children: a systematic review of reported cases

SummaryObjectiveCentral nervous system (CNS) aspergillosis is a life-threatening disease that has had a published mortality of >80%. Little is known about this serious infection in the pediatric population. We conducted this study to analyze characteristics of CNS aspergillosis in infants and children.MethodsThe English literature was reviewed and all CNS aspergillosis cases in patients younger than 18 years of age were analyzed.ResultsNinety cases were recorded up to June 2005. The median age of the patients was 9 years, ranging from 18 days to 18 years (15.6% younger than 1 year). CNS aspergillosis most commonly presented as brain abscess(es), either single or multiple. While prematurity was the predominant underlying condition among infants, leukemia was the most frequent underlying disease in children. Aspergillus fumigatus was isolated from 75.5% of the cases. The overall mortality in published cases was 65.4%. In multivariate analysis, surgical treatment was independently associated with survival.ConclusionCNS aspergillosis in infants and children predominantly presents as brain abscess(es) and has significantly better outcome compared to published adult data. The findings of this systematic review could assist future investigations for improved outcome of this life-threatening infection in pediatric patients

Standardising neonatal and paediatric antibiotic clinical trial design and conduct: the PENTA-ID network view.

Antimicrobial development for children remains challenging due to multiple barriers to conducting randomised clinical trials (CTs). There is currently considerable heterogeneity in the design and conduct of paediatric antibiotic studies, hampering comparison and meta-analytic approaches. The board of the European networks for paediatric research at the European Medicines Agency (EMA), in collaboration with the Paediatric European Network for Treatments of AIDS-Infectious Diseases network (www.penta-id.org), recently developed a Working Group on paediatric antibiotic CT design, involving academic, regulatory and industry representatives. The evidence base for any specific criteria for the design and conduct of efficacy and safety antibiotic trials for children is very limited and will evolve over time as further studies are conducted. The suggestions being put forward here are based on the adult EMA guidance, adapted for neonates and children. In particular, this document provides suggested guidance on the general principles of harmonisation between regulatory and strategic trials, including (1) standardised key inclusion/exclusion criteria and widely applicable outcome measures for specific clinical infectious syndromes (CIS) to be used in CTs on efficacy of antibiotic in children; (2) key components of safety that should be reported in paediatric antibiotic CTs; (3) standardised sample sizes for safety studies. Summarising views from a range of key stakeholders, specific criteria for the design and conduct of efficacy and safety antibiotic trials in specific CIS for children have been suggested. The recommended criteria are intended to be applicable to both regulatory and clinical investigator-led strategic trials and could be the basis for harmonisation in the design and conduct of CTs on antibiotics in children. The next step is further discussion internationally with investigators, paediatric CTs networks and regulators

Epidemiology of Invasive Fungal Disease in Children

Financial support. A.W. is supported by the Wellcome Trust Strategic Award (grant 097377) and the MRC Centre for Medical Mycology at University of Aberdeen (grant MR/N006364/1). Supplement sponsorship. This article appears as part of the supplement “State of the Art Diagnosis of Pediatric Invasive Fungal Disease: Recommendations From the Joint European Organization for the Treatment of Cancer/Mycoses Study Group (EORTC/MSG) Pediatric Committee,” sponsored by Astellas.Peer reviewedPostprin

Treatment and timing in invasive mould disease

Invasive mould disease is a growing threat for immunocompromised patients. The optimum time to use mould-active antifungal agents is much debated. Current approaches to antifungal prophylaxis, early treatment (empirical and pre-emptive therapy) and treatment of documented mould infections in onco-haematology patients are discusse

ESCMID-ECMM guideline : diagnosis and management of invasive aspergillosis in neonates and children

ACKNOWLEDGEMENT Prof Warris is supported by the Wellcome Trust Strategic Award (grant 097377) and the MRC Centre for Medical Mycology (grant MR/N006364/1) at the University of Aberdeen. FUNDING European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM)Peer reviewedPostprintPostprin

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) due to AIRET16M mutation in a consanguineous Greek girl

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) or autoimmune polyendocrine syndrome type 1 (APS-1) is a rare autosomal recessive disease caused by mutations of the AutoImmune REgulator (AIRE) gene, an important mediator of tolerance to self-antigens. It is characterized by two out of three major components: chronic mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. We present an 11-year-old girl suffering from recurrent episodes of mucocutaneous candidiasis and onychomycosis from 1 to 6years of age, and transient alopecia at the age of 4years. Hypoparathyroidism and dental enamel hypoplasia were diagnosed at 8years. Autoantibodies to thyroid and adrenal glands were not detected and all other endocrine functions have remained normal. Genetic analysis revealed that the patient was homozygous for the mutation T16M in exon 1 of the AIRE gene (p.T16M, c.47C>T). This is the first APECED case reported for carrying this mutation in homozygous form. Parents were third cousins and heterozygous carriers of this mutatio

Microbiological and molecular characteristics of carbapenemase-producing klebsiella pneumoniae endemic in a tertiary Greek hospital during 2004-2010

We report 570 carbapenemase-producing Klebsiella pneumoniae (CPKP) clinical isolates in a 1,040-bed Greek tertiary hospital during 2004 to 2010. The first CPKP (VIM-producing) was isolated in September 2004. Despite initial containment, VIM producers have become endemic since 2006. KPC-producing K. pneumoniae was first isolated in August 2007 from a patient who came from Israel, spread rapidly, and outcompeted VIM. Overall, 267 (47%) VIM-producing and 301 (53%) KPC-producing strains were isolated, including 141 (24.7%) from patients with bacteraemia. Two isolates carrying both VIM and KPC were isolated in two consecutive months in 2009, but not since. The prevalence of CPKP increased from 0% in 2003 to 38.3% in 2010 (

Free Flap Coverage of Extensive Soft Tissue Defect in Cutaneous Aspergillosis: A Case Report

Isolated fungal soft-tissue infections are uncommon, but may cause severe morbidity or mortality. Aspergillosis infection is rare, but the frequency in increasing over the last two decades. Here, we present a patient with cutaneous aspergillosis of his right elbow with unusual clinical and radiological features suggestive of a malignant disease, which remained undiagnosed for an extended period of time. The patient presented with necrotic, black-colored skin ulcerations. We completely removed the skin ulcer with the surrounding erythematous skin lesion, and then we reconstructed the area with thoracodorsal perforator free flap. The biopsy specimen contained septate hyphae with dichotomous branching, which is morphologically consistent with a finding of Aspergillus. After surgery, we initiated antifungal medication therapy with amphotericin B and itraconazole. At the time of follow-up, the elbow with the reconstructed flap had fully healed, and no recurrent disease was found