Showing papers in "Mycoses in 2013"

Epidemiology and sites of involvement of invasive fungal infections in patients with haematological malignancies: a 20-year autopsy study.

Abstract: Autopsy studies remain an essential tool for understanding the patterns of fungal disease not detected ante mortem with current diagnostic approaches. We collected data concerning the microbiological trends, patient clinical characteristics and sites of involvement for invasive fungal infections (IFIs) identified at autopsy in a single large cancer treatment centre over a 20-year period (1989-2008). The autopsy rate and IFI prevalence both declined significantly during the study period. The prevalence of Aspergillus spp. decreased significantly from the first 15 years of the study (from 0.12 to 0.14 cases per 100 autopsies to 0.07 in 2004-2008; P = 0.04), with only Mucorales accounting for a greater proportion of IFIs over the duration of the study period (0.06 to 0.2 cases per 100 autopsies, P = 0.04). After 2003, moulds accounted for the majority of infections identified at autopsy in the spleen, kidney, heart and gastrointestinal tract. Despite a trend of decreasing prevalence from 1989 to 2004, invasive candidiasis increased in prevalence during later periods 2004-2008 (0.02-0.05 per 100 autopsies) with decreasing kidney, heart and spleen involvement. Despite a declining autopsy rate, these data suggest a decreasing prevalence overall of IFIs with changing patterns of dissemination in patients with haematological malignancies.

Environmental study of azole-resistant Aspergillus fumigatus with TR34/L98H mutations in the cyp51A gene in Iran.

Abstract: Azole resistance in Aspergillus is emerging in European and Asian countries. As azoles are mainstay of therapy in the management of aspergillosis, azole resistance has serious implications in patient management. We report the emergence of resistance to triazoles in environmental Aspergillus fumigatus isolates in Iran. The TR34/L98H mutation was the only resistance mechanism. Overall 3.3% of the A. fumigatus isolates from hospital surroundings in Sari and Tehran had the same TR34/L98H STRAf genotype and were related to some resistant clinical and environmental TR34/L98H isolates from the Netherlands and India. It is emphasised that routine resistance surveillance studies focusing on environmental and clinical samples are warranted to yield the true prevalence of azole resistance in A. fumigatus in Iran.

Itraconazole in chronic cavitary pulmonary aspergillosis: a randomised controlled trial and systematic review of literature.

Abstract: Summary Patients with aspergilloma can be safely managed with supportive therapy in absence of massive haemoptysis. We hypothesised that chronic cavitary pulmonary aspergillosis (CCPA) could also be managed on similar grounds. The aim of this prospective, randomised controlled trial was to evaluate the efficacy and safety of itraconazole in CCPA. Consecutive patients of CCPA with presence of chronic pulmonary/systemic symptoms; and pulmonary cavities; and presence of Aspergillus (immunological or microbiological) were randomised to receive either supportive treatment alone or itraconazole 400 mg daily for 6 months plus supportive therapy. Response was assessed clinically, radiologically and overall after 6 months therapy. A total of 31 patients (mean age, 37 years) were randomised to itraconazole (n = 17) or the control (n = 14) group. The number of patients showing overall response was significantly higher in the itraconazole group (76.5%) vs. the control (35.7%) group (P = 0.02). The numbers of patients demonstrating clinical or radiological response were also significantly higher in the itraconazole group (P = 0.016 and 0.01 respectively). Adverse events were noted in eight patients in the itraconazole group, however, none was serious or led to discontinuation of the study drug. Itraconazole was found to be superior to standard supportive treatment alone in stabilising cases of CCPA. (clinicaltrials.gov; NCT01259336).

Schizophyllum commune as an emerging fungal pathogen: a review and report of two cases

Abstract: We report Schizophyllum commune as the aetiological agent of one case each of allergic broncho-pulmonary mycosis (ABPM) and pulmonary fungal ball, and present a literature review. The fungus was characterised by clamp connections, hyphal spicules, and formation of basidiocarps with basidiospores. The phenotypic identification was confirmed by sequencing of the ITS region. To-date, ABPM and pulmonary fungal ball to S. commune have been reported exclusively from Japan and North America respectively. Of the 71 globally reported cases due to S. commune, 45 (63%) were bronchopulmonary, 22 (31%) sinusitis and 4 extrapulmonary. Taken together, cases of bronchopulmonary disease and sinusitis numbered 67 (94%), indicating the respiratory tract as the primary target of disease. Concerning the country-wise distribution, Japan topped the list with 33 cases (46%), followed by Iran - 7 cases (10%), U.S.A. - 6 cases (9%), and a lower prevalence of 1.4-6% for the remaining 12 countries. The preponderance of the disease in Japan may be attributed to its greater awareness vis-a-vis that in other countries rather than to any geographical/climatic factors. We believe that the burden of S. commune-incited disease is currently underestimated, warranting comprehensive prospective studies to determine its prevalence.

Antifungal activity of silver nanoparticles in combination with nystatin and chlorhexidine digluconate against Candida albicans and Candida glabrata biofilms.

Abstract: The authors thank CAPES (grant BEX 1221/10-8) and FAPESP (2009/15146-5), Brazil, for supporting Douglas Roberto Monteiro work. They also thank David Williams (Cardiff University, Cardiff, UK) for providing the strain 324LA/94, and Valentim Adelino Ricardo Barao for the English review. Silver colloidal nanoparticles used herein were prepared and characterised by LIEC-CMDMC and INCTMN/FAPESP-CNPq, Sao Carlos, Brazil.

Histoplasmosis: a new endemic fungal infection in China? Review and analysis of cases.

Abstract: Histoplasmosis occurs in specific endemic areas, including the mid-western United States, Africa and most of Latin America. Sporadic cases have also been reported in China. The aim of this study was to summarise the epidemiological and clinical data of histoplasmosis in China. We searched the PubMed, CBMdisk and CNKI databases to identify publications related to histoplasmosis in China. Case reports/series on patients with histoplasmosis were included. A comprehensive literature review identified additional cases. The relevant material was evaluated and reviewed. Overall, 300 cases of histoplasmosis were reported in China from 1990 to 2011, and 75% were from regions through which the Yangtze River flows. Most of the patients were autochthonous infections. Of these, 43 patients had pulmonary histoplasmosis and 257 patients had disseminated histoplasmosis. Common underlying diseases included HIV infection, diabetes mellitus and liver diseases. Fever was the most frequently reported clinical feature in disseminated histoplasmosis, followed by splenomegaly and hepatomegaly. Cases of histoplasmosis had a prominent geographical distribution in China. Histoplasmosis should be considered in the diagnosis of patients with relevant symptoms and a history of travel to or residence in these areas.

Prevalence of biofilm formation in clinical isolates of Candida species causing bloodstream infection

Abstract: Summary Candida species are the fourth most common cause of nosocomial invasive infections. Biofilm formation is recognised as one virulence factor of Candida species. A total of 243 Candida albicans, 81 C. glabrata, 33 C. parapsilosis, 14 C. dubliniensis, 8 C. tropicalis, 8 C. lusitaniae, 5 C. krusei and 1 C. pelliculosa isolates causing bloodstream infections were evaluated for biofilm formation. The biofilm formed on silicone elastomer preincubated with human serum was quantified by estimation of the metabolic activity through XTT assay and visualised by light and scanning electron microscopy. Forty per cent of the C. albicans isolates formed biofilm compared to 88.7% of the non-albicans Candida isolates (P < 0.0001). Among non-albicans Candida spp., biofilm formation was most commonly observed in C. tropicalis and C. lusitaniae (100%), followed by C. glabrata (95%), C. dubliniensis (85.7%) and C. parapsilosis (66.7%). A quantitative correlation was observed between the amount of biofilm observed microscopically, and that determined by metabolic activity measurements. The biofilms of all Candida species were composed of basal yeast cells with the exception of C. parapsilosis which produced biofilms consisting of pseudohyphae and aggregated yeast cells. These results suggest that biofilm formation as a virulence factor might have a higher significance for non-albicans Candida species than for C. albicans.

Confocal laser scanning microscopy as a new valuable tool in the diagnosis of onychomycosis - comparison of six diagnostic methods.

Abstract: Summary Onychomycosis is common and can mimic several different nail disorders. Accurate diagnosis is essential to choose the optimum antifungal therapy. The aim of this study was to evaluate the use of confocal laser scanning microscopy (CLSM) and optical coherence tomography (OCT) as new non-invasive diagnostic tools in onychomycosis and to compare them with the established techniques. In a prospective trial, 50 patients with suspected onychomycosis and 10 controls were examined by CLSM and OCT. Parallel KOH preparation, culture, PAS-staining and PCR were performed. PCR showed the highest sensitivity, followed by CLSM, PAS and KOH preparation. OCT offered the second best sensitivity but displayed the lowest specificity. CLSM and KOH preparation showed a high specificity and CLSM offered the best positive predictive value, similar to KOH preparation and OCT. Fungal culture showed the lowest sensitivity and the worst negative predictive value, yet culture and PCR are the only techniques able to identify genus and species. In summary, CLSM was comparable to PAS staining and superior to KOH preparation. Due to the low specificity we assess OCT not as appropriate. In the differentiation of species PCR outplays the fungal culture in terms of time and sensitivity.

Minireview: host defence in invasive aspergillosis.

Abstract: Summary Aspergillus is a saprophytic fungus, which mainly becomes pathogenic in immunosuppressed hosts. A failure of host defences results in a diverse set of illnesses, ranging from chronic colonisation, aspergilloma, invasive disease and hypersensitivity. A key concept in immune responses to Aspergillus species is that host susceptibility determines the morphological form, antigenic structure and physical location of the fungus. Traditionally, innate immunity has been considered as a first line of defence and activates adaptive immune mechanisms by the provision of specific signals; innate and adaptive immune responses are intimately linked. The T-helper cell (TH1) response is associated with increased production of inflammatory cytokines IFN-γ, IL-2 and IL-12 and stimulation of antifungal effector cells. Alternatively, TH2-type responses are associated with suppression of antifungal effector cell activity, decreased production of IFN-γ and increased concentrations of IL-4 and IL-10, which promote humoral responses to Aspergillus. The host’s defensive capacity is defined by the sum of resistance and tolerance. Resistance displays the ability to limit fungal burden and elimination of the pathogen, and tolerance means the ability to limit host damage caused by immune response.

Evaluation of novel nystatin nanoemulsion for skin candidosis infections.

Abstract: One of the most common fungal skin infections is candidosis. Topical application of drugs at the pathological sites offers potential advantage of direct drug delivery to the site of action. The main aim of this work was to evaluate an optimal nystatin nanoemulsion for topical application avoiding undesirable side effects as systemic absorption and toxicity. Surface morphology and droplet size distribution of nystatin nanoemulsion was determined by transmission electronic microscopy and dynamic light scattering. Vertical diffusion Franz-type cells and high-performance liquid chromatography were used to perform the in vitro release and ex vivo human skin permeation studies. Transdermal permeation parameters were estimated from the permeation values using different theoretical approaches. Microbiological studies were performed to evaluate the antifungal effect. Nanoemulsion exhibited a spherical shape with smooth surface and mean droplet size between 70 and 80 nm. The pharmacokinetic release showed the nanoemulsion is faster than commercial ointment Mycostatin(®) improving the potential therapeutic index. Permeation studies demonstrated nystatin was not absorbed into systemic circulation and the retained amount in the skin was sufficient to ensure an antifungal effect. This antifungal effect was higher for nystatin loaded nanoemulsion than nystatin itself. A therapeutic improvement of the nystatin nanoemulsion treatment compared with the classical ones was achieved.

Fusarium keratitis in South India: causative agents, their antifungal susceptibilities and a rapid identification method for the Fusarium solani species complex.

Abstract: Summary Seventy Fusarium isolates derived from human keratomycosis were identified based on partial sequences of the b-tubulin (b-TUB) and translation elongation factor 1a (EF-1a) genes. Most of the isolates were confirmed as members of the F. solani species complex (75.71%), followed by the F. dimerum species complex (8.57%), the F. fujikuroi species complex (8.57%), the F. oxysporum species complex (4.29%) and the F. incarnatum-equiseti species complex (2.86%). A combined phylogenetic tree was estimated including all the 70 isolates. Isolates belonging to different species complexes formed separate clades. In this study, we also report the first isolation of F. napiforme from human keratomycosis. A new method based on a specific EcoRI restriction site in the EF-1a gene was developed for the rapid identification of F. solani. In vitro antifungal susceptibilities of the isolates to seven antifungals were determined by broth microdilution method. Terbinafine, natamycin and amphotericin B proved to be the most effective drugs, followed by voriconazole. The minimal inhibitory concentrations of clotrimazole, econazole and itraconazole were generally high (64 l gm l 1 ). The interactions between the two most effective antifungals (natamycin and terbinafine) were determined by checkerboard microdilution method. Synergism (71.8%) or no interaction (28.2%) was revealed between the two compounds.

Performance of matrix-assisted laser desorption-time of flight mass spectrometry for identification of clinical yeast isolates

Abstract: Accurate and fast yeast identification is important when treating patients with invasive fungal disease as susceptibility to antifungal agents is highly species related. Matrix-assisted laser desorption-time of flight mass spectrometry (MALDI-TOF-MS) provides a powerful tool with a clear potential to improve current diagnostic practice. Two MALDI-TOF-MS-systems (BioTyper/Bruker and Saramis/AXIMA) were evaluated using: (i) A collection of 102 archived, well characterised yeast isolates representing 14 different species and (ii) Prospectively collected isolates obtained from clinical samples at two participating laboratories. Of the 102 archived isolates, 81 (79%) and 92 (90%) were correctly identified by Saramis/AXIMA and BioTyper/Bruker respectively. Saramis/AXIMA was unable to separate Candida albicans, C. africana and C. dubliniensis in 13 of 32 isolates. After manual interpretation of the mass spectra output, all 13 isolates were correctly identified, resulting in an overall identification performance of 92%. No misidentifications occurred with the two systems. Of the routine isolates one laboratory identified 99/99 (100%) and 90/99 (91%) to species level by Saramis/Axima and conventional identification, respectively, whereas the other laboratory identified 83/98 (85%) to species level by both BioTyper/Bruker and conventional identification. Both MALDI-TOF-MS systems are fast, have built-in databases that cover the majority of clinically relevant Candida species, and have an accuracy that outperforms our conventional identification systems.

Posaconazole after previous antifungal therapy with voriconazole for therapy of invasive aspergillus disease, a retrospective analysis.

Abstract: Invasive aspergillosis is an important cause of morbidity and mortality in haematological patients. Current guidelines recommend voriconazole as first-line therapy. A change in class of antifungal agent is generally recommended for salvage therapy. The focus of this analysis was to assess if posaconazole is suitable for salvage therapy following voriconazole treatment. This was a retrospective investigation on patients with sequential antifungal therapy of posaconazole after voriconazole identified at four German hospitals. Response rates at 30 and 60 days following start of posaconazole application and toxicity of azoles by comparing liver enzymes and cholestasis parameters were evaluated. Data were analysed by descriptive statistics. Overall, the success rate was 72.2% [15 of 36 patients showed complete response (41.7%), 11 patients partial response (30.6%) at any time point], eight patients failed treatment and two were not evaluable. Mean laboratory values increased during voriconazole and decreased during posaconazole treatment: aspartate aminotransferase (increase: 31.9 U l(-1) vs. decrease: 19.6 U l(-1) ), alanine aminotransferase (32.4 U l(-1) vs. 19.8 U l(-1) ), gamma-glutamyl transferase (124.2 U l(-1) vs. 152.3 U l(-1) ) and alkaline phosphatase (71.5 U l(-1) vs. 40.3 U l(-1) ) respectively. No patient discontinued posaconazole therapy due to an adverse event. In this analysis posaconazole was a safe and effective antifungal salvage therapy in patients with prior administration of another triazole.

Inflammatory Tinea capitis: a 12‐year study and a review of the literature

Abstract: Inflammatory Tinea capitis (TC) is a rare form of TC. The aim of this study was to review epidemiological, clinical and mycological profile of inflammatory TC. We present a retrospective study (1999-2010), enrolled all the cases of inflammatory TC observed at a referral hospital in the northern Tunisia. One hundred and twenty-one patients with inflammatory TC, 83 male patients (68.6%) and 38 female patients (31.4%) were enrolled. The mean age was about 8 years. A majority of TC (71.9%) were in patients lesser than 10 years of age. Positive family history and contact with animals were noted in seven and 35 cases respectively. Direct examination was positive in 110 cases (59 ectothrix, 51 endothrix) and positive cultures were obtained in 105 patients (49 Trichophyton violaceum, 31 Microsporum canis, 13 Trichophyton interdigitale complex, 12 Trichophyton verrucosum). Systemic treatment was carried out in 115 patients with griseofulvin, in one with terbinafine. A complete recovery was noted in 88 cases; and persistent alopecia in 28 cases. The inflammatory TC is rare, but more common in rural families. The disease mostly affected male genders (68.6%) and T. violaceum remains the common pathogen of inflammatory TC in northern Tunisia.

In Vitro Antifungal Activity of Topical and Systemic Antifungal Drugs Against Malassezia Species

Abstract: The strict nutritional requirements of Malassezia species make it difficult to test the antifungal susceptibility. Treatments of the chronic and recurrent infections associated with Malassezia spp. are usually ineffective. The objective of this study was to obtain in vitro susceptibility profile of 76 clinical isolates of Malassezia species against 16 antifungal drugs used for topical or systemic treatment. Isolates were identified by restriction fragment length polymorphism. Minimal inhibitory concentrations (MIC) were obtained by a modified microdilution method based on the Clinical Laboratory Standards Institute reference document M27-A3. The modifications allowed a good growth of all tested species. High in vitro antifungal activity of most tested drugs was observed, especially triazole derivatives, except for fluconazole which presented the highest MICs and widest range of concentrations. Ketoconazole and itraconazole demonstrated a great activity. Higher MICs values were obtained with Malassezia furfur indicating a low susceptibility to most of the antifungal agents tested. Malassezia sympodialis and Malassezia pachydermatis were found to be more-susceptible species than M. furfur, Malassezia globosa, Malassezia slooffiae and Malassezia restricta. Topical substances were also active but provide higher MICs than the compounds for systemic use. The differences observed in the antifungals activity and interspecies variability demonstrated the importance to studying the susceptibility profile of each species to obtain reliable information for defining an effective treatment regimen.

Peripheral and total parenteral nutrition as the strongest risk factors for nosocomial candidemia in elderly patients: a matched case-control study.

Abstract: Candidemia is an important cause of morbidity and mortality in the healthcare setting. However, there is limited information about risk factors for such infection among elderly patients. A case-control study was conducted during the period 2008-2011. For each case, two controls were selected among patients admitted to the same hospital, and individually matched by sex, age, time of admission, hospital ward and hospitalisation duration. The adjusted odds ratio (OR) was calculated using multiple conditional logistic regression. We identified 145 episodes of candidemia occurring in 140 patients with a median age of 80 years. Candida albicans caused 55% of all candidemia episodes. After adjustment, candidemia was strongly associated with duration of total [duration > 7 days: OR = 20.09; 95% confidence interval (CI): 3.44-117.52] and peripheral parenteral nutrition (duration > 7 days: OR = 26.83; 95% CI: 6.54-110.17), other central vascular catheters (OR = 5.17; 95% CI: 1.24-23.54) and glycopeptide antibiotics (OR = 6.45; 95% CI: 1.90-21.91). Duration of peripheral and total parenteral nutrition and antibiotics predicted over 50% of all candidemias. Intervention studies should be planned to evaluate effectiveness of candidemia prevention by restricting parenteral nutrition, prompting earlier enteral feeding, and reducing use of antibiotics, especially glycopeptides, in elderly patients.

Epidemiology of Aspergillus keratitis at a tertiary care eye hospital in South India and antifungal susceptibilities of the causative agents.

Abstract: In recent years, Aspergillus species are reported frequently as aetiological agents of fungal keratitis in tropical countries such as India Our aim was to evaluate the epidemiological features of Aspergillus keratitis cases over a 3-year period in a tertiary eye care hospital and to determine the antifungal susceptibilities of the causative agents This study included culture proven Aspergillus keratitis cases diagnosed between September 2005 and August 2008 Data including prevalence, predisposing factors and demography were recorded, the isolates were identified by morphological and molecular methods and the minimum inhibitory concentration values of antifungal agents towards the isolates were determined by the microdilution method Two hundred Aspergillus isolates were identified among 1737 culture proven cases Most of the aspergilli (75%) proved to be A flavus, followed by A fumigatus (115%) Sixteen (8%) isolates belonged to species that are recently identified causative agents of mycotic keratitis Most of the infected patients (88%) were adults ranging from 21 to 70 years of age Co-existing ocular disease was confirmed in 165% of the patients Econazole, clotrimazole and ketoconazole were notably active against A flavus Aspergillus keratitis is a significant problem in patients with ocular lesions in South-Indian States, warranting early diagnosis and initiation of specific antifungal therapy to improve outcome

Multicentre surveillance study on feasibility, safety and efficacy of antifungal combination therapy for proven or probable invasive fungal diseases in haematological patients: the SEIFEM real-life combo study

Abstract: Summary This multicentre observational study evaluated the feasibility, efficacy and toxicity of antifungal combination therapy (combo) as treatment of proven or probable invasive fungal diseases (IFDs) in patients with haematological malignancies. Between January 2005 and January 2010, 84 cases of IFDs (39 proven and 45 probable) treated with combo were collected in 20 Hematological Italian Centres, in patients who underwent chemotherapy or allogeneic haematopoietic stem cell transplantation for haematological diseases. Median age of patients was 34 years (range 1–73) and 37% had less than 18 years. Acute leukaemia was the most common underlying haematological disease (68/84; 81%). The phase of treatment was as follows: first induction in 21/84 (25%), consolidation phase in 18/84 (21%) and reinduction/salvage in 45/84 (54%). The main site of infection was lung with or without other sites. The principal fungal pathogens were as follows: Aspergillus sp. 68 cases (81%), Candida sp. six cases (8%), Zygomycetes four cases (5%) and Fusarium sp. four cases (5%). The most used combo was caspofungin+voriconazole 35/84 (42%), caspofungin + liposomal amphotericin B (L-AmB) 20/84 (24%) and L-AmB+voriconazole 15/84 (18%). The median duration of combo was 19 days (range 3–180). The overall response rate (ORR) was 73% (61/84 responders) without significant differences between the combo regimens. The most important factor that significantly influenced the response was granulocyte (PMN) recovery (P 0.009). Only one patient discontinued therapy (voriconazole-related neurotoxicity) and 22% experienced mild and reversible adverse events (hypokalaemia, ALT/AST increase and creatinine increase). The IFDs-attributable mortality was 17%. This study indicates that combo was both well tolerated and effective in haematological patients. The most used combo regimens were caspofungin + voriconazole (ORR 80%) and caspofungin + L-AmB (ORR 70%). The ORR was 73% and the mortality IFD related was 17%. PMN recovery during combo predicts a favourable outcome. Clinical Trials Registration: NCT00906633.

Epidemiology of candidemia in patients with hematologic malignancies and solid tumours in Brazil

Abstract: Summary Candidemia in cancer patients may differ according to the type of cancer To characterise the epidemiology and outcome of candidemia in cancer patients from Brazilian hospitals, we compared the characteristics of patients with hematologic malignancies (HM) and solid tumours (ST) A retrospective study was performed, based on data collected from laboratory-based surveillance studies in 18 tertiary care hospitals between March/2003 and December/2007 The characteristics of patients with HM (n = 117) were compared with patients with ST (n = 248) Predictors of 30-day mortality were identified by uni- and multivariate analyses Candidemia in HM was more likely to occur in the setting of chemotherapy, corticosteroids, neutropenia, mucositis and tunnelled central venous catheter (CVC), whereas surgery, intensive care unit admission and invasive procedures (mechanical ventilation, parenteral nutrition and CVC) were more frequent in ST The 30-day mortality rate was higher in the ST group (65% vs 46%, P = 0001) Factors significantly associated with 30-day mortality were older age and intensive care unit admission Important differences in the epidemiology and outcome of candidemia in HM and ST were observed The characterisation of the epidemiology is important to drive preventive measures and to select appropriate therapies

Aspergillosis of bones and joints – a review from 2002 until today

Abstract: Poor clinical outcome and complicated neurological complications illustrate the severity of bone and joint infections with Aspergillus species. Host predisposing conditions are immunosuppression, intravenous drug use, a variety of chronic underlying diseases and prior surgical interventions. Nosocomial infections may originate from contaminated air ventilation systems or water pipes. Most common causative pathogen is Aspergillus fumigatus, followed by Aspergillus flavus and Aspergillus nidulans. A. niger, A. tubingensis and A. terreus are rare but stress the need of targeted and adapted antimycotic therapy. Diagnosis has to be pursued by means of MRI imaging techniques and tissue specimens. Multimodal treatment strategy is based on a combination of surgical debridement of necrotic bone and cartilage and systemically active antifungal treatment. Voriconazole combines satisfactory systemic antifungal effect, high oral bioavailability and good bone penetration. Development of fungicidal cement spacers still continues and in vitro data show promising results of bioactive cements. Purpose of this review of literature published between 2002 and 2013 was to provide up-to-date information on pathogenesis, diagnostic approach and treatment recommendations. Properly established treatment guidelines and prophylaxis for patients at risk are required as the high mortality rate continues to pose a future challenge.

Quality of life in patients with toenail onychomycosis.

Abstract: Summary Onychomycosis is a common, chronic fungal nail infection that can have a significant negative impact on patients' physical and social functioning and emotional well-being. This study was undertaken to assess health-related quality of life (HRQoL) in patients with toenail onychomycosis. The Onychomycosis QoL questionnaire (ONYCHO), as a disease-specific instrument, and the Short Form 36 Health Survey (SF-36) as a generic instrument, were applied in 140 consecutive patients affected by onychomycosis. Women and patients who were experiencing toenail onychomycosis for more than 2 years were reporting worse disease-specific HRQoL. The patients working in blue-collar occupations and patients with greater involvement of individual nails were more affected by onychomycosis regarding symptoms. The results of this study confirm that although onychomycosis is not a life-threatening disease, it can significantly reduce patients' QoL.

Major variations in Aspergillus fumigatus arising within aspergillomas in chronic pulmonary aspergillosis

Abstract: Aspergillomas develop from progressive layers of mycelial growth on the walls of pulmonary cavities over months. Aspergillomas are characteristic of chronic pulmonary aspergillosis and are a risk factor for azole resistance. We investigated genotypic and phenotypic alterations in Aspergillus fumigatus recovered from aspergillomas. Aspergillomas were removed from three patients (two at surgery, one at autopsy) and dissected. Overall 92 colonies of A. fumigatus were isolated. Microsatellite typing was conducted to determine genetic type. Itraconazole, voriconazole and posaconazole susceptibilities were performed. The cyp51A gene was sequenced in 22 isolates. Isolates from Patient 1 (n?=?25) were azole susceptible and resistant, although all cyp51A sequences were wild type, the isolates split into two distinct clades. In Patient 2, isolates were less variable (n?=?10), all were azole susceptible. In Patient 3 only azole-resistant strains (n?=?57) were isolated, with M220K or M220T Cyp51A alterations, and microevolution was indicated. Marked diversity was observed in isolates from these patients; revealing differences in azole susceptibility, mechanism of resistance and genetic type. Importantly, routine sampling from respiratory specimens proved suboptimal in all cases; azole resistance was missed (Patient 1), cultures were negative (Patient 2) and high-level posaconazole resistance was not detected (Patient 3).

Sensitivity of galactomannan enzyme immunoassay for diagnosing breakthrough invasive aspergillosis under antifungal prophylaxis and empirical therapy.

Abstract: Summary Data on diagnostic performance of Galactomannan (GM) testing in patients under mould-active regimens are limited. Whether sensitivity of GM testing for diagnosing breakthrough invasive aspergillosis (IA) is decreased under antifungal prophylaxis/therapy remains therefore a point of discussion. We retrospectively analysed GM test results in patients who were admitted with underlying haematological malignancies to two Divisions of the Medical University Hospital of Graz, Austria, between 2009 and 2012. Only cases of probable and proven IA that were diagnosed by other methods than GM testing were included (time of diagnosis = day 0). We compared GM results of patients with/without therapy/prophylaxis for the period of 2 weeks prior (week −2) until 3 weeks postdiagnosis. A total of 76 GM test results in nine patients were identified. Six patients had received antifungal therapy/prophylaxis from week −2, whereas three patients were treated with therapy from the time of diagnosis at week 0. GM testing was positive in 45/76 (59%) of samples. Sensitivity of GM testing for detection of proven or probable IA at week −1 and 0 was 77% and 79% in patients with mould-active regimens. We conclude that GM testing might be a useful diagnostic method for breakthrough IA in patients receiving mould-active prophylaxis/therapy.

Non-Aspergillus fungal infections in chronic granulomatous disease.

Abstract: Summary Chronic granulomatous disease (CGD) is a congenital immunodeficiency, characterised by significant infections due to an inability of phagocyte to kill catalase-positive organisms including certain fungi such as Aspergillus spp. Nevertheless, other more rare fungi can cause significant diseases. This report is a systematic review of all published cases of non-Aspergillus fungal infections in CGD patients. Analysis of 68 cases of non-Aspergillus fungal infections in 65 CGD patients (10 females) published in the English literature. The median age of CGD patients was 15.2 years (range 0.1–69), 60% of whom had the X-linked recessive defect. The most prevalent non-Aspergillus fungal infections were associated with Rhizopus spp. and Trichosporon spp. found in nine cases each (13.2%). The most commonly affected organs were the lungs in 69.9%. In 63.2% of cases first line antifungal treatment was monotherapy, with amphotericin B formulations being the most frequently used antifungal agents in 45.6% of cases. The overall mortality rate was 26.2%. Clinicians should take into account the occurrence of non-Aspergillus infections in this patient group, as well as the possibility of a changing epidemiology in fungal pathogens. Better awareness and knowledge of these pathogens can optimise antifungal treatment and improve outcome in CGD patients.

Exophiala dermatitidis endocarditis on native aortic valve in a postrenal transplant patient and review of literature on E. dermatitidis infections

Abstract: Atul K. Patel, Ketan K. Patel, Prakash Darji, Rachna Singh, M. R. Shivaprakash and Arunaloke Chakrabarti Infectious Diseases Clinic, Vedanta Institute of Medical Sciences, Ahmedabad, India, Department of Nephrology and Renal Transplant, Sterling Hospital, Ahmedabad, India and Division of Mycology, Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

Serum galactomannan assay for the diagnosis of invasive aspergillosis in children with haematological malignancies.

Abstract: Summary Diagnostic efficacy of Galactomannan (GM) assay for invasive aspergillosis (IA) is variably reported. Data from developing countries are scant. Children with haematological malignancies and fever were enrolled prospectively. Blood sample for GM was drawn on the day of admission; levels were measured with Platellia Aspergillus enzyme immunoassay. Diagnostic criteria were adapted from EORTC-MSG-2002. Proven, probable and possible episodes were considered as the disease group. One hundred febrile episodes in 78 patients were evaluated. The mean age was 6.1 years. Majority (75%) episodes were in patients with acute lymphoblastic leukaemia. One episode each was diagnosed with proven and probable IA, while 23 were diagnosed with possible IA. Best results were obtained with a cut-off value of 1.0, with sensitivity, specificity, positive and negative predictive value of 60%, 93%, 75 and 87 respectively. The sensitivity dropped to 40%, at cut-off value of 1.5 and specificity was 38%, at a cut-off of 0.5. A higher value of GM correlated with pulmonary nodules (P = 0.037) and mortality (P = 0.001). GM assay is adjunctive to clinical/radiological evidence. A negative GM assay may not reassure the physician against the use of amphotericin in patients with febrile neutropenia, as it does not exclude the diagnosis of clinically relevant other fungal infections, particular mucormycosis.

Methods for obtaining reliable and reproducible results in studies of Candida biofilms formed in vitro.

Abstract: Biofilm formation is one of the most important attributes for virulence in Candida species and contributes to increased resistance to antifungal drugs and host immune mechanisms. These features have led to the development of several methodologies to reproduce a sessile community in vitro that can be used to study the development of a biofilm, its interaction with other microorganisms and the environment, and its susceptibility to available antifungal agents and also to search for new therapy strategies. The purpose of this review is to describe the most commonly used methods to study Candida biofilms in vitro, to discuss the benefits and limitations of the different methods to induce biofilm formation, and to analyse the architecture, viability and growth kinetics of Candida biofilms.

Sinusitis and frontal brain abscess in a diabetic patient caused by the basidiomycete Schizophyllum commune: case report and review of the literature

Abstract: Martin Hoenigl, Engelbert Aspeck, Thomas Valentin, Bettina Heiling, Katharina Seeber, Robert Krause, Heinz Stammberger, Alfred Beham and Walter Buzina Section of Infectious Diseases, Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria, Department of Neurology, Medical University of Graz, Graz, Austria, Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria, Department of Otorhinolaryngology, Medical University of Graz, Graz, Austria and Institute of Pathology, Medical University of Graz, Graz, Austria

Dermatophytes isolated from superficial fungal infections in Krakow, Poland, between 1995 and 2010

Abstract: Superficial fungal infections due to dermatophytes are common over the world and their frequency is constantly increasing. The aim of our study was to discuss fungal infections with frequency of occurrence, clinical stages and aetiology in patients admitted to dermatological ward and microbiological laboratory of the specialist hospital in Krakow. Investigations performed between 1995 and 2010 included the group of 5333 individuals. Dermatophyte infections, confirmed by culture, were revealed in 1007 subjects (18.9%), i.e. in 553 males and 454 females. The most frequent clinical forms of infections were tinea unguium and tinea pedis, caused mainly by Trichophyton rubrum and by Trichophyton mentagrophytes. Tinea corporis, tinea manuum, tinea capitis and tinea cruris constituted a small percentage of infections and the main aetiological factors of these dermatomycoses were also T. rubrum and T. mentagrophytes. Between 1995 and 2000 there were stated small differences in the number of isolated strains of dermatophytes in comparison with the number of examined patients. Since 2006 there has been observed a decrease in number of patients in our hospital with suspected fungal infections, but per cent of positive cultures has remained unchanged in comparison with earlier period.

Important aspects of oral paracoccidioidomycosis–a literature review

Abstract: Summary Paracoccidioidomycosis is a deep mycosis endemic to Latin America, with considerable morbidity and mortality. It is caused by the dimorphic fungus Paracoccidioides brasiliensis, which affects, among other organs in the human body, the oral cavity. Fungus virulence and immunocompetence of the host determine the establishment of infection or active disease, whose severity and clinical behaviour depend mostly on the cellular immune response of the host. Often, oral lesions constitute the first sign and site of confirmation of diagnosis, which in most cases is delayed. The success of the treatment depends on early and correct diagnosis, as well as on the patient’s adherence to the drug therapy.