To update the knowledge of the epidemiology of fungaemia episodes in Spain, the species implicated and their in vitro antifungal susceptibilities.
Episodes were identified prospectively over 13 ...months at 44 hospitals. Molecular methods were used to determine the cryptic species inside the Candida parapsilosis and Candida glabrata complexes. Susceptibility to amphotericin B, anidulafungin, caspofungin, fluconazole, flucytosine, itraconazole, micafungin, posaconazole and voriconazole was determined by a microdilution colorimetric method. New species-specific clinical breakpoints (SSCBPs) for echinocandins, fluconazole and voriconazole were applied.
The incidence of the 1357 fungaemia episodes evaluated was 0.92 per 1000 admissions. The incidence of Candida albicans fungaemia was the highest (0.41 episodes/1000 admissions), followed by Candida parapsilosis sensu stricto (0.22). Candida orthopsilosis was the fifth cause of fungaemia (0.02), outnumbered by Candida glabrata and Candida tropicalis. Interestingly, the incidence of fungaemia by C. parapsilosis was 11 and 74 times higher than that by C. orthopsilosis and Candida metapsilosis, respectively. Neither Candida nivariensis nor Candida bracarensis was isolated. Fungaemia was more common in non-intensive care unit settings (65.2%) and among elderly patients (46.4%), mixed fungaemia being incidental (1.5%). Overall susceptibility rates were 77.6% for itraconazole, 91.9% for fluconazole and 96.5%-99.8% for the other agents. Important resistance rates were only observed in C. glabrata for itraconazole (24.1%) and posaconazole (14.5%), and in Candida krusei for itraconazole (81.5%).
Fungaemia is more common in non-critical patients. C. albicans is the most common species, followed by C. parapsilosis and C. glabrata. Nearly 90% of yeasts are susceptible to all antifungal agents tested. Resistance rates change moderately when applying the new SSCBPs.
A prospective, population-based surveillance on candidaemia was implemented in five metropolitan areas of Spain from May 2010 to April 2011. We aimed to describe the distribution and susceptibility ...pattern of Candida species, and to evaluate risk factors for mortality in patients with oncological (solid tumours) and haematological malignancies. Adults (≥16 years) with cancer were included in the present report. Impact of therapeutic strategies on 7- and 30-day mortality were analysed by logistic regression, adjusting for propensity score by inverse weighting probability of receiving early antifungal treatment and catheter removal. We included 238 (32.6%) patients (195 oncological, 43 haematological). Compared with oncological patients, haematological patients were more likely to have received chemotherapy (53.5% versus 17.4%, p < 0.001) or corticosteroids (41.9% versus 21%, p < 0.001), and have neutropenia (44.2% versus 1.5%, p < 0.001). Overall, 14.8% of patients developed breakthrough candidaemia. Non-albicans Candida species (71.1% versus 55.6%, p 0.056) and Candida tropicalis (22.2% versus 7.6%, p 0.011) were more frequent in haematological patients. Based on EUCAST breakpoints, 27.6% of Candida isolates were non-susceptible to fluconazole. Resistance to echinocandins was negligible. Mortality at 7 and 30 days was 12.2% and 31.5%, respectively, and did not differ significantly between the patient groups. Prompt antifungal therapy together with catheter removal (≤48 hours) was associated with lower mortality at 7 days (adjusted OR 0.05; 95% CI 0.01–0.42) and 30 days (adjusted OR 0.27; 95% CI 0.16–0.46). In conclusion, non-albicans species are emerging as the predominant isolates, particularly in haematological patients. Prompt, adequate antifungal treatment plus catheter removal may lead to a reduction in mortality.
We sought to evaluate and review the clinical and histopathologic features of cutaneous infections caused by the environmental opportunistic fungus Alternaria observed in transplant recipients.
We ...conducted a retrospective study of cases of cutaneous alternariosis in transplant recipients given a diagnosis in 3 hospitals in Catalonia, Spain, between 1991 and 2001. The clinical and evolution features were reviewed. A panel of histopathologic features was evaluated by two independent observers in all cutaneous biopsy specimens.
In all, 9 transplant recipients (8 men and 1 woman) presenting opportunistic cutaneous alternariosis were studied. The patients were 4 renal, 2 cardiac, 1 liver, and 2 lung transplant recipients. All patients were treated with different immunosuppressive therapeutic regimes. The lesions were solitary (3 patients) or multiple grouped (6 patients): papules (4 patients), plaques (5 patients), inflammatory nodules (2 patients), and recurrent cellulitis with secondary ulceration (1 patient), mainly located on the lower extremities. No extracutaneous involvement was detected. A previous traumatic event was recorded in two patients. A total of 12 cutaneous biopsy specimens were reviewed. Biopsy specimens from early lesions (<3 months evolution) were often characterized by the presence of epidermal changes (3/6 pseudoepitheliomatous hyperplasia; 50%), a diffuse dermal mixed inflammatory infiltrate of lymphocytes, plasma cells, histiocytes, neutrophils, and giant cells, and rare and focal granuloma formation. Dermal abscess or necrotizing folliculitis was occasionally noted. In biopsy specimens from more advanced lesions (>3 months evolution), the presence of a granulomatous inflammatory infiltrate was a constant feature. Suppurative granulomas (2/6; 33%) and sarcoidlike granulomas (2/6; 33%) were noted. In all biopsy specimens, fungal structures with a typical round-to-oval, thick refractile wall were identified.
Different clinical and histopathologic patterns can be noted in cutaneous alternariosis. Clinically the lesions manifest as solitary or grouped papules, plaques, or nodules mainly involving the lower extremities. Histologically, a relationship between the evolution of the cutaneous lesions and granuloma formation is detected. An increased awareness regarding the clinical and histopathologic features of cutaneous alternariosis in transplant recipients is important to achieve early detection and treatment.
Rapidly fatal cases of invasive fungal infections due to a fungus later identified as Saprochaete clavata were reported in France in May 2012. The objectives of this study were to determine the ...clonal relatedness of the isolates and to investigate possible sources of contamination. A nationwide alert was launched to collect cases. Molecular identification methods, whole-genome sequencing (WGS), and clone-specific genotyping were used to analyze recent and historical isolates, and a case-case study was performed. Isolates from thirty cases (26 fungemias, 22 associated deaths at day 30) were collected between September 2011 and October 2012. Eighteen cases occurred within 8 weeks (outbreak) in 10 health care facilities, suggesting a common source of contamination, with potential secondary cases. Phylogenetic analysis identified one clade (clade A), which accounted for 16/18 outbreak cases. Results of microbiological investigations of environmental, drug, or food sources were negative. Analysis of exposures pointed to a medical device used for storage and infusion of blood products, but no fungal contamination was detected in the unused devices. Molecular identification of isolates from previous studies demonstrated that S. clavata can be found in dairy products and has already been involved in monocentric outbreaks in hematology wards. The possibility that S. clavata may transmit through contaminated medical devices or can be associated with dairy products as seen in previous European outbreaks is highly relevant for the management of future outbreaks due to this newly recognized pathogen. This report also underlines further the potential of WGS for investigation of outbreaks due to uncommon fungal pathogens.
Several cases of rapidly fatal infections due to the fungus Saprochaete clavata were reported in France within a short period of time in three health care facilities, suggesting a common source of contamination. A nationwide alert collected 30 cases over 1 year, including an outbreak of 18 cases over 8 weeks. Whole-genome sequencing (WGS) was used to analyze recent and historical isolates and to design a clade-specific genotyping method that uncovered a clone associated with the outbreak, thus allowing a case-case study to analyze the risk factors associated with infection by the clone. The possibility that S. clavata may transmit through contaminated medical devices or can be associated with dairy products as seen in previous European outbreaks is highly relevant for the management of future outbreaks due to this newly recognized pathogen.
Summary Objective To assess the current clinical features and determinants of outcome of Candida tropicalis bloodstream infection (BSI). Methods A population-based surveillance on Candida BSI was ...conducted from May 2010 to April 2011 in 29 Spanish hospitals. Antifungal susceptibility testing (EUCAST methodology) was centrally performed. The characteristics and outcome of C. tropicalis BSI episodes were compared with those due to other species. Results Fifty-nine out of 752 episodes (7.8%) were due to C. tropicalis (annual incidence: 0.62 cases per 100,000 population). Resistance to fluconazole and voriconazole was found in 23.2% and 26.8% of isolates. Breakthrough BSI occurred in 10.5% of episodes. Risk factors for C. tropicalis BSI were age (odds ratio OR: 1.01; P -value = 0.05), underlying leukaemia (OR: 4.77; P -value = 0.001) and chronic lung disease (OR: 2.62; P -value = 0.002). There were no differences in clinical failure (persistent BSI for ≥72 h after initiation of therapy and/or 30-day all-cause mortality) between C. tropicalis (39.6%) and non- C. tropicalis groups (45.6%). The appropriateness of antifungal therapy or the fluconazole MIC values had no significant impact on outcome, whereas early central venous catheter removal exerted a protective effect. Conclusions C. tropicalis BSI was associated with advanced age, haematological malignancy and respiratory comorbidity. We found no correlation between the unexpectedly high resistance rate to azoles observed and outcome.
Summary
The aim of the study was to analyse the epidemiology and prognosis of candidaemia in elderly patients. We performed a comparison of clinical presentation of candidaemia according to age and a ...study of hazard factors within a prospective programme performed in 29 hospitals. One hundred and seventy‐six episodes occurred in elderly patients (>75 years), 227 episodes in middle‐aged patients (61‐75 years) and 232 episodes in younger patients (16‐60 years). Central venous catheter, parenteral nutrition, neutropenia, immunosuppressive therapy and candidaemia caused by Candida parapsilosis were less frequent in elderly patients. These patients received inadequate antifungal therapy (57.3%) more frequently than middle‐aged and younger patients (40.5% P < .001). Mortality during the first week (20%) and 30 days (42%) was higher in elderly patients. The variables independently associated with mortality in elderly patients during the first 7 days were acute renal failure (OR: 2.64), Pitt score (OR: 1.57) and appropriate antifungal therapy (OR: 0.132). Primary candidaemia (OR: 2.93), acute renal failure (OR: 3.68), Pitt score (OR: 1.38), appropriate antifungal therapy (OR: 0.3) and early removal of the central catheter (OR: 0.47) were independently associated with 30‐day mortality.In conclussion, inadequate antifungal treatment is frequently prescribed to elderly patients with candidaemia and is related with early and late mortality.
We aimed to develop a simple prediction score to identify fluconazole non-susceptible (Flu-NS) candidaemia using simple clinical criteria. A derivation cohort was extracted from the CANDIPOP study, a ...prospective, multicentre, population-based surveillance programme on candidaemia conducted in 29 hospitals in Spain from April 2010 to May 2011. The score was validated with an external, multicentre cohort of adults with candidaemia in six tertiary hospitals in three countries. The prediction score was based on three variables selected by a logistic regression model together with the severity of disease. In total, 617 and 297 cases of candidaemia were included in the derivation and validation cohorts, respectively; of these, 134 (21.7%) and 57 (19.2%) were caused by Flu-NS strains. Factors independently associated with Flu-NS were transplant recipient status (adjusted odds ratio (AOR) 2.13; 95% CI 1.01–4.55; p 0.047), hospitalization in a unit with a high prevalence (≥15%) of Flu-NS strains (7.53; 4.68–12.10; p < 0.001), and previous azole therapy for at least 3 days (2.04; 1.16–3.62; p 0.014). The area under the receiver operating characteristics curve (AUC) was 0.76 (0.72–0.81), and using 2 points as the Flu-NS prediction score cut-off gave a sensitivity of 82.1%, a specificity of 65.6%, and a negative predictive value of 93%. The AUC in the validation cohort was 0.72 (95% CI 0.65–0.79). Hence, the Flu-NS prediction score helped to exclude Flu-NS Candida strains. This could improve the selection of empirical treatments for candidaemia in the future.
Airway colonization by Potentially Pathogenic Microorganisms (PPM) in bronchiectasis is associated with worse clinical outcomes. The electronic nose is a non-invasive technology capable of ...distinguishing volatile organic compounds (VOC) in exhaled breath. We aim to explore if an electronic nose can reliably discriminate airway bacterial colonization in patients with bronchiectasis.
Seventy-three clinically stable bronchiectasis patients were included. PPM presence was determined using sputum culture. Exhaled breath was collected in Tedlar bags and VOC breath-prints were detected by the electronic nose Cyranose 320®. Raw data was reduced to three factors with principal component analysis. Univariate ANOVA followed by post-hoc least significant difference test was performed with these factors. Patients were then classified using linear canonical discriminant analysis. Cross-validation accuracy values were defined by the percentage of correctly classified patients.
Forty-one (56%) patients were colonized with PPM. Pseudomonas aeruginosa (n = 27, 66%) and Haemophilus influenzae (n = 7, 17%) were the most common PPM. VOC breath-prints from colonized and non-colonized patients were significantly different (accuracy of 72%, AUROC 0.75, p < 0.001). VOC breath-prints from Pseudomonas aeruginosa colonized patients were significantly different from those of patients colonized with other PPM (accuracy of 89%, AUROC 0.97, p < 0.001) and non-colonized patients (accuracy 73%, AUROC 0.83, p = 0.007).
An electronic nose can accurately identify VOC breath-prints of clinically stable bronchiectasis patients with airway bacterial colonization, especially in those with Pseudomonas aeruginosa.
•VOC breath-prints from colonized and non-colonized bronchiectasis patients are different.•Patients with colonization by P. aeruginosa and other potentially pathogenic microorganisms have different VOC profiles.•An e-nose can identify Pseudomonas aeruginosa and airway bacterial colonization in Bronchiectasis.
Ibrexafungerp (SCY-078) is the newest oral and intravenous antifungal drug with broad activity, currently undergoing clinical trials for invasive candidiasis.
The aim of this study was to assess the
...activity of ibrexafungerp and comparators against a collection of 434 European blood isolates of
.
Ibrexafungerp, caspofungin, fluconazole, and micafungin minimum inhibitory concentrations (MICs) were collected from 12 European laboratories for 434 blood isolates, including 163
, 108
, 60
, 40
, 29
, 20
, 6
, 2
, 2
, and 1 isolate each of
,
, and
. MICs were determined by the EUCAST broth microdilution method, and isolates were classified according to recommended clinical breakpoints and epidemiological cutoffs. Additionally, 22
from different clinical specimens were evaluated.
Ibrexafungerp MICs ranged from 0.016 to ≥8 mg/L. The lowest ibrexafungerp MICs were observed for
(geometric MIC 0.062 mg/L, MIC range 0.016-0.5 mg/L) and the highest ibrexafungerp MICs were observed for
(geometric MIC 0.517 mg/L, MIC range 0.06-≥8 mg/L). Modal MICs/MIC
s (mg/L) against
spp. were 0.125/0.06 for
, 0.5/0.5 for
, 0.25/0.25 for
, 0.5/0.5 for
, 1/1 for
, 4/2 for
, and 0.5/0.5 for
. Ibrexafungerp showed activity against fluconazole- and echinocandin-resistant isolates. If adopting wild-type upper limits, a non-wild-type phenotype for ibrexafungerp was only observed for 16/434 (3.7%) isolates: 11 (4.6%)
, 4 (5%)
, and 1 (2.5%)
.
Ibrexafungerp showed a potent
activity against
.
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