A prospective comparison of galactomannan in bronchoalveolar lavage fluid for the diagnosis of pulmonary invasive aspergillosis in medical patients under intensive care: comparison with the diagnostic performance of galactomannan and of (1→ 3)-ß-d-glucan chromogenic assay in serum samples.

Diagnosis of fungal pneumonia (FP) in critically ill patients is challenging. Circulating biomarkers for the diagnosis of FP have limitations and the combination of different assays in serum samples and directly from the target organ may further improve the diagnosis of FP. We prospectively assessed the diagnostic utility of paired galactomannan (GM) in bronchoalveolar lavage fluid (BAL) and serum GM and (1→3)-ß-D-glucan (BG) assays in critically ill patients at risk of FP. Patients with FP were classified according to European Organisation for Research and Treatment of Cancer-Mycoses Study Group criteria, with modifications. Out of 847 admissions, 51 patients were eligible. There were nine invasive aspergillosis (IA) cases (four proven, five probable), three proven Pneumocysitis jirovecii pneumonia (PJP) cases and one mixed FP case (probable IA and proven PJP). The diagnostic accuracy as given by the area under the receiver operating characteristic curve in IA cases (proven and probable) for GM in BAL was 0.98 (95% CI, 0.94-1.00), whilst for GM and BG in serum it was 0.85 (95% CI, 0.74-0.96) and 0.815 (95% CI, 0.66-0.96), respectively. For IA cases (proven and probable) AUC for GM in BAL was significantly higher than GM and BG in serum (p 0.025 and p 0.032, respectively). In one of four proven and one of six probable IA cases, GM in serum remained negative, whereas GM in BAL was positive. In patients with IA, GM (90%) and BG (80%) appeared a mean of 4.3 days (range, 1-10 days) before Aspergillus was cultured. GM detection in BAL appears to improve the diagnosis of IA in critical patients.

Clinical significance of the detection of Candida albicans germ tube-specific antibodies in critically ill patients.

The present study, comprising a prospective multicentre study including 53 non-neutropenic patients from intensive care units (ICU) in six Spanish tertiary-care hospitals, was carried out to determine the clinical significance and influence on mortality of Candida albicans germ tube-specific antibodies (CAGTA). There were 22 patients (41.5%) for whom the CAGTA results were positive, although none of had a blood culture positive for Candida. The intra-ICU mortality rate was significantly lower (p = 0.004) in CAGTA-positive patients (61.2% vs. 22.7%). Multivariate analysis confirmed that a positive CAGTA result was the only protective factor to be independently associated with ICU mortality (beta coefficient = -0.3856; 95% confidence interval = -0.648 to -0.123).

Estado actual del diagnóstico precoz de las infecciones invasoras causadas por Aspergillus y otros hongos filamentosos emergentes / Early diagnosis of invasive fungal infections of caused by Aspergillus and other emerging mycelial fungi

La utilidad de los marcadores serológicos en el diagnóstico de las infeccionesfúngicas invasoras causadas por Aspergillus y otros hongos filamentososemergentes se fundamenta en la capacidad de estos marcadores de detectarla infección causada por las distintas especies de hongos filamentosos.Los procedimientos microbiológicos tradicionales para el diagnóstico de lainfección fúngica son lentos y poco sensibles. La detección de antígenoso de (1-3)-ß-D-glucano en sangre han sido desarrollados y validados enlaboratorios clínicos. Se revisan estas nuevas herramientas diagnósticas,así como su aplicación clínica e impacto(AU)

The usefulness of surrogate markers in the diagnosis of invasive fungalinfections caused by Aspergillus and other emerging mycelial fungi is basedon the ability of surrogate markers to detect the infection caused by differentspecies of mycelial fungi. Conventional microbiological methods for diagnosisof fungal disease are slow and insensitive. Antigen based assays ormeasurement of (1-3)-ß-D-glucan in blood have been developed and validatedin clinical laboratories. We review these diagnostic contemporary tools, theirclinical application and impact(AU)

False positive galactomannan results in adult hematological patients treated with piperacillin-tazobactam

Se han estudiado prospectivamente dos veces por semana los niveles séricosde galactomanano (GM) (Platelia Aspergillus) en 78 pacientes con cáncerhematológico (90 episodios) para el diagnóstico de aspergilosis invasora (AI).Hubo cinco casos de AI probada y cuatro de AI probable. La sensibilidad,especificidad y valor predictivo positivo y negativo fueron de 100, 88, 47y 100% respectivamente. Hubo ocho pacientes con GM falsos positivos(10,2%). En seis enfermos la falsa reactividad de GM fue debida a laadministración de piperacilina-tazobactam (P-T), encontrándose unaasociación significativa entre galactomananos falsos positivos y laadministración de P-T (p < 0.01). Otros dos pacientes sin AI y GM falsospositivos (2,5%) tuvieron como posible causa de falsa positividad laenfermedad injerto contra huésped y uno de ellos además tenía mucositisgrado IV. En el trabajo se han analizado los patrones cinéticos con falsareactividad de GM en relación a P-T(AU)

In this prospective study including 78 adult patients with hematologicalmalignancy (90 episodes) we performed galactomannan (GM)(Platelia Aspergillus) screening twice weekly for the diagnosis of invasiveaspergillosis. There were five proven and four probable invasive aspergillosiscases. The sensitivity, specificity and positive and negative predictive valueswere 100, 88, 47 and 100%, respectively. There were eight patients with falsepositive GM (10.2%). In six patients the false GM reactivity was due to theadministration of piperacillin-tazobactam (P-T). A significant association wasfound between false positive GM ( 0.5) and the administration of P-T(p < 0.01). Two other patients with no invasive aspergillosis (2.5%) and falseGM reactivity had graft versus host disease (GVHD) and one of them had alsomucositis grade IV. The kinetic patterns of false positive GM due to P-T isdiscussed(AU)

Diagnóstico microbiológico tradicional de la candidiasis invasora en el enfermo crítico no neutropénico / Traditional microbiological diagnosis for invasive candidiasis in critical non-neutropenic patients

La candidiasis invasora (CI) en el paciente crítico no neutropénico es la infecciónfúngica más frecuente (80%), y se asocia a una elevada morbimortalidad. Eldiagnóstico microbiológico de la CI es difícil, siendo la positividad de las pruebastradicionales de laboratorio de aparición tardía. En este trabajo se presenta lautilidad del examen directo y de los cultivos de diversas muestras, así como elvalor de los cultivos de vigilancia para establecer el diagnóstico de la CI

Invasive candidiasis is the most prevalent fungal infection in the critical non neutropenicpatient (80%) and is associated with high morbimortality. Microbiologicaldiagnosis is difficult and the positivity of traditional tests appears late in the courseof infection. We herein discuss the utility of direct examination and culturesfrom different sites and the value of surveillance cultures for establishing the likelihoodof invasive candidiasis

Factores de riesgo de la candidiasis invasora: estratificación / Risk factors in invasive candidiasis: stratification

Los factores de riesgo de candidiasis invasora en el enfermo crítico no neutropénicoson bien conocidos, aunque actualmente es necesario desarrollar y validarde forma multicéntrica y prospectiva estrategias de estratificación que prediganla probabilidad de candidiasis invasora. La aplicabilidad clínica sería definir quepacientes deberían recibir profilaxis antifúngica y en cuales se deberían estudiarprospectivamente durante el periodo de riesgo las nuevas técnicas microbiológicasde diagnóstico indirecto de candidiasis invasora, con la finalidad de instaurarun tratamiento precoz

Risk factors of invasive candidiasis in the setting of non neutropenic criticalpatients are well known, although currently there is a need to define and validatein prospective multicenter studies risk assesment strategies that would predictaccuretely the likelihood of invasive candidiasis. The clinical application in orderto define which patients should be treated with antifungal prophylaxis and whichgroups or subgroups of patients should be assessed prospectively during therisk period in order to validate the new diagnostic microbiological indirect techniquesfor invasive candidiasis and preemptive treatment should be based in thesestrategies

Estrategias de tratamiento: profilaxis, tratamiento empírico, precoz (anticipado) y dirigido de candidiasis invasora en el enfermo crítico no neutropénico / Management strategies: prophylaxis, empirical and pre-emptive treatment and treatment of established invasive candidiasis in the critically ill non-neutropenic patient

Para el manejo antifúngico de los enfermos críticos no neutropénicos con candidiasisinvasora hay cuatro estrategias terapéuticas: profilaxis, tratamiento empírico,precoz (anticipado) y dirigido. Todas estas modalidades de tratamiento enrelación con las estrategias de riesgo y los datos microbiológicos de técnicasindirectas diagnósticas de candidiasis invasora serán discutidas en este trabajo

In critically ill non neutropenic patients there are four broad approaches for themanagement of antifungal treatment for invasive candidiasis: prophylaxis, empirical,pre-emptive therapy and treatment of established infections. All these approachesin relationship with risk strategies and microbiological indirect laboratorytechniques for establishing invasive candidiasis will be discussed

Randomized prospective comparative study: short-term treatment with ciclopiroxolamine (cream and solution) versus boric acid in the treatment of otomycosis.

Sixty-four patients with symptomatic otomycosis (80 infected ears) confirmed by direct microscopy and culture were randomly treated for I week with ciclopiroxolamine cream 11% (group A, 20 infected ears, 17 patients), ciclopiroxolamine solution 1% (group B, 20 infected ears, 17 patients) and boric acid (group C, 40 infected ears, 30 patients) and daily mechanical suction aspiration of the debris. An attempt was made to match 11 clinical parameters with both the mycological and bacteriological findings. There was no significant association between the fungal species cultured and the clinical parameters did not vary with the presence or absence of different bacteria; pus was never present in fungal otitis externa (Fisher's test, P < 0.001). Before therapy, a significant number of ears had completely sterile bacterial cultures (p < 0.01, chi2 test); saprophytic Gram-positive bacteria increased after treatment, whilst Gram-negative bacteria, Pseudomonas aeruginosa and Proteus species, decreased after treatment. Clinical total cure rates 3 days after the end of therapy ranged from 50% in group A, 25% in group B to 22.5% in group C. Mycological cure rates were 80% (group A), 95% (group B) and 72.5% (group C). Two weeks after the end of therapy the clinical cure rates were 60% (group A), 65% (group B) and 80% (group C) and the mycological cure rates was 65% for group A and 75% for both group B and C. Eleven patients relapsed with otitis externa: four (20%) in groups A and C and three (15%) in group B. In four cases the infection was due to bacteria and the remaining seven were due to fungi. Six sites relapsed with the same fungal species as that isolated at the start of the study. In this short-term assessment the relapse rate was not significantly associated with predisposing conditions. The tolerance was excellent in group A. Four patients (20%) in group B had mild (two patients) or moderate (two patients) burning and itching with each application. Twelve patients (30%) in group C had severe stinging and five of these patients who had perforated tympanic membranes also experienced pain. In terms of clinical and mycological effectiveness, there were no significant differences between the three treatment groups, although group A (ciclopiroxolamine cream 1%) and B (ciclopiroxolamine solution 1%) both showed significantly better tolerance (Fisher's test, P < 0.05) when compared with boric acid (group C).

Comparative in vitro antifungal activity of amphotericin B lipid complex, amphotericin B and fluconazole.

Amphotericin B (AMB) is considered the gold standard in the treatment of serious systemic mycoses in spite of its nephrotoxicity and adverse effects. Association with lipids enables larger doses of AMB to be given with a longer t((1/2)) and C(max), without the toxic effects at lower concentrations. Liposome-encapsulated AMB shows a lower affinity for mammalian cells and improves V(d), thus decreasing toxicity. Amphotericin B lipid complex (ABLC) is an AMB formulation associated with a biodegradable phospholipid matrix (5% molar) from which the drug is released by cell phospholipases. ABLC is recommended for serious mycoses refractory to conventional antifungal therapy or when AMB is contraindicated. We compared the in vitro antifungal activity of ABLC, AMB and fluconazole (FLZ) against 328 strains of clinically significant opportunistic fungi using a microdilution method (NCCLS, M-27A). 64.9% of the yeasts were inhibited by MIC of ABLC

Nódulo eritematoso en una enferma hematológica / Erythema nodosum in hematology patients

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[Dermatophytes isolated in Hospital Universitario 12 de Octubre (Madrid, Spain).]. / Cambios epidemiológicos observados en un decenio en las dermatofitosis del hospital universitario 12 de Octubre de Madrid: nuevas especies emergentes.

Over a 10 year period (January 1988 - December 1997), 3,241 dermatophyte strains were isolated from 18,465 specimens from patients in whom dermatophytosis was suspected clinically. This represents a 17.5% rate of isolation. Trichophyton rubrum (38.44%), Microsporum canis (28.75%), Epidermophyton floccosum (14.5%) and Trichophyton mentagrophytes (13.5%) were the dominant species, and Trichophyton tonsurans (2.09%) has emerged, whilst in the previous decade it had virtually disappeared. Our study is basically based on an out-patient selected population, and tinea corporis (30.79%), followed by tinea cruris (16.69%) and tinea unguium (16.69%) were the most prevalent clinical forms.

Prevalence of undetected tinea capitis in a prospective school survey in Madrid: emergence of new causative fungi.

From October 1994 to December 1996, a prospective study was undertaken in 10,000 unselected school children in Madrid, aged between 2 and 16 years (mean +/- SD 8.5 +/- 3.6 years). Fifty-two (0.52%) (including 13 immigrants from Africa) had dermatophytes in the scalp: 33 (0.33%) (including 10 immigrants from Africa) had tinea capitis and 19 were scalp carriers. Almost half of the symptomatic cases were caused by Trichophyton tonsurans (12 of 33 cases) and Microsporum canis (16 of 33 cases). T. tonsurans (13 of 19 cases) was the predominant species in the scalp carriers. Twenty-four per cent of the subjects with tinea capitis and 42% of the asymptomatic scalp carriers also had ringworm in other body sites. There was a significantly higher occurrence of tinea capitis (P < 0.001) (particularly due to T. tonsurans: P < 0.001) and of asymptomatic scalp carriers (P < 0.05) (particularly due to anthropophilic species: P < 0.01) in the immigrant population from Africa.