Sumisión química en los Servicios de Urgencias de la Red Hospitalaria / Chemical submission in the Emergency Services of the Hospital Network

Antecedentes y objetivos: la escopolamina se emplea de forma subrepticia para cometer actos ilícitos. El número de casos de sospecha de consumo de esta sustancia en los servicios sanitarios de urgencias parece haber aumentado en los últimos años. No existe una clara y rigurosa relación con el número de casos descritos en la literatura científica, debido a la dificultad que supone su detección en los sujetos que se encuentran bajo sus efectos. Se plantea la profundización sobre la sumisión química, al describirse un caso clínico registrado en el Servicio de Urgencias del Hospital Central de la Defensa Gómez Ulla y una mejora del abordaje de este tipo de casos desde el triaje. Material y método: el estudio del caso registrado se ha basado en la descripción del método de detección analítico de la escopolamina y se ha apoyado en una revisión bibliográfica empleando distintas bases especializadas en referencia a intoxicación por escopolamina y su empleo en actos delictivos. Resultados: se identificó escopolamina. Al ser una sustancia cuya detección es tiempo-dependiente, el Hospital Central de la Defensa Gómez Ulla estableció un protocolo junto con el Instituto de Toxicología de la Defensa en 2018, a fin de realizar analíticas de identificación de sustancias empleadas en los casos de sospecha de sumisión química. Conclusiones: se plantea la necesidad de establecer protocolos de tipo multidisciplinar adecuados en los servicios de urgencias, estableciendo un diagnóstico diferencial en casos con alteraciones en el nivel de consciencia, al existir la posibilidad de intoxicación por escopolamina y sospecha de sumisión química, ya que la detección de la sustancia es tiempo-dependiente. (AU)

Antecedents and objectives: Scopolamine is used to commit illegal acts. The number of suspected cases of this substance in the Emergency Services seems to have increased in recent years. There is no clear and rigorous relationship with the number of cases described in the scientific literature, due to the difficulty of its detection in subjects who are under its effects. A further study on Chemical Submission is proposed, by describing a clinical case registered in the Emergency Service of the Gómez Ulla Central Defense Hospital and an improvement in the approach to this type of cases from triage. Material and methods: The study of the registered case has been based on the description of the analytical method and supported by a bibliographic review using different specialized bases in reference to Escopolamine poisoning and its use in criminal acts. Results: Being a substance whose detection is time-dependent, the Gómez Ulla Central Defense Hospital established a protocol together with the Defense Toxicology Institute in 2018 in order to carry out identification analyzes of substances used in cases of Suspected Submission Chemistry. Conclusions: The need to establish appropriate multidisciplinary protocols in the Emergency Services arises. Propose a differential diagnosis in cases with alterations in the level of consciousness, as there is the possibility of scopolamine intoxication and suspicion of Chemical Submission, since the detection of the substance is time-dependent. (AU)

Océano, viento y soledad. Anestesia y reanimación a bordo del Buque Escuela de la Armada Española Juan Sebastián de Elcano, nuestra experiencia / Ocean, wind and loneliness. Anaesthesia and reanimation on board the Spanish Navy Training Ship Juan Sebastián de Elcano, our experience

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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).

[In vitro activity of voriconazole against yeast and algae isolates according to new resistance pattern cut-off points]. / Actividad in vitro del voriconazol frente a levaduras y algas con los nuevos puntos de corte del patrón de resistencia.

Voriconazole is a second-generation triazole derived from fluconazole but with greater potency and spectrum of activity, showing good in vitro activity against Candida, Cryptococcus and Aspergillus species, and other filamentous and dimorphic fungi. It can be administered orally or intravenously. It was initially approved in 2002 by the U.S. Food and Drug Administration as a treatment option for invasive aspergillosis and Fusarium and S. apiospermum infections showing resistance or intolerance to other antifungals; later on, it also received approval in the United States and Europe as a treatment option for esophageal candidiasis; candida infection in non-neutropenic patients; disseminated candidiasis of skin, abdomen, kidney and bladder; and injuries. Recently, the Clinical Laboratory Standard Institute established some provisional break points for voriconazole, classifying isolates with an MICor=4 mg/l as resistant. In line with these new data, we performed a systematic review of literature on in vitro activity of voriconazole against yeast and algae isolates, and compared it to that of fluconazole and itraconazole. The review included a total of 27,340 yeast isolates, 24,177 of Candida species, 2,726 of Cryptococcus species, 453 of other species, and 104 Prototheca. The yeast isolates resistant to voriconazole is approximately 1%, and 71% of fluconazole-resistant isolates are susceptible to voriconazole.

Actividad in vitro del voriconazol frente a levaduras y algas con los nuevos puntos de corte del patrón de resistencia / In vitro activity of vorivonazole against yeast and algae isolates according to new resistance pattern break points

El voriconazol es un triazol de segunda generación derivado del fluconazol, pero con una potencia y espectro de actividad mayores, con buena actividad in vitro sobre las especies de Candida, Cryptococcus, Aspergillus, otros hongos filamentosos y hongos dimórficos. Se puede administrar por vía oral o intravenosa. Inicialmente fue aprobado en 2002 por la Food and Drug Administration (FDA) para su utilización en el tratamiento de la aspergilosis invasora y de las infecciones por Fusarium y Scedosporium apiospermum en caso de intolerabilidad o resistencia a otros antifúngicos; posteriormente, tanto en EE.UU. como en Europa se aprobó para tratar la candidiasis esofágica, la candidemia en los pacientes no neutropénicos y las candidiasis diseminadas de piel, abdomen, riñón, vejiga y heridas. Recientemente, el Clinical Laboratory Standard Institute (CLSI) ha establecido los puntos de corte provisionales para el voriconazol, según los cuales una cepa se clasifica como sensible si la CMI es ≤1 mg/l, sensible dependiendo de la dosis si la CMI es 2 mg/l y resistente si la CMI es ≥4 mg/l. Según esta nueva información, hemos revisado los trabajos publicados en la literatura sobre la actividad in vitro del voriconazol frente a levaduras y algas, comparándola con la de fluconazol e itraconazol. Incluimos un total de 27.340 aislamientos de levaduras, 24.177 del género Candida, 2726 del género Cryptococcus, 453 de otros géneros y 104 Prototheca. Aproximadamente, el porcentaje de resistencia de las levaduras al voriconazol es del 1%, y el 71% de los aislamientos resistentes al fluconazol son sensibles al voriconazol

Voriconazole is a second-generation triazole derived from fluconazole but with greater potency and spectrum of activity, showing good in vitro activity against Candida, Cryptococcus and Aspergillus species, and other filamentous and dimorphic fungi. It can be administered orally or intravenously. It was initially approved in 2002 by the U.S. Food and Drug Administration as a treatment option for invasive aspergillosis and Fusarium and S. apiospermum infections showing resistance or intolerance to other antifungals; later on, it also received approval in the United States and Europe as a treatment option for esophageal candidiasis; candida infection in non-neutropenic patients; disseminated candidiasis of skin, abdomen, kidney and bladder; and injuries. Recently, the Clinical Laboratory Standard Institute established some provisional break points for voriconazole, classifying isolates with an MIC ≤1 mg/l as susceptible, those with a 2 mg/l MIC as susceptible-dose dependent, and those with an MIC ≥4 mg/l as resistant. In line with these new data, we performed a systematic review of literature on in vitro activity of voriconazole against yeast and algae isolates, and compared it to that of fluconazole and itraconazole. The review included a total of 27,340 yeast isolates, 24,177 of Candida species, 2,726 of Cryptococcus species, 453 of other species, and 104 Prototheca. The yeast isolates resistant to voriconazol is approximately 1%, and 71% of fluconazole-resistant isolates are susceptible to voriconazole

Actividad del voriconazol sobre levaduras aisladas de hemocultivo determinada por dos métodos / Activity of voriconazole against yeasts isolated from blood culture determined by two methods

Se ha determinado la actividad in vitro del voriconazol por dos métodos: el de referencia M27-A2 y el colorimétrico comercializado SensititreYeastOne®. Se ha calculado la concordancia (±2 diluciones) y la correlación entre métodos, así como el porcentaje de errores. Se ensayaron144 cepas (47 Candida albicans, 52 C. parapsilosis, 13 C. tropicalis, 10 C. krusei, 9 C. glabrata, 2 C. guilliermondii, 1 C. colliculosa, 1 C. dubliniensis,2 Trichosporum asahii, 1 T. mucoide, 1 Trichosporum spp., 1 Kloakera apis, 2 Pichia ohmeri y 2 Rhodotorula glutinis) aisladas de hemocultivodesde septiembre de 2002 hasta mayo de 2005. El voriconazol mostró muy buena actividad. La tasa de sensibilidad (CMI ≤1 mg/l)fue del 97% y la CMI90 de 0,25 mg/l por los dos métodos. La concordancia entre métodos fue del 86% (44,23% a 100%) y el coeficientede correlación de Pearson fue 0,961. La concordancia por categorías dependió de la especie, entre el 84,6% para levaduras emergentes yel 100% para el resto de las especies excepto C. glabrata (66,6%). El porcentaje de errores leves fue del 1,38%. Una cepa de C. tropicalis yotra de C. glabrata fueron resistentes al voriconazol (CMI ≥4 mg/l) por el método de referencia (1,38%). No se detectaron errores graves nimuy graves. El método colorimétrico identificó bien la cepa de C. tropicalis, y clasificó como sensible dependiendo de la dosis la de C. glabrata.El método colorimétrico es adecuado para estudiar la sensibilidad al voriconazol. Identifica bien las cepas sensibles (100% concordancia).No obstante, se necesitan más estudios con mayor número de cepas resistentes para determinar su capacidad de identificarlas, objetivode las pruebas de sensibilidad

The in vitro activity of voriconazole has been determined by two methods: the reference M27-A2 and the marketed Sensititre YeastOne®microdilution colorimetric method. The agreement (±2 dilutions) and correlation between methods as well as the percentage of errors hasbeen determined. A total of 144 yeasts (47 Candida albicans, 52 C. parapsilosis, 13 C. tropicalis, 10 C. krusei, 9 C. glabrata, 2 C. guilliermondii,1 C. colliculosa, 1 C. dubliniensis, 2 Trichosporum asahii, 1 T. mucoide, 1 Trichosporum spp., 1 Kloakera apis, 2 Pichia ohmeri, and2 Rhodotorula glutinis) isolated from blood culture between October 2002 and May 2005 were assayed. Voriconazole has shown goodin vitro activity. The rate of voriconazole-susceptible (MIC ≤1 mg/l) strains was 97% and the MIC90 0.25 mg/l by the two methods. The overallpercentage of agreement between methods was 86% (range 44.23-100%) and the Pearson’s coefficient of correlation was 0.961.Categorical agreement was strain dependent and ranged from 84.6% for emergent yeasts to 100% for the other species tested exceptfor C. glabrata (66,6%). No major or very major errors were found, the percentage of minor errors being 1.38%. Only one C. tropicalisand one C. glabrata strain were resistant (MIC ≥4 mg/l) to voriconazole (1.38%) by the reference method. The colorimetric method identifiedthe voriconazole-resistant C. tropicalis strain, and classified the C. glabrata as susceptible-dose dependent. The colorimetric methodis a potential alternative method for testing the susceptibility of yeast in a clinical laboratory and identifies the susceptible strains (100%agreement) very well. Nevertheless, further studies including more voriconazole-resistant strains are required to determine the ability ofthe method to identify resistance, which is the goal of susceptibility tests

[Activity of voriconazole against yeasts isolated from blood culture determined by two methods]. / Actividad del voriconazol sobre levaduras aisladas de hemocultivo determinada por dos métodos.

The in vitro activity of voriconazole has been determined by two methods: the reference M27-A2 and the marketed Sensititre YeastOne microdilution colorimetric method. The agreement (+/-2 dilutions) and correlation between methods as well as the percentage of errors has been determined. A total of 144 yeasts (47 Candida albicans, 52 C. parapsilosis, 13 C. tropicalis, 10 C. krusei, 9 C. glabrata, 2 C. guilliermondii, 1 C. colliculosa, 1 C. dubliniensis, 2 Trichosporum asahii, 1 T. mucoide, 1 Trichosporum spp., 1 Kloakera apis, 2 Pichia ohmeri, and 2 Rhodotorula glutinis) isolated from blood culture between October 2002 and May 2005 were assayed. Voriconazole has shown good in vitro activity. The rate of voriconazole-susceptible (MIC < or =1 mg/l) strains was 97% and the MIC90 0.25 mg/l by the two methods. The overall percentage of agreement between methods was 86% (range 44.23-100%) and the Pearson's coefficient of correlation was 0.961. Categorical agreement was strain dependent and ranged from 84.6% for emergent yeasts to 100% for the other species tested except for C. glabrata (66.6%). No major or very major errors were found, the percentage of minor errors being 1.38%. Only one C. tropicalis and one C. glabrata strain were resistant (MIC > or =4 mg/l) to voriconazole (1.38%) by the reference method. The colorimetric method identified the voriconazole-resistant C. tropicalis strain, and classified the C. glabrata as susceptible-dose dependent. The colorimetric method is a potential alternative method for testing the susceptibility of yeast in a clinical laboratory and identifies the susceptible strains (100% agreement) very well. Nevertheless, further studies including more voriconazole-resistant strains are required to determine the ability of the method to identify resistance, which is the goal of susceptibility tests.

Tissue invasiveness and non-acidic pH in human candidiasis correlate with "in vivo" expression by Candida albicans of the carbohydrate epitope recognised by new monoclonal antibody 1H4.

BACKGROUND: The morphogenetic conversion between yeast and hyphal growth forms appears to be crucial in the pathogenesis of invasive candidiasis, and can be regulated by environmental signals such as extracellular pH. AIMS: To characterise the epitope recognised by monoclonal antibody 1H4, and to evaluate the expression of its corresponding epitope in Candida albicans cells under different conditions of pH and temperature, and "in vivo", in tissue samples from patients with human candidiasis. METHODS: Monoclonal antibody 1H4 was generated against the 58 kDa cell wall mannoprotein of C albicans (mp58), and was further characterised by immunoblot analysis, periodate treatment of the antigenic preparations, and agglutination experiments of C albicans strains 3153A, SC5314, and 412, cultured under different environmental conditions (growth media and pH). An immunohistochemical study was performed in 24 human tissue samples from patients with mucocutaneous and systemic candidiasis. RESULTS: 1H4 recognises a pH sensitive carbohydrate epitope on the surface of C albicans cells, and this epitope is not restricted to mp58, but is shared with other cell wall mannoproteins. Immunohistochemical findings indicated that expression of the 1H4 epitope on C albicans cells in tissue sections from human candidiasis correlates with tissue invasion and pH of the niche. 1H4 immunoreactivity was also found in candida remnants within macrophages. CONCLUSIONS: The fact that 1H4 epitope expression selectively identifies invasive forms of C albicans, in addition to candida remnants within macrophages, supports its potential value in the diagnosis and management of human candidiasis.

Candidemia at a tertiary-care hospital: epidemiology, treatment, clinical outcome and risk factors for death.

The demographic, clinical and microbiological data of patients with candidemia at the "Hopital Universitario La Fe", a tertiary-care hospital in Valencia, Spain, from 1995 to 1997 was analyzed retrospectively. Candida spp. were isolated in blood cultures from 145 patients, 32% of whom were children (25% of these were neonates). The most common species isolated was Candida albicans, followed by Candida parapsilosis, Candida krusei and Candida tropicalis. Risk factors for candidemia included underlying disease, therapy with broad-spectrum antibiotics and the presence of a central venous catheter. The majority of children were treated with amphotericin B, whereas 52% of adults received fluconazole. Overall mortality was 44% (30% in children and 50% in adults), and attributable mortality was 30% (24% in children and 33% in adults). Multivariate analysis indicated that neutropenia, corticosteroid therapy, lack of antifungal treatment, and failure to replace the central venous catheter were factors associated with candidemia-related death. Among the adult population, an APACHE II score greater than 15 predicted candidemia-related death.

Actividad in vitro de posaconazol frente a levaduras aisladas en hemocultivo / In vitro activity of posaconazole against yeasts isolated in blood cultures

Se ha valorado la actividad in vitro de posaconazol comparándola con la de fluconazol en especies de levaduras aisladas en hemocultivo, así como el factor tiempo de incubación para la detección de resistencias a estos azoles. Se estudiaron un total de 112 levaduras: 32 Candida albicans, 33 C. parapsilosis, 17 C. tropicalis, 8 C. glabrata, 8 C. guilliermondii, 3 C. famata, 2 C. lusitaniae, 1 C. lipolytica, 1 C. inconspicua, 1 C. lambica, 3 Saccharomyces cerevisiae,1 Blastoschizomyces capitatus, 1 Geotricum spp. y 1 Pichia omheri. La CMI se determinó mediante el método de microdilución M27-A descrito por el NCCLS para Candida spp. y Cryptococcus neoformans. Las especies más sensibles a posaconazol fueron C. parapsilosis (CMI90 0,016 mg/l), C. glabrata (CMI90 0,5 mg/l), C. guilliermondii (CMI90 0,12 mg/l) y el grupo de Candida spp. (CMI90 0,25 mg/l). Sin embargo, este azol no mejora la actividad de fluconazol frente a C. tropicalis (CMI90 8 mg/l) y C. albicans (CMI90 8 mg/l). El tiempo de lectura influyó a la hora de detectar resistencias, ya que a las 48 horas el número de cepas resistentes fue mayor que a las 24 horas, en el caso de C. albicans y C. tropicalis; el resto de las especies estudiadas fueron igual de sensibles en los dos tiempos de lectura. (AU)

Two cases of fungemia due to Candida lusitaniae and a literature review.

Reported here are two cases of candidemia caused by Candida lusitaniae that occurred in two immunocompromised patients at Hospital Universitario "La Fe" in Valencia, Spain. Case 1 involved a low-birth-weight premature infant with congenital nephrotic syndrome who was successfully treated with amphotericin B, and case 2 involved a 50-year old woman with a high-grade malignancy lymphoma who succumbed to the infection. Antifungal susceptibility testing of the Candida lusitaniae isolates recovered from both patients revealed sensitivity to amphotericin, 5-flucytosine and fluconazole. Results are presented and discussed together with a comprehensive review of the literature, covering all previously reported cases of fungemia caused by this emerging pathogen.

Sensibilidad de Staphylococcus aureus aislados de hemocultivo a 11 antimicrobianos y revisión de la literatura / Susceptibility of Staphylococcus aureus isolated from blood to 11 antimicrobial agents and a review of the literature

Entre noviembre de 1998 y febrero de 2000 se estudió la sensibilidad in vitro, mediante el método E-test®, de 91 aislamientos de Staphylococcus aureus procedentes de hemocultivo frente a 11 agentes antimicrobianos. Cincuenta y dos cepas fueron sensibles a meticilina (SASM) y 39 resistentes (SARM). Todos los SASM fueron sensibles a gentamicina, ciprofloxacino, vancomicina, teicoplanina, rifampicina, ácido fusídico, quinupristina-dalfopristina y linezolid, el 90 por ciento fueron sensibles a eritromicina y el 83 por ciento a mupirocina. Todos los SARM fueron sensibles a vancomicina, teicoplanina, rifampicina y linezolid, el 95 por ciento fueron sensibles a quinupristina-dalfopristina y el 92 por ciento a gentamicina, mupirocina y ácido fusídico. Ningún SARM fue sensible a eritromicina ni a ciprofloxacino. La tasa de aislamientos de SARM sensibles a eritromicina o ciprofloxacino fue baja, mientras que el resto de los antibióticos estudiados continúan siendo efectivos frente a S. aureus. (AU)

Correlación entre las pruebas de sensibilidad in vitro a los antifúngicos y la evolución clínica de los pacientes con candidiasis y criptococosis / Correlation between in vitro susceptibility to antifungal drugs and the clinical evolution of patients with candidiasis and cryptococcosis

El aumento del número de infecciones fúngicas, así como la descripción de resistencias frente a los diversos antifúngicos, ha puesto de manifiesto la necesidad de realizar estudios de sensibilidad in vitro que sean útiles para predecir la evolución clínica de los pacientes con este tipo de infecciones. Recientemente, el National Committee for Clinical Laboratory Standards (NCCLS) aprobó un método de referencia para las pruebas de sensibilidad a los antifúngicos que reflejó en el documento M27-A. Este avance importante en la estandarización de las pruebas de sensibilidad in vitro ha permitido también comparar los resultados obtenidos en el laboratorio con la evolución de los pacientes. En este artículo se revisan los estudios de correlación de la sensibilidad in vitro con la evolución clínica de los pacientes con infecciones fúngicas. En general se puede predecir la evolución clínica, sobre todo en los pacientes infectados por el VIH con candidiasis orofaríngea tratados con fluconazol. Sin embargo, en otros grupos más heterogéneos de pacientes no es fácil relacionar la sensibilidad in vitro con la evolución clínica (AU)

[In vitro activity of posaconazole against yeasts isolated in blood cultures]. / Actividad in vitro de posaconazol frente a levaduras aisladas en hemocultivo.

The in vitro activity of posaconazole against Candida species isolated from blood cultures and the influence of incubation time was studied and compared with that of fluconazole. A total of 112 isolates were studied: 32 Candida albicans, 33 C. parapsilosis, 17 C. tropicalis, 8 C. glabrata, 8 C. guilliermondii, 3 C. famata, 2 C. lusitaniae, 1 C. lipolytica, 1 C. inconspicua, 1 C. lambica, 3 Saccharomyces cerevisiae, 1 Blastoschizomyces capitatus, 1 Geotricum spp. and 1 Pichia omheri. The MIC was obtained using the M27-A microdilution method described by the NCCLS for Candida spp. and Cryptococcus neoformans. The species most susceptible to posaconazole were C. parapsilosis (MCI90 0.016 mg/l), C. guilliermondii (MIC90 0.12 mg/l), C. glabrata (MCI90 0.5 mg/l) and Candida spp. (MCI90 0.25 mg/l). However, this azole did not improve the activity of fluconazole against C. tropicalis (MIC90 8 mg/l) and C. albicans (MCI90 mg/l). The time of reading was important in the detection of resistance, as the number of strains resistant to fluconazole or posaconazole was higher at 48 hours than at 24 hours for C. albicans and C. tropicalis. All the other species of Candida were susceptible at both reading times.

[Correlation between in vitro susceptibility to antifungal drugs and the clinical evolution of patients with candidiasis and cryptococcosis]. / Correlación entre las pruebas de sensibilidad in vitro a los antifúngicos y la evolución clínica de los pacientes con candidiasis y criptococosis.

The increase in the incidence of fungal infections and the emergence of resistance call for the development of techniques for measuring in vitro antifungal susceptibility that are useful for predicting clinical outcome in patients suffering from these infections. In the past, the lack of standardized testing techniques led to poor intra- and interlaboratory reproducibility. Recently, the National Committee for Clinical Laboratory Standards (NCCLS) has developed a reference method for antifungal susceptibility testing, document M27A. This document is a necessary and important step towards the standardization of antifungal susceptibility testing, which has important implications in the analysis of clinical and microbiological data. This article provides a comprehensive review of studies correlating in vitro antifungal susceptibility testing and clinical outcome. In general, it is possible to predict the therapeutic outcome, especially in HIV infected patients with oropharyngeal candidiasis treated with fluconazole. However, in other more heterogeneous groups of patients it is more difficult to correlate the in vitro and in vivo data.

[Susceptibility of Staphylococcus aureus isolated from blood to 11 antimicrobial agents and a review of the literature]. / Sensibilidad de Staphylococcus aureus aislados de hemocultivo a 11 antimicrobianos y revisión de la literatura.

From November 1998 to February 2000, a total of 91 strains of Staphylococcus aureus isolated from blood were analyzed for their susceptibility to 11 antimicrobial agents using the E-test method. Fifty-two isolates were methicillin-susceptible (MSSA) and 39 were oxacillin-resistant (MRSA). All the MSSA were susceptible to gentamicin, ciprofloxacin, vancomycin, teicoplanin, rifampicin, fusidic acid, quinupristin-dalfopristin and linezolid; 90% were susceptible to erythromycin and 83% to mupirocin. All the MRSA were susceptible to vancomycin, teicoplanin, rifampicin and linezolid; 95% were susceptible to quinupristin-dalfopristin; and 92% to gentamicin, mupirocin, fusidic acid. None of the MRSA were susceptible to erythromycin or ciprofloxacin. The susceptibility of SARM to erythromycin and ciprofloxacin was low, while the susceptibility to the rest of the antimicrobial agents remained active.

[The activity of systemic antimycotic drug combinations]. / Actividad de las asociaciones de antifúngicos sistémicos.

The treatment of deep mycoses is complex, especially in immunosuppressive patients, owing to several factors: the scarcity of antimycotic drugs, the difficulty of carrying out antimycotic susceptibility tests, the scarcity of in vitro/in vivo correlation studies, the lesser response to therapy in comparison to antibacterial treatment, etc. Aside from this, the adverse effects, therapeutic failure and the appearance of resistance are serious problems that may emerge with the use of antimycotic drugs. These problems can be partly avoided by using combinations of antimycotics. In this article, the results obtained by different authors when using systemic antimycotics in combined therapy are reviewed. The effect of the combination of amphotericin B and azoles varies according to the moment of administration: when the azole is administered before amphotericin B, antagonism between the two has been observed; however, when they are administered simultaneously the effect is synergistic with the hydrophylic azoles (fluconazole), antagonistic with lipophilic azoles (itraconazole) or indifferent. The combination of flucytosine with azoles has been demonstrated to be synergistic on Candida albicans (itraconazole, fluconazole) and on Cryptococcus neoformans (fluconazole). With the combinations of an equinocandine and amphotericin B or fluconazole, synergism has been observed on C. neoformans.

Identification of continuous B-cell epitopes on the protein moiety of the 58-kiloDalton cell wall mannoprotein of Candida albicans belonging to a family of immunodominant fungal antigens.

The 58-kiloDalton mannoprotein (mp58) on the surface of Candida albicans is highly immunogenic, is expressed by all C. albicans isolates tested, and elicits strong antibody responses during candidiasis. It belongs to a family of immunodominant fungal antigens with representatives also in different species of Aspergillus. The amino acid sequence of the protein portion of mp58 as deduced from the DNA sequence of its encoding gene (FBP1/PRA1) was used to synthesize a complete set of overlapping dodecapeptides (overlap, 7; offset, 5) covalently attached to the surface of derivatized polyethylene pins. The pin-coupled peptides were used in a modified enzyme-linked immunosorbent assay (ELISA) to identify continuous epitopes recognized by a number of antiserum preparations containing anti-mp58 antibodies. This comprehensive epitope-scanning study revealed the presence of multiple immunoreactive continuous B-cell epitopes within the protein sequence. Regions of increased reactivity included both the amino and carboxy termini of the mature protein (encompassing amino acid residues 16 to 50 and 286 to 299, respectively) and four internal regions spanning amino acids at positions 66 to 92, 121 to 142, 148 to 192, and 211 to 232. Further delineation of epitopic regions and identification of the boundaries of the antigenic sites was performed upon ELISA testing with a second Pepset consisting of completely overlapping 8-mer peptides spanning these reactive regions in the protein moiety of mp58. The highly reactive epitopic region at the C terminus of the protein was further evaluated using both window net and replacement net analyses. A synthetic peptide corresponding to the last 10 amino acid residues at the C terminus of the protein was immunogenic when injected into mice after being coupled to a carrier protein. Moreover, antibodies in the resulting sera specifically recognized the homologous mp58 in ELISAs and immunoblot assays. Delineation of the antibody responses to mp58 could provide the basis for the development of novel immunity-based prophylactic, therapeutic, and diagnostic techniques for the management of candidiasis.

Actividad de las asociaciones de antifúngicos sistémicos / The activity of combinations of systemic antimycotic drugs

El tratamiento de las micosis profundas resulta complejo, sobre todo en los pacientes inmunodeprimidos, a causa de varios factores: escaso número de antifúngicos disponible, dificultad para la realización de las pruebas de sensibilidad antifúngica, escasez de estudios de correlación in vitro in vivo, menor respuesta al tratamiento en comparación con los tratamientos antibacterianos, etc. Por otra parte, los efectos adversos, los fracasos terapéuticos y la aparición de resistencias son importantes problemas que aparecen con el empleo de los fármacos antifúngicos. Estos problemas pueden ser evitados, en parte, utilizando asociaciones de antifúngicos. En este artículo se revisan los resultados obtenidos por diferentes autores al emplear antifúngicos sistémicos en terapia combinada. El efecto de la asociación de amfotericina B y azoles varía según el momento de su administración: cuando el azol se administra antes que la amfotericina B, se ha observado un antagonismo entre ambos; sin embargo, cuando se administran simultáneamente el efecto es sinérgico con los azoles hidrofílicos (fluconazol), antagónico con los azoles lipofílicos (itraconazol) o indiferente. La asociación de 5-fluorocitosina con los azoles ha demostrado ser sinérgica sobre Candida albicans (itraconazol, fluconazol) y sobre Cryptococcus neoformans (fluconazol). Con la asociación de una equinocandina y amfotericina B o fluconazol también se ha observado sinergismo sobre C. neoformans (AU)