Voriconazole plus terbinafine combination antifungal therapy for invasive Lomentospora prolificans infections: analysis of 41 patients from the FungiScope® registry 2008-2019.

OBJECTIVES: Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections. METHODS: We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies. RESULTS: Over the study period, 41 individuals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy; p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%-85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%-51%, p 0.053). In Kaplan-Meier survival analysis there was a higher survival probability in individuals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days). CONCLUSIONS: While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.

Time trends in the aetiology of prosthetic joint infections: a multicentre cohort study.

It is important to know the spectrum of the microbial aetiology of prosthetic joint infections (PJIs) to guide empiric treatment and establish antimicrobial prophylaxis in joint replacements. There are no available data based on large contemporary patient cohorts. We sought to characterize the causative pathogens of PJIs and to evaluate trends in the microbial aetiology. We hypothesized that the frequency of antimicrobial-resistant organisms in PJIs has increased in the recent years. We performed a cohort study in 19 hospitals in Spain, from 2003 to 2012. For each 2-year period (2003-2004 to 2011-2012), the incidence of microorganisms causing PJIs and multidrug-resistant bacteria was assessed. Temporal trends over the study period were evaluated. We included 2524 consecutive adult patients with a diagnosis of PJI. A microbiological diagnosis was obtained for 2288 cases (90.6%). Staphylococci were the most common cause of infection (1492, 65.2%). However, a statistically significant rising linear trend was observed for the proportion of infections caused by Gram-negative bacilli, mainly due to the increase in the last 2-year period (25% in 2003-2004, 33.3% in 2011-2012; p 0.024 for trend). No particular species contributed disproportionally to this overall increase. The percentage of multidrug-resistant bacteria PJIs increased from 9.3% in 2003-2004 to 15.8% in 2011-2012 (p 0.008), mainly because of the significant rise in multidrug-resistant Gram-negative bacilli (from 5.3% in 2003-2004 to 8.2% in 2011-2012; p 0.032). The observed trends have important implications for the management of PJIs and prophylaxis in joint replacements.

Characteristics of prosthetic joint infections due to Enterococcus sp. and predictors of failure: a multi-national study.

The objective of this study was to review the characteristics and outcome of prosthetic joint infections (PJI) due to Enterococcus sp. collected in 18 hospitals from six European countries. Patients with a PJI due to Enterococcus sp. diagnosed between January 1999 and July 2012 were retrospectively reviewed. Relevant information about demographics, comorbidity, clinical characteristics, microbiological data, surgical treatment and outcome was registered. Univariable and multivariable analyses were performed. A total of 203 patients met the inclusion criteria. The mean (SD) was 70.4 (13.6) years. In 59 patients the infection was diagnosed within the first 30 days (29.1%) from arthroplasty, in 44 (21.7%) between 31 and 90 days, in 54 (26.6%) between 91 days and 2 years and in 43 (21%) after 2 years. Enterococcus faecalis was isolated in 176 cases (89%). In 107 (54%) patients the infection was polymicrobial. Any comorbidity (OR 2.53, 95% CI 1.18-5.40, p 0.01), and fever (OR 2.65, 95% CI 1.23-5.69, p 0.01) were independently associated with failure. The only factor associated with remission was infections diagnosed later than 2 years (OR 0.25, 95% CI 0.09-0.71, p 0.009). In conclusion, prosthetic joint infections due to Enterococcus sp. were diagnosed within the first 2 years from arthroplasty in >70% of the patients, almost 50% had at least one comorbidity and infections were frequently polymicrobial (54%). The global failure rate was 44% and patients with comorbidities, fever, and diagnosed within the first 2 years from arthroplasty had a poor prognosis.

Lack of association between genotypes and haematogenous seeding infections in a large cohort of patients with methicillin-resistant Staphylococcus aureus bacteraemia from 21 Spanish hospitals.

There is increasing concern regarding the association between certain methicillin-resistant Staphylococcus aureus (MRSA) genotypes and poor clinical outcome. To assess this issue, a large cohort of 579 subjects with MRSA bacteraemia was prospectively followed from June 2008 to December 2009, in 21 hospitals in Spain. Epidemiology, clinical data, therapy, and outcome were recorded. All MRSA strains were analysed in a central laboratory. Presence of a haematogenous seeding infection was the dependent variable in an adjusted logistic regression model. Of the 579 patients included in the study, 84 (15%) had haematogenous seeding infections. Microdilution vancomycin median MIC (IQR) was 0.73 (0.38-3) mg/L. Most MRSA isolates (n = 371; 67%) belonged to Clonal Complex 5 (CC5) and carried an SCCmec element type IV and agr type 2. Isolates belonging to ST8-agr1-SCCmecIV, ST22-agr1-SCCmecIV and ST228-agr2-SCCmecI--a single locus variant of ST5--accounted for 8%, 9% and 9% of the isolates, respectively. After adjusting by clinical variables, any of the clones was associated with increased risk of haematogenous seeding infections. Higher vancomycin MIC was not identified as an independent risk factor, either. In contrast, persistent bacteraemia (OR 4.2; 2.3-7.8) and non-nosocomial acquisition (3.0; 1.7-5.6) were associated with increased risk.

[New therapeutic options for the treatment of multiresistant bacteria in the ICU]. / Nuevas opciones terapéuticas para el tratamiento de las bacterias multirresistentes en Unidades de Cuidados Intensivos.

The number of new antimicrobial drugs in the health care clinical practice has decreased gradually and significantly in the last 15 years. At the same time, there has been an increase in the appearance of microorganisms with resistance to conventional antibiotics, above all in intensive care units (ICU). Within this group, Methicillin-resistant Staphylococcus aureus (MSRA) and methicillin-resistant coagulase- negative staphylococci, vancomycin-resistant enterococci, Pseudomonas aeruginosa and Acinetobacter baumanii resistant to carbapenemics and extended-spectrum betalactamase-producing (ESBL) Enterobacteria are the most important. These pathogens are frequently also resistant to other groups of antibiotics such as aminoglycosides, fluoroquinolones and macrolides. New recently introduced antimicrobial agents are available to combat these resistances. These are active mainly against gram positive bacteria resistant strains and in a more timely way against gram negative ones or both. Among the first group, the following stand out: daptomycin (a lipopeptide bactericide for parenteral use) and linezolid (oxazolidinone with bacteriostatic activity for parenteral and oral use). On its part, ertapenem (a carbapenem parenteral bactericide) and tigecyclin (a parenteral bacteriostatic tetracycline) are active against ESBL enterobacteria, the latter also being active against non-fermented gram positives and gram negatives, except for P. aeruginosa. Possibly, the introduction of these new compounds and other futures ones pending introduction will not only improve antimicrobial diversification but also serve to limit the spreading of these microorganisms.

Nuevas opciones terapéuticas para el tratamiento de las bacterias multirresistentes en Unidades de Cuidados Intensivos / New therapeutic options for the treatment of multiresistant bacteria in the ICU

El número de nuevos antimicrobianos en la clínica asistencialha descendido de forma gradual y significativa enlos últimos 15 años. Paralelamente se ha producido un incrementoen la aparición de microorganismos con resistenciaa los antibióticos convencionales, sobre todo en las Unidadesde Cuidados Intensivos (UCI). Dentro de este grupo, laresistencia a la meticilina de Staphylococcus aureus (SARM) yde estafilococos coagulasa negativos resistentes a la meticilina,enterococos resistentes a la vancomicina, Pseudomonasaeruginosa y Acinetobacter baumannii resistentes a carbapenémicosy Enterobacterias productoras de betalactamasasde espectro extendido (BLEE) son las más destacables. Estospatógenos con frecuencia son además resistentes a otrosgrupos de antibióticos, como aminoglucósidos, fluorquinolonasy macrólidos. Para hacer frente a estas resistenciasdisponemos de nuevos antimicrobianos de reciente introducción.Éstos son activos principalmente frente a cepas resistentesde bacterias grampositivas, y de manera más puntualfrente a gramnegativos o a ambos. Entre los primerosdestacan: daptomicina (lipopéptido bactericida de uso parenteral)y linezolid (oxazolidinona bacteriostática de usoparenteral y oral). Por su parte, el ertapenem (carbapenembactericida parenteral) y la tigeciclina (tetraciclina bacteriostáticaparenteral) son activos frente a enterobacterias BLEE,siendo esta última además activa frente a grampositivos ygramnegativos no fermentadores, excepto P. aeruginosa. Posiblementela introducción de estos nuevos compuestos yotros futuros pendientes salir, aparte de mejorar la diversificaciónantimicrobiana, sirva para limitar la dispersión de estosmicroorganismos (AU)

The number of new antimicrobial drugs in the healthcare clinical practice has decreased gradually and significantlyin the last 15 years. At the same time, there hasbeen an increase in the appearance of microorganisms withresistance to conventional antibiotics, above all in intensivecare units (ICU). Within this group, Methicillin-resistantStaphylococcus aureus (MSRA) and methicillin-resistant coagulase-negative staphylococci, vancomycin-resistant enterococci,Pseudomonas aeruginosa and Acinetobacter baumaniiresistant to carbapenemics and extended-spectrumß-lactamase-producing (ESBL) Enterobacteria are themost important. These pathogens are frequently also resistantto other groups of antibiotics such as aminoglycosides,fluoroquinolones and macrolides. New recentlyintroduced antimicrobial agents are available to combatthese resistances. These are active mainly against grampositive bacteria resistant strains and in a more timelyway against gram negative ones or both. Among the firstgroup, the following stand out: daptomycin (a lipopeptidebactericide for parenteral use) and linezolid (oxazolidinonewith bacteriostatic activity for parenteral andoral use). On its part, ertapenem (a carbapenem parenteralbactericide) and tigecyclin (a parenteral bacteriostatictetracycline) are active against ESBL enterobacteria, thelatter also being active against non-fermented gram positivesand gram negatives, except for P. aeruginosa.Possibly, the introduction of these new compounds andother futures ones pending introduction will not onlyimprove antimicrobial diversification but also serve tolimit the spreading of these microorganisms (AU)

Cirugía intracraneal e hiperamilasemia secundaria transitoria / Transitory hiperamylasemia due to intracranial surgery

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[Total prosthetic knee and hip joint infection. Descriptive epidemiology, therapeutics and evolution in a secondary hospital during ten years]. / Infección de prótesis total de rodilla y cadera. Epidemiología descriptiva, terapéutica y evolución en un hospital de segundo nivel durante 10 años.

OBJECTIVE: Epidemiological description, retrospective in its classification, evolution and therapeutics of total prosthesis knee and hip infected among the arthoplasties made between 1st of January 1994 and 31st of December 2003 in our hospital. RESULTS: The global infection rate was 2.4% (confidence interval of 95% [CI 95%], 1.6%-3.2%) over 40 cases in 1,666 joint implants. The average age +/- standard deviation (SD) was 69.5 years old +/- 5.1 years, mainly in women (67.5%). The most common location was the knee, 31 cases (77.5%). In 90.0% of the patients the aetiology was identified: 64,0% were gram-positive cocci (plasmacoagulase-negative staphylococci, and Staphylococcus aureus); 14.0% were gram-negative bacilli and mixed flora (11.0%). Acute infections were found in most of the cases (45,0%). The joint replacement had a healing rate of 66.7% in the first replacement and of 83.3% in the second replacement. CONCLUSIONS: The gram-positive cocci are the main microorganisms in these infections. More extensive studies about multiple aspects are necessary to evaluate the effectiveness of the different surgical techniques, the new antibiotics and the combined antibiotic therapies.

Infección de prótesis total de rodilla y cadera. Epidemiología descriptiva, terapéutica y evolución en un hospital de segundo nivel durante 10 años / Total prosthetic knee and hip joint infection. Descriptive epidemiology, therapeutics and evolution in a secondary hospital during ten years

Objetivo: Descripción epidemiológica retrospectiva en su clasificación,evolución y terapéuticas de las prótesis totales de cadera y rodilla infectadas entre las artroplastias realizadas desde el 1 de enero de 1994 al 31 de diciembre del 2003 en nuestro hospital. Resultados: La tasa de infección global de artroplastias fue 2,4% (intervalo de confianza del 95% [IC 95%], 1,6% -3,2%) sobre 40 casos de 1666 implantes articulares. La media de edad ± desviación estándar (DE) fue de 69,5 ± 5,1 años, en su mayoría mujeres (67,5%). La localización más frecuente fue rodilla, 31 casos (77,5%). En un 90,0% de los enfermos se filió la etiología, siendo un 64,0% cocos grampositivos (Staphylococcus plasmocoagulasa negativos y S. aureus), un 13,0% bacilos gramnegativos y flora mixta (11,0%). Predominaron las infecciones agudas (45,0%). El recambio articular en un tiempo tuvo una curación del 66,7% frente a un 83,3% en recambio en 2 tiempos. Conclusiones: Los cocos gram positivos son los principales microrganismos en estas infecciones. Son necesarios estudios amplios multicéntricos para valorar la eficacia de las distintas técnicas quirúrgicas, los nuevos antibióticos y las terapias antibióticas combinadas

Objective: Epidemiological description, retrospective in its classification, evolution and therapeutics of total prosthesis knee and hip infected among the arthoplasties made between 1st of January 1994 and 31st of December 2003 in our hospital. Results: The global infection rate was 2.4% (confidence interval of 95% [CI 95%], 1.6%-3.2%) over 40 cases in 1,666 joint implants. The average age +/- standard deviation (SD) was 69.5 years old +/- 5.1 years, mainly in women (67.5%). The most common location was the knee, 31 cases (77.5%). In 90.0% of the patients the aetiology was identified: 64,0% were gram-positive cocci (plasmacoagulase-negative staphylococci, and Staphylococcus aureus); 14.0% were gram-negative bacilli and mixed flora (11.0%). Acute infections were found in most of the cases (45,0%). The joint replacement had a healing rate of 66.7% in the first replacement and of 83.3% in the second replacement. Conclusions: The gram-positive cocci are the main microorganisms in these infections. More extensive studies about multiple aspects are necessary to evaluate the effectiveness of the different surgical techniques, the new antibiotics and the combined antibiotic therapies

[Nosocomial infection by multiresistant pathogens during one year in a secondary hospital: clinical an epidemiological analysis]. / Infección nosocomial por gérmenes multirresistentes durante 1 año en un hospital de segundo nivel: análisis clínico y microbiológico.

BACKGROUND: Currently growing medical and social significance of nosocomial infection by multiresistant pathogens (NIMP) prompted us to establish its incidence, nosology, presenting forms in admission areas, and mortality in a secondary hospital, Lleida (Spain). METHOD: For that purpose, we analyzed the first year experience of a unit for the control of nosocomial infection (NI) created in our hospital. From January to December 2000, 79 patients with a NIMP admitted to the University Hospital Arnau de Vilanova entered in this prospective, descriptive study. RESULTS: The overall annual incidence of NIMP was 4.0 per 103 patients admitted. Acinetobacter baumannii showed the highest individual rate of incidence, particularly, at the Intensive Care Unit (15.4 per 103 patients admitted; p < 0.001). By nosologies, infection prevailed over colonization (69.6% vs 30.4%; p < 0.001). Mean hospital stay length increased in colonized patients (38.9 days). Finally, overall mortality was high (29.1%); again, A. baumannii was the agent most frequently detected in death cases (66.6%; p < 0.001). CONCLUSIONS: Surveillance and control measures are required for the prevention of NIMP. Incidence studies how this, can be useful to create a database to establish the distribution and occurrence of NI, including the detection of multiresistant pathogen outbreaks.

Infección nosocomial por gérmenes multirresistentes durante 1 año en un hospital de segundo nivel: análisis clínico y microbiológico / Nosocomial infection by multiresistant pathogens during one year in a secondary hospital: clinical and epidemiological analysis

Fundamento: Dada la gran relevancia actual, médica y social, de la infección nosocomial por gérmenes multirresistentes (INGM), se pretendió determinar su incidencia, nosología, formas de presentación en las áreas de ingreso y mortalidad en un hospital de 2º nivel en Lleida (España). Método: Se utilizó la experiencia de una unidad para el control de la Infección Nosocomial (IN), en su primer año de funcionamiento en este hospital. Por medio de la unidad, se practicó un estudio descriptivo prospectivo sobre todos los pacientes ingresados, en el Hospital Universitario Arnau de Vilanova, entre enero y diciembre de 2000 en los que se detectó una INGM. Resultados: En total fueron 79 pacientes los que presentaron una INGM. La tasa de incidencia global anual de INGM fue de 4,0 por 103 pacientes ingresados. A. baumannii fue el germen que obtuvo la tasa de incidencia individual más elevada, y en especial en la Unidad de Cuidados Intensivos (15,4 por 103 pacientes ingresados; p < 0,001). Por nosologías,la infección predominó sobre la colonización (69,6 frente 30,4%; p < 0,001). En general, se observó una estancia media más prolongada en los pacientes colonizados 38,9 días. Por último, la mortalidad total fue elevada (29,1%), destacando de nuevo A. baumannii, como el agente más frecuentemente detectado en los pacientes que fallecieron (66,6%; p < 0,001). Conclusiones: En la prevención de la INGM son necesarias medidas de vigilancia y control. Los estudios de incidencia como éste, pueden ser útiles a la hora de establecer una base de datos con la que observar la distribución y ocurrencia de la IN, incluyendo la detección de brotes epidémicos por gérmenes multirresistentes

Background: Currently growing medical and social significance of nosocomial infection by multiresistant pathogens (NIMP) prompted us to establish its incidence, nosology, presenting forms in admission areas, and mortality in a secondary hospital, Lleida (Spain). Method: For that purpose, we analyzed the first year experience of a unit for the control of nosocomial infection (NI) created in our hospital. From January to December 2000, 79 patients with a NIMP admitted to the University Hospital Arnau de Vilanova entered in this prospective, descriptive study. Results: The overall annual incidence of NIMP was 4.0 per 103 patients admitted. Acinetobacter baumannii showed the highest individual rate of incidence, particularly, at the Intensive Care Unit (15.4 per 103 patients admitted; p < 0.001). By nosologies, infection prevailed over colonization (69.6% vs 30.4%; p < 0.001). Mean hospital stay length increased in colonized patients (38.9 days). Finally, overall mortality was high (29.1%); again, A. baumannii was the agent most frequently detected in death cases (66.6%; p < 0.001). Conclusions: Surveillance and control measures are required for the prevention of NIMP. Incidence studies how this, can be useful to create adatabase to establish the distribution and occurrence of NI, including the detection of multiresistant pathogen outbreaks

Pancitopenia en mujer joven de raza negra como forma de presentación de una anemia megaloblástica / Pancytopaenia in a young black woman as a way that megaloblastic anaemia presents

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[Cuttoff values of biochemical tests on pleural fluid: their usefulness in differential diagnosis of 1,040 patients with pleural effusion]. / Puntos de corte de los parámetros bioquímicos del líquido pleural: su utilidad en el diagnóstico diferencial de 1.040 pacientes con derrame pleural.

OBJECTIVE: The aim of biochemical pleural fluid testing is to reach an etiological diagnosis of the pleural effusion. We assessed the utility of considering cuttoff points for the wide range of analytes used to investigate pleural fluid. PATIENTS AND METHODS: Among 1,040 patients with pleural effusion, we sought the etiologies of those fluids which showed any of the following characteristics: red blood cell count = 10 x 109/L, leukocytes = 10 x 109/L, percentage of neutrophils or lymphocytes >50%, protein = 50 g/L, glucose = 60 mg/dL, pH = 7.2, lactate dehydrogenase = 1,000 U/L, adenosine deaminase = 40 U/L, amylase = 100 U/L or cholesterol = 60 mg/dL. RESULTS: Some of the more prominent findings were: a) a sixth of transudates were blood-tinged or contained predominantly neutrophils; b) a groosly bloody fluid suggests malignant disease, trauma, or pulmonary embolization; c) nearly 90% of fluids containing = 10 x 10(9) leukocytes/L were parapneumonics; d) 73% of tuberculous pleural fluids had protein > or = 50 g/L, e) tuberculosis and parapneumonics explained more than 90% of fluids with high adenosine deaminase content; f) one third of amylase-rich pleural effusions were malignant; g) a low pleural glucose or pH levels indicate that patient probably has a parapneumonic, tuberculous or malignant etiology; y h) the diagnostic yield of pleural fluid cytology in malignant effusions was 57%, a percentage which raised to 94% in those with low glucose fluid level. CONCLUSIONS: Cuttof values of biochemical pleural fluid tests may greatly support particular causes of pleural effusions.

Puntos de corte de los parámetros bioquímicos del líquido pleural: su utilidad en el diagnóstico diferencial de 1.040 pacientes con derrame pleural / Cutoff values of biochemical tests on pleural fluid: their usefulness in differential diagnosis of 1,040 patients with pleural effusion

Objetivo: El análisis bioquímico del líquido pleural tiene como objetivo alcanzar un diagnóstico etiológico del derrame pleural. Hemos evaluado la utilidad de diversos puntos de corte aplicados al amplio abanico de parámetros bioquímicos que pueden determinarse en el líquido pleural. Pacientes y métodos: En 1.040 pacientes con derrame pleural se analizaron las causas de aquellos líquidos que presentaban alguna de las siguientes características: hematíes >=10 x 109/L, leucocitos >=10 x 109/L, porcentaje de neutrófilos o linfocitos >50 por ciento, proteínas 50 g/L, glucosa = 1.000 U/L, adenosina desaminasa >= 40 U/L, amilasa >= 100 U/L o colesterol = 50 g/L; e) los derrames tuberculosos y paraneumónicos explican más del 90 por ciento de líquidos con concentraciones elevadas de adenosina desaminasa; f) un tercio de los derrames ricos en amilasa son malignos; g) unas cifras bajas de glucosa o pH pleurales indican que el paciente probablemente tiene un derrame paraneumónico, tuberculoso o maligno; y h) la rentabilidad de la citología en los derrames malignos fue del 57 por ciento, porcentaje que se elevó al 94 por ciento en los líquidos con bajo contenido de glucosa. Conclusiones: La consideración de determinados puntos de corte de los parámetros bioquímicos del líquido pleural puede apoyar fuertemente algunas etiologías de derrame pleural (AU)

Prevención del síndrome respiratorio agudo grave en la unidad de cuidados intensivos / Prevention of severe respiratory syndrome in the intensive care unit

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Pérdida de visión aisladade curso clínico regresivocomo única manifestaciónde un infarto bilateralen el territorio de la arteriacerebral posterior / Isolated loss of vision with a regressive clinical course as the only sign of a bilateral infarct in the territory of the posterior cerebral artery

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