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.

[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.

[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.

[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.

[Malignant pleural mesothelioma with an unusual radiologic manifestation]. / Mesotelioma pleural maligno con manifestación radiológica inusual.

The malignant pleural mesothelioma is a rare neoplastic consequence observed in people with previous exposition to asbestos essentially. The malignant mesothelioma like a term, not only reports to primary malignant extended tumors that are derived of pleural mesothelioma but also, pericardial and peritoneal (about 20%). The exposition of asbestos stands for a sequential cellular reaction with oncogenic potential and with a typical majority clinical presentation. We described the case a patient complaint of malignant pleural mesothelioma with unusual radiology presentation with the result that unilateral calcified pleural plaques with pleural thickening and pleural effusion absence. Definitive diagnostic was achieved by thoracotomy.

[Epidemiology of acute cerebrovascular disease in Lleida from 1996 to 1997. Predictive factors of mortality at short and medium term]. / Epidemiología de la enfermedad cerebrovascular aguda en la provincia de Lleida durante el período 1996-1997. Factores predictivos de mortalidad a corto y medio plazo.

INTRODUCTION: Given the great clinical relevance of the cerebrovascular disease, the incidence, nosology, vascular risk factors and factors predicting short and medium-term survival after stroke were evaluated in Lleida (Spain). PATIENTS AND METHODS: Five hundred forty-five consecutive patients with an acute stroke admitted to the Hospital Universitario Arnau de Vilanova during the period 1996-1997 were evaluated. A descriptive epidemiological study and a multivariate logistic regression analysis of predictive factors of mortality at 1-month and 1-year after the stroke were made. The latter provided a clinical scoring system for predicting survival. RESULTS: The incidence rate of stroke was 138.3/100,000 inhabitants. Significant risk factors were hypertension and peripheral vasculopathy. There were 80.1% of ischemic and 19.9% of hemorrhagic strokes (p < 0.001). A Glasgow scale < or = 7, hemianopsia and hemorraghic stroke were significant predictors of 1-month mortality, whereas age > or = 70 years, diabetes, atrial fibrillation and limb weakness decreased survival at 1 year. CONCLUSIONS: The incidence rate of stroke in Lleida is low respect to other studies in Spain. Simple clinical measures may help to establish a prognosis at short and medium-term.

[Obstructive colitis: analysis of 7 patients]. / Colitis obstructiva: un análisis de 7 enfermos.

The term "obstructive colitis" is defined by the presence of ulcero-inflammatory lesions in a colonic area proximal to a potentially obstructive lesion. Seven cases retrospectively identified during a 5-year period are here reported. They illustrate the clinico-pathological spectrum of this entity. Most patients were women, with a mean age of 66 years and with history of chronic underlying disease (diabetes mellitus and arterial hypertension). Abdominal distension and pain, as well as acute constipation were the main clinical symptoms. An adenocarcinoma predominantly located at the rectosigmoidal region accounted for the obstructive nature in 100% of cases. Macroscopically the colitis area was moderately dilated and there were single or confluent ulcers in the luminal surface. Characteristically, there was always a transitional preserved area between the obstruction and the colitis area. Microscopically, the mucosa was totally replaced by a granulation tissue with a relevant inflammatory infiltrate involving up to the muscularis propria. The cytometric study revealed and increase in the cell cycle (S-phase) and proliferation index, at the level of the obstructive lesion, with marked aneuploidy in cases with advanced neoplastic invasion. The role of mural hypoperfusion with localized ischemia in the pathogenesis is discussed. The similarities with other colonic inflammatory diseases are emphasized.