Transforming a public university hospital and its area of influence into a comprehensive resource in response to the COVID-19 pandemic.

INTRODUCTION AND OBJECTIVES: The outbreak of COVID-19 has overwhelmed healthcare systems all over the world. The aim of this article is to describe the process of transforming the Vall d'Hebron University Hospital, the second largest hospital in Spain, into a COVID-19 centre coordinating response to the pandemic in its reference area. MATERIALS AND METHODS: The study draws on the experience of the authors in transforming the hospital into a comprehensive resource in response to the COVID-19 pandemic. The strategy is based on four central strategies: early planning, coordination of all healthcare agents in its reference area, definition of clear leadership roles, and the organisation of care based on multidisciplinary teams with minimal recruitment of new staff. RESULTS: The transformation strategy enabled the hospital to cope with the surge in patients without exceeding its capacity. During the response phases, which amounted to a period of 57 days, 3106 patients consulted the ER and 2054 were admitted, 346 of whom were treated at the ICU. To accommodate the number of adult COVID-19 patients, adult ICU availability was progressive increased by 371%, and ordinary beds increased by 240. A total of 671 staff members went on sick leave after testing positive for COVID-19. CONCLUSION: The transformation experience of the hospital provides insight into how effectively adapt the structures and functioning of large hospitals. The relevance of territorial coordination during the pandemic is stressed as an effective strategy that contributed coping the pandemic.

Correction to: Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies.

[This corrects the article DOI: 10.1093/ofid/ofab250.].

Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies.

BACKGROUND: There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection. METHODS: This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007-2016). The impact of ED and factors associated with mortality were assessed. RESULTS: Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48-10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94-9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14-5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48-10.61), and prior surgery (OR, 0.29; 95% CI, 0.08-0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16-1.53). CONCLUSIONS: Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies.

In vitro and in vivo antimicrobial activity of sodium colistimethate and amikacin-loaded nanostructured lipid carriers (NLC).

Sodium colistimethate (SCM) and amikacin (AMK) are among the few antibiotics effective against resistant P. aeruginosa, K. pneumoniae and A. baumannii; however, their toxicity severely limits their use. Enclosing antibiotics into nanostructured lipid carriers (NLC) might decrease drug toxicity and improve antibiotic disposition. In this work, SCM or AMK was loaded into different NLC formulations, through high pressure homogenization, and their in vitro and in vivo effectiveness was analyzed. The encapsulation process did not reduce drug effectiveness since in vitro SCM-NLC and AMK-NLC drug activity was equal to that of the free drugs. As cryoprotectant, trehalose showed better properties than dextran. Instead, positive chitosan coating was discarded due to its limited cost-efficiency. Finally, the in vivo study in acute pneumonia model revealed that intraperitoneal administration was superior to the intramuscular route and confirmed that (-) SCM-NLC with trehalose, was the most suitable formulation against an extensively drug-resistant A. baumannii strain.

Necrotizing fasciitis in haematological patients: a different scenario.

To describe and compare the characteristics of necrotizing fasciitis (NF) in patients with and without haematological malignancy. All adult patients diagnosed with NF and treated at our hospital were included (January 2010-March 2019). Diagnosis was based on intraoperative findings or consistent clinical/radiological characteristics, and patients were classified as group A (with haematological malignancy) or group B (without haematological malignancy). Student's t (quantitative), Fisher's exact (qualitative), and Kaplan-Meyer tests were used for the statistical analysis. The study included 29 patients: 8 in group A and 21 in group B. All haematological patients had severe neutropenia (0.2 [0.02-0.5] ×109 cells/L; p < 0.001) and positive blood cultures (100% vs. 61.9%; p = 0.04) at diagnosis. Gram-negative bacilli NF was more common in group A (87.5% vs. 9.5%; p = 0.001), predominantly due to Escherichia coli (50% vs. 9.5%; p = 0.056). Surgical treatment was less common in haematological patients (5 [62.5%] vs. 21 [100%]; p = 0.015). Overall, 9 (31%) patients died: 4 (50%) in group A and 5 (23.8%) in group B (p = 0.17). The univariate analysis showed that mortality tended to be higher (OR 3.2; 95%CI 0.57-17.7; p = 0.17) and to occur earlier (2.2 ± 2.6 vs. 14.2 ± 19.9 days; p = 0.13) in haematological patients. The LRINEC index > 6 did not predict mortality in either group. In our study, NF in patients with haematological malignancies was mainly due to Gram-negative bacilli, associated to high and early mortality rates. In our experience, the LRINEC scale was not useful for predicting mortality.

Recommendations for the diagnosis and treatment of Clostridioides difficile infection: An official clinical practice guideline of the Spanish Society of Chemotherapy (SEQ), Spanish Society of Internal Medicine (SEMI) and the working group of Postoperative Infection of the Spanish Society of Anesthesia and Reanimation (SEDAR).

This document gathers the opinion of a multidisciplinary forum of experts on different aspects of the diagnosis and treatment of Clostridioides difficile infection (CDI) in Spain. It has been structured around a series of questions that the attendees considered relevant and in which a consensus opinion was reached. The main messages were as follows: CDI should be suspected in patients older than 2 years of age in the presence of diarrhea, paralytic ileus and unexplained leukocytosis, even in the absence of classical risk factors. With a few exceptions, a single stool sample is sufficient for diagnosis, which can be sent to the laboratory with or without transportation media for enteropathogenic bacteria. In the absence of diarrhoea, rectal swabs may be valid. The microbiology laboratory should include C. difficile among the pathogens routinely searched in patients with diarrhoea. Laboratory tests in different order and sequence schemes include GDH detection, presence of toxins, molecular tests and toxigenic culture. Immediate determination of sensitivity to drugs such as vancomycin, metronidazole or fidaxomycin is not required. The evolution of toxin persistence is not a suitable test for follow up. Laboratory diagnosis of CDI should be rapid and results reported and interpreted to clinicians immediately. In addition to the basic support of all diarrheic episodes, CDI treatment requires the suppression of antiperistaltic agents, proton pump inhibitors and antibiotics, where possible. Oral vancomycin and fidaxomycin are the antibacterials of choice in treatment, intravenous metronidazole being restricted for patients in whom the presence of the above drugs in the intestinal lumen cannot be assured. Fecal material transplantation is the treatment of choice for patients with multiple recurrences but uncertainties persist regarding its standardization and safety. Bezlotoxumab is a monoclonal antibody to C. difficile toxin B that should be administered to patients at high risk of recurrence. Surgery is becoming less and less necessary and prevention with vaccines is under research. Probiotics have so far not been shown to be therapeutically or preventively effective. The therapeutic strategy should be based, rather than on the number of episodes, on the severity of the episodes and on their potential to recur. Some data point to the efficacy of oral vancomycin prophylaxis in patients who reccur CDI when systemic antibiotics are required again.

Biomarkers of fungal infection: Expert opinion on the current situation.

The introduction of non-culture-based diagnostic techniques is revolutionizing the world of microbiological diagnosis and infection assessment. Fungi are no exception, and the introduction of biomarkers has opened up enormous expectations for better management of these entities. Biomarkers are diverse, their targets are also diverse and their evaluation has been done preferably in an individualized use and with deficient designs. Less is known about the value of the combined use of biomarkers and the impact of the negativity of two or more biomarkers on antifungal treatment decisions has been poorly studied. Given the paucity of prospective, randomized and definitive studies, we have convened experts from different fields, with an interest in invasive fungal infections, to answer some questions about the current relevant use of fungal biomarkers. This document summarizes the answers of these experts to the different questions.

Weighting the impact of virulence on the outcome of Pseudomonas aeruginosa bloodstream infections.

OBJECTIVES: We assessed the association between the lethality of Pseudomonas aeruginosa in a Caenorhabditis elegans model and outcomes of P. aeruginosa bloodstream infections. METHODS: A total of 593 P. aeruginosa bloodstream isolates recovered from a prospective Spanish multicentre study were analysed. Clinical variables, susceptibility profiles and Type III Secretion System (TTSS) genotypes (exoU/exoS genes) were available from previous studies. A C. elegans virulence score (CEVS) was used, classifying the isolates into high (CEVS 4-5), intermediate (CEVS 3) and low (CEVS 1-2) virulence. The main outcome analysed was 30-day mortality. RESULTS: Up to 75% (446/593) of the isolates showed a high-virulence phenotype, and 17% (101/593) a low-virulence one. No association between virulence phenotype and the main outcome variable (30-day mortality) was found (29/101 (28.7%) versus 127/446 (28.5%), p 1). However, an inverse association between C. elegans virulence and multidrug-resistant and extensively drug-resistant profiles was documented (OR 0.655 (95% CI 0.571-0.751) and OR 0.523 (95% CI 0.436-0.627), p <0.001, respectively), whereas the exoU genotype was significantly more frequent among isolates showing high virulence (10/101 (9.9%) versus 112/446 (25.1%), p <0.001). Moreover, although significance was not reached, strains showing a high-virulence phenotype tended to be associated with community-acquired infections (1/101 (1%) versus 25/446 (5.6%), p 0.065), whereas low-virulence phenotypes tended to be associated with a higher illness severity (such as higher median Pitt score: 2 (1-4) versus 1 (0-3), p 0.036, or initial multiorgan dysfunction: 17/101 (16.8%) versus 41/446 (9.2%), p 0.024), with some underlying conditions (such as chronic renal failure 24/101 (23.8%) versus 59/446 (13.2%), p 0.013), and with the respiratory source of infections (17/101 (16.8%) versus 45/446 (10.1%), p 0.058). CONCLUSIONS: Our results indicate that the P. aeruginosa virulence phenotype in a C. elegans model correlates with virulence genotype (TTSS) and resistance profile, but it is a poor prognostic marker of mortality in bloodstream infections.

[Recommendations from a panel of experts on the usefulness of fidaxomicin for the treatment of infections caused by Clostridium difficile]. / Recomendaciones de un panel de expertos sobre la utilidad de fidaxomicina para el tratamiento de las infecciones causadas por Clostridium difficile.

OBJECTIVE: Clostridium difficile infections have a high recurrence rate, which can complicate the prognosis of affected patients. It is therefore important to establish an early detection and an appropriate therapeutic strategy. The objective of this manuscript was to gather the opinion of an expert group about the predictive factors of poor progression, as well as when to use fidaxomicin in different groups of high-risk patients. METHODS: A scientific committee of three experts in infectious diseases reviewed the most recent literature on the management of C. difficile infections, and the use of fidaxomicin. They developed a questionnaire of 23 items for consensus by 15 specialists in this type of infection using a modified Delphi method. RESULTS: The consensus reached by the panelists was 91.3% in terms of agreement. The most important agreements were: recurrence is a risk criterion per se; fidaxomicin is effective and safe for the treatment of infections caused by C. difficile in critical patients, immunosuppressed patients, or patients with chronic renal failure; fidaxomicin is recommended from the first episode of infection to ensure maximum efficacy in patients with well-contrasted recurrence risk factors. CONCLUSIONS: The experts consulted showed a high degree of agreement on topics related to the selection of patients with poorer prognosis, as well as on the use of fidaxomicin in groups of high-risk patients, either in the first line or in situations of recurrence.

Predictors of outcome in patients with severe sepsis or septic shock due to extended-spectrum ß-lactamase-producing Enterobacteriaceae.

PURPOSE: There are few data in the literature regarding sepsis or septic shock due to extended-spectrum ß-lactamases (ESBL)-producing Enterobacteriaceae (E). The aim of this study was to assess predictors of outcome in septic patients with bloodstream infection (BSI) caused by ESBL-E. METHODS: Patients with severe sepsis or septic shock and BSI due to ESBL-E were selected from the INCREMENT database. The primary endpoint of the study was the evaluation of predictors of outcome after 30 days from development of severe sepsis or septic shock due to ESBL-E infection. Three cohorts were created for analysis: global, empirical-therapy and targeted-therapy cohorts. RESULTS: 367 septic patients were analysed. Overall mortality was 43.9% at 30 days. Escherichia coli (62.4%) and Klebsiella pneumoniae (27.2%) were the most frequent isolates. ß-lactam/ß-lactamase inhibitor (BLBLI) combinations were the most empirically used drug (43.6%), followed by carbapenems (29.4%). Empirical therapy was active in vitro in 249 (67.8%) patients, and escalation of antibiotic therapy was reported in 287 (78.2%) patients. Cox regression analysis showed that age, Charlson Comorbidity Index, McCabe classification, Pitt bacteremia score, abdominal source of infection and escalation of antibiotic therapy were independently associated with 30-day mortality. No differences in survival were reported in patients treated with BLBLI combinations or carbapenems in empirical or definitive therapy. CONCLUSIONS: BSI due to ESBL-E in patients who developed severe sepsis or septic shock was associated with high 30-day mortality. Comorbidities, severity scores, source of infection and antibiotic therapy escalation were important determinants of unfavorable outcome.

A pragmatic approach for mortality prediction after surgery in infective endocarditis: optimizing and refining EuroSCORE.

OBJECTIVE: To simplify and optimize the ability of EuroSCORE I and II to predict early mortality after surgery for infective endocarditis (IE). METHODS: Multicentre retrospective study (n = 775). Simplified scores, eliminating irrelevant variables, and new specific scores, adding specific IE variables, were created. The performance of the original, recalibrated and specific EuroSCOREs was assessed by Brier score, C-statistic and calibration plot in bootstrap samples. The Net Reclassification Index was quantified. RESULTS: Recalibrated scores including age, previous cardiac surgery, critical preoperative state, New York Heart Association >I, and emergent surgery (EuroSCORE I and II); renal failure and pulmonary hypertension (EuroSCORE I); and urgent surgery (EuroSCORE II) performed better than the original EuroSCOREs (Brier original and recalibrated: EuroSCORE I: 0.1770 and 0.1667; EuroSCORE II: 0.2307 and 0.1680). Performance improved with the addition of fistula, staphylococci and mitral location (EuroSCORE I and II) (Brier specific: EuroSCORE I 0.1587, EuroSCORE II 0.1592). Discrimination improved in specific models (C-statistic original, recalibrated and specific: EuroSCORE I: 0.7340, 0.7471 and 0.7728; EuroSCORE II: 0.7442, 0.7423 and 0.7700). Calibration improved in both EuroSCORE I models (intercept 0.295, slope 0.829 (original); intercept -0.094, slope 0.888 (recalibrated); intercept -0.059, slope 0.925 (specific)) but only in specific EuroSCORE II model (intercept 2.554, slope 1.114 (original); intercept -0.260, slope 0.703 (recalibrated); intercept -0.053, slope 0.930 (specific)). Net Reclassification Index was 5.1% and 20.3% for the specific EuroSCORE I and II. CONCLUSIONS: The use of simplified EuroSCORE I and EuroSCORE II models in IE with the addition of specific variables may lead to simpler and more accurate models.

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.

Impact of Staphylococcus aureus phenotype and genotype on the clinical characteristics and outcome of infective endocarditis. A multicentre, longitudinal, prospective, observational study.

OBJECTIVE: We aimed to evaluate the impact of Staphylococcus aureus phenotype (vancomycin MIC) and genotype (agr group, clonal complex CC) on the prognosis and clinical characteristics of infective endocarditis (IE). METHODS: We performed a multicentre, longitudinal, prospective, observational study (June 2013 to March 2016) in 15 Spanish hospitals. Two hundred and thirteen consecutive adults (≥18 years) with a definite diagnosis of S. aureus IE were included. Primary outcome was death during hospital stay. Main secondary end points were persistent bacteraemia, sepsis/septic shock, peripheral embolism and osteoarticular involvement. RESULTS: Overall in-hospital mortality was 37% (n = 72). Independent risk factors for death were age-adjusted Charlson co-morbidity index (OR 1.20; 95% CI 1.08-1.34), congestive heart failure (OR 3.60; 95% CI 1.72-7.50), symptomatic central nervous system complication (OR 3.17; 95% CI 1.41-7.11) and severe sepsis/septic shock (OR 4.41; 95% CI 2.18-8.96). In the subgroup of methicillin-susceptible S. aureus IE (n = 173), independent risk factors for death were the age-adjusted Charlson co-morbidity index (OR 1.17; 95% CI 1.03-1.31), congestive heart failure (OR 3.39; 95% CI 1.51-7.64), new conduction abnormality (OR 4.42; 95% CI 1.27-15.34), severe sepsis/septic shock (OR 5.76; 95% CI 2.57-12.89) and agr group III (OR 0.27; 0.10-0.75). Vancomycin MIC ≥1.5 mg/L was not independently associated with death during hospital nor was it related to secondary end points. No other genotype variables were independently associated with in-hospital death. CONCLUSIONS: This is the first prospective study to assess the impact of S. aureus phenotype and genotype. Phenotype and genotype provided no additional predictive value beyond conventional clinical characteristics. No evidence was found to justify therapeutic decisions based on vancomycin MIC for either methicillin-resistant or methicillin-susceptible S. aureus.

[Candidemia and invasive candidiasis approach in critically ill patients: role of the echinocandins]. / Abordaje de la candidemia y la candidiasis invasiva en el paciente crítico: papel de las equinocandinas.

OBJECTIVE: Invasive infections caused by Candida spp. in critically ill patients may significantly worsen their prognosis, so it is of great importance to establish an early detection and a suitable therapeutic strategy. The objective of this study was to define the differential role of echinocandins in treating certain critical patient profiles. METHODS: A scientific committee of 9 experts in infectious diseases, critical care, microbiology, and hospital pharmacy reviewed the existing evidence on the treatment of candidemia and invasive candidiasis in critically ill patients. After that, a questionnaire with 35 items was elaborated to be agreed by 26 specialists in the aforementioned disciplines using a modified Delphi method. RESULTS: After two rounds of evaluation, a consensus was reached in terms of agreement in 66% of the items. Some of the consensuses achieved included: it is not necessary to adjust the dose of echinocandins during renal replacement therapy; the echinocandins are the empirical and/or directed treatment of choice for candidemia and invasive candidiasis associated with biofilms; these drugs may be used in the antifungal prophylaxis of high-risk liver transplantation. In the absence of additional clinical data, it should be noted that micafungin is the echinocandin with the most available scientific evidence. CONCLUSIONS: The experts consulted showed a high degree of agreement on some of the most controversial aspects regarding the management of candidemia and invasive candidiasis in critical patients, which could inform of practical recommendations for their treatment.

The changing epidemiology of spinal tuberculosis: the influence of international immigration in Catalonia, 1993-2014.

The overall incidence of spinal tuberculosis (TB) appears to be stable or declining in most European countries, but with an increasing proportion of cases in the foreign-born populations. We performed a retrospective observational study (1993-2014), including all cases of spinal TB diagnosed at a Barcelona hospital to assess the epidemiological changes. Fifty-four episodes (48·1% males, median age 52 years) of spinal TB were diagnosed. The percentage of foreign-born residents with spinal TB increased from 14% to 45·2% in the last 10 years (P = 0·017). Positive Mycobacterium tuberculosis testing in vertebral specimens was 88·2% (15/17) for GeneXpert MTB/RIF. Compared with natives, foreign-born patients were younger (P < 0·01) and required surgery more often (P = 0·003) because of higher percentages of paravertebral abscess (P = 0·038), cord compression (P = 0·05), and persistent neurological sequelae (P = 0·05). In our setting, one-third of spinal TB cases occurred in non-native residents. Compared with natives, foreign-born patients were younger and had greater severity of the disease. The GeneXpert MTB/RIF test may be of value for diagnosing spinal TB.

Impact of fluconazole susceptibility on the outcome of patients with candidaemia: data from a population-based surveillance.

OBJECTIVES: The clinical correlation of fluconazole antifungal susceptibility testing (AST) for Candida isolates and its integration with pharmacokinetics/pharmacodynamics (PK/PD) parameters is unclear. We analysed the impact of fluconazole minimum inhibitory concentration (MIC) values, 24-hour area under the concentration-time curve (AUC24) and AUC24/MIC ratio on the outcome of candidemic patients. METHODS: We included 257 episodes of candidaemia treated with fluconazole monotherapy for ≥72 hours from a population-based surveillance conducted in 29 hospitals (CANDIPOP Project). AST was centrally performed by European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) microdilution methods. Primary outcome was clinical failure (30-day mortality and/or persistent candidaemia for ≥72 hours from initiation of therapy). Secondary outcomes included early (3-7 days) and late (3-30 days) mortality. RESULTS: Rates of clinical failure, early and late mortality among evaluable episodes were 32.3% (80/248), 3.1% (8/257) and 23.4% (59/248). There was no relationship between fluconazole MIC values or PK/PD parameters and clinical failure. Although MIC values ≥2 mg/L by EUCAST (positive predictive value 32.1%, negative predictive value 68.7%) and ≥0.5 mg/L by CLSI (positive predictive value 34.8%, negative predictive value 74.4%) appeared to be optimal for predicting clinical failure, no significant associations remained after multivariate adjustment (odds ratio 1.67; 95% confidence interval 0.48-5.79; p 0.423). Lack of association was consistent for alternative thresholds (including proposed clinical breakpoints). The only association found for secondary outcomes was between an AUC24/MIC ratio >400 h by CLSI and early mortality (odds ratio 0.18; 95% confidence interval 0.04-0.98; p 0.026). CONCLUSIONS: High fluconazole MIC values did not negatively impact outcome of patients with candidaemia treated with fluconazole. No effect of PK/PD targets on the risk of clinical failure was found.

Infectious encephalitis: utility of a rational approach to aetiological diagnosis in daily clinical practice.

In this study we attempt to assess the utility of a simplified step-wise diagnostic algorithm to determinate the aetiology of encephalitis in daily clinical practice and to describe the main causes in our setting. This was a prospective cohort study of all consecutive cases of encephalitis in adult patients diagnosed between January 2010 and March 2015 at the University Hospital Vall d'Hebron in Barcelona, Spain. The aetiological study was carried out following the proposed step-wise algorithm. The proportion of aetiological diagnoses achieved in each step was analysed. Data from 97 patients with encephalitis were assessed. Following a simplified step-wise algorithm, a definite diagnosis was made in the first step in 53 patients (55 %) and in 12 additional cases (12 %) in the second step. Overall, a definite or probable aetiological diagnosis was achieved in 78 % of the cases. Herpes virus, L. monocytogenes and M. tuberculosis were the leading causative agents demonstrated, whereas less frequent aetiologies were observed, mainly in immunosuppressed patients. The overall related mortality was 13.4 %. According to our experience, the leading and treatable causes of encephalitis can be identified in a first diagnostic step with limited microbiological studies. L. monocytogenes treatment should be considered on arrival in some patients. Additional diagnostic effort should be made in immunosuppressed patients.

Evaluation of the possible influence of trailing and paradoxical effects on the clinical outcome of patients with candidemia.

OBJECTIVE: Paradoxical growth (PG) and trailing effect (TE) are frequently observed during antifungal susceptibility testing (AFST). These two phenomena interfere with the determination of the minimal inhibitory concentration (MIC). The aim of this study was to assess the clinical impact of TE and PG. METHODS: We analysed the frequency of TE and PG of 690 Candida isolates collected from a population-based study performed in Spain (CANDIPOP) and correlated the results with clinical outcome of the patients. RESULTS: Around 70% (484/690) of the isolates exhibited TE to azoles. Candida tropicalis showed the highest presence of TE (39/53 isolates exhibited residual growth >25% of control). No TE was seen in most of the isolates from the psilosis complex. PG was mainly associated with echinocandins. In patients treated with fluconazole within the first 48 hours after blood sampling (n = 221), the presence of TE to azoles tended to be associated with lower 30-day mortality (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25-1.00) but not with clinical failure (OR 0.85, 95% CI 0.45-1.54). In the subgroup of 117 patients treated with echinocandins, the presence of PG was not associated with patient's response to antifungal treatment (OR for 30-day mortality 1.63, 95% CI 0.76-4.03; OR for clinical failure 1.17, 95% CI 0.53-2.70). CONCLUSIONS: TE or PG are widely expressed among Candida spp., although they do not seem to influence clinical outcome.