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Introduction: An echinocandin, such as micafungin, is recommended as first-line treatment for invasive Candida infections in immunocompromised patients. This multicenter, observational, prospective, non- interventional study evaluated the real-world use of micafungin in clinical practice in Slovenia and Romania, as this remains unexplored. Methodology: The primary endpoint was evaluation of micafungin use, including rationale for prescription, treatment duration, and daily dose. Secondary endpoints included recordings of patient baseline characteristics and evaluations of efficacy and safety. Across 11 centers in two countries, 118 patients (18 children [< 16 years] and 100 adults [≥ 16 years]) received micafungin for the first time according to their clinic’s standard practice. Results: Micafungin was prescribed for treatment in 57.6% of patients and for prophylaxis in 40.7% of patients. The median (range) treatment duration was 9.0 (0 – 54) days and 13.0 (2 – 6)] days, respectively. The median dose of micafungin was higher than recommended for children receiving prophylaxis or treatment for invasive candidiasis and for adults receiving prophylaxis. Fever was the most commonly observed clinical sign at baseline (16 children [88.9%] and 31 adults [31%]) and hematologic malignancy was the most frequent primary diagnosis at admission (11 children [61.1%] and 40 adults [40%]). Candida species were the most commonly identified causal agents of invasive fungal infections (2 children [11.1%] and 48 adults [48%]). Conclusions: The efficacy and safety profiles of micafungin use in Slovenia and Romania based on clinician’s own experiences in local clinical practice were consistent with those reported in other real-world studies.

We present a case of a 28-year-old patient who underwent spinal anaesthesia for caesarean section, and developed meningitis, Streptococcus salivarius was isolated in the cerebrospinal fluid. The Viridans streptococci are a part of a normal human mouth flora, therefore the patient most likely developed iatrogenic meningitis due to droplet transmission of bacteria intrathecally. We discuss etiology, pathogenesis, clinical presentation, diagnostic tools, treatment and prognosis of meningitis afer intrathecal procedures and we emphasize the importance of strict aseptic technique while performing neuraxial procedures. Iatrogenic meningitis should be considered as a possible differential diagnosis in patients who present with symptoms and signs of meningitis after neuraxial blockade.

Background Herpes simplex virus (HSV) encephalitis is associated with adverse clinical outcomes in 50% of patients. The use and impact of adjunctive steroids in improving the prognosis of this devastating disease is unknown. Methods A multicenter international retrospective study of adults (age >15 years) with confirmed HSV encephalitis. An adverse clinical outcome was defined as death or survived with sequelae. Results A total of 438 adults with HSV encephalitis were enrolled. The mean age was 50.58 years (15.94, SD), 226 (51.6%) were female and 59 (13.5%) were immunosuppressed. New onset seizures were seen in 91 (20.8%) patients and the median Glasgow coma scale was 14 (13–15, IQR). A total of 73 (16.6%) patients received adjunctive steroids during their hospitalization. Adjunctive steroids were given more frequently to patients with fever (84.5% vs. 66.7%, P = 0.003), seizures (38.3% vs. 17.3%, P < 0.001), abnormalities on MRI (77.7% vs. 61.8%, P = 0.017), lower mean Glasgow coma scales (10.42 vs. 11.3, P = 0.013) and it was also associated with a longer length of stay (median duration of 23 days vs. 20 days, P = 0.012). Adjunctive steroids were not associated with an impact on adverse clinical outcomes (46.6% vs. 46.9%, P = 0.95). Conclusion Adjunctive steroids in HSV encephalitis are used more commonly in the sicker patients and are not associated with a benefit in clinical outcomes. Disclosures All authors: No reported disclosures.

WOS: 000379252100027, PubMed ID: 27085724, There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. Overall, 501 adult patients with PCR-proven HME were included retrospectively from 35 referral centres in 10 countries; 496 patients were found to be eligible for the analysis. Cerebrospinal fluid (CSF) analysis using a PCR assay yielded herpes simplex virus (HSV)-1 DNA in 351 patients (70.8%), HSV-2 DNA in 83 patients (16.7%) and undefined HSV DNA type in 62 patients (12.5%). A total of 379 patients (76.4%) had at least one of the specified characteristics of encephalitis, and we placed these patients into the encephalitis presentation group. The remaining 117 patients (23.6%) had none of these findings, and these patients were placed in the nonencephalitis presentation group. Abnormalities suggestive of encephalitis were detected in magnetic resonance imaging (MRI) in 83.9% of the patients and in electroencephalography (EEG) in 91.0% of patients in the encephalitis presentation group. In the nonencephalitis presentation group, MRI and EEG data were suggestive of encephalitis in 33.3 and 61.9% of patients, respectively. However, the concomitant use of MRI and EEG indicated encephalitis in 96.3 and 87.5% of the cases with and without encephalitic clinical presentation, respectively. Considering the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection. (C) 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

In hantavirus infections levels of serum leukocytes or C-reactive protein are usually elevated to levels found in serious bacterial infections. However, procalcitonin in patients infected with hantavirus has not yet been discussed in the literature. A total of 29 adult patients with hantavirus infection, 30 with sepsis, and 19 with tick-borne encephalitis were included in this observational retrospective study. The median procalcitonin level in patients with hantavirus infection was 0.53 μg/L (range 0.09-11.71 μg/L), in the group with sepsis 4.33 μg/L (range 0.08-161.1 μg/L) and in patients with viral meningitis 0.08 μg/L (range 0.05-0.12 μg/L). The difference between all three groups was statistically significant (p < 0.001). A higher procalcitonin level was found in patients with hemorrhagic fever with renal syndrome caused by Dobrava virus (0.74 μg/L; range 0.09-2.83 μg/L) than in those with Puumala virus infections (0.50 μg/L; range 0.10-11.71 μg/L). However, the difference was not statistically significant (p = 0.895). This study confirmed previous findings demonstrating the association of elevated procalcitonin with bacterial infection. However, increased procalcitonin serum level was also found in hantavirus infections with overlapping results between viral and severe bacterial infections.

WOS: 000358623200015, PubMed ID: 25779579, Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral treatment. Samples from 501 patients with molecular confirmation from cerebrospinal fluid were included from 35 referral centers in 10 countries. Four hundred thirty-eight patients were found to be eligible for the analysis. Overall, 232 (52.9%) patients experienced unfavorable outcomes, 44 died, and 188 survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome.

Theoretical background: Procalcitonin (PCT) is diagnostic and prognostic biomarker of sepsis. The objective of this study was to evaluate the correlation between sepsis causative agent and serum PCT concentration, since it would influence the initial empirical antimicrobial therapy selection. Methods: This retrospective study included 96 patients with sepsis who were admitted to Intensive Care Unit of Department of Infectious Diseases and Febrile Illnesses of University Clinical Center Ljubljana from September of 2011 through March of 2013. Sepsis was established clinically and defined aetiologically by haemoculture growth. Statistical evaluation was conducted in 76 patients who had not received proper antimicrobial therapy prior to blood collection. For PCT determination imunoluminometric method was used and concentrations above 5 mg/L were considered elevated. Results: Serum PCT concentration was significantly higher in Gram-negative sepsis (PCT median was 26,3 μg/L ) compared to Gram-positive sepsis (PCT median was 11,2 μg/L ) (p = 0,016). Differences in PCT concentrations between Gram-positive pathogens were not statistically significant (p = 0,09), however, S. aureus sepsis is linked to higher serum PCT concentration ( median PCT 12,8 μg/L ) than all other Gram-positive agents put together (median PCT of 5,9 μg/L ) (p = 0,016). Difference in PCT concentration in E. coli sepsis (median PCT of 38,2 μg/L ) compared to other enterobacteria (median PCT of 26,3 μg/L ) is not statistically significant (p = 0,902). Conclusions: Causative agent has a significant effect on serum PCT concentration in patients with sepsis. Higher values were present in Gram-negative than in Gram-positive sepsis. Amongst Gram-positive pathogens, S. aureus caused greater rise in PCT than other Gram-positive bacteria put together.

Necrotizing fasciitis is a potentially life-threatening infection of deep skin layers and subcutaneous tissues that can easily spread across the fascia plate and is usually the result of a combined infection with anaerobic and aerobic microorganisms. The patient typically complains of excruciating pain, which is not necessarily in accordance with clinical signs. Early recognition of the condition is very important, and aggressive treatment with a combination of antibiotics and surgical procedure is crucial. We present a case of a 15-year-old girl with acute lymphoblastic leukemia who developed necrotizing fasciitis after venous access port implantation during induction chemotherapy.

In Europe infection with Puumala or Dobrava viruses causes hemorrhagic fever with renal syndrome (HFRS). In the course of HFRS, mild neurological symptoms such as headache, vertigo, and nausea are common. However, the data about the occurrence of severe, potentially life-threatening neurological manifestations are rather scarce. Here, we present a case of HFRS with serologically proven Dobrava virus infection complicated by epileptic seizures and hemiparesis due to focal encephalitis.

The aim of this retrospective study was to assess some clinical, epidemiological and laboratory parameters of severe tick-borne encephalitis in Slovenia in the last five years, to compare them with published data, and to estimate need for providing a policy of active immunization. Thirty-three adult patients with a severe course of the disease, admitted to the intensive care unit of the Department of Infectious Diseases, University Medical Centre Ljubljana, Slovenia during a five year period, participated. All the patients had specific serum IgM antibodies against tick-borne encephalitis virus at admissions and IgG antibodies were present in 29 out of 33 patients. Twenty-two patients were admitted because of severe consciousness disturbances, nine suffered from spinal nerve paralysis, in two patients cranial nerve paralysis was observed, and one suffered from generalized tonic-clonic seizures. Ten patients were mechanically ventilated and three died. Leukocytosis in peripheral veins was found in twenty-one patients and nine had a C-reactive protein serum concentration over 50 mg/l. Nineteen patients had a cerebrospinal fluid leukocyte count exceeding 100 x 10(6)/l and a cerebrospinal fluid protein concentration was over the cut-off value of 0.45 g/l in majority. The findings of the present study confirmed some previous reports about clinical, epidemiological and laboratory characteristics of patients with severe tick-borne encephalitis. We have found that tick-borne encephalitis in Slovenia has a relatively low fatality rate. However, the severe course with long-lasting sequelae of the disease justifies vaccination of a risk population in endemic areas.

Background: The value of serum and cerebrospinal fluid (CSF) procalcitonin for differentiating between acute bacterial and viral meningitis was assessed and compared to other parameters which are usually used in clinical practice. Patients: 45 adult patients (20 with bacterial and 25 with tick-borne encephalitis, TBE) were included in this prospective study. Results: The median serum procalcitonin level in patients with bacterial meningitis was 6.45 ng/ml (range 0.25–43.76 ng/ml) and in the group with viral meningitis 0.27 ng/ml (range 0.05–0.44 ng/ml). 11 patients with bacterial meningitis had an elevated procalcitonin concentration not only in serum, but also in CSF. A serum procalcitonin level > 0.5 ng/ml had a positive predictive value for bacterial meningitis of 100% and a negative predictive value of 93%, while corresponding values for CSF procalcitonin were 100% and 74%, respectively. Conclusion: Serum and CSF procalcitonin concentrations > 0.5 ng/ml appear to be a reliable indicator of bacterial central nervous system (CNS) infection, with maximal positive predictive values and high negative predictive values.

Tick-borne encephalitis has occurred regularly in Europe since it was first diagnosed in 1931 by Schneider. The mortality rate of patients with this disease is 1-2%. Death usually occurs in the acute stage of illness. A case report of a 28-year-old patient from Slovenia, who died shortly after the onset of tick-borne encephalitis, is described. The clinical course of disease, results of serological tests, neuropathological findings and polymerase chain reaction amplification of parts of viral genome from postmortem brain tissues are presented.

BACKGROUND: Herpetic meningoencephalitis is the most frequent form of sporadic fatal encephalitis in the world and accounts for 10- 20% of all viral encephalitides. There were studies assessing the outcomes particularly by comparing the efficacies of antiviral drugs in the past. To the best of our knowledge, no datum exists in the literature on the mortality indicators of HME patients with definite microbiological diagnosis. Thus, our study makes use of the largest case series ever reported in the literature to provide data for the predictors of unfavorable outcome in HME cases. METHODS: This multicenter study enrolled HME patients from referral participant centers in 10 countries (Croatia, Czech Republic, Denmark, Egypt, France, Iraq, Italy, Lebanon, Slovenia, and Turkey). The study had a retrospective design and included patients hospitalized between 2000 and 2013. Only the adult patients with HME over the age of 15 were enrolled. Dr Lütfi Kirdar Training and Research Hospital’s Review Board in Istanbul approved the study. The inclusion criteria were as follows: 1. Symptoms and/or signs of parenchymatous disease of the brain such as focal neurological signs, seizures, decreased consciousness or disorientation often concomitant with fever and pathological neuroradiology or neurophysiology findings 2. Positive CSF-PCR result for HSV-1 or HSV-2 or both. 3. The unlikely presence of another parenchymatous disease of the brain. Unfavorable Outcome included death and sequelae. RESULTS: In this study, 501 patients with microbiologically confirmed HME were enrolled from 35 referral centers in 10 countries [Turkey (n=144), Denmark (n=127), France (n=64), Slovenia (n=54), Croatia (n=32), Iraq (n=30), Czech Republic (n=23), Italy (n=12), Lebanon (n=8), Egypt (n=7)]. However, 438 patients were found to be eligible for outcome analysis and 63 HME cases were excluded due to missing data. In this study 44 (10 %) patients died and 188 (42.9 %) experienced unfavorable outcome. Hence, 232 (52.9 %) cases experienced unfavorable outcome. The results of multivariate analysis are presented in the table. The interrelation between the elapsed time since the onset of symptoms to anti-viral treatment and unfavorable outcome is presented in the figure. CONCLUSION: Advancing age, lower GCS scores, delayed start of antivirals exceeding one week in particular, and new onset of convulsions seem to increase unfavorable outcome in HME. Thus, it appears that both host and therapeutic parameters contribute to success in these cases. Table. Final model including independent predictors of unfavorable outcome 95% CIs OR [1] Low High p Age (years) 1.04 1.02 1.05 0.000 Glasgow coma scale 0.84 0.77 0.93 0.000 Elapsed time [2] >2 days 7 days 3.75 1.72 8.15 0.001 New onset convulsion [3] 1.61 0.93 2.76 0.088 constant 1.08 0.27 4.43 0.910 [1] OR, odds ratio [2] Elapsed time between unset of symptoms and administration of anti-viral treatment [3] Newly unset convulsion before hospital admission