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Herein we describe the isolation of homarine and piridiniumbetaine B from the sponge Aaptos sp. Although homarine has a common occurrence among animals, piridiniumbetaine B was only recently isolated from the marine sponge Agelas dispar. The isolation of piridiniumbetaine B from two taxonomically distant marine sponges corroborate previous assumptions that such betaines should be regarded rather as primary metabolites. We have also isolated (9-[5'-(methylthio)-beta-D-xylofuranosyl]adenine (xylosyl-MTA) from the mantle of a nudibranch identified as Doris aff. verrucosa. The occurrence of xylosyl-MTA in the mantle of this animal strongly suggests that it is the same nudibranch species described for the Mediterranean sea. We have been unable to detect any other compound in the mantle extract of D. aff. verrucosa other than xylosil-MTA and sterols. GC-MS analysis of the sterol fraction from the nudibranch and its prey, the sponge Hymeniacidon aff. heliophila, revealed the occurrence of the ubiquitous sterols, cholesterol, brassicasterol, cholestanol, 24-methylcholesterol and 24-ethylcholesterol, as the only common metabolites, therefore precluding any assumption concerning the sequestration of secondary metabolites by the nudibranch from H. aff. heliophila.

The COVID-19 pandemic affected the epidemiology of infectious diseases and changed the operation of health care systems and health care seeking behavior. Our study aimed to analyze the utilization of systemic antibiotics in ambulatory care in Hungary after the COVID-19 pandemic and compare it to the period before COVID. We defined three periods (24 months each): Before COVID, COVID, and After COVID. Monthly trends in systemic antibiotic (J01) use were calculated using the WHO ATC-DDD index and expressed as DDD/1000 inhabitants/day (DID) and number of exposed patients per active agent. The data were further categorized by the WHO AWaRe classification. In the After COVID period, we detected almost the same (11.61 vs. 11.11 DID) mean monthly use of systemic antibiotics in ambulatory care compared to the Before COVID period. We observed a decrease in the seasonality index in the After COVID period (46.86% vs. 39.86%). In the After COVID period, the use of cephalosporins and quinolones decreased significantly, while in the case of macrolides, a significant increase was observed compared to the Before COVID period, with excessive azithromycin use (66,869 vs. 97,367 exposed patients). This study demonstrated significant changes in the pattern of ambulatory care antibiotic use in Hungary.

Purpose: Favipiravir has been used in the therapy of COVID-19, including patients with mild to moderate symptoms in certain countries. The aim of our systematic review and meta-analysis was to investigate its efficacy and safety in mild-to-moderate COVID-19 infections., Methods: The PubMed, Embase, Web of Science, and Cochrane databases were systematically reviewed for articles reporting the results of randomized controlled trials published until January 6, 2023, resulting in the identification of 20 eligible studies., Results: There were no significant differences in viral clearance time (HR = 1.20, p = 0.09) compared to those without favipiravir therapy. However, in the subgroup analyses, favipiravir treatment significantly increased viral clearance by 59 % (HR = 1.59, p < 0.01) and 42 % (HR = 1.42, p < 0.01], I 2  = 20 %) compared to the comparator group in patients with moderate severity of COVID-19 and in the inpatient care setting, respectively. Favipiravir had no beneficial effects in the case of patients with mild symptoms and treated in ambulatory care., Conclusions: The use of favipiravir is questionable in the treatment of outpatients with COVID-19 with mild symptoms. Moderate beneficial effects in the case of patients with moderate symptoms and inpatients should be treated with care due to the limitations of the analysed trials., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Extensive use of carbapenems may lead to selection pressure for Stenotrophomonas maltophilia (SM) in hospital environments. The aim of our study was to assess the possible association between systemic antibiotic use and the incidence of SM. A retrospective, observational study was carried out in a tertiary-care hospital in Hungary, between January 1st 2010 and December 31st 2019. Incidence-density for SM and SM resistant to trimethoprim-sulfamethoxazole (SXT) was standardized for 1000 patient-days, while systemic antibiotic use was expressed as defined daily doses (DDDs) per 100 patient-days. Mean incidence density for SM infections was 0.42/1000 patient-days; 11.08% were were resistant to SXT, the mean incidence density for SXT-resistant SM was 0.047/1000 patient-days. Consumption rate for colistin, glycopeptides and carbapenems increased by 258.82, 278.94 and 372.72% from 2010 to 2019, respectively. Strong and significant positive correlations were observed with the consumption of carbapenems (r: 0.8759; P < 0.001 and r: 0.8968; P < 0.001), SXT (r: 0.7552; P = 0.011 and r: 0.7004; P = 0.024), and glycopeptides (r: 0.7542; P = 0.012 and r: 0.8138; P < 0.001) with SM and SXT-resistant SM incidence-density/1000 patient-days, respectively. Implementation of institutional carbapenem-sparing strategies are critical in preserving these life-saving drugs, and may affect the microbial spectrum of infections in clinical settings.

The aim of this study was to assess antibiotic use in the Hungarian hospital care sector during and before the pandemic. Aggregated systemic antibiotic (ATC: J01) utilisation data were obtained for the 2010-2021 period. Classifications and calculations were performed according to the WHO ATC/DDD index and expressed as DDD per 1000 inhabitants and per day (DID), DDD per 100 patient-days (DHPD) and DDD/discharge. A linear regression (trend analysis) was performed for the pre-COVID years (2010-2019) and a prediction interval was set up to assess whether the pandemic years' observed utilisation fit in. Antibiotic utilisation was constant in DID before and during the pandemic (2019: 1.16; 2020: 1.21), while we observed a substantial increase in antibiotic use when expressed in DDD per 100 patient-days (2019: 23.3, 2020: 32.2) or DDD/discharge (2019: 1.83, 2020: 2.45). The observed utilisation level of penicillin combinations; first-, third- and fourth-generation cephalosporins; carbapenems; glycopeptides; nitroimidazoles and macrolides exceeded the predicted utilisation values in both pandemic years. Before the pandemic, co-amoxiclav headed the top list of antibiotic use, while during the pandemic, ceftriaxone became the most widely used antibiotic. Azithromycin moved up substantially on the top list of antibiotic use, with a 397% increase (2019: 0.45; 2020: 2.24 DHPD) in use. In summary, the pandemic had a major impact on the scale and pattern of hospital antibiotic use in Hungary.

The COVID-19 pandemic and related restrictions have potentially impacted the use of antibiotics. We aimed to analyze the use of systemic antibiotics (J01) in ambulatory care in Hungary during two pandemic years, to compare it with pre-COVID levels (January 2015-December 2019), and to describe trends based on monthly utilization. Our main findings were that during the studied COVID-19 pandemic period, compared to the pre-COVID level, an impressive 23.22% decrease in the use of systemic antibiotics was detected in ambulatory care. A significant reduction was shown in the use of several antibacterial subgroups, such as beta-lactam antibacterials, penicillins (J01C, -26.3%), and quinolones (J01M, -36.5%). The trends of antibiotic use moved in parallel with the introduction or revoking of restriction measures with a nadir in May 2020, which corresponded to a 55.46% decrease in use compared to the previous (pre-COVID) year's monthly means. In general, the systemic antibiotic use (J01) was lower compared to the pre-COVID periods' monthly means in almost every studied pandemic month, except for three months from September to November in 2021. The seasonal variation of antibiotic use also diminished. Active agent level analysis revealed an excessive use of azithromycin, even after evidence of ineffectiveness for COVID-19 emerged.

Background: Hepatitis E virus (HEV) is one of the most important causes of hepatitis worldwide. Despite this, limited data published more than ten years ago are only available about HEV epidemiology in Hungary., Objectives: We aimed to determine the epidemiological features of HEV infections among patients submitted to various departments of our university hospital in Hungary with signs and symptoms referring to acute hepatitis., Study Design: One thousand four hundred thirty-one sera samples from 1,383 patients were analyzed by enzyme-linked immunosorbent assays (ELISA). In some patients, HEV RNA was detected by broad-range nested polymerase chain reaction (PCR) if acute hepatitis was confirmed. PCR products were sequenced and compared with other available sequences in GenBank., Results: Five hundred eighteen sera from 429 patients proved positive (31.0%) for HEV-specific immunoglobulin G (IgG) with a mean age of 60.0 years. Most sera with anti-HEV IgG antibodies were collected from adults and elderly patients. Anti-HEV IgM positive results were found in the case of 95 sera samples from 70 patients (5.1%). Acute HEV infections were confirmed mostly over 40 (n = 67, 95.7%). The number of males (n = 47, 67.1%) was higher than females (n = 23, 32.9%). We detected HEV-specific PCR products in seven patients (10.9%). Genotyping was successful for 5 out of 7 PCR-positive samples. All sequences belonged to genotype 3 (subgenotypes: e, f)., Conclusions: In our survey, we confirmed the constant presence of acute HEV infections in Hungary and an increased seroprevalence of anti-HEV IgG antibodies compared to a previous study., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

BackgroundIn 2019, the World Health Organization published the 21st Model list of Essential Medicines and updated the Access, Watch Reserve (AWaRe) antibiotics classification to improve metrics and indicators for antibiotic stewardship activities. Reserve antibiotics are regarded as last-resort treatment options.AimWe investigated hospital-sector consumption quantities and trends of Reserve group antibiotics in European Union/European Economic Area countries and the United Kingdom (EU/EEA/UK).MethodsHospital-sector antimicrobial consumption data for 2010-2018 were obtained from the European Centre for Disease Prevention and Control. Antibacterials' consumption for systemic use (Anatomical Therapeutic Chemical classification (ATC) group J01) were included in the analysis and expressed as defined daily doses (DDD) per 1,000 inhabitants per day. We defined reserve antibiotics as per AWaRe classification and applied linear regression to analyse trends in consumption of reserve antibiotics throughout the study period.ResultsEU/EEA/UK average hospital-sector reserve-antibiotic consumption increased from 0.017 to 0.050 DDD per 1,000 inhabitants per day over the study period (p = 0.002). This significant increase concerned 15 countries. In 2018, four antibiotics (tigecycline, colistin, linezolid and daptomycin) constituted 91% of the consumption. Both absolute and relative (% of total hospital sector) consumption of reserve antibiotics varied considerably (up to 42-fold) between countries (from 0.004 to 0.155 DDD per 1,000 inhabitants per day and from 0.2% to 9.3%, respectively).ConclusionAn increasing trend in reserve antibiotic consumption was found in Europe. The substantial variation between countries may reflect the burden of infection with multidrug-resistant bacteria. Our results could guide national actions or optimisation of reserve antibiotic use.

The antimicrobial susceptibilities of Bacteroides strains isolated from the feces of imipenem-treated patients from Belgium and Hungary were compared with those isolated from the normal microbiota from these two and five other European countries and assessed. Of the 10 antibiotics tested, highly significant differences were found with cefoxitin (decrease for Belgium and for this two and the five countries from the previous study), clindamycin (decrease for Belgium and for this two and the five countries from the previous study) and moxifloxacin (increase for Belgium and for this two and the five countries from the previous study) relative to normal microbiota strains reported earlier. Imipenem treatment brought about modest, but notable differences in the compositions of the microbiomes where there was less diversity in the treated group relative to the non-treated group., Competing Interests: Declaration of competing interest We declare no conflict of interests., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Összefoglaló. Bevezetés: Az antibiotikumok észszerű alkalmazása kulcsfontosságú a hatékonyságuk megőrzésében és a néhol kritikus méreteket öltő antibiotikumrezisztencia visszaszorításában. Célkitűzés: A hazai ambuláns antibiotikumfelhasználás jellemzőinek, trendjeinek bemutatása. Módszer: A 2010 és 2019 közötti időszakra vonatkozó, dobozszámban kifejezett ambuláns szisztémás antibiotikumfelhasználási adatokat - a WHO 2019. évi indexe alapján - "defined daily dose" (DDD - napi átlagdózis) egységbe konvertáltuk. Standardizált technikai egységünk a DDD/1000 fő/nap volt (DID). Az antibiotikumfelhasználás értékelésére nemzetközileg elfogadott minőségi indikátorokat alkalmaztunk. Eredmények: Az antibiotikumfelhasználás mértéke kismértékű ingadozást mutatott (min.: 12,9 DID, max.: 14,7 DID), viszont a szezonális ingadozás a teljes megfigyelt időszakban jelentős mértékű volt. A széles versus szűk spektrumú béta-laktámok és makrolidek felhasználási hányadosa évről évre tovább emelkedett (2010: 13,3 vs. 2019: 71,6), a fluorokinolonok alkalmazási aránya továbbra is meghatározó (2010: 14,3%, 2019: 14,5%). A vizsgált 12 minőségi indikátor közül a tanulmány nyitó évében 4, a tanulmány záró évében 6 indikátor esetében a legkedvezőtlenebbül teljesítő európai országok közé tartoztunk. Megbeszélés: A hazai antibiotikumalkalmazás mértéke európai mérce szerint nem magas, de csökkentésére látszik lehetőség; mintázata szuboptimális, és az évek során kedvezőtlen irányba változott. Következtetés: A kapott antibiotikumfelhasználási adatok s azok értelmezése alapján rendkívül sürgető morális kötelesség a szakmai és hatósági intervenciókra épülő hazai antibiotikumstratégia és -akcióterv mielőbbi kidolgozása, implementálása. Orv Hetil. 2022; 163(4): 140-149., Introduction: Prudent antibiotic use is an important tool to preserve their effectiveness as well as reverse and confine antibiotic resistance., Objective: To evaluate the trends and characteristics of Hungarian outpatient antibiotic use., Methods: Crude, package level antibiotic sales data for the period 2010-2019 were converted into DDD (defined daily dose) and were standardized for 1000 inhabitants and per year (ATC-DDD index, version 2019). Internationally validated drug-specific quality indicators were used to evaluate antibiotic use., Results: The scale of antibiotic use was stagnating with minimal fluctuation (min.: 12.9 DID, max.: 14.7 DID), and with high intra-year seasonality index. The ratio of the consumption of broad to narrow spectrum beta-lactams and macrolides increased gradually from year to year (2010: 13.3 vs. 2019: 71.6) and the relative consumption of fluoroquinolones is still remarkable (2010: 14.3%, 2019: 14.5%). Out of the twelve surveyed drug-specific quality indicators in the first and last year of analysis, we were ranked among the weakest European countries in the case of four and six indicators, respectively., Discussion: The scale of Hungarian outpatient antibiotic use is not high, in European comperison, but has some reserve capacity for reduction. The pattern of Hungarian antibiotic use is suboptimal and had further decreased quality through the years., Conclusion: Based on the recorded data of antibiotic use and their interpretation, the development of national antibiotic strategy (including both professional and authority interventions) is a pressing moral obligation. Orv Hetil. 2021; 163(4): 140-149.

Background: West Nile virus (WNV) infections have become increasingly prevalent in certain European countries, including Hungary. Although most human infections do not cause severe symptoms, in approximately 1% of cases WNV infections can lead to severe WNV neuroinvasive disease (WNND) and death. The goal of our study was to assess the neurological status changes of WNV -infected patients admitted to inpatient care and to identify potential risk factors as underlying reasons for severe neurological outcome., Methods: We conducted a retrospective chart review of 66 WNV-infected patients from four Hungarian medical centers. Patients' neurological status at hospital admission and at two follow-up intervals (1st follow-up, within 60-90 days and 2nd follow-up, within 150-180 days, after hospital discharge) were assessed. All of the 66 patients in the initial sample had some type of neurological symptoms and 56 patients were diagnosed with WNND. The modified Rankin Scale (mRS) and the West Nile Virus Neurological Index (WNV-N Index), a scoring system designed for the purpose of this study, were used for neurological status assessment. Patients were dichotomized into two categories, "moderately severe" and "severe" based on their neurological status. Descriptive analysis for sample description, stratified analysis for calculation of odds ratio (OR) and logistic regression for continuous input variables, were performed., Results: The average number of days between the onset of neurological symptoms and hospital admission (the neurological symptom interval) was 6.01 days. Complications during the hospital stay arose in almost a fifth of the patients (18.2%) and 5 patients died. Each day's increase in the neurological symptom interval significantly increased the risk for developing a severe neurological status following hospital admission (0.799-fold and 0.688-fold, based on the WNV-N Index and mRS, respectively). Patients' age, comorbidity, presence of complications and symptoms of malaise, and gait uncertainty were shown to be independent risk factors for severe neurological status., Conclusions: Timely hospital admission of patients with neurological symptoms as well as risk assessment by clinicians - possibly with an optimal assessment tool for estimating neurological status- could improve the neurological outcome of WNV-infected patients.

Antibiotic treatments initiated on Emergency Departments (ED) are empirical. Therefore, knowledge of local susceptibility patterns is important. Despite this, data on expected pathogens and their resistance profile are scarce from EDs internationally. The study aim was to assess the epidemiology and resistance patterns of bacterial isolates from a tertiary-care ED over 5 years, focusing on ESKAPE bacteria (including the Enterobacterales group). After removal of duplicates, n = 6887 individual bacterial isolates were recovered, out of which n = 4974 (72.22%) were ESKAPE isolates. E. coli was the most frequent isolate (2193, 44.1%), followed by the Klebsiella genus (664; 13.4%). The third most frequent isolate was S. aureus (561, 11.3%). In total, multi-drug resistance (MDR) was present in 23.8% and was most prevalent in A. baumanii (65.5%), P. mirabilis (42.7%), and K. pneumoniae (32.6%). MRSA was isolated in 19.6%, while ESBL-producing Enterobacterales in 17.7%, and these were associated with remarkably higher resistance to other antibacterials as well. Difficult-to-treat resistance (DTR) was detected in 0.5%. The frequent isolation of some ESKAPE bacteria and the detected considerable acquired resistance among ED patients raise concern. The revealed data identified problematic pathogens and will guide us to set up the optimal empiric antibiotic protocol for clinicians.

The prevalence of testicular adrenal rest tumours varies in different forms of congenital adrenal hyperplasia. Patients with 21-hydroxilase deficiency usually have bilateral and palpable testicular nodules. Although adrenal rest tumours are well documented in the literature, the diagnosis and management require a multidisciplinary approach: the cooperative work of endocrinologists, urologists, pathologists and radiologists is essential. In the case of an early diagnosis, appropriately increased corticosteroid treatment may reduce the tumour mass. In advanced stages, tumours can lead to irreversible parenchymal damage causing infertility. The importance of an early and accurate diagnosis cannot be emphasized enough, since the therapy differs significantly from other benign or malignant testicular neoplasia. A case of a testicular adrenal rest tumour is presented along with the multidisciplinary perspectives of the diagnosis and management of these lesions. Orv Hetil. 2020; 161(16): 623–631., (© Szerző(k)/The Author(s))

Here, we sought to assess the levels of antibiotic resistance among intestinal Bacteroides and Parabacteroides strains collected between 2014 and 2016 in Europe and also attempted to compare resistance levels between clinical and commensal isolates. Bacteroides and Parabacteroides isolates were recovered from faecal samples via the novel Bacteroides Chromogenic Agar (BCA) method. Antibiotic susceptibilities were determined by agar dilution for ten antibiotics. The values obtained were then statistically evaluated. Altogether 202 Bacteroides/Parabacteroides isolates (of which 24, 11.9%, were B. fragilis) were isolated from the faecal specimens of individuals taken from five European countries. The percentage values of isolates resistant to ampicillin, amoxicillin/clavulanate, cefoxitin, imipenem, clindamycin, moxifloxacin, metronidazole, tetracycline, tigecycline and chloramphenicol were 96.6, 4.5, 14.9, 2.0, 47.3, 11.4, 0, 66.2, 1.5 and 0%, respectively. These values are close to those reported in the previous European clinical Bacteroides antibiotic susceptibility survey except for amoxicillin/clavulanate and clindamycin, where the former was lower and the latter was higher in normal microbiota isolates. To account for these latter findings and to assess temporal effects we compared the data specific for Hungary for the same period (2014-2016), and we found differences in the resistance rates for cefoxitin, moxifloxacin and tetracycline., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The aim of the present work was to assess systemic hemodynamic changes using PiCCo monitoring in a porcine model of E. coli-induced fulminant sepsis., Methods: Thirty-one healthy female Hungahib pigs were randomly assigned into control (n = 15) or septic groups (n = 16). In the sepsis group Escherichia coli culture was intravenously administrated in a continuously increasing manner according to the following protocol: 2 ml of bacterial culture suspended in physiological saline was injected in the first 30 min, then 4 ml of bacterial culture was administered within 30 min, followed by infusion of 32 ml bacterial culture for 2 h. Control animals received identical amount of saline infusion. Systemic hemodynamic parameters were assessed by PiCCo monitoring in both groups., Results: Resting hemodynamic parameters were identical in the two groups. In control animals, systemic hemodynamic variables were relatively stable during the entire procedure. In septic animals shock developed in 165 (IQR: 60-255) min after starting the injection of E. coli solution. Blood pressure values gradually decreased, whereas pulse rate increased. A decrease in cardiac index, an increased systemic vascular resistance, and a decreased stroke volume variation were observed., Conclusions: These results may serve as additional pathophysiological information of hemodynamic changes occurring during hypodynamic sepsis and may contribute to a better understanding of the pathomechanism of septic multiple organ failure.

Introduction: The activation of blood coagulation has been demonstrated in most cases of sepsis, however previous studies in humans could not detect hypercoagulability with global hemostasis assays. In a fulminant porcine sepsis model we analysed coagulation screening tests and thrombin generation to evaluate hemostatic alterations., Materials and Methods: Live Escherichia coli bacteria were inoculated to female pigs and prothrombin time, activated partial thromboplastin time, thrombin time and fibrinogen were measured by coagulometry. Platelet counts, platelet aggregates and platelet phosphatidyl serine (PS) expression were studied, furthermore in in vitro experiments the PS-inducing ability of septic and control plasmas was investigated by flow cytometry. Thrombin generation was carried out by the Ascent Fluoroscan reader and results were evaluated by the Thrombinoscope software., Results: Clotting assays showed a large variability, but no systematic changes during the 4-hour observation period. Platelet count significantly decreased and the number of platelet aggregates increased already by 2h compared to baseline values and to control animals. Although the increase in platelet PS expression was non-significant in the septic group, the septic plasma elicited PS expression on normal human red blood cells. Thrombin generation became significantly faster, but the quantity of formed thrombin demonstrated both hypo- and hypercoagulability depending on the setting of the assay., Conclusions: Enhanced thrombin generation without activators and the PS-inducing capacity of septic plasma are signs of hemostatic activation during fulminant sepsis while the decreased amount of generated thrombin upon tissue factor and phospholipid induced activation demonstrates attenuated thrombin forming ability., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Patients undergoing general anesthesia and mechanical ventilation during major abdominal surgery commonly develop pulmonary atelectasis and/or hyperdistention of the lungs. Recent studies show benefits of lung-protective mechanical ventilation with the use of low tidal volumes, a moderate level of positive end-expiratory pressure (PEEP) and regular alveolar recruitment maneuvers during general anesthesia, even in patients with healthy lungs. The purpose of this clinical trial is to evaluate the effects of intraoperative lung-protective mechanical ventilation, using individualized PEEP values, on postoperative pulmonary complications and the inflammatory response., Methods/design: A total number of 40 patients with bladder cancer undergoing open radical cystectomy and urinary diversion (ileal conduit or orthotopic bladder substitute) will be enrolled and randomized into a study (SG) and a control group (CG). Standard lung-protective ventilation with a PEEP of 6 cmH 2 O will be applied in the CG and an optimal PEEP value determined during a static pulmonary compliance (Cstat)-directed PEEP titration procedure will be used in the SG. Low tidal volumes (6 mL/Kg ideal bodyweight) and a fraction of inspired oxygen of 0.5 will be applied in both groups. After surgery both groups will receive standard postoperative management. Primary endpoints are postoperative pulmonary complications and serum procalcitonin kinetics during and after surgery until the third postoperative day. Secondary and tertiary endpoints will be: organ dysfunction as monitored by the Sequential Organ Failure Assessment Score, in-hospital stay, 28-day and in-hospital mortality., Discussion: This trial will assess the possible benefits or disadvantages of an individualized lung-protective mechanical ventilation strategy during open radical cystectomy and urinary diversion regarding postoperative pulmonary complications and the inflammatory response., Trial Registration: ClinicalTrials.gov, ID: NCT02931409 . Registered on 5 October 2016.

Background: The aim of the present work was to assess cerebral hemodynamic changes in a porcine model of E.coli induced fulminant sepsis., Methods: Nineteen healthy female Hungahib pigs, 10-12 weeks old, randomly assigned into two groups: Control (n = 9) or Septic Group (n = 10). In the Sepsis group Escherichia coli culture suspended in physiological saline was intravenously administrated in a continuously increasing manner according to the following protocol: 2 ml of bacterial culture suspended in physiological saline was injected in the first 30 min, then 4 ml of bacterial culture was administered within 30 min, followed by infusion of 32 ml bacterial culture for 2 h. Control animals received identical amount of saline infusion. Systemic hemodynamic parameters were assessed by PiCCo monitoring, and cerebral hemodynamics by transcranial Doppler sonography (transorbital approach) in both groups., Results: In control animals, systemic hemodynamic variables and cerebral blood flow velocities and pulsatility indices were relatively stable during the entire procedure. In septic animals shock developed in 165 (IQR: 60-255) minutes after starting the injection of E.coli solution. Blood pressure values gradully decreased, whereas pulse rate increased. A decrease in cardiac index, an increased systemic vascular resistance, and an increased stroke volume variation were observed. Mean cerebral blood flow velocity in the middle cerebral artery did not change during the procedure, but pulsatility index significantly increased., Conclusions: There is vasoconstriction at the level of the cerebral arterioles in the early phase of experimental sepsis that overwhelmes autoregulatory response. These results may serve as additional pathophysiological information on the cerebral hemodynamic changes occurring during the septic process and may contribute to a better understanding of the pathomechanism of septic encephalopathy.

Objective: In a fulminant porcine sepsis model, we determined the kinetics of hypoxia induced changes in relation to sepsis parameters and markers of organ damage., Methods: Female pigs were challenged by live Escherichia coli and samples were analysed up to 4 hours. Bone marrow reactions were determined by analysing immature forms of peripheral blood cells by a hematology analyser and light microscopy. Platelet mitochondrial membrane depolarisation was determined by flow cytometry., Results: Core temperature, modified shock index and lactate levels all became significantly elevated compared to baseline values at 4 hours in septic animals. At 2 hours already the reticulocyte count, nucleated red blood cell count and the absolute number of dysplastic platelets became significantly elevated. The platelet mitochondrial membrane depolarisation was significantly decreased by 2 hours in septic animals compared to the baseline values and to control animals. No massive organ damage was evident during the 4-hour observation period, but uric acid levels in septic animals became significantly elevated already by 2 hours., Conclusions: In this Escherichia coli induced porcine model, severe sepsis was evident by conventional criteria at 4 hours while several - mostly hypoxemia induced - biomarkers were already altered by 2 hours.

Despite the development in the identification of Nocardia spp., common challenges exist in the laboratory diagnosis and management of nocardiosis. We report two cases of disseminated nocardiosis in a patient with hematologic disorder and in a patient with systemic lupus erythematosus, where the cooperation between various specialists was essential to set up the adequate diagnosis of disseminated nocardiosis.

Introduction: Growing bacterial resistance threatens public health, which can be tempered by prudent antibiotic use., Aim: To quantify systemic antibacterial use in Hungarian hospitals., Method: Consumption data were analysed using the Anatomical-Therapeutic-Chemical - Defined Daily Dose (ATC/DDD) methodology. Data were standardized for patient turnover and also for population to enable international benchmarking., Results: Hospital antibiotic use was quite constant (22.4 ± 1.5 DDD/100 patient-days), but its composition changed substantially. The use of parenteral products rose gradually (in 1996 26.4% and in 2015 41.6%). The pattern of use was homogenised due to the headway of co-amoxiclav use. A substantial increase of fluoroquinolone (2.3 vs. 4.2 DDD/100 patient-days) and third generation cephalosporin (1.0 vs. 2.9 DDD/100 patient-days) use was detected. In parallel the use of narrow spectra penicillins diminished., Conclusion: Hungarian hospital antibiotic use is low. The causes and the justification of this low use together with the internationally outstanding use of certain antibacterials should be addressed in future studies. Orv. Hetil., 2016, 157(46), 1839-1846.

Purpose: The purpose was to investigate the value of procalcitonin (PCT) kinetics in predicting the appropriateness of empirical antimicrobial treatment in critically ill patients., Materials and Methods: This prospective observational study recruited patients in whom empirical antimicrobial therapy was started for suspected infection. Biochemical and physiological parameters were measured before initiating antimicrobials (t0), 8 hourly (t8, t16, t24), and then daily (day2-6). Patients were grouped post hoc into appropriate (A) and inappropriate (IA) groups., Results: Of 209 patients, infection was confirmed in 67%. Procalcitonin kinetics were different between the IA (n = 33) and A groups (n = 108). In the IA group, PCT levels (median [interquartile range]) increased: t0= 2.8 (1.2-7.4), t16= 8.6 (4.8-22.1), t24= 14.5 (4.9-36.1), P< .05. In the A group, PCT peaked at t16 and started to decrease by t24: t0= 4.2 (1.9-12.8), t16= 6.99 (3.4-29.1), t24= 5.2 (2.0-16.7), P< .05. Receiver operating characteristic analysis revealed that a PCT elevation greater than or equal to 69% from t0 to t16 had an area under the curve for predicting inappropriate antimicrobial treatment of 0.73 (95% confidence interval, 0.63-0.83), P< .001; from t0 to t24, a greater than or equal to 74% increase had an area under the curve of 0.86 (0.77-0.94), P< .001. Hospital mortality was 37% in the A group and 61% in the IA group (P= .017)., Conclusions: Early response of PCT in the first 24 hours of commencing empirical antimicrobials in critically ill patients may help the clinician to evaluate the appropriateness of therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose. To investigate whether absolute value of procalcitonin (PCT) or the change (delta-PCT) is better indicator of infection in intensive care patients. Materials and Methods. Post hoc analysis of a prospective observational study. Patients with suspected new-onset infection were included in whom PCT, C-reactive protein (CRP), temperature, and leukocyte (WBC) values were measured on inclusion (t 0) and data were also available from the previous day (t -1). Based on clinical and microbiological data, patients were grouped post hoc into infection- (I-) and noninfection- (NI-) groups. Results. Of the 114 patients, 85 (75%) had proven infection. PCT levels were similar at t -1: I-group (median [interquartile range]): 1.04 [0.40-3.57] versus NI-group: 0.53 [0.16-1.68], p = 0.444. By t 0 PCT levels were significantly higher in the I-group: 4.62 [1.91-12.62] versus 1.12 [0.30-1.66], p = 0.018. The area under the curve to predict infection for absolute values of PCT was 0.64 [95% CI = 0.52-0.76], p = 0.022; for percentage change: 0.77 [0.66-0.87], p < 0.001; and for delta-PCT: 0.85 [0.78-0.92], p < 0.001. The optimal cut-off value for delta-PCT to indicate infection was 0.76 ng/mL (sensitivity 80 [70-88]%, specificity 86 [68-96]%). Neither absolute values nor changes in CRP, temperature, or WBC could predict infection. Conclusions. Our results suggest that delta-PCT values are superior to absolute values in indicating infection in intensive care patients. This trial is registered with ClinicalTrials.gov identifier: NCT02311816.