High prevalence of Staphylococcus aureus nasal carriage among children in Szolnok, Hungary

We collected nasal samples from 1,390 healthy 3–7 years old children in Szolnok city, Hungary, in 2012. We detected 476 Staphylococcus aureus isolates from 474 children. In two occasions, two different S. aureus were isolated, based on hemolysis type and pulsed-field gel electrophoresis pattern. S. aureus carriage rate was calculated to be 34.1% similar to others studies. Male gender was found to be a risk factor for carriage by statistical analysis. Altogether, four methicillin-resistant S. aureus (MRSA) strains were detected by mecA polymerase chain reaction, which means 0.8% community-acquired MRSA prevalence among the S. aureus isolates. All MRSA strains harbored the SCCmec type IV cassette (typical for CA-MRSA) and belonged to ST45 by multilocus sequence typing. During antibiotic susceptibility testing, we measured the following resistance rates: 0.0% for mupirocin, 0.2% for ciprofloxacin, 0.6% for gentamicin and oxacillin, 3.4% for tetracycline, 9.5% for clindamycin, 10.3% for erythromycin, and 91.4% for penicillin, which are generally lower compared with Hungarian clinical isolates

Prevalence of Staphylococcus aureus in wild hedgehogs (Erinaceus europaeus) and first report of mecC-MRSA in Hungary

In 2011 mecC, a new mecA gene homologue, was described in a bovine isolate in the UK. Since then, mecC-positive methicillin-resistant Staphylococcus aureus (mecC-MRSA) has also been found in wild animals. An especially high prevalence of mecC-MRSA has been reported among hedgehogs in Sweden (64%) and Denmark (61%). Based on these findings we aimed to survey the hedgehog population for mecC-MRSA in Hungary. Altogether 200 hedgehogs were screened for Staphylococcus aureus using a culture-based method. The antibiotic susceptibility of the isolates to nine drugs was determined, their genetic relatedness was established by PFGE and spa-typing, and virulence genes were identified by PCR. Whole genome sequencing was performed for the single mecC-MRSA isolate found. Of the 200 animals, 13 were carriers of S. aureus (6.5%). Among these, one isolate was mecA positive and one was mecC positive. The isolates were susceptible to non-beta-lactam antibiotics. Toxin genes were not found, but the majority carried genes responsible for adhesion and biofilm production. The mecC-MRSA isolate was a single-locus variant of ST130, had a new spa type (t19701) and belonged to SCCmec type XI. It carried a recently described, novel exfoliative toxin (etE). This is the first report of mecC-MRSA in Hungary and the first survey of staphylococcus carriage among wild animals in the country. The mecC prevalence was much lower than in Northern European countries and rather similar to other countries in our region. MecC-MRSA could potentially emerge as a novel human pathogen, especially where close contact occurs between humans and animals

LIFEStyle, prevention and risk of Acute PaNcreatitis (LIFESPAN): protocol of a multicentre and multinational observational case-control study

Introduction Acute pancreatitis (AP) is a life-threatening inflammatory disease of the exocrine pancreas which needs acute hospitalisation. Despite its importance, we have significant lack of knowledge whether the lifestyle factors elevate or decrease the risk of AP or influence the disease outcome. So far, no synthetising study has been carried out examining associations between socioeconomic factors, dietary habits, physical activity, chronic stress, sleep quality and AP. Accordingly, LIFESPAN identifies risk factors of acute pancreatitis and helps to prepare preventive recommendations for lifestyle elements. Methods and analysis LIFESPAN is an observational, multicentre international case–control study. Participating subjects will create case and control groups. The study protocol was designed according to the SPIRIT guideline. Patients in the case group (n=1700) have suffered from AP (alcohol-induced, n=500; biliary, n=500; hypertriglyceridemiainduced, n=200; other, n=500); the control group subjects have no AP in their medical history. Our study will have three major control groups (n=2200): hospital-based (n=500), population-based (n=500) and aetiology-based (alcohol, n=500; biliary, n=500 and hypertriglyceridemia, n=200). All of them will be matched to the case group individually by gender, age and location of residence. Aggregately, 3900 subjects will be enrolled into the study. The study participants will complete a complex questionnaire with the help of a clinical research administrator/study nurse. Analysis methods include analysis of the continuous and categorical values. Ethics and dissemination The study has obtained the relevant ethical approval (54175-2/2018/EKU) and also internationally registered (ISRCTN25940508). After obtaining the final conclusions, we will publish the data to the medical community and will also disseminate our results via open access

Prospective, Multicentre, Nationwide Clinical Data from 600 Cases of Acute Pancreatitis

OBJECTIVE: The aim of this study was to analyse the clinical characteristics of acute pancreatitis (AP) in a prospectively collected, large, multicentre cohort and to validate the major recommendations in the IAP/APA evidence-based guidelines for the management of AP. DESIGN: Eighty-six different clinical parameters were collected using an electronic clinical research form designed by the Hungarian Pancreatic Study Group. PATIENTS: 600 adult patients diagnosed with AP were prospectively enrolled from 17 Hungarian centres over a two-year period from 1 January 2013. MAIN RESULTS: With respect to aetiology, biliary and alcoholic pancreatitis represented the two most common forms of AP. The prevalence of biliary AP was higher in women, whereas alcoholic AP was more common in men. Hyperlipidaemia was a risk factor for severity, lack of serum enzyme elevation posed a risk for severe AP, and lack of abdominal pain at admission demonstrated a risk for mortality. Abdominal tenderness developed in all the patients with severe AP, while lack of abdominal tenderness was a favourable sign for mortality. Importantly, lung injury at admission was associated with mortality. With regard to laboratory parameters, white blood cell count and CRP were the two most sensitive indicators for severe AP. The most common local complication was peripancreatic fluid, whereas the most common distant organ failure in severe AP was lung injury. Deviation from the recommendations in the IAP/APA evidence-based guidelines on fluid replacement, enteral nutrition and timing of interventions increased severity and mortality. CONCLUSIONS: Analysis of a large, nationwide, prospective cohort of AP cases allowed for the identification of important determinants of severity and mortality. Evidence-based guidelines should be observed rigorously to improve outcomes in AP

High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial

Introduction Acute pancreatitis (AP) is an inflammatory disease with no specific treatment. Mitochondrial injury followed by ATP depletion in both acinar and ductal cells is a recently discovered early event in its pathogenesis. Importantly, preclinical research has shown that intracellular ATP delivery restores the physiological function of the cells and protects from cell injury, suggesting that restoration of energy levels in the pancreas is therapeutically beneficial. Despite several high quality experimental observations in this area, no randomised trials have been conducted to date to address the requirements for energy intake in the early phase of AP. Methods/design This is a randomised controlled two-arm double-blind multicentre trial. Patients with AP will be randomly assigned to groups A (30 kcal/kg/day energy administration starting within 24 hours of hospital admission) or B (low energy administration during the first 72 hours of hospital admission). Energy will be delivered by nasoenteric tube feeding with additional intravenous glucose supplementation or total parenteral nutrition if necessary. A combination of multiorgan failure for more than 48 hours and mortality is defined as the primary endpoint, whereas several secondary endpoints such as length of hospitalisation or pain will be determined to elucidate more detailed differences between the groups. The general feasibility, safety and quality checks required for high quality evidence will be adhered to. Ethics and dissemination The study has been approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (55961-2/2016/EKU). This study will provide evidence as to whether early high energy nutritional support is beneficial in the clinical management of AP. The results of this trial will be published in an open access way and disseminated among medical doctors

Caskin fehérje hallásban betöltött szerepének vizsgálata

A Caskin egy multi-domén adaptor protein, ami kapcsolódik a CASK fehérjéhez (kálcium/kalmodulin (CaM) dependens szerin kináz). A CASK egy olyan horgonyzó (scaffold) fehérje, ami nagy mennyiségben található az emlősök idegrendszerében, legfőképpen a szinapszisokban. A Caskinnak két közeli izoformája ismert (Caskin 1 és 2), amelyek pre- és posztszinaptikusan is kifejeződnek. Feltehetően jelentős idegrendszeri szerepük van, de pontos funkciójuk még ismeretlen. Kutató partnereink még nem publikált eredményei igazolják a Caskin szerepét hippokampális sejttenyészetekben a dendritikus tüskék formálásában, továbbá különféle tanulási és memóriatesztekben. Egy friss közlemény bizonyította jelenlétét a retina ribbon szinapszisaiban46. A belső és külső szőrsejtekben is kimutattak CASK expressziót11. Ehhez fontos hozzátenni, hogy a szőrsejtek szintén ribbon szinapszisok által lépnek kapcsolatba a hallópálya bipoláris neuronjainak perifériás nyúlványaival. Diákköri munkám célja a Caskin hallásban betöltött szerepének feltérképezése volt. Ennek érdekében agytörzsi auditoros kiváltott válasz potenciál méréseket végeztünk (ABR, n=20-20) 37-42 napos, anesztetizált, Caskin 1,2 génkiütött (KO) egereken és vad típusú (WT) alomtestvéreiken. Az ABR egy objektív hallásvizsgáló módszer, ami a belső fül, a VIII. agyideg és az agytörzsi hallópálya szakasz funkcióját méri. Vizsgálataink során nem találtunk szignifikáns különbséget a KO és WT egerek hallásküszöb értékei között sem alacsony, sem magas frekvenciákon (4 - 65 kHz). Következő lépésként az ABR válaszok egyedi hullámait – ezek a hallópálya szinaptikus átkapcsolódásait jellemzik – egyedileg fogjuk elemezni annak érdekében, hogy a finomabb eltéréseket is észrevegyünk. Egyes megfigyelések szerint a Caskin funkciója életkor függő, ezért a vizsgálatokat idősebb egereken is tervezzük elvégezni

Genomic Evidence for Direct Transmission of <i>mecC</i>-MRSA between a Horse and Its Veterinarian

Methicillin-resistant Staphylococcus aureus bearing the mecC gene (mecC-MRSA) has been reported from animals and humans in recent years. This study describes the first mecC-MRSA isolates of human and equine origin in Hungary (two isolates from horses and one from a veterinarian, who treated one of the infected horses, but was asymptomatic). MRSA isolates were identified by cultivation and PCR detection of the species-specific spa gene and mecA/mecC methicillin resistance genes. The isolates were characterized by antibiotic susceptibility testing, MLST, spa, SCCmec typing, PFGE and whole genome sequencing (WGS). All three isolates belonged to the ST130-t843-SCCmec XI genotype, and carried the mecC and blaZ genes. Apart from beta-lactam drugs, they were sensitive to all tested antibiotics. The isolates of the infected horse and its veterinarian had the same PFGE pulsotype and showed only slight differences with WGS. Hence, this is the first description of direct transmission of a mecC-carrying MRSA between a horse and its veterinarian. The emergence of mecC in the country highlights the importance of the appropriate diagnostics in MRSA identification

Co-carriage of Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis among three different age categories of children in Hungary.

BACKGROUND:The nasopharynx can from time to time accommodate otherwise pathogenic bacteria. This phenomenon is called asymptomatic carriage. However, in case of decreased immunity, viral infection or any other enhancing factors, severe disease can develop. Our aim in this study was to survey the nasal carriage rates of four important respiratory pathogens in three different age groups of children attending nurseries, day-care centres and primary schools. This is the first study from Hungary about the asymptomatic carriage of H. influenzae and M. catarrhalis. METHODS:Altogether 580 asymptomatic children were screened in three Hungarian cities. Samples were collected from both nostrils with cotton swabs. The identification was based on both colony morphology and species-specific PCRs. Serotyping was performed for S. pneumoniae, H. influenzae and M. catarrhalis. Antibiotic susceptibility was determined with agar dilution, according to the EUCAST guidelines. Clonality was examined by PFGE. RESULTS AND CONCLUSIONS:Whereas the carriage rates of S. pneumoniae, H. influenzae and M. catarrhalis clearly decreased with age, that of S. aureus showed an opposite tendency. Multiple carriage was least prevalent if S. aureus was one of the participants. The negative association between this bacterium and the others was statistically significant. For pneumococcus, the overall carriage rate was lower compared to earlier years, and PCV13 serotypes were present in only 6.2% of the children. The majority of H. influenzae isolates was non-typeable and no type b was detected; serotype A was dominant among M. catarrhalis. All four bacteria were more sensitive to antibiotics compared to clinical isolates. No MRSAs were detected, but we found three mupirocin resistant strains. The positive effect of Hib- and PCV-vaccination is undoubted. Continued surveillance of these pathogens is required

Whole genome sequencing of coagulase positive staphylococci from a dog-and-owner screening survey.

BackgroundStaphylococcus aureus and S. pseudintermedius are the two most common coagulase positive staphylococci (CPS). S. aureus is more prevalent among humans, whereas S. pseudintermedius is more commonly isolated from dogs, however, both can cause various community and hospital acquired diseases in humans.MethodsIn the current study we screened 102 dogs and 84 owners in Hungary. We tested the antibiotic susceptibility of the strains and in order to get a better picture of the clonal relationship of the strains, we used pulsed-field gel electrophoresis. In addition, three pairs of isolates with identical PFGE patterns were whole genome sequenced, MLST and spa types were established.ResultsCarriage rate of S. aureus was 23.8% in humans and 4.9% in dogs and two cases of co-carriage were found among dogs and owners. S. pseudintermedius carriage rate was 2.4% and 34.3%, respectively, with only one co-carriage. The isolates were generally rather susceptible to the tested antibiotics, but high tetracycline resistance of S. pseudintermedius strains was noted. The co-carried isolates shared almost the same resistance genes (including tet(K), bla(Z), norA, mepR, lmrS, fosB) and virulence gene pattern. Apart from the common staphylococcal enzymes and cytotoxins, we found enterotoxins and exfoliative toxins as well. The two S. aureus pairs belonged to ST45-t630, ST45-t671 and ST15-t084, ST15-t084, respectively. The co-carried S. pseudintermedius isolates shared the same housekeeping gene alleles determining a novel sequence type ST1685.ConclusionsBased on the genomic data, dog-owner co-carried strains displayed only insignificant differences therefore provided evidence for potential human-to-dog and dog-to-human transmission