[Uncommon non-fermenting Gram-negative rods as pathogens of lower respiratory tract infection]. / Ritkábban eloforduló, alsó légúti fertozést okozó Gram-negatív nem fermentáló pálcák.

INTRODUCTION: Glucose non-fermenting Gram-negative bacteria are ubiquitous environmental organisms. Most of them are identified as opportunistic, nosocomial pathogens in patients. Uncommon species are identified accurately, mainly due to the introduction of matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) in clinical microbiology practice. Most of these uncommon non-fermenting rods are isolated from lower respiratory tract samples. Their significance in lower respiratory tract infections, such as rules of their testing are not clarified yet. AIM: The aim of this study was to review the clinical microbiological features of these bacteria, especially their roles in lower respiratory tract infections and antibiotic treatment options. METHOD: Lower respiratory tract samples of 3589 patients collected in a four-year period (2013-2016) were analyzed retrospectively at Semmelweis University (Budapest, Hungary). Identification of bacteria was performed by MALDI-TOF MS, the antibiotic susceptibility was tested by disk diffusion method. RESULTS: Stenotrophomonas maltophilia was revealed to be the second, whereas Acinetobacter baumannii the third most common non-fermenting rod in lower respiratory tract samples, behind the most common Pseudomonas aeruginosa. The total number of uncommon non-fermenting Gram-negative isolates was 742. Twenty-three percent of isolates were Achromobacter xylosoxidans. Beside Chryseobacterium, Rhizobium, Delftia, Elizabethkingia, Ralstonia and Ochrobactrum species, and few other uncommon species were identified among our isolates. The accurate identification of this species is obligatory, while most of them show intrinsic resistance to aminoglycosides. Resistance to ceftazidime, cefepime, piperacillin-tazobactam and carbapenems was frequently observed also. CONCLUSIONS: Ciprofloxacin, levofloxacin and trimethoprim-sulfamethoxazole were found to be the most effective antibiotic agents. Orv Hetil. 2018; 159(1): 23-30.

[Clinical aspects of severe infections caused by antibiotic-resistant Gram-negative bacteria. The Empire strikes back?] / Antibiotikumokkal szemben ellenálló Gram-negatív baktériumok okozta súlyos fertozések a klinikus szemével. A Birodalom visszavág?

In our days, growing incidence of antibiotic resistant bacteria has become an eminent public health problem. For survival Gram-negative species possess several different tools to withstand antibiotics: they produce degrading and modifying enzymes, decrease their permeability or expel drug molecules. An increasing proportion of severe nosocomial infections are caused by strains resistant to several antimicrobials (multiresistant, extensively resistant or panresistant species). Development of new antibiotic compounds may serve as a possible solution to this problem. Ceftolozane-tazobactam is a new beta-lactam+beta-lactamase-inhibitor combination resistant to most extended spectrum beta-lactamase enzymes showing excellent anti-Pseudomonas activity. It is also effective against strains when beta-lactam resistance is related to porin loss or efflux pump activity. The spectrum of ceftazidime-avibactam also includes carbapenemase-(KPC)-producing Enterobacteriaceae. In addition to novel therapy, an effective infection control system together with the prudent use of antimicrobials (antimicrobial stewardship) is of paramount importance. Orv Hetil. 2017; 158(39): 1528-1534.

[Comparison of the effect of multidrug resistance modifiers on prostate cancer, mouse lymphoma and colon cancer cells]. / Rezisztenciamódosítók összehasonlítása multidrog-rezisztens prosztata-, egérlymphoma- és vastagbélrák-sejtvonalakon.

INTRODUCTION: The reason for unsuccessful tumor chemotherapy is related to multidrug resistance. An important factor is the overexpression of efflux pumps, such as P-glycoprotein. AIM: Amino- and amide-substituted steroid compounds and phenothiazine derivatives were investigated in tumor models in vitro. METHOD: The inhibition of P-glycoprotein was evaluated by flow cytometry and the interaction of these compounds with doxorubicin was investigated as well. Molecular docking was used to estimate the binding energies of the compounds to P-glycoprotein. RESULTS: The aminosteroids showed anticancer activity on multidrug resistant mouse T-lymphoma and prostate cancer cell lines. The combination of steroids and doxorubicin potentiated its effect in hormone resistant prostate cancer cells. Among the N-hydroxyalkyl-2-aminophenothiazines, secondary amines exhibited anticancer effects on multidrug resistant colon adenocarcinoma cells. CONCLUSIONS: The tested phenothiazine and steroid derivatives showed potent anticancer activity, furthermore, the stereoisomerism of thioridazine did not play a role in the antitumor properties. Neither steroids nor thioridazine influenced apoptosis in hormone resistant cells. Orv. Hetil., 2016, 157(37), 1489-1495.

[Clopidogrel resistance in cerebrovascular disease -- results of one-year follow-up]. / Clopidogrelrezisztencia vizsgálata cerebrovascularis betegségben -- egyéves utánkövetés.

INTRODUCTION: In an earlier study the authors reported short-term benefits of clopidogrel treatment in patients with cerebrovascular disease. AIM: The aim of the authors was to analyze findings during a 12-month follow-up period. METHOD: 100 patients with a history of acute stroke or transient ischaemic attack have been included in the study. The efficacy of the therapy was assessed 7 and 28 days as well as 3, 6 and 12 months after initiation of medical therapy. Patients were divided into two parts (clopidogrel responder and resistant) based on their initial laboratory findings. Risk profiles, medical therapy, laboratory parameters and vascular events were compared between the two patient groups. RESULTS: After 7 days of treatment, clopidogrel seemed to be ineffective in 11 patients (11%). Strong, clinically significant correlations were found among blood pressure values, blood glucose and lipid parameters, serum C-reactive protein levels and platelet aggregation levels. An aggressive secondary preventive therapy resulted in a decrease of clopidogrel resistance and improvement in laboratory parameters. Patients who were clopidogrel resistant at baseline had significantly higher rate of vascular events compared to those who were clopidogrel responders (18.1 vs. 4.5%, p<0.01), although clopidogrel resistance was not an independent risk factor of unfavourable vascular outcome using a multivariate analysis. No adverse events or hemorrhagic complications were observed. CONCLUSIONS: Clopidogrel resistance and unfavourable outcome seems to be associated with "classical" risk factors underlying the importance of aggressive secondary prevention.

[Bacterial infection after orthotopic liver transplantation]. / Bakteriális infekciók májátültetés után.

INTRODUCTION: The authors reviewed the prevalence of postoperative infections, the results of bacterium cultures, and the incidence of multidrug resistance in their liver transplanted patients during a period between 2003 and 2012. AIM: The aim of this study was to analyse risk factors and colonisations of bacterial infections. METHOD: The files of 408 patients (281 bacterium cultures) were reviewed. RESULTS: Of the 408 patients 70 had a postoperative infection (17%); 58 patients (14.2%) had positive and 12 patients (2.9%) negative bacterial culture results. Cholangitis was found in 7 cases (12.1%), abdominal infection in 17 cases (29.3%), and pulmonary infection in 28 cases (48.3%). Postoperative infection was more frequent in patients with initial poor graft function, acute renal insufficiency, biliary complication, and in those with intraabdominal bleeding. The 1-, 3- and 5-year cumulative survival of patients who had infection was 70%, 56% and 56%, respectively, whereas the cumulative survival data of patients without infection was 94%, 87% and 85%, respectively (p<0.001). Multidrug resistance was found in 56% of the positive cultures, however, the one-year survival was not different in patients who had multidrug resistance positive and negative bacterial infection (both 70.2%). CONCLUSIONS: Infection control must target the management of multidrug resistance microbes through encouraging prevention, hygienic, and isolation rules, improving the operative, transfusion, and antimicrobial policy in a teamwork setting.

[Significance of hepatitis C virus baseline polymorphism during the antiviral therapy]. / A hepatitis C-vírus-bázispolimorfizmus jelentosége a kezelésben.

The treatment of chronic hepatitis C has developed significantly during the last 25 years. In patients with genotype 1 infection 40-50% sustained virologic response could be achieved using pegylated interferon and ribavirin dual combination, which could be increased significantly with the introduction of direct acting antivirals. Three major groups of direct acting antivirals are known, which directly inhibit different phases of viral life cycle, by inhibiting the function of several non-structural proteins (NS3/4A protease, NS5A protein and NS5B polymerase). Due to the rapid replication rate of hepatitis C virus and the error-prone NS5B polymerase activity, mutant virions are generated, which might have reduced susceptibility to direct acting antiviral therapy. Since these resistance associated variants might exist before the antiviral therapy, they are still able to replicate during the direct acting antiviral treatment. Due to this selection pressure, the resistant virus will replace the wild type. This was especially detected during monotherapy, therefore, the first generation of direct acting antivirals have been combined with pegylated interferon and ribavirin, while recently interferon-free combinations are being developed including 2 or 3 direct acting antivirals. Using the first generation protease inhibitors boceprevir and telaprevir, it could have been seen, that the rate of resistance associated variants is higher and the therapeutic outcome is worse in patients with hepatitis C virus genotype 1a, than in 1b. Similar phenomenon was seen with the second generation of NS3/4A protease inhibitors as well as with NS5A or NS5B polymerase. This is due to the lower genetic barrier to resistance, ie. usually fewer mutations are enough for the emergence of resistance in genotype 1a. The selection of resistance associated variants is one of the most important challenges during the interferon-free therapy.

[Deletion 15q26 syndrome]. / 15q26-microdeletio-szindróma.

The association of short stature, microcephaly, congenital cardiac anomaly and intellectual deficit should always raise the suspicion of chromosomal etiology. If G-banded karyotyping fails to detect large chromosomal aberrations, array comparative genomic hybridization (array CGH) should be performed to screen for submicroscopic pathological copy number changes. The authors present a six-year-old girl whose symptoms arose from a 4.1 Mb loss in the 15q26.2-26.3 telomeric region. The syndrome is characterized by a resistance to the insulin-like growth factor 1 - in our case the increased level of the insulin-like growth factor 1 together with the persistent longitudinal growth failure was an important finding and differential diagnostic feature. A brief overview of the literature is provided.

[Physicians' opinions towards antibiotic use and resistance in the southeastern region of Hungary]. / Orvosok antibiotikumfelhasználással és -rezisztenciával kapcsolatos véleményének vizsgálata Magyarország délkeleti részén.

Introduction: Without antibiotics, today's modern medicine would be unimaginable, but the emergence of antimicrobial resistance threatens their effectiveness. Aim: The aim of this study was to investigate the knowledge and attitudes of general practitioners towards antibiotic use and resistance, prevention and their opinion on their personal liability related to these areas. Method: An exploratory, quantitative study was carried out among physicians (n = 105) working in the southeastern region of Hungary. Results: Among the respondents, the ones who do not comprehend the severity of the issue of antibiotic resistance and their role in the prudent use of these drugs, are much fewer. The majority of the answerers attribute an important role to prevention in the fight against infectious disease. Negative practical attitude was found to be significantly correlated to gappy knowledge and improper theoretical attitude. Conclusions: A heterogeneous dispersion in the general practitioners' attitudes was found. Continuous professional development (CPD) of general practitioners in the topic of antibiotic resistance could be of great importance. Orv Hetil. 2020; 161(9): 330-339.

[Changes in antibiotic resistance in cholangitis. Our clinical experience]. / Az antibiotikumrezisztencia változása cholangitisben. Klinikai tapasztalataink.

Introduction: Due to the inappropriate use of antibiotics (AB), more pathogens become multiresistant. One of the most severe sources of sepsis is cholangitis. To avoid fatal outcome, an effective AB policy plays a key role. Aim: To investigate the AB resistance of bacteria causing cholangitis and the efficacy of AB treatment. Patients and method: Microbiological tests of bile samples collected during cholangitis-indicated endoscopic retrograde cholangiopancreatographies were analysed at the First Department of Medicine, University of Szeged, in 2006 and in 2016. Results: 29 and 111 patients had bile sample collection in 2006 and in 2016, respectively. Of that, 22 (75%) and 106 (95%) were positive. Mean age: 61 ± 14 vs. 71 ± 14 years, no difference between men/women ratio. In 2006, 10 cases empirical AB (ciprofloxacine with metronidazole or imipenem) were used. In 9 cases (90%), the AB was adequate based on the microbiological results. In 2016, in 88 cases empirical AB was applied (ciprofloxacine and metronidazole, ceftriaxone with metronidazole or imipenem with metronidazole). In 29 cases, the empirical AB was ineffective. The efficacy of ciprofloxacine decreased to 64% in 2016. The profile of the most frequent cholangitis-causing pathogens (Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae) was the same, but their resistency against ciprofloxacine increased. The rates of polymicrobal infections were 73% and 63%, respectively. Conclusion: The rates of positive bile samples were significantly higher in 2016. The profile of the most frequent pathogens was the same. The efficacy of the first-choice empirical AB ciprofloxacine decreased in 2016. The types of the most frequent cholangitis-causing bacteria are in line with the ones included in the Tokyo Guideline. Orv Hetil. 2019; 160(36): 1437-1442.