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Összefoglaló. Az élelmiszer-eredetű megbetegedések igen gyakoriak, bár pontos adatok nem állnak rendelkezésre, mivel az enyhe, gyorsan múló gastrointestinalis tünetekkel a betegek nem fordulnak orvoshoz, vagy nem történik diagnosztikus vizsgálat. Az amerikai Járványügyi és Betegségmegelőzési Központ (CDC) adatai szerint az USA-ban évente 6 lakosból 1 esik át élelmiszer okozta tüneteken. Az ételintoxikációk során a baktérium által termelt toxinok okozzák a tüneteket, közülük a leggyakoribb a Clostridium perfringens, a Staphylococcus aureus és a Bacillus cereus okozta, élelmiszer-eredetű intoxikáció. A nem megfelelően tárolt vagy hőkezelt élelmiszerekben - beleértve a S. aureus által szennyezett anyatejet - ezen baktériumok életképesek maradnak, elszaporodnak, és toxint termelhetnek, illetve toxinjaik megőrzik megbetegítőképességüket. Az étel elfogyasztása után 3-12 órával hányást, hasmenést okoznak. A tünetek többnyire 24 órán belül megszűnnek. A Clostridium botulinum súlyos neurológiai tünetei miatt emelkedik ki a többi toxikoinfekció sorából. C. botulinum okozta tünetekre felnőtteknél házi készítésű konzervek és húskészítmények elfogyasztása után jelentkező gastrointestinalis vagy neurológiai tünetek esetén kell gondolnunk. A Clostridioides difficile szintén a toxinjai révén okoz súlyos, életveszélyes megbetegedést, továbbá az esetek 20-30%-ában számolnunk kell az infekció relapsusával. Növekvő gyakorisága miatt ismernünk érdemes a laboratóriumi és klinikai diagnosztika részleteit és a legmodernebb kezelési lehetőségeket, úgymint megfelelő mintavétel, mintatárolás és -szállítás, tenyésztés, toxinkimutatás, helyes tüneti kezelés, antibiotikumkombinációk, széklettranszplantáció és monoklonálisantitest-kezelés. Orv Hetil. 2020; 161(48): 2019-2028. Summary. Foodborne diseases are quite common, however, accurate data are not available because patients do not visit doctors with mild, rapidly resolving symptoms and diagnostic tests are not performed. The Centers of Disease Control and Prevention (CDC) estimates that, in the USA, 1 in 6 citizens gets food poisoning yearly. Symptoms of intoxication are due to the toxins produced by bacteria, mostly by Clostridium perfringens, Staphylococcus aureus and Bacillus cereus. These bacteria can survive in not properly stored or heated food, including S. aureus contaminated breastmilk. They can multiply and produce toxins causing intoxications. The gastrointestinal symptoms start 3-12 hours after consumption of the contaminated food and resolve in 24 hours. Clostridium botulinum causes severe neurological symptoms that should be suspected after consumption of home-made cans, smoked hams and sausages. The disease caused by Clostridioides difficile is not a foodborne one, but C. difficile causes severe infection via its toxins. Another problem is that C. difficile infection recurs in 20-30% of cases. Due to the increasing incidence of foodborne diseases, it is worth to learn the precise clinical and laboratory diagnostic algorithms including sampling, storage and transportation of samples, cultivation of bacteria and differential diagnosis of these diseases, furthermore the most up-to-date symptomatic and causative treatment options like antibiotic combinations, stool transplantation and monoclonal antibodies. Orv Hetil. 2020; 161(48): 2019-2028.

Bis-alkylthio maleimido derivatives have been prepared from teicoplanin pseudoaglycon by reaction of its primary amino group with N-ethoxycarbonyl bis-alkylthiomaleimides. Some of the new derivatives displayed excellent antibacterial activity against resistant bacteria.

The primary amino function of teicoplanin pseudoaglycon has been transformed into arylthioisoindole or benzoisoindole and glycosylthioisoindole derivatives, in a reaction with o-phthalaldehyde or naphtalene-2,3-dicarbaldehyde and various thiols. All of the obtained semisynthetic antibiotics exhibited potent antibacterial activities against Gram-positive bacteria in the ng per ml concentration range. A few of them showed antiviral activity, in particular against influenza virus. ispartof: Bioorganic & Medicinal Chemistry Letters vol:22 issue:23 pages:7092-7096 ispartof: location:England status: published

From January 1, 2009 through December 31, 2011, from 33,753 blood samples for syphilis screening, Treponema pallidum infections were confirmed in 241 pregnant women at the Department of Dermatology, Venerology, and Dermatooncology of Semmelweis University Budapest. In this period, four children born to inadequately or untreated women were confirmed to have connatal syphilis. The height of rapid plasma reagin (RPR) titer was measured to determine the stage of the infection and to examine the success of the antilues therapy. The diagnosis of maternal syphilis infection was confirmed with enzyme linked immunosorbent assay (ELISA), T. pallidum particle agglutination (TPPA), and IgG and IgM immunoblots. Maternal IgM immunoblot results identify mothers at risk of delivering babies with connatal syphilis better than the height of maternal RPR titer. The standard serological tests are less useful in newborns because of IgG transfer across the placenta. IgM test which depends on the infant's response has more specificity in diagnosing connatal syphilis.

Ureaplasma urealyticum and Mycoplasma hominis have important role among the causative agents of sexually transmitted diseases. Aim: The aim of the study was to determine the frequency and antibiotic resistance of Ureaplasma urealyticum and Mycoplasma hominis in genital samples obtained from patients examined in the Sexually Transmitted Diseases Centre of the Department of Dermatology, Venerology and Dermatooncology, Semmelweis University, Budapest between May 1, 2008 and July 31, 2010. Patients and methods: Samples were taken from the urethra in men and from the cervix and urethra in women by universal swab (Biolab®) into Urea-Myco DUO kit (Bio-Rad®) and were incubated for 48 hours at 37 C°. Antibiotic sensitivity of positive samples was determined in U9 bouillon using SIR Mycoplasma kit (Bio-Rad®). Results: Samples for 4154 patients aged 16-60 years were examined. In 247/4154 samples (6%) U. urealyticum and in 26/4154 samples (0.63%) M. hominis was isolated from the genital tract. Most U. urealyticum and M. hominis strains (75% and 77%, respectively) were cultured from cervix, while the remaining 25%, and 23% from the male and female urethra, respectively. U. urealyticum and M. hominis were most commonly detected in patients aged between 21 and 40 years. The majority of U. urealyticum strains were sensitive to tetracycline (94%), doxycycline (95%), azithromycin (88%) and josamycin (90%), but were resistant to ofloxacin (21%), erythromycin (85%) and clindamycin (79%). Seventy-seven percent of the U. urealyticum strains were simultaneously resistant to erythromycin and clindamycin, suggesting that ex iuvantibus therapies may select cross-resistant strains to both antibiotics. The resistance of M. hominis to clindamycin, doxycycline, ofloxacin and tetracycline varied between 4% and 12 %. Conclusions: Because none of the strains was sensitive to all examined antibiotics, the antibiotic sensitivity of U. urealyticum and M. hominis strains should be determined. The high rate of ofloxacin, erythromycin and clindamycin resistance should be considered in the therapy of U. urealyticum infections in Hungary. This is the firstsuch a clinical microbiological study in this topic in Hungary. Orv. Hetil., 2011, 152, 1698–1702.

Although the designer proline-rich antimicrobial peptide A3-APO has only modest activity against Escherichia coli and Acinetobacter baumannii in vitro, in mouse models of systemic and wound infections it shows superior efficacy compared with conventional antibiotics. In this study, the efficacy of A3-APO in several additional mouse models was investigated, including Staphylococcus aureus wound infection, mixed Klebsiella pneumoniae-A. baumannii-Proteus mirabilis wound infection and K. pneumoniae lung infection, mimicking blast wound infections, foot ulcers and ventilator-induced nosocomial infections, respectively. Whilst the peptide practically did not kill the strains in vitro, when administered intramuscularly or as an aerosol it significantly improved mouse survival and reduced bacterial counts at the infection site and in blood. In the lung infection study, the blood bacterial counts following A3-APO treatment were as low as after treatment with colistin and were lower than after treatment with imipenem or amikacin. The wounds of treated animals, unlike their untreated counterparts, lacked pus and signs of inflammation. In human peripheral blood mononuclear cells, A3-APO upregulated the expression of the anti-inflammatory cytokines interleukin-4 and interleukin-10 by four- to six-fold. One of the mechanisms mediating the in vivo protective effects might be the prevention of inflammation around bacterial infiltration.

The aim of this study was to compare the quantitative susceptibility of methicillin-resistant and -susceptible Staphylococcus aureus (MRSA and MSSA) strains from three European countries to nine antistaphylococcal agents. The antibiotic susceptibility of 274 MRSA and 284 MSSA strains from Hungary, Austria and macedonia was tested by the broth microdilution method. The clonal relationship of strains was determined by pulsed-field gel electrophoresis. Intermediate susceptibility to vancomycin appeared in Macedonian MRSA strains. Macedonian MRSA strains had high-level amikacin and gentamicin resistance. MSSA strains generally were susceptible to all drugs at minimum inhibitory concentrations (MIC(50)) except for gentamicin resistance in Macedonian strains. In Hungary and Austria a common antibiotic resistance phenotype of MRSA predominated, while in macedonia three other phenotypes were also prevalent. Geographical differences in the resistance of S. aureus are still high. Since resistance levels of MRSA and MSSA strains differ extensively, they should be considered separately for antibiotic resistance analysis.

A nosocomialis fertőzések fő okozói az egészségügyi többletkiadásoknak és szoros összefüggésben állnak a betegbiztonság problémakörével is. Hatékony infekciókontrollal, szigorított higiénés intézkedésekkel, célzott szűrővizsgálatokkal a kórházi fertőzések 30%-a megelőzhető. Napjainkban a methicillinrezisztens Staphylococcus aureus az egyik legfontosabb nosocomialis patogén. Az ellene történő védekezés lépései jól ismertek, ezért választottuk ezt a kórokozót költséghatékonysági vizsgálatainkhoz. Kiszámoltuk a győri Petz Aladár Megyei Oktatókórházban kétéves periódus alatt lezajlott methicillinrezisztens Staphylococcus aureus okozta járvány költségeit és szembeállítottuk a szűrővizsgálatok költségeivel. Eredményeinket összehasonlítottuk a nemzetközi szakirodalmi adatokkal is. Megállapíthatjuk, hogy a szűrővizsgálatok költségei jóval alacsonyabbak, mint a kórházi fertőzések kezelésének költségei, ezért elsődleges szerepe a prevenciónak van.

New sugar derivatives of ristocetin were prepared by copper-catalyzed 1,3-dipolar cycloaddition reaction using azido-ristocetin aglycon and various propargyl glycosides. Some of them were found to be active against gram-positive bacteria and showed favorable antiviral activity against the H1N1 subtype of influenza A virus. ispartof: Bioorganic & Medicinal Chemistry Letters vol:20 issue:9 pages:2713-7 ispartof: location:England status: published

In the STD Centre of Hungary at our department, we have been providing care for patients with syphilis, gonorrhoea and other STD infections since 2004. Our STD centre includes a screening station where we perform anonymous screening for HIV and syphilis. Between the 1st of January 2005 and the 31st of December 2008, there were a total of 42,114 patient-doctor encounters. We performed 25,362 screening examinations for HIV and syphilis, in association with a medical visit (HIV: 12,337; syphilis: 13,025). Voluntary screening examinations were performed in 18,883 cases (HIV: 16,614; syphilis: 2,269). During the 4 years, we diagnosed 600 and 339 new cases of syphilis and gonorrhoea, respectively. The obligatory HIV screening of STI patients resulted in a total of 47 new HIV infections, and we diagnosed 63 new infections of syphilis or gonorrhoea among the known HIV-seropositive patients under care. By including the network of care providers in the whole country, we performed successful contact tracing...

Antimicrobial resistance is an emerging worldwide concern in light of the widespread antimicrobial drug use in humans, livestock and companion animals. The treatment of life-threatening infections is especially problematic because clinical strains rapidly acquire multiple-drug resistance. Antimicrobial peptides have long been considered to be viable alternatives to small molecule antibiotics. However, the peptides' parenteral use is frequently hampered by inadequate safety margins and rapid renal clearance leaving them suitable only for topical applications. The proline-rich peptide A3-APO represents a family of a new class of synthetic dimers that kill bacteria by a dual mode of action and carry domains for interaction with both the bacterial membrane and an intracellular target. From a series of designer antibacterial peptides, A3-APO emerged as a viable preclinical candidate by virtue of its superior ability to disintegrate the bacterial membrane, inhibit the 70-kDa heat shock protein DnaK alone or in synergy with small molecule antibiotics, lack of eukaryotic toxicity and withstand proteolytic degradation in body fluids. As many other proline-rich peptides, A3-APO binds to the C-terminal helical lid of bacterial DnaK and inhibits chaperone-assisted protein folding in bacteria but not in mammalian Hsp70. In this review, the structure, pharmacokinetic properties, antimicrobial spectrum of peptide A3-APO and its in vivo metabolite are summarized and the in vitro and in vivo antimicrobial effects (antimicrobial susceptibilities, postantibiotic effects, resistance induction) are discussed in detail.

Klinikánk STD Centrumában 2004 óta végezzük a syphilis, gonorrhoea és egyéb STD-fertőzésben szenvedők ellátását. STD Centrumunkon szűrőállomás működik, ahol anonim HIV- és syphilisszűrést végzünk. 2005. január 1-jétől 2008. december 31-ig összesen 42 114 orvos–beteg találkozás történt. 25 362 HIV- és syphilisszűrő vizsgálatot végeztünk el, orvosi vizittel egybekötve (HIV: 12 337, syphilis: 13 025). Önkéntes szűrővizsgálat 18 883 esetben történt (HIV: 16 614, syphilis: 2269). Négy év alatt 600 új syphilis- és 339 új gonorrhoeafertőzést diagnosztizáltunk. A kötelezően ajánlott HIV-szűrés során a 4 év alatt összesen 47 új HIV-fertőzést találtunk, illetve ismert és gondozott HIV-szeropozitív betegek közül 63 esetben állapítottunk meg új syphilis- vagy gonorrhoeafertőzést. Országosan, a gondozói hálózat bevonásával sikeres kontaktuskutatást syphilisnél évente 400, gonorrhoeánál évi 150–200 alkalommal végeztünk. Cikkünk célja, hogy felhívjuk a figyelmet a klasszikus nemi betegségek közé számító syphilis- és gonorrhoeafertőzések, valamint a többszörös STD-betegségek jelentőségére.

Cytotoxin genes in 128 Austrian (AT) MSSA, 48 MRSA, 94 Hungarian (HU) MSSA, 110 MRSA and 67 Macedonian (MK) MSSA, 81 MRSA strains were examined. The presence of alfa-haemolysin gene (hla) was more common in HU MSSA strains compared to AT and MK (99%, 86%, 72%: p0.001). AT and MK MRSA harboured hlb genes more frequently compared to HU (60%, 62%, 33%: p0.001). HU and MK MRSA strains carried gamma-haemolysin gene (hlg) in higher percentage in contrast to AT (88%, 83%, 69%: p=0.01). Haemolysin gamma-variant gene (hlgv) was more prevalent in HU MSSA compared to AT and MK (84%, 56%, 69%: p0.001). Panton-Valentine leukocidin genes were found only in AT, HU, MK MSSA and MK MRSA in 2.3%, 4%, 1.5% (p=0.53) and 1% (p=0.38), respectively. The 3-gene combination pattern comprising of hla, hlg and hld genes showed increased prevalence among AT MSSA compared to HU (27%, 11%: p0.001). The 4-gene pattern composed of hla, hlg, hlgv and hld genes was significantly characteristic for HU MRSA in contrast to AT and MK MRSA (56%, 12.5%, 27%: p0.001). Frequency of certain cytotoxin genes and combinations differed significantly in Staphylococcus aureus strains according to geographical origin and methicillin-resistance.

In this report we examined the glycopeptide susceptibility of enterococci, isolated in 2005, from slaughtered animals, within the confines of Hungarian Antibiotic Resistance Monitoring System. We determined the presence of the van genes as well as their genetic relatedness in enterococci from poultry. Enterococcus sp. strains (n=175) were collected from intestinal samples of slaughtered poultry in 2005. The origin of the samples was registered at county level. After screening the strains with 30 mg vancomycin disc 19 (86%) intermediate resistant and 4 (3%) fully resistant strains were found. The distribution of minimum inhibitory concentration (MIC)-values among 23 enterococcus strains which were intermediate or resistant to vancomycin were 0.25 mg/L (4.4%), 2 mg/L (8.6%), 4 mg/L (8.6%), 8 mg/L (61%), 16 mg/L (8.6%) and 256 mg/L (8.6%). The MICs of teicoplanin were 0.25 mg/L (4.3%), 1 (8.6%), 4 mg/L (78.3%), 16 mg/L (4.3%) and 256 mg/L (4.3%). The two most vancomycin-resistant strains were vanA carriers (1 E. faecalis and 1 E. faeciuum). The farms that produced these strains can be reservoirs of VRE and the affected farms should change the technology of disinfection and breeding in order to prevent the emergence of high numbers of human VRE isolates in Hungary.

The purpose of this study was to characterise methicillin-resistant Staphylococcus aureus (MRSA) strains isolated in 2005 at the university hospitals of Debrecen, Hungary. Three hundred and thirty-nine MRSA strains were isolated from 102 patients at 18 different clinics. Their sensitivity to oxacillin and ten other antibiotics was determined. For genotypic analysis, phage typing and pulsed-field gel electrophoresis (PFGE) was performed. The rate of MRSA strains increased to 7.2% in 2005, especially at the clinics of surgery, pulmonology and paediatrics. No vancomycin- or teicoplanin-resistant strains were found. The resistance to erythromycin, clindamycin and ciprofloxacin was nearly 100% and multi-resistance was very frequent. Fifty-eight percent of the isolates belonged to mixed phage types and 8% was non-typable. One PFGE clone contained 58.2% of all strains and two further major clones were found at a separately located clinical block, indicating intra-hospital spread. We can conclude that MRSA exhibits an increasing nosocomial problem also in Hungary.

The proline-rich designer antibacterial peptide dimer A3-APO is currently under preclinical development for the treatment of systemic infections caused by antibiotic-resistant Gram-negative bacteria. The peptide showed remarkable stability in 25% mouse serum in vitro, exhibiting a half-life of approximately 100 min as documented by reversed-phase chromatography. Indeed, after a 30-min incubation period in undiluted mouse serum ex vivo, mass spectrometry failed to identify any degradation product. The peptide was still a major peak in full blood ex vivo, however, with degradation products present corresponding to amino-terminal cleavage. When injected into mice intravenously, very little, if any unmodified peptide could be detected after 30 min. Nevertheless, the major early metabolite, a full single-chain fragment, was detectable until 90 min, and this fragment exhibited equal or slightly better activity in the broth microdilution antimicrobial assay against a panel of resistant Enterobactericeae strains. The Chex1-Arg20 metabolite, when administered three times at 20 mg/kg to mice infected with a sublethal dose (over LD(50)) of an extended spectrum beta-lactamase-producing Escherichia coli strain, completely sterilized the mouse blood, similar to imipenem added at a higher dose. The longer and presumably more immunogenic prodrug A3-APO, injected subcutaneously twice over a 3-wk period, did not induce any antibody production, indicating the suitability of this peptide or its active metabolite for clinical development.

The presence of the vanA gene was determined in enterococci from healthy poultry, originating from the Hungarian resistance monitoring system between 2001 and 2004. Enterococci (n = 562) were collected from intestinal samples of slaughtered broiler chickens. The presence of van genes was detected by polymerase chain reaction (PCR). The vancomycin-resistant enterococcus (VRE) strains carried only the vanA gene. Genus- and species-level identification of the vanA gene carrier strains was carried out by PCR using specific primers. In 2001, 25 out of the 289 isolated strains (8.6%) were vanA carriers (1 Enterococcus mundtii , 13 E. durans and 11 E. faecium ). In 2002 (n = 87), 20 (23%) strains were vanA positive (11 E. durans and 9 E. faecium ). In 2003 and 2004, none of the strains (n = 95 and 91, respectively) were positive for the most common van genes. In 2003, there was only one strain for which higher minimum inhibitory concentrations (MIC) of vancomycin (4 mg/L) and teicoplanin (8 mg/L) were found. In 2004 there were three strains for which the MIC of vancomycin was 8 mg/L, and 2 strains and 1 strain with teicoplanin MICs of 4 mg/L and 8 mg/L, respectively. The potential similarity of these strains was studied by pulsed-field gel electrophoresis (PFGE). The VRE strains were not closely related to one another. The annual data of vancomycin resistance indicate an association between the recovery of vancomycin-resistant enterococci and the use of avoparcin in animal feeds. This study indicates that with the reduced use of antibiotics in food animals, it is possible to decrease the rate of resistant bacteria. Although the use of avoparcin had been banned in 1998, the VRE strains disappeared only five years later.

The extended-spectrum beta-lactamase (ESBL)-producing Klebsiella spp. cause worldwide problems in intensive care units. The aim of this study was to investigate the molecular epidemiology of ESBL-producing Klebsiella pneumoniae and K. oxytoca strains in a neonatal intensive care unit (NICU) in Budapest, Hungary and to determine the risk factors of the infections and the epidemiological features. Infections with Klebsiella spp. were analyzed retrospectively by reviewing the medical records between January 2001 and December 2005. Antibiotic susceptibility tests, isoelectric focusing, pulsed field gel electrophoresis, plasmid analysis, PCR for bla(TEM) and bla(SHV) and DNA sequencing analysis were performed on ESBL-producing Klebsiella isolates. A total of 45 babies were found to be infected with non-ESBL-producing Klebsiella spp. and 39 with ESBL-producing Klebsiella spp. Of the parameters analyzed, including sex, gestational age, twin pregnancy, birth weight, presence of central vascular catheter, mechanical ventilator use, parenteral nutrition, polymicrobial infection, caesarean section, transfusion and mortality, we found no statistically significant difference between the ESBL and the non-ESBL groups, or between the K. pneumoniae and K. oxytoca species. Further characterization of the ESBL-producing K. pneumoniae and K. oxytoca strains isolated between February 2001 and January 2003 revealed three distinct PFGE patterns of SHV-5-producing K. pneumoniae (A, B, E) and two distinct patterns of SHV-12-producing K. oxytoca (C,D) isolates; these had different plasmid profiles. From July to November 2005, a new SHV-5 producing K. oxytoca (F) was isolated. The molecular epidemiology of ESBL-producing organisms in a NICU over time shows substantial shifts in predominant strains. The ESBL production of the infected organisms has an impact on the survival of newborn babies with infections caused by Klebsiella spp.

In vitro and in vivo activities of amikacin and imipenem alone, and in combination, were studied against an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain. The strain was in vitro susceptible to both antimicrobials at 10(5) and 10(7) CFU/mL. In time-kill studies amikacin, imipenem, and amikacin plus imipenem decreased the bacterial counts; difference between the bactericidal effects was not observed. Chequerboard technique showed no interaction between the tested drugs. Mice infected with 10(7) CFU/g of the K. pneumoniae were treated by amikacin (15 mg/kg every 8 h), imipenem (40 mg/kg every 4 h), or amikacin plus imipenem for 24 h. Blood bacterial counts in the group treated with amikacin plus imipenem did not differ significantly from the groups treated with amikacin or imipenem alone. Combination of amikacin and imipenem did not demonstrate any advantage over imipenem alone either in vitro or in vivo.

The simulation of human serum levels is essential in animal models to extrapolate the experimental results to clinical practice. Administration of a nephrotoxic drug such as cisplatin can be used to cause renal dysfunction as an approach to mimic human serum levels of renally excreted drugs. We aimed to determine the dose of cisplatin that did not affect the survival rate of mice and to achieve human-like serum concentrations of cefepime. Different doses of cisplatin (0, 10, 14, 18, 22 and 26 mg/kg) were given by intraperitoneal (i.p.) injection to mice three days prior to the i.p. administration of 80 mg/kg cefepime. With cisplatin doses of 18 and 22 mg/kg, the half-life of cefepime was significantly prolonged ( P

The distribution of 3497 Staphylococcus aureus strains according to methicillin resistance, specimens, departmental profession and antibiotic resistance patterns was analysed. The strains were cultured from the patients of the Clinical Center of Skopje, Macedonia, between 1 January 2002 and 31 December 2004. The majority of the isolates was obtained from suppurated wounds (28.5%), nares (21%), intratracheal tubes (13%) and blood cultures (11.8%). Overall 1100 (31.4%) of the isolates was methicillin-resistant with 1 microg oxacillin disc. Of these 35.5%, 30.5% and 10.4% were cultured from wounds, intratracheal tubes and blood samples, respectively. The prevalence of MRSA strains was 78.6%, 75%, 44.2% and 37.3% in specimens of ICU, Coma Center, General Surgery and Haematology patients. There were extremely big differences in the frequency of MRSA between departments with particular specialisation. The 2397 MSSA isolates belonged to practically one antibiotic resistance pattern characterised with penicillin resistance and susceptibility to other antistaphylococcal drugs. The 1100 MRSA isolates distributed to four antibiotic resistance patterns on the basis of their resistance to oxacillin, penicillin, amoxicillin+clavulanic acid, azithromycin, clindamycin, amikacin, gentamicin, ciprofloxacin, trimethoprim+sulphamethoxasole, vancomycin and teicoplanin. All the MRSA isolates were multidrug resistant but sensitive to glycopeptides.

The relatedness of 112 penicillin-non-susceptible isolates of Streptococcus pneumoniae from Hungary was determined by pulsed-field gel electrophoresis (PFGE), serotyping and antibiotic susceptibility tests. The differences in PFGE patterns closely mirrored the changes in resistance. Some genotypes comprised multiple serotypes, and the genetic diversity among certain serotypes was considerable. Generally, serotyping alone was insufficient for epidemiological mapping of pneumococcal isolates. There was considerable serotype diversity, but the five most frequent international serotypes (6, 9, 14, 23, 19) were the most prevalent. In addition, the presence of some well-defined resistant international pneumococcal clones in the Hungarian population was identified.

The macrolide resistance of 304 Hungarian Streptococcus pneumoniae isolates was investigated. Antibiotic sensitivity testing was performed in air and in 5% CO2. More erythromycin resistance was noted when growth was in CO2. A resistance determinant was found in almost all isolates: erm(B) gene (87.4%), mef genes (9.2%) and one strain with the erm(TR) gene. This indicates that screening for carriage of resistance determinants should always be done in the presence of 5% CO2. We found three isolates with mef(E), which were highly resistant to erythromycin. These contained multiple and some novel, ribosomal mutations. The most prevalent serogroups were 6, 19 and 14. Based on the PFGE pattern, we found identity between the Hungarian isolates and two PMEN clones.

Thirty-five clinical isolates of coagulase-negative staphylococci with decreased glycopeptide sensitivity were examined by a penicillin-binding protein (PBP2') latex agglutination (LA) test and were compared to the detection of the mecA gene by PCR, and oxacillin susceptibility determined minimum inhibitory concentrations. The latex test demonstrated high sensitivity and specificity for detecting methicillin resistance in coagulase-negative staphylococci after PBP2' induction with oxacillin.

A 19-year-old man had been admitted to the Hospital because of septic shock and large scale suffusions all over the body. The pathogen had proved to be Neisseria meningitidis serogroup C. In his stabilization period two superinfectious attacks arose. One of them was a bacteremia, caused by a vancomycin-sensitive Enterococcus faecium. The second was a wound infection in his deep colliquating necrotised tissue of the heel. Vancomycin-resistant Enterococcus faecalis (VREF) was isolated from this lesion with some Gram-negative oppurtunistic pathogens. The strain contained the vanA gene. After systemic and topical treatment, furthermore plastic surgical interventions the patient recovered. This is the second report on VREF from Hungary colonizing/infecting a patient with an underlying disease.

OBJECTIVE Hungary has reported one of the highest incidences of penicillin resistance in Streptococcus pneumoniae in Europe since the 1970s and is still cited accordingly. However, since the end of the 1990s the resistance of pneumococci in Hungary has not been investigated. In this study we assessed the current situation, particularly to establish whether the incidence of resistance is increasing and if this could be related to the spread of specific strain types. METHODS Isolates of S. pneumoniae (n = 304) were collected by five diagnostic laboratories in Hungary in 2000-2002. Their identity was confirmed and their susceptibilities to 16 antibiotics were determined by the agar dilution method according to NCCLS guidelines. Representative strains were serotyped (n = 112). RESULTS AND CONCLUSIONS We found significantly lower resistance rates for penicillin compared with the data previously reported from Hungary, but the intermediate resistance was high, at 37%. Macrolide resistance was a bigger problem ( approximately 40% for erythromycin), although there was full susceptibility to telithromycin. The strains with the highest MICs were isolated from carriers and young children. The fluoroquinolones were very effective, especially moxifloxacin and gatifloxacin. There was full susceptibility to vancomycin and linezolid. We found inconsistencies with previous reports in the survey of the resistance and identification of S. pneumoniae in the country. The serotype distribution of the isolates showed a much greater diversity than had previously been reported; however, there was correlation between serotype and resistance.

The effects of the alkali metal ions (Li+, Na+ and K+) on the growth and on certain virulence factors (adhesion, cell-surface hydrophobicity and germinating ability) of Candida albicans were determined. High concentrations of these ions displayed an inhibitory effect on the growth of the Candida cells; preincubation in their presence showed a negative effect on all virulence factors studied. The changes induced during the preincubation remained there even when high concentration of the ions was removed from the cell suspension. In contrast, a considerable growth was found at high Na+ and K+ concentrations. Although alkali metal ions significantly decreased certain virulence traits of the fungus they did not totally inhibit adhesion and germ-tube formation. This suggests that C. albicans may represent a health hazard even at a high salt concentration.

Despite the close structural similarity between the heptapeptide cores of the glycopeptide antibiotics teicoplanin and ristocetin, synthetically modified derivatives of their aglycons show significantly different antibacterial and antiviral properties. The teicoplanin aglycon derivatives with one exception proved to be potent antibacterials but they did not exhibit anti-influenza virus activity. In contrast, the aglycoristocetin derivatives generally showed high anti-influenza virus activity and possessed moderate antibacterial activity. A systematic structure-activity relationship study has been carried out on ristocetin and teicoplanin aglycon derivatives, to explore which structural differences are responsible for these markedly different biological activities. According to electronic circular dichroism and in silico conformational studies, it was found that the differences in anti-influenza virus activity are mainly determined by the conformation of the heptapeptide core of the antibiotics controlled by the presence or absence of chloro substituents. Knowledge of the bioactive conformation will help to design new analogs with improved anti-influenza virus activity. For the teicoplanin derivatives, it was shown that derivatization to improve the antiviral efficacy was accompanied by a significant decrease in antibacterial activity.

Activities of ciprofloxacin and levofloxacin against an SHV-5 extended-spectrum s-lactamase (ESBL)-producing Klebsiella pneumoniae strain were studied in vitro and in vivo in septic mice using a high inoculum. Susceptibility to ciprofloxacin and levofloxacin was independent of the inoculum size. In killing curve studies, after 24 hours the initial 7.69 log 10 CFU / ml increased in the control to 9.34, while it was reduced to 4.83 by ciprofloxacin and to 4.25 by levofloxacin. Mice were infected with 10 7 CFU / g of K. pneumoniae intraperitoneally. Treatment started 2 hours later, when the mean blood bacterial counts were 7.33 log 10 CFU / ml, and lasted for 26 hours from the time of infection. Blood bacterial count was reduced from 7.33 log 10 CFU / ml to 4.08 log 10 CFU / ml by ciprofloxacin (20mg / kg / 6 hours), and to 3.60 log 10 CFU / ml by levofloxacin (50 mg / kg / 6 hours) 8 hours after the infection, which differed significantly from the infected untreated group. Ciprofloxacin and levofloxacin prolonged significantly the survival of mice compared with the infected untreated group (p < 0.001 for both groups). There were not significant differences either in the survival (p=1.0) or in the blood bacterial counts (p=0.216 after 8 hours) between ciprofloxacin and levofloxacin group. Based on these results both ciprofloxacin and levofloxacin could be alternative therapeutic agents for the infection caused by ESBL-producing Klebsiella strains.

Molecular mechanisms of the action of b-lactam and glycopeptide antibiotics, as well as genetic background and phenotipical features of the resistance of staphylococci, streptococci and enterococci to these antibiotics are reviewed. Furthermore, susceptibility patterns concerning b-lactam and glycopeptide drugs of staphylococcal, streptococcal, as well as enterococcal strains isolated from clinical specimens at the Semmelweis University of Medicine, Budapest, Hungary between January 1997 and December 2000 are also presented.

The clinical significance of the oral candidiasis (either as independent disorder, or as a part of another disease) is increasing with time. The diagnosis and local treatment of the oral candidiasis may not be satisfactory, this disorder cannot be eliminated without the correct diagnosis and management of the underlying disease. At the same time, some disorders, such as Candida induced leukoplakia, may significantly enhance tumor development. Fungal infection of the mouth is often the initial sign of several immunodeficiency diseases. It is, therefore, very important to clarify the background of a fungal infection, since this may be critical regarding the prognosis.

The in vitro and in vivo effectiveness of amikacin, cefepime, and imipenem was studied using a high inoculum of an extended-spectrum β-lactamase-producing Klebsiella pneumoniae strain. An in vitro susceptibility test at the standard inoculum predicted the in vivo outcome of amikacin or imipenem while it did not do so for cefepime due to the inoculum effect.

Of more than 3500 isolates of enterobacteriaceae, 48–69% were resistant to aminopenicillins and 11–45% to amoxycillin+clavulanic acid. Resistance to second and third generation cephalosporins was present in 11–17 and 3–8% of Escherichia coli , 47–56 and 15–52% of Klebsiella – Enterobacter , 36–57 and 16–27% of Proteus , Providencia and Morganella isolates. Pseudomonas aeruginosa strains varied in their resistance to antipseudomonal β-lactams. Isoelectric points, inhibitor profiles and substrate profiles of β-lactamases extracted from representatives of the resistant strains indicated that the resistance was mainly due to the hyperproduction of chromosomally encoded AmpC β-lactamases. This was confirmed by plasmid profile and PCR investigations. Extended-spectrum β-lactamase and metallo-penicillinase producing strains were not found. One Pseudomonas maltophilia strain produced an oxacillinase.

Interleukin-1 receptor-associated kinase (IRAK)-4 deficiency is a rare primary immunodeficiency disorder characterized by severe, invasive infections with Streptococcus pneumoniae. Using the PFGE technique a genetic linkage was found between two S. pneumoniae serotype 14 isolates causing arthritis and meningitis at 3 and 5½ years of age, respectively, in a boy with IRAK-4 deficiency. This finding suggested that patients with IRAK-4 deficiency may harbour persistent strains of pneumococci. Alternatively, reinfection with strains from close contacts of the patient might cause recurrent invasive disease. It is proposed that eradication of pneumococci from the nasopharynx, and immunization of household contacts may prevent recurrent infection in IRAK-4-deficient patients.

Background: STIs like HIV and syphilis are acquired as comorbidities by high risk populations and may influence their original course and prognosis. Methods: Be- tween January of 2005 and 2013 data of syphilis and HIV patients were collected at the Department of Dermatology of Semmelweis University, Budapest . Diagnostic proce- dures included clinical analysis and screening of serum samples for Treponema pallidum and HIV antibodies. Results: A total of 1,401 new syphilitic and 338 new HIV infections were diagnosed. In syphilis patients 86.58% had monoinfection, 7.92% already had an HIV infection and 5.5% had acquired syphilis and HIV infection simultaneously, so 22.78% of the new HIV patients acquired the infection with syphi - lis together. Male gender, MSM (men who had sex with men) orientation and positive past venerological history were dominant in all groups. Most patients were diagnosed in a latent infectious stage based on the result of a serological check-up. Secondary stage and neurosyphilis were more common in coinfections. Conclusion: (i) male gen - der, MSM orientation, and positive venerological history are risk factors for acquiring new STIs, (ii) clinical course were different in HIV infected patients, (iii) but their timely and regular check-ups resulted in earlier diagnosis of syphilis, suggesting the necessity for frequent screening.

The aim of this study was to examine the incidence and antibiotic sensitivity of Ureaplasma urealyticum and Mycoplasma hominis strains cultured from the genital discharges of sexually active individuals who attended our STD outpatient service. Samples were taken with universal swab (Biolab®, Budapest, Hungary) into the Urea-Myco DUO kit (Bio-Rad®, Budapest, Hungary) and incubated in ambient air for 48 h at 37 °C. The determination of antibiotic sensitivity was performed in U9 and arginin broth using the SIR Mycoplasma kit (Bio-Rad®, Budapest, Hungary) under the same conditions. Between 01.05.2008 and 31.12.2011, 373/4,466 (8.35 %) genito-urethral samples with U. urealyticum and 41/4,466 (0.91 %) genito-urethral samples with M. hominis infection were diagnosed in sexually active individuals in the National STD Center, Semmelweis University. U. urealyticum was isolated in 12.54 % in the cervix and 4.1 % in the male urethra, while M. hominis was isolated in 1.33 % in the cervix and 0.51 % in the male urethra. The affected age group was between 21 and 60 years old. U. urealyticum strains were sensitive to tetracycline (95.9 %), doxycycline (97.32 %), and azithromycin (85.79 %), and resistant to erythromycin (81.23 %), clindamycin (75.06 %), and ofloxacin (25.2 %). Cross-resistance occurred in 38.71 % of patients to erythromycin and clindamycin. M. hominis strains were sensitive to clindamycin, ofloxacin, and doxycycline in more than 95 %, to tetracycline in 82.92 %, and no cross-resistance was detected among the antibiotics. Our study confirms that the continuously changing antibiotic resistance of ureaplasmas and mycoplasmas should be followed at least in a few centers in every country, so as to determine the best local therapy options for sexually transmitted infection (STI) patients.

Glycopeptide antibiotic derivative teicoplanin ψ-aglycone has been bound covalently to a fullerenopyrrolidine derivative using azide-alkyne 1,3-dipolar cycloaddition reaction. The aggregation of the antibiotic-fullerene conjugate in aqueous solution has been studied. The conjugate exhibited antibacterial activity against enterococci resistant to teicoplanin.

Isoindole and benzoisoindole derivatives of ristocetin aglycon have been prepared by reaction with o-phthalaldehyde or naphthalene-2,3-dialdehyde and various thiols. The new compounds exhibited potent antibacterial and anti-influenza virus activity. The cluster forming and fluorescent properties of the aglycon derivatives were also studied. ispartof: European Journal of Medicinal Chemistry vol:58 pages:361-367 ispartof: location:France status: published

1-Hydroxybisphosphonate derivatives of ciprofloxacin, gatifloxacin and moxifloxacin have been synthesized using Cu(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction. The 1,2,3-triazol linked hydroxybisphosphonate derivative of ciprofloxacin exhibited antibacterial activity comparable to the parent antibiotic and all fluoroquinolone-bisphosphonates displayed osteotropic properties in a bone model.

Most antibacterial peptides exhibit low therapeutic indices in vivo. Peptide A3-APO was shown to exhibit high potency against Escherichia coli bacteremia when added intraperitoneally. To extend the studies to systemic infections against multidrug-resistant organisms, we studied the efficacy of A3-APO in mouse models of carbapenem-resistant Acinetobacter baumannii infection. When administered either intravenously at 2.5 mg/kg or intramuscularly (im) at 5 mg/kg twice or three times to mice infected with a carbapenem-resistant A. baumannii strain, peptide A3-APO reduced the bacterial counts by at least two log10 units and increased the survival rate compared with untreated animals or mice treated with 40 mg/kg imipenem. Unlike after intraperitoneal or intravenous administration, A3-APO did not show toxic effects at 60 mg/kg dose im.

The occurrence of Candida spp. was investigated during a three-year period in two neonatal intensive care units, Budapest, Hungary. The species distribution among the 41 analysed cases was the following: C. albicans (30/41, 73%), C. parapsilosis (10/41, 24%) and C. glabrata (1/41, 3%). All of the isolates were susceptible to the tested drugs. There was a significant difference in the birth weight, the gestational age30 weeks and the occurrence of caesarean section between the C. albicans and the C. parapsilosis groups of the cases. Respiratory tract colonization was the same (76-77%) in the extremely low birth weight (ELBW) and the very low birth weight (VLBW) groups. Comparing the ELBW, VLBW, and1500 g birth weight groups, significant difference was found in the parenteral nutrition, the gestation weeks36 or30, the polymicrobial infection and the transfusion. The ratio of C. albicans, C. parapsilosis and C. glabrata was 9:7:1 in ELBW group; 6:3:0 in VLBW group and 15:1:0 in1500 g group. The mortality rate for C. parapsilosis was higher than for C. albicans.

Background and aims The 7-valent conjugate pneumococcal vaccine (Prevenar) was introduced as a recommended (but not yet obligatory) vaccine in Hungary in April 2009 and there was a sharp increase in the number of children vaccinated. Hence there is an urgent need for in-depth epidemiological data on invasive pneumococci before vaccination becomes widespread. Such a study has never been done before in Hungary. Methods 144 pneumococcal isolates, obtained from invasive infections or pneumonia, were collected from eight Hungarian diagnostic laboratories between 2000 and 2008. After confirmation of species identity, their susceptibilities to nine antibiotics were determined by Etest and agar dilution method. The serotypes and pulsed-field gel electrophoresis genotypes of the strains were also determined. Results In this cohort, most of the isolates were from patients at the extreme of life. Only 1.4% of the strains were resistant to penicillin, but nearly 40% were resistant to erythromycin (mainly due to erm(B) gene). Higher incidences of resistance were found in the very young and very old. The most prevalent serotypes in the cohort in descending order were 14, 6A, 6, 6B, 23F, 3, 19F and 11A. Conclusions Results showed a similar but not identical profile to previously examined strains causing pulmonary infections in Hungary. The serotypes could be correlated to patient groups. Furthermore, there were examples of serotype switching in strains showing identical genotype but different serotype. The study also shows a good coverage by the conjugate vaccines over the invasive pneumococcal strains in Hungary based on the detected serotypes.

A novel series of tetraethylene glycol (TEG) triazolyl and squaramide containing oxazolidinones were synthesized and tested for their antibacterial activity against a selected panel of Gram-positive and Gram-negative bacteria. The 4-TEG-triazolyl derivatives were prepared by ‘click reaction’. The introduction of the TEG and squaramide groups did not favor antibacterial activity. The three nucleoside-containing oxazolidinones were also prepared by ‘click ’ ’ methodology resulted in weak antibacterial activity.