Synthesis and antimicrobial activity of novel heterocyclic sulfamoyl-phenyl-carboximidamides derived from clinically applied sulfonamides.

A series of novel heterocyclic sulfamoyl-phenyl-carboximidamides were synthesized in satisfactory yields via condensation of clinically applied sulfonamides with heterocyclic methyl carbimidates. New structures were confirmed by IR and NMR spectra as well as elemental analyses. All the compounds were screened for their antibacterial, antifungal, and tuberculostatic activities. Preliminary results indicated that some target compounds exhibited promising antibacterial potency. Especially, N-[4-(thiazol-2-sulfamoyl)phenyl]pyrazine-2-carboximidamide (16) was found to be as potent as clinically applied sulfamethoxypyridazine.

Outbreak of bullous impetigo caused by Staphylococcus aureus strains of phage type 3C/71 in a maternity ward linked to nasal carriage of a healthcare worker.

We describe an outbreak of bullous impetigo (BI) that occurred in a maternity unit and show phenotypic and genotypic properties and relatedness of isolated Staphylococcus aureus strains. Clinical material was obtained from 11 affected neonates. Additionally, nasal swabs from 67 healthy care workers (HCWs) as well as 107 environmental swabs were investigated. All isolates were screened for exfoliative toxin genes (eta, etb), antibiotic susceptibility and phage typed. Chromosomal DNA was genotyped by MLVF method and PCR/RFLP of coagulase gene were tested. Affected neonates were infected by two clusters of eta-positive S. aureus of phage type 3C/71: (1) MLVF type A isolates resistant only to penicillin, and (2) MLVF type B isolates resistant to penicillin and erythromycin/clindamycin. All isolates were susceptible to methicillin. We found 19 of 67 HCWs to be S. aureus nasal carriers. Two nasal isolates from HCWs were related to the outbreak on the basis of phage typing, PCR detection of eta/etb genes, antibiotyping and genotyping. Additionally, environmental swabs from the maternity unit revealed a 3C/71 S. aureus in the mattress of a baby bed. This is the first documented case of an outbreak of BI caused by phage type 3C/71 eta-positive strain of S. aureus.

Synthesis, structure, and antimicrobial activity of heterocyclic phenylsulfonyl- and 4-aminophenylsulfonyl-carboximidamides.

ABSTRACT: A series of novel phenylsulfonyl- and 4-aminophenylsulfonyl-carboximidamides were synthesized by condensation of sulfonamides with heterocyclic methyl carbimidates obtained from heterocyclic carbonitriles and used 'at its inception.' The molecular structure of the obtained compounds is discussed. Compounds possessing heterocyclic systems with a nitrogen atom in the α position to the functional group showed a different single-crystal structure than expected. The synthesized derivatives were evaluated for antimicrobial activities: tuberculostatic, antibacterial, and antifungal. GRAPHICAL ABSTRACT: .

Staphylococcus aureus isolated from patients with recurrent furunculosis carrying Panton-Valentine leukocidin genes represent agr specificity group IV.

Recurrent furunculosis (RF) caused by Staphylococcus aureus presents a difficult clinical problem and causes significant morbidity. The study aim was to characterise agr groups and detect toxin genes among S. aureus strains isolated from RF patients. Microbiological material was obtained from evacuated furuncules of 44 RF patients. Nasal swabs were obtained from both the RF patients and the controls (150 healthy volunteers with no history of RF). All strains were screened for the presence of lukS/lukF-PV, tst, sea, seb, sec, sed, eta, and etb genes. Moreover, agr specificity groups (I-IV) were identified. Antibiotic-susceptibility tests were performed by disk diffusion method and methicillin susceptibility was verified by mecA gene amplification. The investigated strains were resistant to penicillin, clindamycin, erythromycin, and tetracycline. All showed susceptibility to methicillin. Thirty-five of 44 strains tested were positive for leukocidin lukS/lukF-PV genes and 12/44 for enterotoxin seb gene. The coexistence of PVL genes and seb gene concerned 7/44 strains. The remaining toxin genes were not found. Forty-three strains belonged to agr specificity group IV including all strains with lukS/lukF-PV genes. Nasal carriage of S. aureus was observed in 27/44 (61.3%) RF patients and in 43/150 (28.6%) controls (p = 0.001). In all RF subjects, nasal strains did not differ from those isolated from furuncules in terms of lukS/lukF-PV gene status and agr specificity. To the best of our knowledge, it is the first study that shown such a predominance of agr group IV strains in RF patients.

[Diversification of agr locus among Staphylococcus aureus isolated from carriers and from hospital patients with infection syndromes]. / Zróznicowanie locus agr wsród Staphylococcus aureus izolowanych od nosicieli oraz od chorych z objawami zakazenia.

In Staphylococcus aureus, the accessory gen regulator (agr) system globally controls the production of virulence factors. Strains of S. aureus can be divided into four major agr groups (I-IV) on the basis of agrD and agrC polymorphisms. The aim of this study was to estimate the prevalence of the four agr specificity groups among S. aureus strains isolated from health carriers and from hospital patients. Fifty S. aureus strains from nose swabs obtained from medical students and fifty strains from hospital patients, mainly from dermatology, were identified by multiplex PCR. Most of S. aureus strains from carriers belonged to I (38%) and III (30%) group agr, in contrast to S. aureus strains from infections, which belonged mainly to IV (50%) and II (24%) group (p < 0.05). A relationship between agr group and type of disease was observed: agr group IV strains were associated with skin infection and agr groups I-III strains with other type of infections (p < 0.05).

Analogues of muramyl dipeptide (MDP) and tuftsin limit infection and inflammation in murine model of sepsis.

Pharmacological manipulation of the balance between pro- and anti-inflammatory mediators emerges as a key aspect of a successful treatment of sepsis. A murine model of septic shock was developed and chosen conjugates (1a, 1b, 8a, 8c) and analogs (T2) of muramyl dipeptide and tuftsin were tested in this model as prospective anti-bacterial drugs or adjuvants. The phagocytic activity of monocytes/macrophages was determined (flow cytometry, bacterial clearance from vital organs). To evaluate cytokines levels (TNFalpha, IFNgamma, IL6, IL10) we used real-time PCR. The most promising immunomodulatory properties were displayed by the analogue T2 and two conjugates: 8a, 8c.

[The prevalence of tetracycline resistance genes in clinical and commensal strains of Enterococcus faecalis isolated in Gdansk]. / Wystepowanie i zróznicowanie genów odpowiedzialnych za opornosc na tetracykline szczepów Enterococcus faecalis izolowanych w regionie gdanskim.

The common use of antibiotics is responsible for selecting of drug resistance not only in pathogenic, clinical bacteria but also in commensal, not pathogenic strains which could cause the rapid dissemination of the resistance to these antibacterial agents. However, information regarding the antibiotic resistance of commensal bacteria is very scarce, and the data is based mostly on phenotypical research. Therefore the use of genotyping methods for detection of tetracycline resistance genes, in commensal and medical isolates of bacteria, is essential, for understanding the spread of antibiotic resistance. In this study 24 commensal and 27 clinical isolates of Enterococcus faecalis has been screened by PCR methods for tet(M), tet(S) genes and Tn916 and Tn5397 transpozons. Subsequently, the tet(M) gene amplicones were sequenced and phylogenetic analysis was performed. We have found that the prevalence of tet(S) gene varied significantly between commensal and clinical strains. Moreover, the frequency of transpozons in clinical isolates was much higher comparing to strains isolated from healthy individuals. The phylogenetic analysis did not show significant differences between clinical and commensal strains but it could suggest that the genetic similarity between these two groups could be favourable factor for broad range spread of tet(M) gene.

[Non-specific adherence of Enterococcus faecalis strains isolated from healthy voluntaries and infection of urinary tract]. / Róznice w nieswoistej adhezji szczepów Enterococcus faecalis izolowanych od nosicieli oraz z zakazen ukladu moczowo-plciowego.

Enterococcus faecalis is a component of human and animal gastrointestinal microflora. However, the adhesion is considered to be the key step in the pathogenesis of enterococcal infections and the first step of biofilm formation. We aimed to compare and evaluate adherence of strains considered to be commensal flora (isolated from healthy volunteers) and strains isolated as a pathogen from medical samples in Gdansk Region The additional aim of this study was to analyze influence of subinhibitory concentration of gentamycin and cAD1 pheromone. Comparison involved 20 strains isolated from healthy voluntaries, 23 strains isolated as etiological agent of urinary tract infection and 16 HLAR strains from other infections. Adherence ability was tasted by turbidymetric method at 550 nm, as o reduction of bacterial inoculum after incubation with hydroksyapatite. Results showed significant difference between commensal and virulent strains as well as between none-inducted and inducted by pheromone. In contrast there was no difference between inducted and non-inducted virulent strains as well as between inducted virulent and inducted not virulent strains. The result shows ability to differentiate this group by non-specific adherence.

[Phage types of Staphylococcus aureus strains and their antibiotic resistance in carriers of medical students population]. / Bakteriofagowe typy Staphylococcus aureus i ich lekoopornosc u nosicieli w populacji studentów kierunkow medycznych.

The phage types of 78 S. aureus strains isolated from nose swabs obtained from a medical students in 2005 -2006 was determined and antibiotic resistance of the phage types was analysed. 680 students were tested in order to obtain the strains and 11.5% of them were carriers of S. aureus. Phage typing was performed using basic set of23 phages and 3 additional phages: 88, 89 and 187. Drug resistance was determined by the disc-diffusion method. The most frequent in studied population were the group III (21.8%) and strains lysed by phages belonging to varied groups (21.8%). Highly different phage patterns were observed among strains belonging to each of the group. Strains belonging to the group III as the strains lysed by phages from varied groups were most frequently resistant only to penicillin (52,9% respectively). Resistance to penicillin was also most often observed in the strains belonging to another groups and phage types. Usefulness of the additional phages 88,89 and 187 was in the investigations as no more than 51% of strains was lysed by this phages.

[Serologic and genetic analysis of group B streptococci isolated from adult patients]. / Serologiczna i genetyczna analiza paciorkowców grupy B izolowanych od doroslych pacjentów.

Serologic and genetic typing with RAPD (Random Amplified Polymorphic DNA) method was used for epidemiologic analysis of GBS. 125 strains isolated from various clinical samples from adult patients were tested. In serologic typing seven serotypes have been found. Serotypes III and R were the most often encountered, containing 37,6% and 20,8% of samples. There was no dependence between serologic type and disease process. Optimalisation of RAPD reaction parameters was based on the standard strains of GBS. In the group of strains tested with the use of RAPD method, eleven genetic profiles were found, with prevalence of profile B (25,8%). Five other profiles occured with similar frequency (8,8% - 12,8%). Among streptococci isolated from patients with the infection of genitourinary tract, great differentiation in the genetic profiles of the strains has been found. Each serologic type contained various genetic profiles. Genetic variety showed by RAPD method indicates the raised ability of this technique to find differences among isolates of GBS.

[Application of PCR-fingerprinting reactions for typing group B Streptococci using ERIC-1 and ERIC-2]. / Zastosowanie reakcji PCR-fingerprinting do typowania paciorkowców grupy B z wykorzystaniem starterów ERIC-1 i ERIC-2.

Usefulness of PCR--fingerprinting technic using ERIC 1 and ERIC 2 primers for epidemiologic analysis of Group B Streptococci was assessed. 120 strains isolated from various clinical samples were tested. Amplification reactions were carried out in automatic termocycler Poly Gen using two primers ERIC 1 and ERIC 2. Products of the amplification were subjected to horizontal electrophoresis in 1.5% agarose gel. Using primer ERIC 1 six DNA patterns were found. Patterns B and C were the most often encountered, containing 34.2% and 35.0% of strains. Less often pattern D occurred including 12.5% of strains. In case of primer ERIC 2 lower differentiation has been achieved, because only four DNA patterns has been found, three of them occurred with similar frequency 29.2% to 33.3%. Taking into consideration the patterns gained by means of two primers thirteen genotypes have been identified. Dominated two patterns CD and BC, comprising 30.0% and 24.1% Group B Streptococci. More rarely DA and BA occurred (10.8% and 8.3%). Remaining patterns make 0.8% to 6.7% strains. Among reference Group B Streptococci strains belonging to nine serologic types using two primers various genetic patterns were obtained.