Introduction of oxetan-3-yl and azetidin-3-yl groups into heteroaromatic bases was achieved by using a radical addition method (Minisci reaction). To demonstrate utility, the process was used to ...introduce an oxetane or azetidine into heteroaromatic systems that have found important uses in the drug discovery industry, such as the marketed EGFR inhibitor gefitinib, a quinolinecarbonitrile Src tyrosine kinase inhibitor, and the antimalarial hydroquinine.
Guidance regarding appropriate use of personal protective equipment in hospitals is in constant flux as research into SARS-COV-2 transmission continues to develop our understanding of the virus. The ...risk associated with procedures classed as 'aerosol generating' is under constant debate. Current guidance is largely based on pragmatic and cautious logic, as there is little scientific evidence of aerosolization and transmission of respiratory viruses associated with procedures. The physical properties of aerosol particles which may contain viable virus have implications for the safe use of personal protective equipment and infection control protocols. As elective work in the NHS is reinstated, it is important that the implications of the possibility of airborne transmission of the virus in hospitals are more widely understood. This will facilitate appropriate use of personal protective equipment and help direct further research into the true risks of aerosolization during these procedures to allow safe streamlining of services for staff and patients.
To enhance the information pertaining to the epidemiology of a collection of 378 Listeria spp. isolates obtained from several food-processing plants in Ireland over a 3- year period (2004-2007). The ...collection was characterized by pulsed-field gel electrophoresis (PFGE). The most prevalent pulse-type was PFGE profile I (n = 14·5%) that consisted mainly of environmental Listeria spp. samples. Serotyping of 145 Listeria monocytogenes isolates was performed. The most common serovar was 1/2a and comprised 57·4% (n = 77) of the L. monocytogenes collection. The other serovars were as follows: 4b (14·1%, n = 19), 1/2b (9·7%, n = 13), 4c (4·4%, n = 6) and 1/2c (6·7%, n = 9), respectively. Eleven isolates were identified as non-Listeria spp., the remaining ten L. monocytogenes isolates were nontypeable. The antimicrobial susceptibility testing revealed the antibiotic that isolates displayed the most resistance to was gentamicin (5%) followed by sulfamethoxazole-trimethoprim (2%), tetracycline and ciprofloxacin (1·5%). The subtyping has indicated the diversity of the Listeria spp. The presence of serotype 1/2a, 1/2b and 4b in both raw and cooked ready-to-eat food products is a public health concern, as these serotypes are frequently associated with foodborne outbreaks and sporadic cases of human listeriosis. In addition, the emergence of antimicrobial-resistant L. monocytogenes isolates could have serious therapeutic consequences. The molecular subtyping and the further characterization of these isolates may be valuable particularly in the context of a suspected common source outbreak in the future.
Reports of methicillin-resistant
Staphylococcus aureus (MRSA) in animals have become more frequent in recent years. This paper documents the recovery of MRSA from animals with respiratory, urinary ...tract or wound infection and from animals subjected to surgical procedures following treatment in one veterinary hospital and 16 private veterinary clinics in different geographical locations throughout Ireland. MRSA was recovered from 25 animals comprising 14 dogs, eight horses, one cat, one rabbit and a seal, and also from 10 attendant veterinary personnel. Clinical susceptibility testing suggested that the 35 isolates fell into two different groups. One group of isolates (Group 1) was resistant to one or more of the following classes of antimicrobials: macrolides, lincosamines, tetracyclines and/or fluoroquinolones. The second group (Group 2) was resistant to macrolides, aminoglycosides, tetracyclines and trimethoprim/sulphamethoxazole and variably resistant to fluoroquinolones, lincosamines and rifampicin. One isolate in Group 2 was susceptible to trimethoprim. Epidemiological typing by antibiogram-resistogram (AR) typing, biotyping and by chromosomal DNA restriction fragment length polymorphism analysis using
SmaI digestion followed by pulsed field gel electrophoresis (PFGE), confirmed these two major clusters. PFGE analysis showed that most isolates from non-equine animals were indistinguishable from each other and from the isolates from personnel caring for these animals. MRSA was isolated from eight horses which attended six different veterinary practices before referral to an equine veterinary hospital. Isolates from the eight horses and from their attendant personnel had PFGE patterns that were indistinguishable and were unlike the patterns obtained from the other isolates. Comparison of PFGE patterns of isolates from veterinary sources with patterns from MRSA recovered in human hospitals showed that the most frequently occurring pattern of MRSA from non-equine animals was indistinguishable from the predominant pattern obtained from the most prevalent MRSA strain in the human population in Ireland. However, the patterns of the isolates from horses were unlike any patterns previously reported in Irish studies of human isolates. This study shows that transmission of two strains of MRSA is occurring in veterinary practices in Ireland and that one strain may have arisen from human hospitals. The source of the second strain remains to be determined.
Clostridium difficile is a major cause of infectious diarrhoea in hospitalised patients. Most pathogenic C. difficile strains produce two toxins, A and B; however, clinically relevant toxin ...A-negative, toxin B-positive (A−B+) strains of C. difficile that cause diarrhoea and colitis in humans have been isolated worldwide. The aims of this study were to isolate and characterise A−B+ strains from two university hospitals in Dublin, Ireland. Samples positive for C. difficile were identified daily by review of ELISA results and were cultured on selective media. Following culture, toxin-specific immunoassays, IMR-90 cytotoxicity assays and PCR were used to analyse consecutive C. difficile isolates from 93 patients. Using a toxin A-specific ELISA, 52 samples produced detectable toxin. All isolates were positive using a toxin A/B ELISA. Similarly, all isolates were positive with the cytoxicity assay, although variant cytopathic effects were observed in 41 cases. PCR amplification of the toxin A and toxin B genes revealed that 41 of the previous A−B+ strains had a c. 1.7-kb deletion in the 3′-end of the tcdA gene. Restriction enzyme analysis of these amplicons revealed the loss of polymorphic restriction sites. These 41 A−B+ isolates were designated toxinotype VIII by comparison with C. difficile strain 1470. PCR ribotyping revealed that all A−B+ isolates belonged to PCR-ribotype 017. A−B+C. difficile isolates accounted for 44% of the isolates examined in this study, and appeared to be isolated more frequently in Dublin, Ireland, than reported rates for other countries.
5,6,7,8-Tetrahydroquinolines and 5,6,7,8-tetrahydronaphthyridines with appended trifluoromethyl groups are valuable chemotypes in medicinal chemistry due to the presence of a partially-saturated ...bicyclic ring and metabolically-stable CF(3) group. (1)H NMR studies were used to optimize the preparation of such compounds, using a three-step/one-pot procedure, to provide novel 2,6-disubstitued derivatives with a tertiary-substituent. Racemic 2,6-disubstituted tetrahydroquinolines were separated by chiral HPLC to provide single enantiomers.
Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from five dogs with wound discharges after surgical procedures at a veterinary practice, and MRSA with similar molecular and phenotypic ...characteristics was isolated from the nares of one veterinary surgeon in the practice. The pulsed-field gel electrophoresis patterns of all the isolates were indistinguishable from each other and from the most common human isolates of MRSA in Ireland.
To investigate the transfer of antibiotic resistance from a donor Salmonella Typhimurium DT104 strain to a recipient Escherichia coli K12 strain. Mating experiments were conducted in broth, milk and ...ground meat (beef) at incubation temperatures of 4, 15, 25 and 37°C for 18 and 36 h. Ampicillin-resistance transfer was observed at similar frequencies in all transfer media at 25 and 37°C (10⁻⁴ to 10⁻⁵ log₁₀ CFU ml g⁻¹, transconjugants per recipient) for 18 h. At 15°C, transfer was observed in ground meat in the recipient strain (10⁻⁶, log₁₀ CFU g⁻¹, transconjugants per recipient), but not in broth or milk. At 4°C, transfer did not occur in any of the examined mediums. Further analysis of the E. coli K12 nalR transconjugant strain revealed the presence of a newly acquired plasmid (21 kbp) bearing the β-lactamase gene blaTEM. Transconjugants isolated on the basis of resistance to ampicillin did not acquire any other resistant markers. This study demonstrates the transfer of antibiotic resistance in food matrices at mid-range temperatures. It highlights the involvement of food matrices in the dissemination of antibiotic-resistant genes and the evolution of antibiotic-resistant bacteria.
A novel series of
N-chloroheterocycles has been prepared and the biological properties are reported.
Antimicrobial compounds with broad-spectrum activity and minimal potential for antibiotic ...resistance are urgently needed. Toward this end, we prepared and investigated a novel series of
N-chloroheterocycles. Of the compounds examined, the
N-chloroamine series were found superior over
N-chloroamide series in regards to exhibiting high antimicrobial activity, low cytotoxicity, and long-term aqueous stability.
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