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Sökning: WFRF:(Melhus Åsa Associate Professor)

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1.
  • Sütterlin, Susanne (författare)
  • Aspects of Bacterial Resistance to Silver
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Bacterial resistance to antibiotics has increased rapidly within recent years, and it has become a serious threat to public health. Infections caused by multi-drug resistant bacteria entail higher morbidity, mortality, and a burden to health care systems. The use of biocides, including silver compounds, may affect the resistance to both biocides and antibiotics and, thereby, can be a driving factor in this development.The aim of the following thesis was to investigate the frequency of silver resistance and the effects of silver exposure on bacterial populations being of clinical significance and from geographically different parts of the world. Furthermore, it explored the genetic background of silver resistance, and if silver could select directly or indirectly for antibiotic resistance.By a range of methods, from culture in broth to whole genome sequencing, bacterial populations from humans, birds and from the environment were characterized.The studies showed that sil genes, encoding silver resistance, occurred at a high frequency. Sil genes were found in 48 % of Enterobacter spp., in 41 % of Klebsiella spp. and in 21 % of all human Escherichia coli isolates with production of certain types of extended-spectrum beta-lactamases (CTX-M-14 and CTX-M-15). In contrast, silver resistance was not found in bird isolates or in bacterial species, such as Pseudomonas aeruginosa and Legionella spp., with wet environments as their natural habitat. One silver-resistant Enterobacter cloacae strain was isolated from a chronic leg ulcer after only three weeks of treatment with silver-based dressings. The in-vivo effects of these dressings were limited, and they failed to eradicate both Gram-positive and Gram-negative bacteria. The activity of silver nitrate in vitro was bacteriostatic on Gram-positive species such as S. aureus and bactericidal on Gram-negative species. In Enterobacteriaceae, sil genes were associated with silver resistance phenotypes in all but one case. Using whole genome sequencing, single nucleotide polymorphisms in the silS gene were discovered after silver exposure in isolates with expressed silver resistance. This resistance could co-select for resistance to beta-lactams, co-trimoxazole and gentamicin.The findings of this thesis indicate that silver exposure may cause phenotypic silver resistance, and it may reduce the susceptibility to mainly beta-lactams and select for bacteria with resistance to clinically important antibiotics.
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2.
  • Hasan, Badrul, 1984- (författare)
  • Antimicrobial Resistance and Production of Extended Spectrum Beta-Lactamases in Enterobacteriaceae from Birds in Bangladesh
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The dissemination of members of the Enterobacteriaceae family with extended spectrum beta-lactamases (ESBLs) and metallo-beta-lactamases (MBLs) has become a global concern. ESBLs and MBLs have been reported in humans, domestic animals, wildlife and the environment, and their isolation frequencies are increasing rapidly worldwide.  Most studies have been performed in developed countries and quite few in developing countries, where the antibiotic consumption is often poorly controlled. To explore the environmental contamination of antibiotic resistance in Bangladesh, and of ESBLs and MBLs in particular, fecal samples from poultry and wild birds were studied in this thesis.Samples were collected from both sick birds (poultry having Escherichia coli infections) and healthy birds (free-range poultry, seagulls and crows) residing in different environmental niches. Samples from patients and fresh/sea water were included, to follow the chain of antibiotic resistance in bacteria from humans to the environment. Information regarding the antibiotic usage in poultry production was also collected. The susceptibility of avian E. coli isolates cultured with and without selective pressure was tested against antibiotics commonly used in human and veterinary medicine in Bangladesh. Special attention was paid to ESBL-producing isolates, which were further characterized genetically.The results of the studies showed that E. coli isolates from commercial poultry, free-range poultry, gulls and crows were resistant to several classes of antibiotics, and that the level and spectrum of antibiotic resistance varied between different bird populations. There was no NDM-producer found among the birds, but ESBL-producing Enterobacteriaceae could be found in up to 59% of the crows, the birds with the highest carriage rate of multiresistant  Enterobacteriaceae of all bird species studied. The most common ESBL-type was CTX-M-15, which also is the most common in the human population in Bangladesh. Birds also shared clinically important sequence types with humans, including E. coli clone O25b-ST131.In conclusion, ESBL-producing bacteria with multiresistance are easily spread to wild birds. Their opportunistic feeding behavior at poorly managed hospital waste dumps and nearby water bodies makes them into both reservoirs and active spreaders. The high level of antibiotic resistant and ESBL-producing bacteria in the bird population of Bangladesh is worrying, and there is no easy solution in sight. Nationwide programs are necessary to both improve the management of hospital waste and sewage and the control of the antibiotic usage to prevent further environmental contamination. 
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