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- Lytsy, Birgitta, 1968-
(author)
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Enterobacteriaceae Producing Extended-Spectrum Beta-Lactamases : Aspects of Detection, Epidemiology and Control
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Enterobacteriaceae belong to the normal enteric flora in humans and may cause infections. Escherichia coli is the leading urinary tract pathogen with septicaemic potential, whereas Klebsiella pneumoniae causes opportunistic infections and often outbreaks in hospital settings. Beta-lactams are the first choice for treatment of infections caused by Enterobacteriaceae, and might be destroyed by extended-spectrum beta-lactamases, ESBLs. ESBLs hydrolyse all beta-lactams except cephamycin and carbapenems, and constitute a large heterogeneous group of enzymes with different origins. The phenotypic and molecular characteristics of a K. pneumoniae strain causing a major outbreak at Uppsala University Hospital between 2005 and 2008 were described. The strain was multiresistant and produced CTM-M-15, a common ESBL type in Europe. Due to the lack of obvious epidemiological links between patients, a case-control study was performed, which identified risk factors for the acquisition of the outbreak strain in urine cultures. The complex chain of transmission facilitated by patient overcrowding and the interventions applied to curb the outbreak, was revealed in the subsequent study. In the final study, the genetic background of the observed increase in ESBL-producing E. coli isolates during the K. pneumoniae outbreak was explored. The utility of six typing methods in epidemiological investigations of a local outbreak with ESBL-producing E. coli was compared. The increase of ESBL-producing E. coli isolates was not secondary to the K. pneumoniae outbreak. Twentytwo per cent belonged to the epidemic O25b-ST131 clone and only a limited number of infections were caused by nosocomial transmission. ESBL-producing Enterobacteriaceae are a challenge to clinical microbiology laboratories and infection control teams. To investigate their dissemination, typing methods need to be continuously adapted to the current situation. Proper hand disinfection and structural key problems such as over-crowding, under-staffing, lack of single rooms and bathrooms must be adressed to limit transmission.
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| 2. |
- Starlander, Gustaf, 1986-
(author)
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Dissemination of Multiresistant Bacteria : Their Selection, Transmission, Virulence and Resistance
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Multiresistant bacteria are an emerging threat in modern medicine. Consumption of antimicrobial agents among humans, animals and in agriculture causes a selection of resistance genes. Dissemination of bacteria carrying resistance genes occurs both globally and locally, and hospital settings pose a special risk for spread when staff, environment and vulnerable patients interact. The overall aim of this thesis was to analyse underlying factors that facilitate the dissemination of multiresistant pathogenic bacteria in hospital settings.Clusters of resistant bacteria from six occasions were investigated. Vancomycin-Resistant Enterococci (VRE), Methicillin-Resistant Staphylococcus pseudintermedius (MSRP), ESBL-producing Escherichia coli and Klebsiella pneumoniae, and carbapenemase-producing Pseudomonas aeruginosa were analysed by a range of methods, from cultures on broth to PCR and whole genome sequencing. Type of resistance, clonality, virulence factors, mobile genetic elements, epidemiology, survival in the environment, and patient history were examined variously depending on study.The results showed that VRE resistance genes can be acquired during treatment with vancomycin. Furthermore, contamination of the hospital environment could quickly cause an outbreak, when patients are frequently relocated and exposition to contaminated rooms increase. Resistant bacteria emerging among companion animals, such as the dog-associated MRSP, can pose a zoonotic threat, when a virulent clone finds a new niche in humans.The ability of Gram-negative bacteria to survive in a hospital environment is probably better than expected, given the right prerequisites; incorrect use of sinks enabled the spread of ESBL-producing K. pneumoniae and carbapenemase-producing P. aeruginosa. Additionally, the survival on hospital associated materials was longer for ESBL-producing E. coli than the AmpC-producing counterpart, which could tell part of why ESBL-producing E. coli is increasing. Hence, the survival in the environment calls for consideration when choosing materials and equipment for hospitals and nursing homes.Exchange of bacteria occurs continuously between humans and our surroundings. Outbreaks of multiresistant bacteria are rare in Sweden but expose the weaknesses in healthcare when occurring. The organization, materials and equipment of hospitals facilitate the dissemination of resistant bacteria, as does animals and humans around us and even the genes in our own microbiota.
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| 3. |
- Tano, Eva, 1957-
(author)
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Survival of infectious agents and detection of their resistance and virulence factors
- 2015
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Doctoral thesis (other academic/artistic)abstract
- In the first study, three different transport systems for bacteria were evaluated. The CLSI M40-A guideline was used to monitor the maintenance of both mono- and polymicrobial samples during a simulated transportation at room temperature that lasted 0-48 h. All systems were able to maintain the viability of all organisms for 24 h, but none of them could support all tested species after 48 h. The most difficult species to recover was Neisseria gonorrhoeae, and in polymicrobial samples overgrowth was an observed problem. The aim of the second study was to study the presence of TSST-1 and three other important toxin genes in invasive isolates of Staphylococcus aureus collected during the years 2000-2012 at two tertiary hospitals. The genes encoding the staphylococcal toxins were detected by PCR, and whole-genome sequencing was used for analyzing the genetic relatedness between isolates. The results showed that the most common toxin was TSST-1, and isolates positive for this toxin exhibited a clear clonality independent of year and hospital. The typical patient was a male aged 55-74 years and with a bone or a joint infection. The third study was a clinical study of the effect of silver-based wound dressings on the bacterial flora in chronic leg ulcers. Phenotypic and genetic silver-resistance were investigated before and after topical silver treatment, by determining the silver nitrate MICs and by detecting sil genes with PCR. The silver-based dressings had a limited effect on primary wound pathogens, and the activity of silver nitrate on S. aureus was mainly bacteriostatic. A silver-resistant Enterobacter cloacae strain was identified after only three weeks of treatment, and cephalosporin-resistant members of the Enterobacteriaceae family were relatively prone to developed silver-resistance after silver exposure in vitro. The last study was undertaken in order to develop an easy-to-use method for simulating the laundering process of hospital textiles, and apply the method when evaluating the decontaminating efficacy of two different washing temperatures. The laundering process took place at professional laundries, and Enterococcus faecium was used as a bioindicator. The results showed that a lowering of the washing temperature from 70°C to 60°C did not affect the decontamination efficacy; the washing cycle alone reduced the number of bacteria with 3-5 log10 CFU, whereas the following tumble drying reduced the bacterial numbers with another 3-4 log10 CFU, yielding the same final result independent of the washing temperature. To ensure that sufficient textile hygiene is maintained, the whole laundering process needs to be monitored. The general conclusion is that all developmental work in the bacterial field requires time and a large strain collection.
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| 4. |
- Tegehall, Angelica, et al.
(author)
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A decisive bridge between innate immunity and the pathognomonic morphological characteristics of type 1 diabetes demonstrated by instillation of heat-inactivated bacteria in the pancreatic duct of rats
- 2022
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In: Acta Diabetologica. - : Springer Nature. - 0940-5429 .- 1432-5233. ; 59:8, s. 1011-1018
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Journal article (peer-reviewed)abstract
- Aims Periductal inflammation and accumulation of granulocytes and monocytes in the periislet area and in the exocrine pancreas is observed within hours after instillation of heat-inactivated bacteria in the ductal compartment of the pancreas in healthy rats. The present investigation was undertaken to study how the acute inflammation developed over time. Methods Immunohistochemical evaluation of the immune response triggered by instillation of heat-inactivated bacteria in the ductal compartment in rats. Results After three weeks, the triggered inflammation had vanished and pancreases showed normal morphology. However, a distinct accumulation of both CD4+ and CD8+ T cells within and adjacent to affected islets was found in one-third of the rats instilled with heat-inactivated E. faecalis, mimicking the insulitis seen at onset of human T1D. As in T1D, this insulitis affected a minority of islets and only certain lobes of the pancreases. Notably, a fraction of the T cells expressed the CD103 antigen, mirroring the recently reported presence of tissue resident memory T cells in the insulitis in humans with recent onset T1D. Conclusions The results presented unravel a previously unknown interplay between innate and acquired immunity in the formation of immunopathological events indistinguishable from those described in humans with recent onset T1D.
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