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Dissemination of Multiresistant Bacteria: Their Selection, Transmission, Virulence and Resistance
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. , p. 84
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1527
National Category
Infectious Medicine
Research subject
Clinical Bacteriology
Identifiers
URN: urn:nbn:se:uu:diva-369302ISBN: 978-91-513-0537-0 (print)OAI: oai:DiVA.org:uu-369302DiVA, id: diva2:1270320
Public defence
2019-02-15, Jupiter, The Hub, Science Park, Dag Hammarskjölds väg 38, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2019-01-22 Created: 2018-12-12 Last updated: 2019-02-18
List of papers
1. Fatal acquisition of vanD gene during vancomycin treatment of septicaemia caused by Enterococcus faecium
Open this publication in new window or tab >>Fatal acquisition of vanD gene during vancomycin treatment of septicaemia caused by Enterococcus faecium
2016 (English)In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 92, no 4, p. 409-410Article in journal, Letter (Refereed) Published
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-299109 (URN)10.1016/j.jhin.2016.01.002 (DOI)000373282000019 ()26876745 (PubMedID)
Available from: 2016-07-15 Created: 2016-07-14 Last updated: 2018-12-12Bibliographically approved
2. Cluster of Infections Caused by Methicillin-Resistant Staphylococcus pseudintermedius in Humans in a Tertiary Hospital
Open this publication in new window or tab >>Cluster of Infections Caused by Methicillin-Resistant Staphylococcus pseudintermedius in Humans in a Tertiary Hospital
Show others...
2014 (English)In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 52, no 8, p. 3118-3120Article in journal (Refereed) Published
Abstract [en]

The dog-associated Staphylococcus pseudintermedius is a rare pathogen in humans. Here we describe a cluster of infections caused by the methicillin-resistant S. pseudintermedius clone ST71-J-t02-II-III. It involved four elderly patients at a tertiary hospital. Three patients had wound infections, and the strain had a tendency to cause bullous skin lesions.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:uu:diva-231237 (URN)10.1128/JCM.00703-14 (DOI)000339544200062 ()
Available from: 2014-09-08 Created: 2014-09-05 Last updated: 2018-12-12Bibliographically approved
3. The Initial Epidemiology of a Major Clonal Outbreak Caused by VanB-Carrying Enterococcus faecium Clone ST192
Open this publication in new window or tab >>The Initial Epidemiology of a Major Clonal Outbreak Caused by VanB-Carrying Enterococcus faecium Clone ST192
(English)Manuscript (preprint) (Other academic)
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-369413 (URN)
Available from: 2018-12-12 Created: 2018-12-12 Last updated: 2018-12-12
4. Minor outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in an intensive care unit due to a contaminated sink
Open this publication in new window or tab >>Minor outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in an intensive care unit due to a contaminated sink
2012 (English)In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 82, no 2, p. 122-124Article in journal (Refereed) Published
Abstract [en]

During a period of seven months four patients on the neurosurgical intensive care unit at a tertiary care hospital in Sweden became infected or colonized by an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain. The investigation revealed that the source of the outbreak was a contaminated sink. By replacing the sink and its plumbing and improving routines regarding sink practices, the outbreak was successfully controlled.

Keywords
Environmental source, Extended-spectrum, beta-lactamase, Klebsiella pneumoniae, Outbreak
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-183561 (URN)10.1016/j.jhin.2012.07.004 (DOI)000309045400007 ()
Available from: 2012-12-07 Created: 2012-10-29 Last updated: 2018-12-12Bibliographically approved
5. The first Swedish outbreak with VIM-2-producing Pseudomonas aeruginosa was prolonged and probably due to contaminated hospital sinks
Open this publication in new window or tab >>The first Swedish outbreak with VIM-2-producing Pseudomonas aeruginosa was prolonged and probably due to contaminated hospital sinks
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa is an increasing clinical problem worldwide. VIM-2 is the predominant enzyme, and it has been linked to several outbreaks. During the spring of 2006, a cluster of patients were colonized or infected with multiresistant Pseudomonas aeruginosa at two neighbouring hospitals in southeast Sweden.

Aim: To describe the first documented outbreak of a VIM-2-producing P. aeruginosa strain in Sweden.

Methods: The isolates were characterized with PCR, pulse-field gel electrophoresis (PFGE), and whole genome sequencing. Patient charts, laboratory records and hygiene routines were reviewed, and patients, staff and the environment were screened.

Findings: The investigation revealed that it was a clonal outbreak of a VIM-2-producing P. aeruginosa strain susceptible only to gentamicin and colistin. It belonged to the high-risk clonal complex 111. No direct contact between patients could be established, but most of them had stayed in the same room/wards with weeks to months apart. Environmental cultures from two sinks yielded growth of P. aeruginosa with the same PFGE-pattern as the patient isolates. The outbreak ended when control measures against the sinks were taken.

Conclusions: Contaminated hospital sinks were the probable reservoir in the first nosocomial outbreak of MBL-producing P. aeruginosa in Sweden. When facing prolonged outbreaks with this bacterium, sinks and other water sources in the hospital environment should be considered. By implementing proactive control measures to limit the bacterial load in sinks and plumbing systems, the waterborne transmission of P. aeruginosa could probably be reduced.

National Category
Infectious Medicine
Research subject
Clinical Bacteriology
Identifiers
urn:nbn:se:uu:diva-369296 (URN)
Available from: 2018-12-11 Created: 2018-12-11 Last updated: 2018-12-12
6. Survival in the environment is a possible key factor for the expansion of Escherichia coli strains producing extended-spectrum beta-lactamases
Open this publication in new window or tab >>Survival in the environment is a possible key factor for the expansion of Escherichia coli strains producing extended-spectrum beta-lactamases
2014 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 1, p. 59-67Article in journal (Refereed) Published
Abstract [en]

Acquired resistance to cephalosporins in Enterobacteriaceae is a global problem. After an outbreak at Uppsala University Hospital of extended-spectrum -lactamase (ESBL)-positive Klebsiella pneumoniae producing CTX-M-15, there was a shift from AmpC to ESBL production among Escherichia coli isolates. To explore the basis for this epidemiological shift, 46 E. coli isolates (ESBLs, n=23; AmpC, n=23) were characterized with regard to genetic relatedness, -lactamase, replicon and integron types, antibiotic resistance profiles, and genes encoding virulence factors. In addition, the survival in the environment and on hospital-associated materials was analysed. CTX-M-15 was the most frequent ESBL (78%). Only three (13%) of the AmpC enzymes were harboured on plasmids (CMY-2, DHA-1). Independent of plasmid-mediated beta-lactamase, IncF plasmids predominated and only class I integrons were detected. The ESBL producers carried more virulence genes (p=0.04), exhibited a broader resistance phenotype (p=0.01) and survived significantly longer (p=0.03) on different materials than the AmpC-producing isolates. In conclusion, ESBL-producing isolates had properties which are likely to augment their competitiveness. Apart from antibiotic resistance and virulence factors, extended survival in the environment could be a selective trait for successful ESBL-producing E. coli strains.

Keywords
E-coli, AmpC, ESBL, environment, virulence genes, plasmids
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-216726 (URN)10.1111/apm.12102 (DOI)000328909100008 ()
Available from: 2014-01-27 Created: 2014-01-24 Last updated: 2018-12-12Bibliographically approved
7. Lack of hygiene routines among patients and family members at patient hotels - a possible route for transmitting puerperal fever
Open this publication in new window or tab >>Lack of hygiene routines among patients and family members at patient hotels - a possible route for transmitting puerperal fever
2010 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 42, p. 554-556Article in journal (Refereed) Published
Abstract [en]

The use of patient hotels for ambulatory care of women with uncomplicated deliveries has become a routine in Sweden. This report describes a minor outbreak of a group A Streptococcus strain in 2 newly delivered mothers and their newborn babies at a patient hotel.

National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-366358 (URN)10.3109/00365541003699656 (DOI)
Available from: 2018-11-20 Created: 2018-11-20 Last updated: 2018-12-12
8. First documented case of a Staphylococcus lugdunensis strain carrying the mecA gene in Northern Europe
Open this publication in new window or tab >>First documented case of a Staphylococcus lugdunensis strain carrying the mecA gene in Northern Europe
2011 (English)In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 1, p. 8410-Article in journal (Refereed) Published
Abstract [en]

Staphylococcus lugdunensis is a clinically common wound pathogen belonging to coagulase-negative staphylococci. We herein report the first case of a S. lugdunensis isolate carrying the mecA gene in Northern Europe.

National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-248751 (URN)10.3402/iee.v1i0.8410 (DOI)22957119 (PubMedID)
Available from: 2015-04-08 Created: 2015-04-08 Last updated: 2018-12-12Bibliographically approved

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