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Antibiotic resistance gone wild: A One Health perspective on carriage, selection and transmission of Extended-Spectrum Cephalosporinase- and Carbapenemase-producing Enterobacteriaceae
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Josef Järhult)ORCID iD: 0000-0001-7360-5383
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Antibiotics have saved millions of lives since they came into clinical use during the Second World War in the 1940s. Today, our effective use of antibiotics is under great threat due to emerging antibiotic resistance in bacteria. This thesis addresses the problems of antibiotic resistance from a ”One Health” perspective. The focus is on antibiotic resistant Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) in the environment and wildlife, and also considering the situation in healthy humans and livestock. 

In Paper I-III, high occurrence of Extended-Spectrum Beta-Lactamase (ESBL) -producing E. coli and/or K. pneumoniae was detected in fecal samples from wild birds, and the bacteria had genetic similarities to bacteria that cause disease in humans. Proximity to humans was associated with higher occurrence of cephalosporinase (ESBL and pAmpC)-producing E. coli in wild gulls. In Paper IV, ciprofloxacin resistant E. coli was enriched in the gut of mallards exposed to low concentrations of ciprofloxacin, and plasmid conjugation between E. coli bacteria readily took place. In Paper V, carbapenem resistant and blaOXA-48 harbouring- E. coli/K. pneumoniae was rare, but present in healthy humans in rural Cambodia, while cephalosporinase-producing E. coli/K. pneumoniae was common in both humans and livestock. The same ESBL/pAmpC genes were detected in humans and livestock, and exposure to animal manure and slaughter products were risk factors for fecal carriage in humans.

In conclusion, wild birds can function as potential resistance reservoirs and sentinels for antibiotic resistant E. coli. Environmental pollution from humans is the primary source for antibiotic resistant Enterobacteriaceae found in wildlife, but selection for antibiotic resistant bacteria may also occur in wild birds. The results indicate that transmission of cephalosporinase-producing E. coli/K. pneumoniae occur between wildlife, humans and livestock, but more in-depth molecular work is needed to determine the mechanisms of dissemination. The high community carriage of multidrug-resistant bacteria in rural Cambodia is worrying and highlights Southeast Asia as a hotspot for antibiotic resistance. Antibiotic resistance surveillance is biased towards high-income countries and research should be focused more on low- and middle-income countries, and also include the important “One Health” perspective.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. , p. 79
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1617
Keywords [en]
Antibiotic resistance, E. coli, K. pneumoniae, ESBL, AmpC, Carbapenemase, ciprofloxacin resistance, colistin resistance, rural, wildlife, birds, sub-MIC, MSC, Cambodia, environment, epidemiology
National Category
Microbiology in the medical area
Research subject
Infectious Diseases
Identifiers
URN: urn:nbn:se:uu:diva-397218ISBN: 978-91-513-0817-3 (print)OAI: oai:DiVA.org:uu-397218DiVA, id: diva2:1371704
Public defence
2020-01-24, Tripple room, Navet ground floor, BMC, Husargatan 3, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2019-12-18 Created: 2019-11-20 Last updated: 2020-01-13
List of papers
1. ESBL-producing Escherichia coli in Swedish gulls: A case of environmental pollution from humans?
Open this publication in new window or tab >>ESBL-producing Escherichia coli in Swedish gulls: A case of environmental pollution from humans?
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 12, article id e0190380Article in journal (Refereed) Published
Abstract [en]

ESBL-producing bacteria are present in wildlife and the environment might serve as a resistance reservoir. Wild gulls have been described as frequent carriers of ESBL-producing E. coli strains with genotypic characteristics similar to strains found in humans. Therefore, potential dissemination of antibiotic resistance genes and bacteria between the human population and wildlife need to be further investigated. Occurrence and characterization of ESBL-producing E. coli in Swedish wild gulls were assessed and compared to isolates from humans, livestock and surface water collected in the same country and similar time-period. Occurrence of ESBL-producing E. coli in Swedish gulls is about three times higher in gulls compared to Swedish community carriers (17% versus 5%) and the genetic characteristics of the ESBL-producing E. coli population in Swedish wild gulls and Swedish human are similar. ESBL-plasmids IncF-and IncI1-type carrying ESBL-genes blaCTX-M-15 or blaCTX-M-14 were most common in isolates from both gulls and humans, but there was limited evidence of clonal transmission. Isolates from Swedish surface water harbored similar genetic characteristics, which highlights surface waters as potential dissemination routes between wildlife and the human population. Even in a low-prevalence country such as Sweden, the occurrence of ESBL producing E. coli in wild gulls and the human population appears to be connected and the occurrence of ESBL-producing E. coli in Swedish gulls is likely a case of environmental pollution.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2017
National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-340463 (URN)10.1371/journal.pone.0190380 (DOI)000419033400056 ()29284053 (PubMedID)
Available from: 2018-02-15 Created: 2018-02-15 Last updated: 2019-11-20Bibliographically approved
2. High Prevalence and Temporal Variation of Extended Spectrum β-Lactamase–Producing Bacteria in Urban Swedish Mallards
Open this publication in new window or tab >>High Prevalence and Temporal Variation of Extended Spectrum β-Lactamase–Producing Bacteria in Urban Swedish Mallards
2018 (English)In: Microbial Drug Resistance, ISSN 1076-6294, E-ISSN 1931-8448Article in journal (Refereed) Published
Abstract [en]

Antibiotic resistant bacteria present a growing global healthcare challenge. Previous research demonstrates that wild birds harbor extended spectrum -lactamase (ESBL)-producing Enterobacteriaceae and may contribute to their dissemination. We aimed to assess prevalence and temporal variation in the detection rate of ESBL-producing bacteria in urban wild birds and to evaluate methods regarding sample handling. Monthly fecal sampling was performed in 2013 at an urban pond in Sweden. ESBL-producing Escherichia coli and Klebsiella pneumoniae were analyzed by polymerase chain reaction targeting bla(CTX-M). Subsets of samples were analyzed in multiple replicates and without previous freezing. Pond water samples were screened for 12 antibiotics. Out of 813 fecal samples, 47% grew ESBL-producing E. coli, a higher prevalence than in similar studies. Detection rate varied considerably between months, ranging from 4.2% in May to 84% in July, and was significantly higher during warm months. A majority of isolates harbored CTX-M-15 type ESBL. Detection rates were increased by duplicating samples and by avoiding freezing. No antibiotics were detected in pond water. This study demonstrates high prevalence and a previously undescribed temporal variation in detection rate of ESBL-producing Enterobacteriaceae in wild birds. The distribution of CTX-M genes corresponds well with Swedish human isolates, indicating communication between the genetic pools of ESBLs in humans and wild birds. Urban ponds may serve as important natural reservoirs for antimicrobial resistance.

Keywords
Enterobacteriaceae, E.Coli, K. Pneumoniae, antibiotic resistance, wild birds, CTX-M-15
National Category
Microbiology Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-341493 (URN)10.1089/mdr.2017.0263 (DOI)000419439800001 ()
Available from: 2018-02-19 Created: 2018-02-19 Last updated: 2019-11-20Bibliographically approved
3. Increased prevalence of antibiotic resistant E. coli in gulls sampled in Southcentral Alaska is associated with urban environments
Open this publication in new window or tab >>Increased prevalence of antibiotic resistant E. coli in gulls sampled in Southcentral Alaska is associated with urban environments
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2016 (English)In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 6, no 1, article id 32334Article in journal (Refereed) Published
Abstract [en]

Background : Antibiotic-resistant bacteria pose challenges to healthcare delivery systems globally; however, limited information is available regarding the prevalence and spread of such bacteria in the environment. The aim of this study was to compare the prevalence of antibiotic-resistant bacteria in large-bodied gulls ( Larus spp.) at urban and remote locations in Southcentral Alaska to gain inference into the association between antibiotic resistance in wildlife and anthropogenically influenced habitats. Methods : Escherichia coli was cultured ( n 115 isolates) from fecal samples of gulls (n 160) collected from a remote location, Middleton Island, and a more urban setting on the Kenai Peninsula. Results : Screening of E. coli from fecal samples collected from glaucous-winged gulls ( Larus glaucescens )at Middleton Island revealed 8% of isolates were resistant to one or more antibiotics and 2% of the isolates were resistant to three or more antibiotics. In contrast, 55% of E. coli isolates derived from fecal samples collected from large-bodied gulls (i.e. glaucous, herring [ Larus argentatus ], and potentially hybrid gulls) on the Kenai Peninsula were resistant to one or more antibiotics and 22% were resistant to three or more antibiotics. In addition, total of 16% of the gull samples from locations on the Kenai Peninsula harbored extended-spectrum cephalosporin-resistant E. coli isolates (extended-spectrum beta-lactamases [ESBL] and plasmid-encoded AmpC [pAmpC]), in contrast to Middleton Island where no ESBL- or pAmpC-producing isolates were detected. Conclusion : Our findings indicate that increased prevalence of antibiotic resistance is associated with urban environments in Southcentral Alaska and presumably influenced by anthropogenic impacts. Further investigation is warranted to assess how migratory birds may maintain and spread antimicrobial-resistant bacteria of relevance to human and animal health.

Keywords
ESBL, pAmpC, antimicrobial resistance, anthropogenic, gull
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-319621 (URN)10.3402/iee.v6.32334 (DOI)27649798 (PubMedID)
Available from: 2017-04-06 Created: 2017-04-06 Last updated: 2019-11-20Bibliographically approved
4. Spread of resistance plasmids and selection of resistant bacteria among Mallards exposed to sub-inhibitory concentrations of antibiotics in their water environment
Open this publication in new window or tab >>Spread of resistance plasmids and selection of resistant bacteria among Mallards exposed to sub-inhibitory concentrations of antibiotics in their water environment
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(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Research subject
Microbiology
Identifiers
urn:nbn:se:uu:diva-397213 (URN)
Available from: 2019-11-18 Created: 2019-11-18 Last updated: 2019-11-28
5. Carriage of carbapenemase- and extended-spectrum cephalosporinase-producing Escherichia coli and Klebsiella pneumoniae in humans and livestock in rural Cambodia: gender and age differences and detection of blaOXA-48 in humans
Open this publication in new window or tab >>Carriage of carbapenemase- and extended-spectrum cephalosporinase-producing Escherichia coli and Klebsiella pneumoniae in humans and livestock in rural Cambodia: gender and age differences and detection of blaOXA-48 in humans
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2019 (English)In: Zoonoses and Public Health, ISSN 1863-1959, E-ISSN 1863-2378, Vol. 66, no 6, p. 603-617Article in journal (Refereed) Published
Abstract [en]

Objectives: This study investigates the frequency and characteristics of carbapenemase‐producing Escherichia coli/Klebsiella pneumoniae (CPE/K) and extended‐spectrum cephalosporinase‐producing E. coli/K. pneumoniae (ESCE/K) in healthy humans and livestock in rural Cambodia. Additionally, household practices as risk factors for faecal carriage of ESCE/K are identified.

Methods: Faecal samples were obtained from 307 humans and 285 livestock including large ruminants, pigs and poultry living in 100 households in rural Cambodia in 2011. Each household was interviewed, and multilevel logistic model determined associations between household practices/meat consumption and faecal carriage of ESCE/K. CPE and ESCE/K were detected and further screened for colistin resistance genes.

Results: CPE/K isolates harbouring blaOXA‐48 were identified in two humans. The community carriage of ESCE/K was 20% in humans and 23% in livestock. The same ESBL genes: blaCTX‐M‐15, blaCTX‐M‐14, blaCTX‐M‐27, blaCTX‐M‐55, blaSHV‐2, blaSHV‐12, blaSHV‐28; AmpC genes: blaCMY‐2, blaCMY‐42, blaDHA‐1; and colistin resistance genes: mcr‐1‐like and mcr‐3‐like were detected in humans and livestock. ESCE/K was frequently detected in women, young children, pigs and poultry, which are groups in close contact. The practice of burning or burying meat waste and not collecting animal manure indoors and outdoors daily were identified as risk factors for faecal carriage of ESCE/K.

Conclusions: Faecal carriage of E. coli and K. pneumoniae harbouring extended‐spectrum cephalosporinase genes are common in the Cambodian community, especially in women and young children. Exposure to animal manure and slaughter products are risk factors for intestinal colonization of ESCE/K in humans.

 

Keywords
AmpC, Cambodia, ESBL, carbapenemase, colistin, risk factors, rural population, zoonoses
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-388725 (URN)10.1111/zph.12612 (DOI)000473968900001 ()31264805 (PubMedID)
Funder
Swedish Civil Contingencies AgencySida - Swedish International Development Cooperation Agency, 2010-7876Swedish Research Council, 2016-02606
Available from: 2019-07-03 Created: 2019-07-03 Last updated: 2019-11-20Bibliographically approved

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