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Rachel A. Hickman
Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, 27272, UAE

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Discussion
Published: 01 December 2020 in Journal of Global Antimicrobial Resistance
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The emergence of antimicrobial-resistant, livestock-associated Escherichia coli represents a great public health concern. Here, we report the draft genome sequences of two multidrug-resistant, livestock-associated E. coli strains isolated from sheep in South Africa. The genomic DNA of E. coli strains MEZEC8 and MEZEC10 was sequenced using an Illumina MiSeq platform. Generated reads were trimmed and de novo assembled. The assembled contigs were analyzed for antimicrobial resistance genes and chromosomal mutations, extra-chromosomal plasmids and multi-locus sequence type (MLST). To compare the strains MEZEC8 and MEZEC10 to other previously sequenced E. coli strains, raw read sequences of E. coli from livestock were downloaded from NCBI’s sequence read archive, and all sequence files were treated identically to generate a core genome bootstrapped maximum likelihood phylogenetic tree. Multidrug resistance genes were detected in both MEZEC8 and MEZEC10 toward tetracycline and macrolides. MEZEC10 harbored two extra-chromosomal plasmids (p0111 and Incl2) while MEZ8 did not contain any extrachromosomal plasmids. MEZEC8 and MEZEC10 serotypes were H25:O9 and H49:O8 respectively, and MEZEC8 belonged to ST58 and MEZEC10 belonged to ST1844. The genome sequences of strains MEZEC8 and MEZEC10 will serve as a reference point for molecular epidemiological studies of livestock-associated antibiotic-resistant E. coli in Africa. In addition, this study allows in-depth analysis of genomic structure and will provide valuable information that enable us understand the antimicrobial resistance of livestock associated E. coli.

ACS Style

Ahmed E. El Zowalaty; Rachel A. Hickman; Sydney M. Gambushe; Oliver T. Zishiri; Josef D. Järhult. Genome sequences of two multidrug-resistant Escherichia coli strains MEZEC8 and MEZEC10 isolated from livestock in South Africa. Journal of Global Antimicrobial Resistance 2020, 23, 445 -449.

AMA Style

Ahmed E. El Zowalaty, Rachel A. Hickman, Sydney M. Gambushe, Oliver T. Zishiri, Josef D. Järhult. Genome sequences of two multidrug-resistant Escherichia coli strains MEZEC8 and MEZEC10 isolated from livestock in South Africa. Journal of Global Antimicrobial Resistance. 2020; 23 ():445-449.

Chicago/Turabian Style

Ahmed E. El Zowalaty; Rachel A. Hickman; Sydney M. Gambushe; Oliver T. Zishiri; Josef D. Järhult. 2020. "Genome sequences of two multidrug-resistant Escherichia coli strains MEZEC8 and MEZEC10 isolated from livestock in South Africa." Journal of Global Antimicrobial Resistance 23, no. : 445-449.

Journal article
Published: 21 November 2020 in Antibiotics
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Monitoring antimicrobial resistance (AMR) and use (AMU) is important for control. We used Escherichia coli from healthy young calves as an indicator to evaluate whether AMR patterns differ between Swedish organic and conventional dairy herds and whether the patterns could be related to AMU data. Samples were taken twice, in 30 organic and 30 conventional dairy herds. Selective culturing for Escherichia coli, without antibiotics and with nalidixic acid or tetracycline, was used to estimate the proportions of resistant isolates. Microdilution was used to determine the minimum inhibitory concentrations (MICs) for thirteen antimicrobial substances. AMU data were based on collection of empty drug packages. Less than 8% of the bacterial growth on non-selective plates was also found on selective plates with tetracycline, and 1% on plates with nalidixic acid. Despite some MIC variations, resistance patterns were largely similar in both periods, and between organic and conventional herds. For most substances, only a few isolates were classified as resistant. The most common resistances were against ampicillin, streptomycin, sulfamethoxazole, and tetracycline. No clear association with AMU could be found. The lack of difference between organic and conventional herds is likely due to a generally good animal health status and consequent low AMU in both categories.

ACS Style

Karin Sjöström; Rachel A. Hickman; Viktoria Tepper; Gabriela Olmos Antillón; Josef D. Järhult; Ulf Emanuelson; Nils Fall; Susanna Sternberg Lewerin. Antimicrobial Resistance Patterns in Organic and Conventional Dairy Herds in Sweden. Antibiotics 2020, 9, 834 .

AMA Style

Karin Sjöström, Rachel A. Hickman, Viktoria Tepper, Gabriela Olmos Antillón, Josef D. Järhult, Ulf Emanuelson, Nils Fall, Susanna Sternberg Lewerin. Antimicrobial Resistance Patterns in Organic and Conventional Dairy Herds in Sweden. Antibiotics. 2020; 9 (11):834.

Chicago/Turabian Style

Karin Sjöström; Rachel A. Hickman; Viktoria Tepper; Gabriela Olmos Antillón; Josef D. Järhult; Ulf Emanuelson; Nils Fall; Susanna Sternberg Lewerin. 2020. "Antimicrobial Resistance Patterns in Organic and Conventional Dairy Herds in Sweden." Antibiotics 9, no. 11: 834.

Journal article
Published: 30 September 2020 in Antibiotics
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The overall aim of the current study was to test the hypotheses that (i) antibiotic resistance in bacteria were more frequent in clinically health pigs in intensified company owned, medium-scale farms (MSFs) (100–500 sows) than in pigs in family-owned, small-scale farms (SSFs) (1–50 sows) and (ii) that farmers working at the MSFs were more prone to attain antibiotic resistant bacteria than farmers working at SSFs. The study was conducted in North-Eastern Thailand, comprising fecal Escherichia coli isolates from pigs, farmers working with the pigs (contact humans) and persons living in the same household as the farmer (non-contact humans) at 51 MSFs and 113 SSFs. Samples from all farms were also screened for methicillin-resistant staphylococcus aureus (MRSA), which was not detected in pig samples, but was found in one human sample. Susceptibility was tested by disc-diffusion for seven antibiotics commonly used in the study area. Resistance in pig isolates from MSFs were more frequent for chloramphenicol which (P < 0.001), trimethoprim/sulfamethoxazole (P < 0.001) and gentamicin (P < 0.05) compared with isolates from SSFs, whereas the opposite was true for tetracycline (P < 0.01). Resistance in the human isolates was lower than those in the isolates from pigs for tetracycline, trimethoprim/sulfamethoxazole and chloramphenicol (P < 0.001). The frequency of resistance in the contact human samples from SSFs and MSFs did not differ. There was no difference between isolates from contact and non-contact humans for any of the tested antibiotics. Multidrug resistance in isolates from pigs was 26%, significantly higher (P < 0.01) than the 13% from humans. The data indicate that (i) resistance to antibiotics, including those critical and highly important for human medicine, were more common in fecal E. coli from pigs at the MSFs than at the SSFs, whereas (ii) the resistance in fecal E. coli from pig farmers seemed not to be influenced by the level of intensification of the farm they were working at.

ACS Style

Kamonwan Lunha; Thongpan Leangapichart; Jatesada Jiwakanon; Sunpetch Angkititrakul; Marianne Sunde; Josef D. Järhult; Gunilla Ström Hallenberg; Rachel A. Hickman; Thomas Van Boeckel; Ulf Magnusson. Antimicrobial Resistance in Fecal Escherichia coli from Humans and Pigs at Farms at Different Levels of Intensification. Antibiotics 2020, 9, 662 .

AMA Style

Kamonwan Lunha, Thongpan Leangapichart, Jatesada Jiwakanon, Sunpetch Angkititrakul, Marianne Sunde, Josef D. Järhult, Gunilla Ström Hallenberg, Rachel A. Hickman, Thomas Van Boeckel, Ulf Magnusson. Antimicrobial Resistance in Fecal Escherichia coli from Humans and Pigs at Farms at Different Levels of Intensification. Antibiotics. 2020; 9 (10):662.

Chicago/Turabian Style

Kamonwan Lunha; Thongpan Leangapichart; Jatesada Jiwakanon; Sunpetch Angkititrakul; Marianne Sunde; Josef D. Järhult; Gunilla Ström Hallenberg; Rachel A. Hickman; Thomas Van Boeckel; Ulf Magnusson. 2020. "Antimicrobial Resistance in Fecal Escherichia coli from Humans and Pigs at Farms at Different Levels of Intensification." Antibiotics 9, no. 10: 662.

Journal article
Published: 14 September 2020 in Viruses
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Background: During the COVID-19 pandemic, the virus evolved, and we therefore aimed to provide an insight into which genetic variants were enriched, and how they spread in Sweden. Methods: We analyzed 348 Swedish SARS-CoV-2 sequences freely available from GISAID obtained from 7 February 2020 until 14 May 2020. Results: We identified 14 variant sites ≥5% frequency in the population. Among those sites, the D936Y substitution in the viral Spike protein was under positive selection. The variant sites can distinguish 11 mutational profiles in Sweden. Nine of the profiles appeared in Stockholm in March 2020. Mutational profiles 3 (B.1.1) and 6 (B.1), which contain the D936Y mutation, became the predominant profiles over time, spreading from Stockholm to other Swedish regions during April and the beginning of May. Furthermore, Bayesian phylogenetic analysis indicated that SARS-CoV-2 could have emerged in Sweden on 27 December 2019, and community transmission started on February 1st with an evolutionary rate of 1.5425 × 10−3 substitutions per year. Conclusions: Our study provides novel knowledge on the spatio-temporal dynamics of Swedish SARS-CoV-2 variants during the early pandemic. Characterization of these viral variants can provide precious insights on viral pathogenesis and can be valuable for diagnostic and drug development approaches.

ACS Style

Jiaxin Ling; Rachel A. Hickman; Jinlin Li; Xi Lu; Johanna F. Lindahl; Åke Lundkvist; Josef D. Järhult. Spatio-Temporal Mutational Profile Appearances of Swedish SARS-CoV-2 During the Early Pandemic. Viruses 2020, 12, 1026 .

AMA Style

Jiaxin Ling, Rachel A. Hickman, Jinlin Li, Xi Lu, Johanna F. Lindahl, Åke Lundkvist, Josef D. Järhult. Spatio-Temporal Mutational Profile Appearances of Swedish SARS-CoV-2 During the Early Pandemic. Viruses. 2020; 12 (9):1026.

Chicago/Turabian Style

Jiaxin Ling; Rachel A. Hickman; Jinlin Li; Xi Lu; Johanna F. Lindahl; Åke Lundkvist; Josef D. Järhult. 2020. "Spatio-Temporal Mutational Profile Appearances of Swedish SARS-CoV-2 During the Early Pandemic." Viruses 12, no. 9: 1026.

Discussion
Published: 01 June 2020 in Journal of Global Antimicrobial Resistance
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Antimicrobial-resistant and livestock-associated Salmonella enterica infections pose a significant public health threat worldwide. Here, we report for the first time the draft genome sequences of two multidrug-resistant and livestock-associated S. enterica strains isolated from a chicken and a cow in South Africa. Genomic DNA of S. enterica strains MEZSAL74 and MEZSAL81 was sequenced using an Illumina MiSeq platform. Generated reads were trimmed and de novo assembled. The assembled contigs were analyzed for antimicrobial resistance genes and chromosomal mutations, extra-chromosomal plasmids and multi-locus sequence type (MLST). To compare bacterial isolates MEZSAL74 and MEZSAL81 to other previously sequenced S. enterica isolates, raw read sequences were downloaded, and all sequence files were treated identically to generate a bootstrapped maximum likelihood phylogenetic tree. Extra-chromosomal plasmids and genetic determinants for antibiotic resistance were detected in both sequenced bacterial isolates toward aminoglycosides and fluoroquinolones. MEZSAL74 belonged to an unknown MLST type and MEZSAL81 to ST33. The genome sequences of strains MEZSAl74 and MEZSAL 81 reported will serve as a reference point for molecular epidemiological studies of livestock-associated and antibiotic-resistant S. enterica in Africa.

ACS Style

Mohamed E. El Zowalaty; Rachel Hickman; Thobeka P. Mthembu; Oliver Zishiri; Josef D. Järhult. Genome sequences of two Salmonella enterica strains (MEZSAL74 and MEZSAL81) harbouring multiple antimicrobial resistance genes isolated from livestock in South Africa. Journal of Global Antimicrobial Resistance 2020, 21, 396 -398.

AMA Style

Mohamed E. El Zowalaty, Rachel Hickman, Thobeka P. Mthembu, Oliver Zishiri, Josef D. Järhult. Genome sequences of two Salmonella enterica strains (MEZSAL74 and MEZSAL81) harbouring multiple antimicrobial resistance genes isolated from livestock in South Africa. Journal of Global Antimicrobial Resistance. 2020; 21 ():396-398.

Chicago/Turabian Style

Mohamed E. El Zowalaty; Rachel Hickman; Thobeka P. Mthembu; Oliver Zishiri; Josef D. Järhult. 2020. "Genome sequences of two Salmonella enterica strains (MEZSAL74 and MEZSAL81) harbouring multiple antimicrobial resistance genes isolated from livestock in South Africa." Journal of Global Antimicrobial Resistance 21, no. : 396-398.

Article
Published: 31 October 2019 in Microbiology Resource Announcements
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Here, we report the draft genome sequence of Listeria innocua strain MEZLIS26, isolated from a healthy goat in Flagstaff, Eastern Cape Province, South Africa. The genome was sequenced using the Illumina MiSeq platform and had a length of 2,800,777 bp, with a G+C content of 37.4%, 2,755 coding DNA sequences (CDSs), 49 transfer RNAs (tRNAs), and 4 noncoding RNAs (ncRNAs).

ACS Style

Mohamed E. El Zowalaty; Rachel A. Hickman; Alexandra Moura; Marc Lecuit; Oliver T. Zishiri; Noelle Noyes; Josef D. Järhult. Genome Sequence of Listeria innocua Strain MEZLIS26, Isolated from a Goat in South Africa. Microbiology Resource Announcements 2019, 8, 1 .

AMA Style

Mohamed E. El Zowalaty, Rachel A. Hickman, Alexandra Moura, Marc Lecuit, Oliver T. Zishiri, Noelle Noyes, Josef D. Järhult. Genome Sequence of Listeria innocua Strain MEZLIS26, Isolated from a Goat in South Africa. Microbiology Resource Announcements. 2019; 8 (44):1.

Chicago/Turabian Style

Mohamed E. El Zowalaty; Rachel A. Hickman; Alexandra Moura; Marc Lecuit; Oliver T. Zishiri; Noelle Noyes; Josef D. Järhult. 2019. "Genome Sequence of Listeria innocua Strain MEZLIS26, Isolated from a Goat in South Africa." Microbiology Resource Announcements 8, no. 44: 1.

Original research article
Published: 24 May 2017 in Frontiers in Microbiology
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Understanding the evolutionary processes that lead to antibiotic resistance can help to achieve better treatment strategies. Yet, little is known about the dynamics of the resistance alleles during adaptation. Here, we use population sequencing to monitor genetic changes in putative resistance loci at several time-points during adaptive evolution experiments involving five different antibiotic conditions. We monitor the mutational spectra in lineages evolved to be resistant to single antibiotics (amikacin, chloramphenicol and ciprofloxacin), as well as antibiotic combinations (amikacin + chloramphenicol and chloramphenicol + ciprofloxacin). We find that lineages evolved to antibiotic combinations exhibit different resistance allele dynamics compared with those of single-drug evolved lineages, especially for a drug pair with reciprocal collateral sensitivity. During adaptation we observed interfering, superimposing and fixation allele dynamics. To further understand the selective forces driving specific allele dynamics, a subset of mutations were introduced into the ancestral wild type enabling differentiation between clonal interference and negative epistasis.

ACS Style

Rachel Hickman; Christian Munck; Morten Otto Alexander Sommer. Time-Resolved Tracking of Mutations Reveals Diverse Allele Dynamics during Escherichia coli Antimicrobial Adaptive Evolution to Single Drugs and Drug Pairs. Frontiers in Microbiology 2017, 8, 893 .

AMA Style

Rachel Hickman, Christian Munck, Morten Otto Alexander Sommer. Time-Resolved Tracking of Mutations Reveals Diverse Allele Dynamics during Escherichia coli Antimicrobial Adaptive Evolution to Single Drugs and Drug Pairs. Frontiers in Microbiology. 2017; 8 ():893.

Chicago/Turabian Style

Rachel Hickman; Christian Munck; Morten Otto Alexander Sommer. 2017. "Time-Resolved Tracking of Mutations Reveals Diverse Allele Dynamics during Escherichia coli Antimicrobial Adaptive Evolution to Single Drugs and Drug Pairs." Frontiers in Microbiology 8, no. : 893.

Journal article
Published: 12 August 2016 in Public Health
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Infectious gastroenteritis is one of the most common diseases among children and has a considerable impact on health and socio-economy. Day care centres are high-risk environments for infections. The aim of this study was to investigate if asymptomatic preschool children constitute a reservoir for potential enteropathogens. In total, 438 individual diapers were collected from day care centres in Uppsala, Sweden, during spring and autumn, and molecular techniques were used to estimate the prevalence of asymptomatic carriage of multiple enteropathogens. Faecal samples were analysed with multiplex polymerase chain reaction (PCR) (xTAG® Gastrointestinal Pathogen Panel; Luminex Corporation, Toronto, Canada) targeting 21 different pathogens. Samples with a median fluorescence intensity above threshold were re-analysed with a second PCR assay. Sixteen of the 438 samples were positive for enteropathogens, 1.6% for enteric adenovirus, 0.7% for Campylobacter spp., and 0.7% for norovirus. Preschool children in Uppsala constitute a limited reservoir for potential enteropathogens.

ACS Style

J. Kaarme; Rachel Hickman; T. Nevéus; J. Blomberg; C. Öhrmalm. Reassuringly low carriage of enteropathogens among healthy Swedish children in day care centres. Public Health 2016, 140, 221 -227.

AMA Style

J. Kaarme, Rachel Hickman, T. Nevéus, J. Blomberg, C. Öhrmalm. Reassuringly low carriage of enteropathogens among healthy Swedish children in day care centres. Public Health. 2016; 140 ():221-227.

Chicago/Turabian Style

J. Kaarme; Rachel Hickman; T. Nevéus; J. Blomberg; C. Öhrmalm. 2016. "Reassuringly low carriage of enteropathogens among healthy Swedish children in day care centres." Public Health 140, no. : 221-227.

Journal article
Published: 01 April 2014 in Clinical Microbiology and Infection
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The increasing prevalence of hospital and community-acquired infections caused by multidrug-resistant (MDR) bacterial pathogens is rapidly limiting the options for effective antibiotic therapy. Systematic studies on combinations of already available antibiotics that could provide an effective treatment against MDR bacteria are needed. We tested combinations of antibiotics that target one important physiological function (peptidoglycan synthesis) at several steps, and studied Enterobacteriaceae (Klebsiella pneumoniae and Escherichia coli) for which multidrug resistance associated with ESBL-producing plasmids has become a major problem. To measure the effectiveness of antibiotics alone and in combination, we used checkerboard assays, static antibiotic concentration time-kill assays, and an improved in-vitro kinetic model that simulates human pharmacokinetics of multiple simultaneously administered antibiotics. The target strains included an MDR K. pneumoniae isolate responsible for a recent major hospital outbreak. A double combination (fosfomycin and aztreonam) and a triple combination (fosfomycin, aztreonam and mecillinam) were both highly effective in reducing bacterial populations in all assays, including the in vitro kinetic model. These combinations were effective even though each of the MDR strains was resistant to aztreonam alone. Our results provide an initial validation of the potential usefulness of a combination of antibiotics targeting peptidoglycan synthesis in the treatment of MDR Gram-negative bacteria. We suggest that a combination of fosfomycin with aztreonam could become a useful treatment option for such infections and should be further studied.

ACS Style

Rachel Hickman; D. Hughes; T. Cars; C. Malmberg; O. Cars. Cell-wall-inhibiting antibiotic combinations with activity against multidrug-resistant Klebsiella pneumoniae and Escherichia coli. Clinical Microbiology and Infection 2014, 20, O267 -O273.

AMA Style

Rachel Hickman, D. Hughes, T. Cars, C. Malmberg, O. Cars. Cell-wall-inhibiting antibiotic combinations with activity against multidrug-resistant Klebsiella pneumoniae and Escherichia coli. Clinical Microbiology and Infection. 2014; 20 (4):O267-O273.

Chicago/Turabian Style

Rachel Hickman; D. Hughes; T. Cars; C. Malmberg; O. Cars. 2014. "Cell-wall-inhibiting antibiotic combinations with activity against multidrug-resistant Klebsiella pneumoniae and Escherichia coli." Clinical Microbiology and Infection 20, no. 4: O267-O273.

Journal article
Published: 06 January 2014 in Antimicrobial Agents and Chemotherapy
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Combination therapy is recommended for infections with carbapenemase-producingKlebsiella pneumoniae. However, limited data exist on which antibiotic combinations are the most effective. The aim of this study was to find effective antibiotic combinations against metallo-beta-lactamase-producingK. pneumoniae(MBL-KP). Two VIM- and two NDM-producingK. pneumoniaestrains, all susceptible to colistin, were exposed to antibiotics at clinically relevant static concentrations during 24-h time-kill experiments. Double- and triple-antibiotic combinations of aztreonam, ciprofloxacin, colistin, daptomycin, fosfomycin, meropenem, rifampin, telavancin, tigecycline, and vancomycin were used. Synergy was defined as a ≥2 log10decrease in CFU/ml between the combination and its most active drug after 24 h, and bactericidal effect was defined as a ≥3 log10decrease in CFU/ml after 24 h compared with the starting inoculum. Synergistic or bactericidal activity was demonstrated for aztreonam, fosfomycin, meropenem, and rifampin in double-antibiotic combinations with colistin and also for aztreonam, fosfomycin, and rifampin in triple-antibiotic combinations with meropenem and colistin. Overall, the combination of rifampin-meropenem-colistin was the most effective regimen, demonstrating synergistic and bactericidal effects against all four strains. Meropenem-colistin, meropenem-fosfomycin, and tigecycline-colistin combinations were not bactericidal against the strains used. The findings of this and other studies indicate that there is great potential of antibiotic combinations against carbapenemase-producingK. pneumoniae. However, our results deviate to some extent from those of previous studies, which might be because most studies to date have included KPC-producing rather than MBL-producing strains. More studies addressing MBL-KP are needed.

ACS Style

T. Tängdén; R. A. Hickman; P. Forsberg; P. Lagerbäck; C. G. Giske; O. Cars. Evaluation of Double- and Triple-Antibiotic Combinations for VIM- and NDM-Producing Klebsiella pneumoniae byIn VitroTime-Kill Experiments. Antimicrobial Agents and Chemotherapy 2014, 58, 1757 -1762.

AMA Style

T. Tängdén, R. A. Hickman, P. Forsberg, P. Lagerbäck, C. G. Giske, O. Cars. Evaluation of Double- and Triple-Antibiotic Combinations for VIM- and NDM-Producing Klebsiella pneumoniae byIn VitroTime-Kill Experiments. Antimicrobial Agents and Chemotherapy. 2014; 58 (3):1757-1762.

Chicago/Turabian Style

T. Tängdén; R. A. Hickman; P. Forsberg; P. Lagerbäck; C. G. Giske; O. Cars. 2014. "Evaluation of Double- and Triple-Antibiotic Combinations for VIM- and NDM-Producing Klebsiella pneumoniae byIn VitroTime-Kill Experiments." Antimicrobial Agents and Chemotherapy 58, no. 3: 1757-1762.