Browsing by Author "Pitout, Johann D. D."

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    Characterization of Escherichia coli involved in extraintestinal infections among patients in North-western Tanzania: circulating sequence types, risk factors and antimicrobial resistance profiles
    (2018-10-29) Seni, Jeremiah; DeVinney, Rebekah; Pitout, Johann D. D.; Mshana, Stephen Eliatosha; Meer, Franciscus Johannes van der; Schryvers, Anthony Bernard
    Limited information is available regarding the population structure of extraintestinal pathogenic Escherichia coli (ExPEC), and especially ST131 in Africa. Delineation of ExPEC clones among patients in Tanzania is pivotal in guiding antimicrobial therapies and infection preventive measures. A cross sectional analytical study was conducted between 2016 and 2017 in seven health care facilities (HCF) in North-western Tanzania, involving 1,828 pregnant women and 950 children under five years of age. Characterization of 226 ExPEC strains (128 from pregnant women, 15 from children and 83 from other patients) into ST-fimH clones (by the 7SNP-qPCR and gene sequencing), and ST131 clades (by multiplex PCR) was performed. The prevalence of urinary tract infections (UTIs) and blood stream infections (BSIs) among pregnant women and children was 17.7% (95%CI: 16.0-19.5%) and 14.2% (95%CI: 12.1%-16.6%), respectively, with predominance of ExPEC, Klebsiella spp. and Staphylococcus aureus. Third generation cephalosporin resistance (3rd gen Ceph-R) among Enterobacteriaceae was 16.6% (43/259) and 79.0% (75/95), respectively in the two groups; and was significantly higher in strains from a tertiary hospital [OR(95%CI): 3.27(1.02-10.49), p-value=0.046] and [4.95(1.15–21.32), p-value=0.032], among pregnant women and children, respectively compared to lower HCF. Approximately, 64.2% (n=145) of ExPEC strains were typeable using the 7SNP-qPCR and gene sequencing, with predominance of CC10 (33.1%), and ST131-fimH30/41 (17.9%). The 7-SNP qPCR correctly typed all dominant global clones in this ExPEC collection (i.e. ST131-fimH30/41, ST95-fimH41, ST73-fimH9/10 and ST69-fimH27). ST131 clades C1 (9, 34.6%) and C2 (10, 38.5%) predominated, and were associated with fluoroquinolone resistance and 3rd gen Ceph-R, respectively. Extended spectrum beta lactamases in E. coli strains were blaCTX-M-15 (89.8%, n=44), blaCTX-M-27 (n=2), blaCTX-M-24 (n=1), blaCTX-M-14 (n=1) and unknown (n=1). The pulsed field gel electrophoresis displayed heterogeneity among non-typeable strains. There is an increase in multidrug-resistant pathogens in the cascade of the referral health care system, underscoring the need to have level-specific antimicrobial stewardship. The 7-SNP qPCR and multiplex clade PCR are feasible, cost effective and simple molecular tools that can be utilized in surveillance programs to track dominant ExPEC clones, especially in low and middle income countries. This is the first report in Tanzania showing ST131 strains producing blaCTX-M-27.
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    Clinical outcome of empiric antimicrobial therapy of bacteremia due to extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae
    (BioMed Central, 2010-04-27) Chaubey, Vikas P.; Pitout, Johann D. D.; Dalton, Bruce; Ross, Terry; Church, Deirdre L.; Gregson, Daniel B.; Laupland, Kevin B.
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    The Significance of Epidemic Plasmids in the Success of Multidrug-Resistant Drug Pandemic Extraintestinal Pathogenic Escherichia coli
    (2023-03-22) Pitout, Johann D. D.; Chen, Liang
    Abstract Epidemic IncF plasmids have been pivotal in the selective advantage of multidrug-resistant (MDR) extraintestinal pathogenic Escherichia coli (ExPEC). These plasmids have offered several advantages to their hosts that allowed them to coevolve with the bacterial host genomes and played an integral role in the success of ExPEC. IncF plasmids are large, mosaic, and often contain various types of antimicrobial resistance (AMR) and virulence associated factor (VAF) genes. The presence of AMR, VAF genes, several addition/restriction systems combined with truncated transfer regions, led to the fixation of IncF plasmids in certain ExPEC MDR clones, such as ST131 and ST410. IncF plasmids entered the ST131 ancestral lineage in the mid 1900s and different ST131 clade/CTX-M plasmid combinations coevolved over time. The IncF_CTX-M-15/ST131-C2 subclade combination emerged during the early 2000s, spread rapidly across the globe, and is one of the greatest clone/plasmid successes of the millennium. The ST410-B3 subclade containing blaCTX-M-15 incorporated the NDM-5 carbapenemase gene into existing IncF platforms, providing an additional positive selective advantage that included the carbapenems. A “plasmid-replacement” clade scenario occurred in the histories of ST131 and ST410 as different subclades gained different AMR genes on different IncF platforms. The use of antimicrobial agents will generate selection pressures that enhance the risks for the continuous emergence of MDR ExPEC clone/IncF plasmid combinations. The reasons for clade/IncF replacements and associations between certain clades and specific IncF plasmid types are unknown. Such information will aid in designing management and prevention strategies to combat AMR.