Concurrence of Porin Loss and Modular Amplification of β-Lactamase Encoding Genes Drives Carbapenem Resistance in a Cohort of Recurrent <i>Enterobacterales</i> Bacteremia

Shropshire, William C; Aitken, Samuel L; Pifer, Reed; Kim, Jiwoong; Bhatti, Micah M.; Li, Xiqi; Kalia, Awdhesh; Galloway-Peña, Jessica; Sahasrabhojane, Pranoti; Arias, César A.; Greenberg, David E.; Hanson, Blake; Shelburne, Samuel A.

doi:10.1101/616961

Cited by 5 publications

(4 citation statements)

References 69 publications

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“…Each assembly was aligned using minimap2 to databases of known serotypes, fimH type, genomic and plasmid sequence types including plasmid incompatibility, virulence factors, and antimicrobial resistance genes, listed in Table S1 (available in the online version of this article) [35][36][37][38][39][40]. Matches were made for each assembly using similar cutoffs to those used by the Centre for Genomic Epidemiology (CGE; https:// cge.…”

Section: Typing Of Isolatesmentioning

confidence: 99%

Genomic epidemiology of Escherichia coli isolates from a tertiary referral center in Lilongwe, Malawi

Tegha¹,

Ciccone²,

Krysiak³

et al. 2021

Microbial Genomics

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Antimicrobial resistance (AMR) is a global threat, including in sub-Saharan Africa. However, little is known about the genetics of resistant bacteria in the region. In Malawi, there is growing concern about increasing rates of antimicrobial resistance to most empirically used antimicrobials. The highly drug resistant Escherichia coli sequence type (ST) 131, which is associated with the extended spectrum β-lactamase blaCTX-M-15 , has been increasing in prevalence globally. Previous data from isolates collected between 2006 and 2013 in southern Malawi have revealed the presence of ST131 and the blaCTX-M-15 gene in the country. We performed whole genome sequencing (WGS) of 58 clinical E. coli isolates at Kamuzu Central Hospital, a tertiary care centre in central Malawi, collected from 2012 to 2018. We used Oxford Nanopore Technologies (ONT) sequencing, which was performed in Malawi. We show that ST131 is observed more often (14.9% increasing to 32.8%) and that the blaCTX-M-15 gene is occurring at a higher frequency (21.3% increasing to 44.8%). Phylogenetics indicates that isolates are highly related between the central and southern geographic regions and confirms that ST131 isolates are contained in a single group. All AMR genes, including blaCTX-M-15 , were widely distributed across sequence types. We also identified an increased number of ST410 isolates, which in this study tend to carry a plasmid-located copy of blaCTX-M-15 gene at a higher frequency than blaCTX-M-15 occurs in ST131. This study confirms the expanding nature of ST131 and the wide distribution of the blaCTX-M-15 gene in Malawi. We also highlight the feasibility of conducting longitudinal genomic epidemiology studies of important bacteria with the sequencing done on site using a nanopore platform that requires minimal infrastructure.

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Section: Typing Of Isolatesmentioning

confidence: 99%

Genomic epidemiology of Escherichia coli isolates from a tertiary referral center in Lilongwe, Malawi

Tegha¹,

Ciccone²,

Krysiak³

et al. 2021

Microbial Genomics

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show abstract

“…[31,32] Typing of isolates : Each assembly was aligned using minimap2 to databases of known serotypes, genomic and plasmid sequence types including plasmid incompatibility, virulence factors, and antimicrobial resistance genes, listed in Supplemental Table 1 . [33][34][35][36][37][38] Matches were made for each assembly using similar cutoffs to those used by the Center for Genomic Epidemiology (CGE; https://cge.cbs.dtu.dk/services/data.php ) tools, where at least 60% of the feature must match at >90% sequence identity.…”

Section: Sample Selectionmentioning

confidence: 99%

Genomic Epidemiology of Escherichia coli Isolates from a Tertiary Referral Center in Lilongwe, Malawi

Tegha¹,

Ciccone

Krysiak³

et al. 2020

Preprint

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Antimicrobial resistance (AMR) is a global threat, including in sub-Saharan Africa. However, little is known about the genetics of resistant bacteria in the region. In Malawi, there is growing concern about increasing rates of antimicrobial resistance to most empirically used antimicrobials. The highly drug resistant Escherichia coli sequence type (ST) 131, which is associated with the extended spectrum β-lactamase bla , has been increasing in prevalence globally. Previous data from isolates collected between 2006-2013 in southern Malawi have shown the presence of ST131 and the bla CTX-M-15 gene in the country. We performed whole genome sequencing (WGS) of 58 clinical E. coli isolates at Kamuzu Central Hospital, a tertiary care center in central Malawi, collected from 2012-2018. We used Oxford Nanopore Technologies (ONT) sequencing, which was performed in Malawi. We show that ST131 has become more prevalent (14.9% increasing to 32.8%) and that the bla gene is occurring at a higher frequency (21.3% increasing to 44.8%). Phylogenetics show isolates are highly related between the central and southern geographic regions and confirm that ST131isolates are contained in a single group consistent with recent expansion. All AMR genes, including bla CTX-M-15 , were widely distributed across sequence types. We also identified an increased number of ST410 isolates, which in this study tend to carry a plasmid-located copy of bla gene at a higher frequency than bla occurs in ST131. This study confirms the expanding nature of ST131 and the wide distribution of the bla gene in Malawi. We also highlight the feasibility of conducting longitudinal genomic epidemiology studies of important bacteria with the sequencing done on site using a nanopore platform that requires minimal infrastructure.

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“…Out of all the antibiotics tested for these two organisms, only colistin, tigecycline, and Fosfomycin demonstrated a favorable susceptibility profile. Though explicit resistance testing for ESBL and carbapenem-resistant Enterobacteriaceae (CRE) was not reported in this study, reduced susceptibility to betalactams is suggestive of the ESBL and CRE resistance lurking in the region [16,17].…”

Section: Discussionmentioning

confidence: 69%

Increased burden of MDR bacterial infections; reflection from an antibiogram of ICUs of a tertiary care hospital

Khan

Ismail

Ullah

et al. 2023

J Infect Dev Ctries

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Introduction: Infectious disease management in intensive care units (ICUs) is becoming more difficult due to increasing antimicrobial resistance. Hence, the aim of this study was to explore the nature of pathogens mostly encountered in an ICU and determine their antibiotic susceptibility through the compilation of ICU-specific antibiogram. Methodology: A descriptive cross-sectional study of the culture and sensitivity reports of ICU patients was conducted in a tertiary care hospital. An antibiogram was created according to the Clinical Laboratory Standards Institute (CLSI) M39-A4 guidelines. Results: Of the total 597 reports, the most common specimen type were respiratory secretions (n = 174), followed by blood (n = 128), wounds (n = 108), and urine (n = 80). Out of 597 isolates, the most frequently isolated bacteria were Klebsiella species (n = 156), Pseudomonas aeruginosa (n = 117), Escherichia coli (n = 112), Enterobacter species (n = 56), Acinetobacter species (n = 52), Proteus species (n = 39), Staphylococcus aureus (n = 34) and coliform species (n = 31). An 84% multidrug resistance (MDR) rate was reported among the isolates studied, with Acinetobacter species being at the top with a 98% MDR rate. Conclusions: A substantial and alarming MDR rate was observed in our study. Furthermore, our findings demonstrated a potential interest in developing an ICU-specific antibiogram that is informative to clinicians in their clinical decision-making related to antibiotic therapy.

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Concurrence of Porin Loss and Modular Amplification of β-Lactamase Encoding Genes Drives Carbapenem Resistance in a Cohort of Recurrent Enterobacterales Bacteremia

Cited by 5 publications

References 69 publications

Genomic epidemiology of Escherichia coli isolates from a tertiary referral center in Lilongwe, Malawi

Genomic epidemiology of Escherichia coli isolates from a tertiary referral center in Lilongwe, Malawi

Genomic Epidemiology of Escherichia coli Isolates from a Tertiary Referral Center in Lilongwe, Malawi

Increased burden of MDR bacterial infections; reflection from an antibiogram of ICUs of a tertiary care hospital

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