Risk of Drug Resistance and Repeated Infection with Klebsiella
pneumoniae and Escherichia coli in Intensive Care Unit Cancer Patients

Refay, Samah M; Ahmed, Ehab A.; Elzaher, Ahmed Refaat Abd; Mohammed, Morsy, Ahmed; Yasser, Manal Mohamed; Mahmoud, Ayman M.

doi:10.2174/1386207324666210121104724

Cited by 5 publications

(3 citation statements)

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“…Recurrence is a major concern following treatment of 3GC-R Kp infections [64, 65], and indeed we observed an approximate 20% recurrence rate when just considering bacteremias. The recurrent strain was nearly always the same ST and highly genetically related to the index isolate suggesting re-infection rather than acquisition of a new 3GC-R Kp strain.…”

Section: Discussionmentioning

confidence: 69%

Identification of A Novel CG307 Sub-clade in Third Generation Cephalosporin ResistantKlebsiella pneumoniaeCausing Invasive Infections in the United States

Anand,

Wu,

Bremer

et al. 2023

Preprint

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Despite the notable clinical impact, recent molecular epidemiology regarding third-generation cephalosporin-resistantKlebsiella pneumoniae(3GC-RKp) in the United States remains limited. We performed whole genome sequencing of 3GC-RKpbacteremia isolates collected from March 2016 to May 2022 at a tertiary care cancer center in Houston, TX using Illumina and Oxford Nanopore Technologies platforms. A comprehensive comparative genomic analysis was performed to dissect population structure, transmission dynamics, and pan-genomic signatures of our 3GC-RKppopulation. Of the 194 3GC-RKpbacteremias that occurred during our study timeframe, we were able to analyze 153 (79%) bacteremia isolates, 126 initial and 27 recurrent isolates respectively. While isolates belonging to the widely prevalent clonal group (CG) 258 were rarely observed, the predominant clonal group, CG307, accounted for 37 (29%) index isolates and displayed a significant correlation (Pearson correlation testP-value = 0.03) with the annual frequency of 3GC-RKpbacteremia. Within our CG307 cohort, 89% (33/37) of our isolates belong to the global rather than previously described Texas-specific clade. Strikingly, we identified a new CG307 sub-clade (i.e.,cluster 1 isolates) comprised of 18 isolates characterized by the chromosomally-encodedblaSHV-205and unique accessory genome content. This CG307 sub-clade was detected in various United States regions, with genome sequences from 24 additional strains becoming recently available in the NCBI SRA database. Collectively, this study underscores the emergence and dissemination of a distinct CG307 sub-clade that is a prevalent cause of 3GC-RKpbacteremia among cancer patients seen in Houston, TX and has recently been isolated throughout the United States.DATA SUMMARYWGS data sequenced during this study period was submitted to NCBI and can be accessed within BioProject PRJNA648389. WGS data from previous study of carbapenem non-susceptibleEnterobacteralescan be accessed from BioProject PRJNA836696. Assembly information and BioAccession numbers are provided in Table S1.IMPACT STATEMENTInfections due to 3rdgeneration cephalosporin resistantKlebsiella pneumoniae(3GC-RKp) are considered among the most urgent public health threats. However, molecular epidemiology studies on 3GC-RKpin the United States are limited. Our analysis indicates a preponderance of genetically diverse 3GC-RKpisolates harboring the key antimicrobial resistance determinantblaCTX-M-15at our institution. Importantly, however, we detected evidence of long duration transmission of highly genetically related CG307 and CG29 specific clusters at our institution. Interestingly, we rarely detected the pandemic CG258 lineage in our cohort and did not detect more than two genetically related CG258 isolates from this lineage. We found that 90% of our isolates from the most prevalent clonal group, CG307, belonged to a novel, nested-population of a “global” CG307 clade in contrast to the more commonly detected “Texas-specific” clade that has circulated in our region. We searched the NCBI SRA database using genomic markers of the novel CG307 clade and found evidence of this clade causing recent invasive infections in other locations across the United States. Our study highlights the shifting population dynamics ofK. pneumoniaecausing invasive infections and the necessity to continue AMR surveillance in order to identify emerging high-risk populations.

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Section: Discussionmentioning

confidence: 69%

Identification of A Novel CG307 Sub-clade in Third Generation Cephalosporin ResistantKlebsiella pneumoniaeCausing Invasive Infections in the United States

Anand,

Wu,

Bremer

et al. 2023

Preprint

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“…Recurrence is a major concern following treatment of 3GC-R K. pneumoniae infections [63, 64], and indeed we observed an approximate 20 % recurrence rate when just considering bacteraemias. The recurrent strain was nearly always the same ST and highly genetically related to the index isolate.…”

Section: Discussionmentioning

confidence: 69%

Identification of a novel CG307 sub-clade in third-generation-cephalosporin-resistant Klebsiella pneumoniae causing invasive infections in the USA

Selvaraj Anand,

Wu,

Bremer

et al. 2024

Microbial Genomics

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Despite the notable clinical impact, recent molecular epidemiology regarding third-generation-cephalosporin-resistant (3GC-R) Klebsiella pneumoniae in the USA remains limited. We performed whole-genome sequencing of 3GC-R K. pneumoniae bacteraemia isolates collected from March 2016 to May 2022 at a tertiary care cancer centre in Houston, TX, USA, using Illumina and Oxford Nanopore Technologies platforms. A comprehensive comparative genomic analysis was performed to dissect population structure, transmission dynamics and pan-genomic signatures of our 3GC-R K. pneumoniae population. Of the 178 3GC-R K. pneumoniae bacteraemias that occurred during our study time frame, we were able to analyse 153 (86 %) bacteraemia isolates, 126 initial and 27 recurrent isolates. While isolates belonging to the widely prevalent clonal group (CG) 258 were rarely observed, the predominant CG, 307, accounted for 37 (29 %) index isolates and displayed a significant correlation (Pearson correlation test P value=0.03) with the annual frequency of 3GC-R K. pneumoniae bacteraemia. Interestingly, only 11 % (4/37) of CG307 isolates belonged to the commonly detected ‘Texas-specific’ clade that has been observed in previous Texas-based K. pneumoniae antimicrobial-resistance surveillance studies. We identified nearly half of our CG307 isolates (n=18) belonged to a novel, monophyletic CG307 sub-clade characterized by the chromosomally encoded bla SHV-205 and unique accessory genome content. This CG307 sub-clade was detected in various regions of the USA, with genome sequences from 24 additional strains becoming recently available in the National Center for Biotechnology Information (NCBI) SRA database. Collectively, this study underscores the emergence and dissemination of a distinct CG307 sub-clade that is a prevalent cause of 3GC-R K. pneumoniae bacteraemia among cancer patients seen in Houston, TX, and has recently been isolated throughout the USA.

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“…Eight of 144 (6%) reporting and modelling several microorganisms focused only on Gram-negative bacteria [58][59][60][61][62][120][121][122] and 1/144 (1%) focused only on fungi [63]. Twelve of 144 (8%) studies studied the family Enterobacterales (especially Escherichia coli and Klebsiella pneumoniae combined), either ESBL-or carbapenemase-producing [38,[64][65][66][67][68][123][124][125][126][127][128]. The most commonly studied single organism was Clostridioides difficile with 27/144 (19%) studies [39][40][41][69][70][71][72][73][74][75][76][77][78][79][80][81][129][130][131][132][133][134][135][136][137][138]…”

Section: Study Characteristicsmentioning

confidence: 99%

Clinical outcomes of antimicrobial resistance in cancer patients: A systematic review of multivariable models

Danielsen

Franconeri

Page

et al. 2022

Preprint

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Background Infections are major causes of disease in cancer patients and pose a major obstacle to the success of cancer care. The global rise of antimicrobial resistance threatens to make these obstacles even greater and hinder continuing progress in cancer care. To prevent and handle such infections, a better understanding of the risk factors are needed. This internally funded systematic review (PROSPERO registration: CRD42021282769) aims to review what risk factors for resistant infections and deaths due to resistant infections have been investigated, and with what methodological approaches. Methods We employed two broad searches of antimicrobial resistance in cancer patients, using terms associated with antimicrobial resistant infections, in MEDLINE and Embase through Ovid, in addition to Cinahl through EBSCOhost and Web of Science Core Collection. Primary, observational studies in English from January 2015 to November 2021 on human cancer patients that explicitly modelled infection or mortality associated with antimicrobial resistance in a multivariable model were included. We extracted data on the study populations and their malignancies, risk factors, the microbial aetiology, methods for variable selection, and assessed the risk of bias using the NHLBI Study Quality Assessment Tools. Results Two searches yielded a total of 27151 unique records, of which 144 studies were included after screening and reading. Of the outcomes studied, mortality was the most common (68/144, 47%). Forty-five percent (65/144) of the studies focused on haemato-oncological patients, and 27% (39/144) studied several bacteria or fungi. Studies included a median of 200 patients and 46 events. One-hundred-and-three (72%) studies used a p-value-based variable selection. Studies included a median of seven variables in the final (and largest) model, which yielded a median of 6.9 events per variable. An in-depth example of vancomycin-resistant enterococci was reported. Conclusions We found the current research on this topic to be heterogeneous, in both the methodological and epidemiological approach. Methodological choices resulting in very diverse models made it difficult or even impossible to draw statistical inferences and summarise what risk factors were of clinical relevance. The development and adherence to more standardised protocols that build on existing literature is urgent.

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Risk of Drug Resistance and Repeated Infection with Klebsiella pneumoniae and Escherichia coli in Intensive Care Unit Cancer Patients

Cited by 5 publications

References 0 publications

Identification of A Novel CG307 Sub-clade in Third Generation Cephalosporin ResistantKlebsiella pneumoniaeCausing Invasive Infections in the United States

Identification of A Novel CG307 Sub-clade in Third Generation Cephalosporin ResistantKlebsiella pneumoniaeCausing Invasive Infections in the United States

Identification of a novel CG307 sub-clade in third-generation-cephalosporin-resistant Klebsiella pneumoniae causing invasive infections in the USA

Clinical outcomes of antimicrobial resistance in cancer patients: A systematic review of multivariable models

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