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  • Oxford University Press (OUP)  (2)
  • Conzemius, Rick  (2)
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  • Oxford University Press (OUP)  (2)
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  • 1
    In: Clinical Infectious Diseases, Oxford University Press (OUP), ( 2023-11-16)
    Abstract: Investigations into antibiotics for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infections (BSIs) have focused on blaCTX-M genes. Outcomes of patients with non-CTX-M-producing ESBL-E BSIs and optimal treatment are unknown. Methods A multicenter observational study investigating 500 consecutive patients with ceftriaxone-resistant Enterobacterales BSIs during 2018–2022 was conducted. Broth microdilution and whole genome sequencing confirmed antibiotic susceptibilities and ESBL gene presence, respectively. Inverse probability weighting (IPW) using propensity scores was employed to ensure patients infected with non-CTX-M and CTX-M ESBL-E BSIs were similar prior to evaluation of outcomes. Results 396 patients (79.2%) were confirmed to have an ESBL-E BSI. ESBL gene family prevalence was as follows: blaCTX-M (n=370), blaSHV (n=16), blaOXY (n=12), and blaVEB (n=5). ESBL gene identification was not limited to Escherichia coli and Klebsiella species. In the IPW cohort, there was no difference in 30-day mortality or ESBL-E infection recurrence between the non-CTX-M and CTX-M groups (OR=.99, 95% CI 0.87–1.11; p=0.83) and (OR=1.10, 95% CI 0.85­–1.42; p=0.47), respectively. In an exploratory analysis limited to the non-CTX-M group, 86% of the 21 patients receiving meropenem were alive on day 30; none of the 5 patients receiving piperacillin-tazobactam were alive on day 30. Conclusions Our findings suggest that non-CTX-M and CTX-M ESBL-producing Enterobacterales BSIs are equally concerning and associated with similar clinical outcomes. Meropenem may be associated with improved survival in patients with non-CTX-M ESBL-E BSIs, underscoring the potential benefit of comprehensive molecular diagnostics to enable early antibiotic optimization for patients with ESBL-E BSI, beyond just blaCTX-M genes.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2002229-3
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  • 2
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 10, No. 7 ( 2023-07-01)
    Abstract: Cefiderocol and ceftazidime-avibactam plus aztreonam (CZA-ATM) are preferred treatment regimens for New Delhi metallo-β-lactamase (NDM)-producing infections. Methods We report the case of a US patient who traveled to India to receive a renal transplant. He subsequently experienced pyelonephritis by an NDM-producing Escherichia coli. Broth microdilution and the broth disk elution method indicated resistance to all β-lactams, including cefiderocol and CZA-ATM. Whole-genome sequencing investigations were undertaken to identify resistance mechanisms. Results An E. coli isolate belonging to sequence type (ST) 167 containing a blaNDM-5 gene was identified on a plasmid of the IncFIA/IncFIB/IncFIC replicon groups. When compared with the genome of another ST167 E. coli clinical isolate containing blaNDM-5 and exhibiting susceptibility to cefiderocol and CZA-ATM, a 12–base pair insertion in ftsI, translating to a 4–amino acid duplication in PBP3, was identified. Moreover, a blaCMY-59 gene was harbored on an IncI-γ replicon type, and frameshift mutations were identified in the cirA iron transport gene. Conclusions This is the first clinical case of a US patient harboring an NDM-producing isolate exhibiting resistance to all available β-lactam agents. The isolate's unexpected resistance to cefiderocol and CZA-ATM was likely due to a combination of (1) a modified PBP3 (increased MICs to both regimens), (2) truncated iron-binding protein (increased cefiderocol MIC), and (3) a blaCMY gene (reduced CZA-ATM activity). E. coli ST167 clinical isolates harboring blaNDM-5 genes are a recognized international high-risk clone. When coupled with the additional mechanisms identified in our patient's isolate, which is not uncommon for this high-risk clone, pan-β-lactam resistance may occur.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2757767-3
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