First worldwide detection of bla IMP-15 in Stenotrophomonas maltophilia isolated from a patient in Lebanon.

  1. Ziad C. Jabbour
  2. Jose Rita Gerges
  3. Hadi M. Hussein
  4. Sara B. Barada
  5. Lama Hamadeh
  6. Rami Mahfouz
  7. Zeina Kanafani
  8. Ghassan M Matar
  9. Antoine Abou Fayad

Reviewed by

Read the full article See related articles

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

Log in to save this article

Abstract

Stenotrophomonas maltophilia is an intrinsically multi-drug resistant (MDR) bacterium initially found in the environment that is emerging worldwide. The rate of isolation from immunocompromised patients combined with limited treatment options make S. maltophilia a new concern in clinical settings. Here we report the first detection of the Metallo-β-Lactamase (MBL) gene bla IMP-15 in S. maltophilia isolated from a patient in Lebanon. The isolate exhibited an extensively drug-resistant profile with high resistance to trimethoprim-sulfamethoxazole, levofloxacin, and minocycline considered by the Clinical and Laboratory Standards Institute (CLSI) as first-line antimicrobials used to treat such infections. Resistance to newly adopted anti- S. maltophilia agents was noted such as ceftazidime-avibactam. However, the isolate only showed susceptibility to cefiderocol and synergy was observed upon treatment with a combination of ceftazidime-avibactam and aztreonam by disk diffusion. Long-read and short-read whole-genome sequencing was performed and generated a hybrid assembly of 8 contigs. The isolate belonged to strain T50-20 and showed a novel sequence type. Moreover, several antimicrobial resistance genes conferring resistance to multiple antimicrobial classes were found. Particularly, bla IMP-15 was detected on insertion sequence IS6100 surrounded by transposition elements. Furthermore, the presence of the IMP gene was confirmed by polymerase chain reaction (PCR) followed by agarose gel electrophoresis and Sanger sequencing. This study highlights that the threat behind the bla IMP-15 gene is not only linked to the high resistance to Ceftazidime-avibactam in the S. maltophilia isolate, but is also of concern due to its transmissibility to other pathogens, conferring alone an MDR profile.

Article activity feed

  1. PREreview

    This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/15079613.

    Does the introduction explain the objective of the research presented in the preprint? Yes The authors report the first global identification of the blaIMP-15 gene in Stenotrophomonas maltophilia, an opportunistic, nosocomial, multidrug-resistant (MDR) Gram-negative bacterium. They provide some literature on the bacterium with no clearly stated objective, which implies the objective is to report and analyze the finding of this gene in this bacterium isolate.
    Are the methods well-suited for this research? Highly appropriate The authors carried out antimicrobial susceptibility testing using Kirby-Bauer disk diffusion against 12 antimicrobials and one combination (ceftazidime-avibactam + aztreonam). They performed whole-genome sequencing using hybrid assembly (Illumina MiSeq short-read and Oxford Nanopore MinION long-read sequencing) and targeted validation by PCR amplification and confirmation via agarose gel electrophoresis and Sanger sequencing. The authors used the Comprehensive Antibiotic Resistance Database (CARD) and NCBI Antimicrobial Resistance Gene Finder in the identification of this AMR gene. These methods are appropriate and robust for identifying resistance genes and characterizing the isolate's antimicrobial susceptibility profile.
    Are the conclusions supported by the data? Somewhat supported The authors did identify the blaIMP-15 gene in this isolate. They suggest potential transmissibility of blaIMP-15 in the abstract and discuss surrounding transposition elements (IS6100, ISPa382/383) in the last sections of the paper. Is this genetic context suggestive of horizontal gene transfer (HGT) potential? The manuscript would benefit from providing more detailed evidence or references demonstrating the transmissibility of blaIMP-15 in S. maltophilia and the potential involvement of these specific transposition elements. Also, the claim that IMP-15 reduces ceftazidime-avibactam efficacy (page 6, paragraph 2) lacks direct experimental evidence for this isolate. The authors should consider emphasizing the observed synergy between ceftazidime-avibactam and aztreonam as a potential alternative treatment option.
    Are the data presentations, including visualizations, well-suited to represent the data? Somewhat appropriate and clear The data visualizations are clear but limited. The paper has a single table showing the antimicrobial susceptibility testing results of the isolate and a visual of the genomic placement of the blaIMP-15 gene with identified transposition elements.
    How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research? Somewhat clearly The authors do clearly discuss the significance of detecting the blaIMP-15 gene in this S. malptophilia isolate, however, they could provide more context on potential next steps such as exploring its transmissibility in this bacterium and its impact on treatment strategies. Future studies should also consider investigating experimentally, how blaIMP-15 impacts the efficacy of ceftazidime-avibactam alone versus combination therapies and assess the additional resistance conferred by this gene in combination with the blaL1 gene.
    Is the preprint likely to advance academic knowledge? Highly likely Yes, the preprint is likely to advance academic knowledge. The identification of the blaIMP-15 gene in S. maltophilia contributes to understanding the evolving landscape of antimicrobial resistance.
    Would it benefit from language editing? No No language editing issues. The authors should consider revising the "and" in the statement "Genome annotation was done using and Prokka (v1.14.6) (15)" on page 4, paragraph 1, line 4.
    Would you recommend this preprint to others? Yes, it's of high quality This preprint is relevant to researchers with interest in AMR, S. maltophilia and carbapenemase-producing bacteria.
    Is it ready for attention from an editor, publisher or broader audience? Yes, as it is

    Competing interests

    The authors declare that they have no competing interests.

  2. Version published to 10.1101/2025.02.28.640784 on bioRxiv