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Cited by 17Antibiotic Resistance in BacteriaBacterial Genetics and BiotechnologyBacterial Identification and Susceptibility Testing

Insight into Antibiotic Synergy Combinations for Eliminating Colistin Heteroresistant Klebsiella pneumoniae

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Rajakani, Sahaya Glingston, Xavier, Basil Britto, Sey, Adwoa, Mariem, El Bounja, Lammens, Christine, Goossens, Herman, Glupczynski, Youri, Malhotra-Kumar, Surbhi·2023·Genes
DOI 10.3390/genes14071426PMC PMC10378790
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Abstract

Colistin heteroresistance has been identified in several bacterial species, including Escherichia coli and Klebsiella pneumoniae, and may underlie antibiotic therapy failures since it most often goes undetected by conventional antimicrobial susceptibility tests. This study utilizes population analysis profiling (PAP) and time–kill assay for the detection of heteroresistance in K. pneumoniae and for evaluating the association between in vitro regrowth and heteroresistance. The mechanisms of colistin resistance and the ability of combination therapies to suppress resistance selection were also analysed. In total, 3 (18%) of the 16 colistin-susceptible strains (MIC ≤ 2 mg/L) were confirmed to be heteroresistant to colistin by PAP assay. In contrast to the colistin-susceptible control strains, all three heteroresistant strains showed regrowth when exposed to colistin after 24 h following a rapid bactericidal action. Colistin resistance in all the resistant subpopulations was due to the disruption of the mgrB gene by various insertion elements such as ISKpn14 of the IS1 family and IS903B of the IS5 family. Colistin combined with carbapenems (imipenem, meropenem), aminoglycosides (amikacin, gentamicin) or tigecycline was found to elicit in vitro synergistic effects against these colistin heteroresistant strains. Our experimental results showcase the potential of combination therapies for treatment of K. pneumoniae infections associated with colistin heteroresistance.

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  • For bacteria, combination of several antibiotics serves as preferred strategy.

    “For bacteria, a combination of several antibiotics serves as the preferred strategy [28,174,175,176].”

    From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [176]

    The Conclusions report a potential benefit of combining colistin with other antibiotics for colistin-heteroresistant K. pneumoniae. The Discussion suggests such combinations may be safer than colistin alone, but calls for in vivo studies. The paper does not establish antibiotic combinations as the preferred strategy for bacteria generally. (LLM, conf=0.86)

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Authors
Rajakani, S. G., Xavier, B. B., Sey, A., Mariem, E. B., Lammens, C., Goossens, H., Glupczynski, Y., & Malhotra-Kumar, S.
Affiliations
  • University of Antwerp (BE)
  • Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, 2610 Antwerp, Belgium
ORCID
Venue
Genes
Publisher
MDPI AG
Published
2023-07-10
Volume
14
Issue
7
Pages
1426
ISSN
2073-4425 (ISSN-L)
DOI
10.3390/genes14071426
PMC
PMC10378790
OpenAlex
W4383877113
Cited by
17
References
2
Citations by year
2026: 5 · 2025: 6 · 2024: 6
FWCI
1.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Genes (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
Funders
  • University of Antwerp BOF Doctoral Project Funds (40179)
  • University of Antwerp Methusalem funding (40179)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
Keywords
colistin heteroresistance, Klebsiella pneumoniae, antibiotic synergy, combination therapy, population analysis profiling, time-kill assay, regrowth, insertion elements, IS1, IS5, carbapenems, aminoglycosides, tigecycline
MeSH terms
Meropenem, Tigecycline, Anti-Bacterial Agents, Colistin, Klebsiella pneumoniae

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