Combined effect of Polymyxin B and Tigecycline to overcome Heteroresistance in Carbapenem-Resistant Klebsiella pneumoniae
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Tigecycline and colistin are two of the last treatment options remaining for carbapenem-resistant Enterobacteriaceae . Unfortunately, tigecycline resistance and colistin heteroresistance are also increasing rapidly.
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Time-kill assays can detect heteroresistance by identifying delayed growth or survival of heteroresistant subpopulations undetected by static MIC assays.
“By measuring the rate of cell death at various time points, this method can identify delayed growth or survival of heteroresistant subpopulations undetected by static MIC assays, and even evaluate the kinetics of heteroresistance and assess whether heteroresistant cells eventually adapt to drug pressure, which makes for wide clinical applicability [172,173,174].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [174]
The Results section (page not provided) reports that time-kill assays showed initial inhibition followed by regrowth of resistant subpopulations, including in isolates whose parental MICs were classified as susceptible. However, the Methods section says population analysis profiling—not the time-kill assay—was used to detect heteroresistance; the paper does not establish time-kill assays as a stand-alone detection method. (LLM, conf=0.84)
Experimental — accuracy not yet measuredFor 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 [174]
The Abstract says clinicians tend to adopt combination therapy in response to bacterial resistance. The Discussion reports that polymyxin B plus tigecycline reduced bacterial counts in heteroresistant carbapenem-resistant K. pneumoniae, but the paper proposes this as a potential strategy for that setting, not a preferred strategy for bacteria generally. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCombination polymyxin B and tigecycline therapy was shown to kill both polymyxin B- and tigecycline-heteroresistant Klebsiella pneumoniae.
“For example, combination polymyxin B and tigecycline therapy was shown to kill both the polymyxin B- and tigecycline-heteroresistant Klebsiella pneumoniae [174].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [174]
Time-kill assays can evaluate kinetics of heteroresistance and assess whether heteroresistant cells eventually adapt to drug pressure.
“By measuring the rate of cell death at various time points, this method can identify delayed growth or survival of heteroresistant subpopulations undetected by static MIC assays, and even evaluate the kinetics of heteroresistance and assess whether heteroresistant cells eventually adapt to drug pressure, which makes for wide clinical applicability [172,173,174].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [174]
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References 41 · Cited by 62
- Authors
- Tian, Y., Zhang, Q., Wen, L., & Chen, J.
- Affiliations
- Union Hospital (CN)
- Corresponding author
- Chen, JianSen
- Venue
- Microbiology Spectrum
- Publisher
- American Society for Microbiology
- Published
- 2021-10-31
- Volume
- 9
- Issue
- 2
- Pages
- e0015221-e0015221
- ISSN
- 2165-0497 (ISSN-L)
- PMC
- PMC8549724
- OpenAlex
- W3209489561
- Cited by
- 62
- References
- 41
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 11 · 2023: 22 · 2022: 6 · 2021: 1
- FWCI
- 3.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Microbiology Spectrum (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Medical Elite Cultivation Program of Fujian, China (2016-ZQN-33)
- Emergency Research Project of Fujian Medical University (2020YJ005)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antibiotic Use and Resistance
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Keywords
- carbapenem-resistant Klebsiella pneumoniae, polymyxin B, tigecycline, heteroresistance, colistin heteroresistance, combination antibiotic therapy, clinical isolates, antimicrobial resistance
- MeSH terms
- Carbapenem-Resistant Enterobacteriaceae, Tigecycline, Anti-Bacterial Agents, Bacterial Proteins, Drug Therapy, Combination, Humans, Klebsiella Infections, Klebsiella pneumoniae, Microbial Sensitivity Tests, Polymyxin B, Drug Resistance, Multiple, Bacterial, ATP-Binding Cassette, Sub-Family C Proteins, Multidrug Resistance-Associated Proteins
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