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Peer-reviewedCC BY 4.0Frontiers in Microbiology

Inoculum-dependent activity of contemporary β-lactam agents against carbapenemase- producing Enterobacterales

  • Tokeshwar Kumar Sahu1
  • Pravin Gadkari2
  • Jaishriram Rathored3,4
4 affiliations
  1. 1Department of Microbiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Sawangi Meghe, Wardha, India
  2. 2Department of Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Sawangi Meghe, Wardha, India
  3. 3Central Research Laboratory and Molecular Diagnostics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Sawangi Meghe, Wardha, India
  4. 4School of Allied Health Sciences, Datta Meghe Institute of Higher Education & Research, Sawangi Meghe, Wardha, India
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Abstract

Carbapenemase-producing Enterobacterales (CPE) pose a major therapeutic challenge because antimicrobial susceptibility measured at standard inoculum may not reflect activity at higher bacterial burdens. This Mini Review examines the biological basis, carbapenemase dependence, and agent-specific expression of inoculum effects among contemporary β-lactams. Increasing bacterial density can enhance β-lactamase burden and extracellular carbapenemase activity, alter the effective drug-to-enzyme relationship, and interact with permeability defects, bacterial physiology, and antimicrobial exposure. Available evidence shows substantial heterogeneity across carbapenemases and agents. Ceftazidime-avibactam appears comparatively stable in several CPE studies, whereas cefiderocol, aztreonam-avibactam, and other β-lactam/β-lactamase inhibitor combinations can show marked density-dependent reductions in activity under specific conditions. However, in vitro MIC increases do not consistently translate into reduced in vivo efficacy. Standardized testing approaches, mechanism-informed susceptibility assessment, and clinically relevant pharmacokinetic and pharmacodynamic studies are needed to clarify the therapeutic significance of inoculum-dependent β-lactam activity.

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Cite

BibTeXRIS
BibTeX
@article{sahu2026inoculumdependent,
  title = {{Inoculum-dependent activity of contemporary β-lactam agents against carbapenemase- producing Enterobacterales}},
  author = {Tokeshwar Kumar Sahu and Pravin Gadkari and Jaishriram Rathored},
  journal = {Frontiers in Microbiology},
  year = {2026},
  month = oct,
  doi = {10.3389/fmicb.2026.1964408},
  url = {https://doi.org/10.3389/fmicb.2026.1964408},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Inoculum-dependent activity of contemporary β-lactam agents against carbapenemase- producing Enterobacterales
AU  - Tokeshwar Kumar Sahu
AU  - Pravin Gadkari
AU  - Jaishriram Rathored
PY  - 2026
DA  - 2026/10/12
JO  - Frontiers in Microbiology
DO  - 10.3389/fmicb.2026.1964408
UR  - https://doi.org/10.3389/fmicb.2026.1964408
AB  - Carbapenemase-producing Enterobacterales (CPE) pose a major therapeutic challenge because antimicrobial susceptibility measured at standard inoculum may not reflect activity at higher bacterial burdens. This Mini Review examines the biological basis, carbapenemase dependence, and agent-specific expression of inoculum effects among contemporary β-lactams. Increasing bacterial density can enhance β-lactamase burden and extracellular carbapenemase activity, alter the effective drug-to-enzyme relationship, and interact with permeability defects, bacterial physiology, and antimicrobial exposure. Available evidence shows substantial heterogeneity across carbapenemases and agents. Ceftazidime-avibactam appears comparatively stable in several CPE studies, whereas cefiderocol, aztreonam-avibactam, and other β-lactam/β-lactamase inhibitor combinations can show marked density-dependent reductions in activity under specific conditions. However, in vitro MIC increases do not consistently translate into reduced in vivo efficacy. Standardized testing approaches, mechanism-informed susceptibility assessment, and clinically relevant pharmacokinetic and pharmacodynamic studies are needed to clarify the therapeutic significance of inoculum-dependent β-lactam activity.
SN  - 1664-302X
ER  -