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Peer-reviewedCC BY 4.0Antimicrobial Agents and Chemotherapy

Relative inhibitory activities of taniborbactam and xeruborbactam against KPC variants conferring reduced susceptibility or resistance to ceftazidime/avibactam, cefiderocol, and cefepime/taniborbactam

  • Salud Rodríguez-Pallares1,2
  • Christophe Le Terrier3,4
  • Tania Blanco-Martín1,2
  • Roberto Rilo-Antelo1
  • Cristina Elías-López2,5
  • Lucía Sánchez-Peña1
  • Carlos Molina-Cáceres1
  • Gloria Pérez-Rodríguez1
  • Lucía González-Pinto1,2
  • Luis Martínez-Martínez2,5,6,7
  • Laurent Poirel3,8
  • Germán Bou1,2,9
1 more authors
  • Jorge Arca-Suárez1,2
9 affiliations
  1. 1Servicio de Microbiología Clínica & Grupo de Investigación en Microbiología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS. Universidade da Coruña (UDC), A Coruña, Spain
  2. 2CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
  3. 3Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
  4. 4Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
  5. 5Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
  6. 6Unidad Clínica de Microbiología, Hospital Universitario Reina Sofía, Córdoba, Spain
  7. 7Departamento de Química Agrícola, Edafología y Microbiología, Universidad de Córdoba, Córdoba, Spain
  8. 8Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland
  9. 9Departamento de Fisioterapia, Medicina y Ciencias Biomédicas, Universidad de A Coruña, A Coruña, Spain
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Abstract

The emergence of KPC variants associated with ceftazidime/avibactam resistance may also compromise the activity of other recently developed β-lactams, including cefiderocol and cefepime/taniborbactam. Xeruborbactam is a boronic acid β-lactamase inhibitor with potent activity against serine- and metallo-β-lactamases and is currently under clinical development in combination with cefiderocol. We evaluated the in vitro activity of cefiderocol/xeruborbactam against a panel of clinical Klebsiella pneumoniae isolates and isogenic Escherichia coli transformants (including both wild-type and porin-deficient backgrounds) producing KPC variants. Xeruborbactam and taniborbactam activities were compared using ceftazidime, cefepime, and cefiderocol as reporter substrates. Inhibitory activity was analyzed by determining the IC₅₀ values for both inhibitors against KPC variants. Most clinical isolates producing KPC variants showed increased MIC values and substantial cross-resistance to ceftazidime/avibactam, cefiderocol, and cefepime/taniborbactam. Cefiderocol/xeruborbactam retained potent activity against all clinical isolates, regardless of the KPC variant produced or the outer membrane permeability status. These findings were confirmed in wild-type and porin-deficient isogenic E. coli models, in which the combination of KPC variants and porin loss synergistically increased resistance to multiple β-lactams, while cefiderocol/xeruborbactam consistently restored susceptibility to wild-type levels. Comparative MIC analyses showed that xeruborbactam enhanced the activity of all β-lactam partners to a greater extent than taniborbactam. IC₅₀ determinations revealed a 17-fold to 73-fold greater inhibitory potency of xeruborbactam, which was maintained across structurally diverse KPC variants. Overall, cefiderocol/xeruborbactam exhibited potent activity against KPC-producing Enterobacterales, including isolates producing KPC variants associated with reduced susceptibility or resistance to ceftazidime/avibactam, cefiderocol, and cefepime/taniborbactam.

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Cite

BibTeXRIS
BibTeX
@article{rodriguezpallares2026relative,
  title = {{Relative inhibitory activities of taniborbactam and xeruborbactam against KPC variants conferring reduced susceptibility or resistance to ceftazidime/avibactam, cefiderocol, and cefepime/taniborbactam}},
  author = {Salud Rodríguez-Pallares and Christophe Le Terrier and Tania Blanco-Martín and Roberto Rilo-Antelo and Cristina Elías-López and Lucía Sánchez-Peña and Carlos Molina-Cáceres and Gloria Pérez-Rodríguez and Lucía González-Pinto and Luis Martínez-Martínez and Laurent Poirel and Germán Bou and Jorge Arca-Suárez},
  journal = {Antimicrobial Agents and Chemotherapy},
  year = {2026},
  month = sep,
  doi = {10.1128/aac.00897-26},
  url = {https://doi.org/10.1128/aac.00897-26},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Relative inhibitory activities of taniborbactam and xeruborbactam against KPC variants conferring reduced susceptibility or resistance to ceftazidime/avibactam, cefiderocol, and cefepime/taniborbactam
AU  - Salud Rodríguez-Pallares
AU  - Christophe Le Terrier
AU  - Tania Blanco-Martín
AU  - Roberto Rilo-Antelo
AU  - Cristina Elías-López
AU  - Lucía Sánchez-Peña
AU  - Carlos Molina-Cáceres
AU  - Gloria Pérez-Rodríguez
AU  - Lucía González-Pinto
AU  - Luis Martínez-Martínez
AU  - Laurent Poirel
AU  - Germán Bou
AU  - Jorge Arca-Suárez
PY  - 2026
DA  - 2026/09/30
JO  - Antimicrobial Agents and Chemotherapy
DO  - 10.1128/aac.00897-26
UR  - https://doi.org/10.1128/aac.00897-26
AB  - The emergence of KPC variants associated with ceftazidime/avibactam resistance may also compromise the activity of other recently developed β-lactams, including cefiderocol and cefepime/taniborbactam. Xeruborbactam is a boronic acid β-lactamase inhibitor with potent activity against serine- and metallo-β-lactamases and is currently under clinical development in combination with cefiderocol. We evaluated the in vitro activity of cefiderocol/xeruborbactam against a panel of clinical Klebsiella pneumoniae isolates and isogenic Escherichia coli transformants (including both wild-type and porin-deficient backgrounds) producing KPC variants. Xeruborbactam and taniborbactam activities were compared using ceftazidime, cefepime, and cefiderocol as reporter substrates. Inhibitory activity was analyzed by determining the IC₅₀ values for both inhibitors against KPC variants. Most clinical isolates producing KPC variants showed increased MIC values and substantial cross-resistance to ceftazidime/avibactam, cefiderocol, and cefepime/taniborbactam. Cefiderocol/xeruborbactam retained potent activity against all clinical isolates, regardless of the KPC variant produced or the outer membrane permeability status. These findings were confirmed in wild-type and porin-deficient isogenic E. coli models, in which the combination of KPC variants and porin loss synergistically increased resistance to multiple β-lactams, while cefiderocol/xeruborbactam consistently restored susceptibility to wild-type levels. Comparative MIC analyses showed that xeruborbactam enhanced the activity of all β-lactam partners to a greater extent than taniborbactam. IC₅₀ determinations revealed a 17-fold to 73-fold greater inhibitory potency of xeruborbactam, which was maintained across structurally diverse KPC variants. Overall, cefiderocol/xeruborbactam exhibited potent activity against KPC-producing Enterobacterales, including isolates producing KPC variants associated with reduced susceptibility or resistance to ceftazidime/avibactam, cefiderocol, and cefepime/taniborbactam.
SN  - 1098-6596
SN  - 0066-4804
ER  -