OMNIvance (xeruborbactam) / Brii Biosci, Shionogi - LARVOL DELTA

Contribution of mutational resistance mechanisms and acquired β-lactamases to cefiderocol/xeruborbactam susceptibility in Pseudomonas aeruginosa. (PubMed, Antimicrob Agents Chemother) - "Xeruborbactam was assessed in combination with cefiderocol and cefepime at 4 and 8 mg/L and compared with taniborbactam. Importantly, xeruborbactam restored susceptibility in 78% of 99 cefiderocol-resistant P. aeruginosa strains, reducing the MIC90 from 64 to 4 mg/L. Cefiderocol/xeruborbactam shows promising activity against P. aeruginosa."

Journal • PER1

Efficacy of cefiderocol in combination with xeruborbactam versus taniborbactam against cefiderocol-resistant NDM-producing Pseudomonas aeruginosa. (PubMed, Antimicrob Agents Chemother) - "One isolate that was unresponsive to taniborbactam carried multiple copies of blaNDM-1. These findings highlight the species-specific limitations of xeruborbactam in P. aeruginosa."

Journal

Sporadic cefiderocol resistance in Escherichia coli from the United Arab Emirates involves multifactorial mechanisms reversible by novel beta-lactamase inhibitors. (PubMed, Sci Rep) - "Zidebactam, with intrinsic antibacterial activity, caused the most significant reduction in CFDC minimum inhibitory concentrations (MICs), while the activity of other inhibitors (taniborbactam and xeruborbactam) was dependent on the genetic makeup of the strains, especially mutations in the siderophore-iron uptake genes. Our findings underscore the importance of genomic surveillance in deciphering antibiotic resistance mechanisms. Novel BLIs and partner antibiotics could be added weapons in the fight against MDR bacteria; thus, we recommend using combinations with novel BLIs as innovative therapeutic options to combat the emerging threat of CFDC resistance, after proper validation of their in vivo efficacy."

Journal • Infectious Disease

Structural Insights into the Role of the Stereochemistry of the Cyclopropyl Ring in the Inhibitory Activity of Xeruborbactam against SME-1 Class A Carbapenemase. (PubMed, Biochemistry) - "In the molecular dynamics, xeruborbactam stabilized SME-1 more than its isomer, which is consistent with our experimental findings. These results together show the strong inhibitory profile of xeruborbactam and highlight the importance of stereochemistry in the design of next-generation β-lactamase inhibitors and diagnostics for AMR."

Journal

A Study to Investigate Safety and Pharmacokinetics of Intravenous Cefiderocol/Xeruborbactam in Participants With Renal Impairment (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Qpex Biopharma, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Renal Disease

Phase 1, randomized, double-blind, placebo-controlled, ascending single- and multiple-dose study of the safety, tolerability, and pharmacokinetics of intravenous xeruborbactam (QPX7728) in healthy adult subjects. (PubMed, Antimicrob Agents Chemother) - "Significant accumulation was noted with 8-hourly dosing. Xeruborbactam at doses up to 1,000 mg daily for 7-10 days was well tolerated, with no serious or life-threatening AEs."

Clinical • Journal • P1 data • PK/PD data • Pain

Pharmacodynamic Assessment of Combination of Cefiderocol with Xeruborbactam in Murine Thigh Infection Model (IDWeek 2025) - No abstract available

PK/PD data • Preclinical • Infectious Disease

Mass Balance Study of [14C]Xeruborbactam (QPX7728) in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Qpex Biopharma, Inc. | Active, not recruiting ➔ Completed

Trial completion

Antibiotics and non-traditional antimicrobial agents for carbapenem-resistant Acinetobacter baumannii in Phase 1, 2, and 3 clinical trials. (PubMed, Expert Opin Investig Drugs) - "Specifically, 9 antibiotics are in Phase 1 (R-327, xeruborbactam/QPX-7728, upleganan/SPR-206, MRX-8, QPX-9003, zifanocycline/KBP-7072, apramycin/EBL-1003, zosurabalpin/RG-6006, and ANT-3310), two in Phase 2 (BV-100, OMN-6), and two in Phase 3 (zidebactam/WCK-5222, funobactam/XNW-4107) clinical trials...In particular, two monoclonal antibodies (TRL-1068, CMTX-101), a phage therapy (Phagebank), an immune-modulating agent (recombinant human plasma gelsolin/Rhu-pGSN), a microbiome-modulating agent (SER-155), and an engineered cationic antibiotic peptide (PLG-0206). Several agents with promising characteristics against CRAB infections are in clinical development (Phases 1, 2, and 3). The urgent need for therapeutic options against CRAB infections necessitates optimizing efforts and time for introducing successfully studied agents into clinical practice."

Journal • Review • Infectious Disease • GSN

Mass Balance Study of [14C]Xeruborbactam (QPX7728) in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Qpex Biopharma, Inc.

New P1 trial

A DDI Study to Investigate PK and Safety of Cefiderocol in Combination With Xeruborbactam in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Qpex Biopharma, Inc. | N=40 ➔ 60

Enrollment change • Infectious Disease

Mass Balance Study of [14C]Xeruborbactam (QPX7728) in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Qpex Biopharma, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Investigate Safety and Pharmacokinetics of Intravenous Cefiderocol/Xeruborbactam in Participants With Renal Impairment (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Qpex Biopharma, Inc.

New P1 trial • Infectious Disease • Renal Disease

Mass Balance Study of [14C]Xeruborbactam (QPX7728) in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: Qpex Biopharma, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed

Amphiphilic nebramine analogs synergize with β-lactam/β-lactamase inhibitor combinations, including cefepime-taniborbactam and meropenem-xeruborbactam against metallo-β-lactamase-carrying Pseudomonas aeruginosa. (PubMed, RSC Med Chem) - "Cefepime-taniborbactam (FEP-TAN) and meropenem-xeruborbactam (MEM-XER) are β-lactam-β-lactamase inhibitor (BL-BLI) combinations currently in development and both projected to treat metallo-β-lactamase (MBL)-producing Gram-negative pathogens. Compound 4 was found to be less toxic than both polymyxin B and its corresponding amphiphilic tobramycin counterpart (compound 7) in human renal cell lines, RPTEC and HK-2. Overall, our study suggests that addition of compound 4 alongside next-generation BL-BLIs such as FEP-TAN, MEM-XER as well as the recently approved ATM-AVI combination can overcome intrinsic and acquired in vitro P. aeruginosa resistance determinants that confer high-level resistance to β-lactam antibiotics."

Journal • Infectious Disease

Broad spectrum of β-lactamase coverage and potent antimicrobial activity of xeruborbactam in combination with meropenem against carbapenemase-producing Enterobacterales, including strains resistant to new β-lactam/β-lactamase inhibitor combinations. (PubMed, Antimicrob Agents Chemother) - "The MICs of meropenem, meropenem/xeruborbactam, meropenem/vaborbactam, imipenem, imipenem/relebactam, cefepime, cefepime/taniborbactam, ceftazidime, ceftazidime/avibactam, aztreonam, and aztreonam/avibactam were determined by reference broth microdilution and interpreted following the European Committee on Antimicrobial Susceptibility Testing guidelines, using the breakpoint of the β-lactam alone for not yet approved combinations. Xeruborbactam restored meropenem activity against the strains carrying resistance mechanisms to β-lactam/β-lactamase inhibitor combinations, including strains producing KPC variants or MBLs in combination with additional chromosomal alterations (MIC range: ≤0.06-0.25 and ≤0.06-4 mg/L, respectively). Our findings highlight the potential of xeruborbactam in combination with meropenem as a promising treatment against carbapenemase-producing Enterobacterales, including strains with emerging resistance to other β-lactam/β-lactamase inhibitor..."

Journal

Cefepime-zidebactam therapy for extensively drug-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae infection as a bridge to liver transplantation. (PubMed, JAC Antimicrob Resist) - "Serial clinical isolates recovered from biliary fluid and ascitic fluid were tested for susceptibility to cefiderocol, aztreonam-avibactam, cefepime-taniborbactam, cefepime-zidebactam, and cefiderocol-xeruborbactam by broth microdilution...The patient was treated with a regimen of cefiderocol and eravacycline, with persistent fever and development of hepatic microabscesses on imaging...Antimicrobial therapy with cefepime-zidebactam along with source control allowed successful liver transplantation in a patient with cefiderocol-resistant K. pneumoniae and P. aeruginosa. Cefepime-zidebactam may be a therapeutic option for extensively drug-resistant Gram-negative organisms."

Journal • Infectious Disease • Pneumonia • Transplantation

Clinical and microbiological analysis of bloodstream infections by four cefiderocol-resistant and not previously exposed NDM-producing Klebsiella pneumoniae. (PubMed, J Antimicrob Chemother) - "This case series highlights the urgent need of new therapeutic agents that will overcome the diffusion of NDM-KP resistant to FDC. The emergence of NDM-KP with an acquired fec operon in nosocomial settings, even without a previous drug exposure, may further compromise cefiderocol efficacy. Further studies will be necessary to assess the in vivo activity of xeruborbactam, a new cyclic boronate β-lactamase inhibitor, which may restore cefiderocol susceptibility in NDM-KP isolates."

Journal • CNS Disorders • Infectious Disease • Pneumonia • Psychiatry • ST14

Antibiotics and non-traditional antimicrobial agents for pseudomonas aeruginosa in clinical phases 1, 2, and 3 trials. (PubMed, Expert Opin Investig Drugs) - "Traditional agents in clinical development include β-lactam/β-lactamase inhibitors (funobactam, taniborbactam, QPX2014-xeruborbactam), aminoglycosides (apramycin), polymyxin derivatives (upleganan, MRX-8, and SPR741), fluoroquinolones (MP-376), and lipopolysaccharide transport inhibitors (murepavadin). Non-traditional antibiotics in clinical development include anti-virulence agents (fluorothiazinone), monoclonal antibodies (INFEX-702, TRL-1068, and CMTX-101), bacteriophages (AP-PA02, YPT-01, BX004-A, and WRAIR-PAM-CF1), and miscellaneous agents (AR-501, PLG-0206, SNSP-113, OligoG CF-5/20, and ALX-009). A considerable number of antimicrobial agents, some with novel mechanisms of action, are in clinical phases of development for treating Pseudomonas aeruginosa infections. The urgent need for more therapeutic options necessitates the rapid optimization of progress to introduce new agents into clinical practice."

Journal • Review • Infectious Disease

Challenges of Carbapenem-Resistant Enterobacteriaceae in the Development of New β-Lactamase Inhibitors and Antibiotics. (PubMed, Antibiotics (Basel)) - "However, compared with taniborbactam, xeruborbactam is the first bicyclic boronate in clinical development with a pan-β-lactamase inhibition spectrum, including the IMP subfamily. A deeper understanding of the mechanistic properties of the active sites enables rational drug design principles to be established for inhibitors targeting both SβLs and MβLs. This review aims to provide a comprehensive overview of current therapeutic strategies and future perspectives for the development of carbapenemase inhibitor drug candidates."

Journal • Review

The Emerging Concern of IMP Variants Being Resistant to the Only IMP-Type Metallo-ß-Lactamase Inhibitor, Xeruborbactam (ASM Microbe 2025) - "Background: Metallo-β-lactamases (MBLs) of IMP-type hydrolyze almost all β-lactams and are not inactivated by currently commercialized ß-lactamase inhibitors, including taniborbactam (TAN) which inhibit other MBLs of the NDM- and VIM-types...Susceptibility testing of cefepime, meropenem in combination with TAN or XER at 4 mg/L or 8mg/L, was performed by broth microdilution... The production of IMP-6, IMP-10, IMP-14, IMP-26 conferred resistance to XER and, therefore, to the combination MER-XER under clinical development. On the other hand, this study highlighted IMP-59, as the only IMP variant sensitive to both TAN and XER."

Infectious Disease

The emerging concern of IMP variants being resistant to the only IMP-type metallo-β-lactamase inhibitor, xeruborbactam. (PubMed, Antimicrob Agents Chemother) - "Metallo-β-lactamases (MBLs) of IMP type are not inhibited by currently commercialized β-lactamase inhibitors, including taniborbactam (TAN), which inhibits only NDM- and VIM-type enzymes. However, the development of xeruborbactam (XER), which additionally inhibits IMP enzymes, may provide effective drug combinations such as meropenem-XER (MEM-XER) against most MBL producers...Finally, structural analyses and molecular modeling simulations indicated that the Ser262Gly mutation in IMP-6 may alter the electronic properties of the active site, whereas the Phe residue in IMP-10 may exert a steric effect counteracting XER binding. Resistance to XER in IMP-6, IMP-10, IMP-14, and IMP-26 variants, conferring resistance to MEM-XER, might be considered a serious concern since MEM-XER will be supposed to be a salvage therapy for MBL-, and especially IMP-producing Enterobacterales infections."

Journal • Infectious Disease

PK & Safety Study of Xeruborbactam Oral Prodrug Combined With Ceftibuten in Participants With Renal Impairment (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Qpex Biopharma, Inc. | Recruiting ➔ Completed

Trial completion • Infectious Disease • Renal Disease

Discovery of 3-methacylic acid substituted benzoxaboroles as dual metallo- and serine-β-lactamase inhibitors. (PubMed, Eur J Med Chem) - "Co-crystallographic analyses revealed their binding modes with VIM-2 and OXA-48, which are similar as those of taniborbactam and xeruborbactam. Bacterial assays demonstrated that compound 10 can potentiate meropenem against multidrug-resistant Gram-negative strains. This work provides new lead compounds and structural basis for developing new drug candidates against MBL/SBL-mediated carbapenem resistance."

Journal • Infectious Disease

Universal beta-lactamase coverage and potent antimicrobial activity of xeruborbactam plus meropenem against carbapenemase-producing Enterobacterales, including strains resistant to new beta-lactam/beta-lactamase inhibitor combinations (ESCMID Global 2025) - No abstract available