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

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

The emerging concern of IMP variants being resistant to the only IMP-type metallo-beta-lactamase inhibitor, xeruborbactam (ESCMID Global 2025) - No abstract available

In vitro potency of ceftibuten with xeruborbactam against β-lactamase-producing isolates of Enterobacterales (ENT) from the SENTRY global surveillance programme (ESCMID Global 2025) - No abstract available

Preclinical

In vitro activity and resistance mechanisms of novel antimicrobial agents against metallo-β-lactamase producers. (PubMed, Eur J Clin Microbiol Infect Dis) - "Cefiderocol and aztreonam/avibactam are already clinically available and recommended by international guidelines. In addition, two new classes of β-lactam/ β-lactamase combinations are under clinical evaluation: (i) combination of β-lactam with novel boronic-derived inhibitors (e.g. taniborbactam and xeruborbactam), (ii) combination of β-lactam with last generation diazabicyclooctane β-lactamase inhibitors (e.g. zidebactam and nacubactam), active on most of serine-β-lactamases but also showing strong intrinsic activity on PBP-2. This review aims to provide up-to-date data on the characteristics, activity and emerging resistance mechanisms of the armamentarium of clinically available or soon-to-be introduced drugs for the treatment of MβL-producing Gram-negative organisms."

Journal • Preclinical • Review • Infectious Disease

PK & Safety Study of Xeruborbactam Oral Prodrug Combined With Ceftibuten in Participants With Renal Impairment (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Qpex Biopharma, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Renal Disease

P1, DDI & MAD PK and Safety Study of Xeruborbactam Oral Prodrug in Combo With Ceftibuten in Healthy Participants (clinicaltrials.gov) - P1 | N=71 | Recruiting | Sponsor: Qpex Biopharma, Inc. | Trial completion date: Dec 2024 ➔ Oct 2025 | Trial primary completion date: Sep 2024 ➔ Aug 2025

Trial completion date • Trial primary completion date • Infectious Disease

β-Lactam/β-Lactamase Inhibitor Combination Antibiotics Under Development. (PubMed, Pathogens) - "The incorporation of ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/cilastatin/relebactam has provided new therapeutic options in the treatment of patients with infections due to MDR pathogens. Cefiderocol along with cefepime/enmetazobactam, avibactam/aztreonam, and sulbactam/durlobactam have been recently added to these agents as therapeutic choices, particularly for metallo-β-lactamase producing Gram-negative bacteria...However, only a few have advanced through phase 1, 2, and 3 clinical trials. Among them, in this article, we focus on the most promising combinations of cefepime/zidebactam, cefepime/taniborbactam, and imipenem/cilastatin/funobactam, which are currently under investigation in phase 3 trials."

Journal • Review • Infectious Disease

Advancements in the fight against globally distributed OXA-48 carbapenemase: evaluating the new generation of carbapenemase inhibitors. (PubMed, Antimicrob Agents Chemother) - "To assess the potential of these compounds, this study compared the efficacy against OXA-48 of novel β-lactamase inhibitors, specifically the 1,6-diazabicyclo[3,2,1]octanes (DBOs) avibactam, relebactam, zidebactam, nacubactam, and durlobactam, along with the cyclic and bicyclic boronates vaborbactam, taniborbactam, and xeruborbactam...Combinations, such as cefepime/zidebactam, meropenem/nacubactam, and sulbactam/durlobactam, show promising activity against OXA-48-producing Enterobacterales, while ceftazidime/avibactam, cefepime/taniborbactam, and meropenem/xeruborbactam combinations also appear highly active, largely due to the excellent kinetics of these new inhibitors. Overall, this comprehensive analysis provides important insights into the effectiveness of new BLIs against OXA-48-producing Enterobacterales, highlighting xeruborbactam, durlobactam, and avibactam as leading candidates. Additionally, BLIs like zidebactam, nacubactam, and taniborbactam also showed..."

Journal • Infectious Disease

Convergent synthesis of bicyclic boronates via a cascade regioselective Suzuki-Miyaura/cyclisation protocol. (PubMed, Chem Commun (Camb)) - "Herein we disclose an operationally simple, regioselective cross-coupling/cyclisation reaction of easily accessible vicinal boronic esters with 2-halophenols to rapidly forge 3-substituted bicyclic boronates. The utility of the platform was demonstrated via expedient access to Xeruborbactam derivatives, chemoselective manipulation of formed products and the convergent approach to bicyclic boronates with a pendent biomolecular probe."

Journal

Assessment of the activity and mechanisms of resistance to cefiderocol and combinations of β-lactams and the novel β-lactamase inhibitors avibactam, taniborbactam, zidebactam, nacubactam, xeruborbactam, and ANT3310 in emerging double-carbapenemase-producing Enterobacterales. (PubMed, Antimicrob Agents Chemother) - "Minimum inhibitory concentration (MIC) values for ceftazidime, ceftazidime/avibactam, aztreonam, aztreonam/avibactam, aztreonam/nacubactam, cefiderocol, cefepime, cefepime/taniborbactam, cefepime/zidebactam, cefepime/nacubactam, imipenem, imipenem/relebactam, meropenem, meropenem/vaborbactam, meropenem/xeruborbactam, and meropenem/ANT3310 were determined by reference broth microdilution. Meropenem/ANT3310 (MIC50/MIC90 = 0.5/≥64 mg/L; 47/57 susceptible) and cefepime/taniborbactam (MIC50/MIC90 = 0.5/16 mg/L; 44/57 susceptible) also retained high levels of activity, although they were affected by NDM-type enzymes in combination with porin deficiency. Our findings highlight that cefiderocol and combinations of β-lactams and the novel β-lactamase inhibitors avibactam, nacubactam, taniborbactam, zidebactam, xeruborbactam, and ANT3310 show promising activity against double-carbapenemase-producing Enterobacterales."

Journal

Potentially effective antimicrobial treatment for pneumonia caused by isolates of carbapenem-resistant and extensively drug-resistant Acinetobacter baumannii complex species: what can we expect in the future? (PubMed, Expert Rev Anti Infect Ther) - "Doubling the routine intravenous maintenance dosages of conventional tigecycline (100 mg every 12 h) and minocycline (200 mg every 12 h) might be recommended for the effective treatment of pneumonia caused by CR/XDR-Abc. Nebulized polymyxin E, novel parenteral rifabutin BV100, and new polymyxin derivatives (SPR206, MRX-8, and QPX9003) could be considered supplementary combination options with other antibiotic classes. Regarding other novel antibiotics, the potency of sulbactam-durlobactam (1 g/1 g infused over 3 h every 6 h intravenously) combined with imipenem-cilastatin, and the β-lactamase inhibitor xeruborbactam, is promising. Continuous infusion of full-dose cefiderocol is likely an effective treatment regimen for CR/XDR-Abc pneumonia. Zosurabalpin exhibits potent anti-CR/XDR-Abc activity in vitro, but its practical use in clinical therapy remains to be evaluated. The clinical application of antimicrobial peptides and bacteriophages requires validation."

Journal • Review • Infectious Disease • Pneumonia • Respiratory Diseases

Relative inhibitory activities of newly developed diazabicyclooctanes, boronic acid derivatives, and penicillin-based sulfone β-lactamase inhibitors against broad-spectrum AmpC β-lactamases. (PubMed, Antimicrob Agents Chemother) - "The relative inhibitory activities of diazabicyclooctanes (avibactam, relebactam, zidebactam, nacubactam, durlobactam), boronic acid derivatives (vaborbactam, taniborbactam, xeruborbactam), and penicillin-based sulfone derivative enmetazobactam were evaluated against several intrinsic and acquired class C β-lactamases. Notably, durlobactam exhibited the most pronounced inhibitory effect. Interstingly, the chromosomal AmpC of Acinetobacter baumannii was the least sensitive enzyme to the newly developed β-lactamase inhibitors."

Journal

The Impact of Xeruborbactam on in vitro Activity of Cefiderocol against a Panel of Enterobacterales Enriched with Isolates with Reduced Cefiderocol Susceptibility (IDWeek 2024) - No abstract available

Preclinical • Infectious Disease

The Impact of Xeruborbactam on in vitro Activity of Cefiderocol against a Panel of Acinetobacter baumannii Enriched in Isolates with Reduced Cefiderocol Susceptibility (IDWeek 2024) - No abstract available

Preclinical • Infectious Disease

A DDI Study to Investigate PK and Safety of Cefiderocol in Combination With Xeruborbactam in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Qpex Biopharma, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease

A DDI Study to Investigate PK and Safety of Cefiderocol in Combination With Xeruborbactam in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Qpex Biopharma, Inc.

Combination therapy • New P1 trial • Infectious Disease

PK & Safety Study of Xeruborbactam Oral Prodrug Combined With Ceftibuten in Participants With Renal Impairment (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Qpex Biopharma, Inc. | Initiation date: Jun 2024 ➔ Oct 2024

Trial initiation date • Infectious Disease • Renal Disease

Impact of chromosomally encoded resistance mechanisms and transferable β-lactamases on the activity of cefiderocol and innovative β-lactam/β-lactamase inhibitor combinations against Pseudomonas aeruginosa. (PubMed, J Antimicrob Chemother) - "Cefiderocol and new β-lactam/β-lactamase inhibitor combinations show promising and complementary in vitro activity against mutational and transferable P. aeruginosa β-lactam resistance. However, the combined effects of efflux pumps, OprD deficiency and efficient β-lactamases could still result in the loss of all therapeutic options. Resistance surveillance, judicious use of new agents and continued drug development efforts are encouraged."

Journal

Unveiling the Secrets of Acinetobacter baumannii: Resistance, Current Treatments, and Future Innovations. (PubMed, Int J Mol Sci) - "Among the most promising alternatives under investigation are the combination sulbactam/durlobactam, cefepime/zidebactam, imipenem/funobactam, xeruborbactam, and the newest molecules such as novel polymyxins or zosurabalpin. Furthermore, the potential of phage therapy, as well as deep learning and artificial intelligence, offer a complementary approach that could be particularly useful in cases where traditional strategies fail. The fight against A. baumannii is not confined to the microcosm of microbiological research or hospital wards; instead, it is a broader public health dilemma that demands a coordinated, global response."

Journal • Review • Infectious Disease

In vitro effects of the new oral β-lactamase inhibitor xeruborbactam in combination with oral β-lactams against clinical Mycobacterium abscessus isolates. (PubMed, Microbiol Spectr) - "We aimed to evaluate the in vitro effects of xeruborbactam, a cyclic boronic acid β-lactamase inhibitor, against M. abscessus when combined with five β-lactams (amoxicillin, tebipenem, cefdinir, cefuroxime, and cefoxitin). Xeruborbactam lowered the MIC90 values of tebipenem by five dilutions, and the number of susceptible isolates increased from 1/43 (2%) to 43/43 (100%). We showed that the tebipenem-xeruborbactam combination might be of interest to explore further as a potentially effective oral regimen for outpatient treatment of M. abscessus pulmonary disease."

Combination therapy • Journal • Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Relative Inhibitory Activities of the Broad-Spectrum ß-Lactamase Inhibitor Xeruborbactam against Metallo-ß-Lactamases (ASM Microbe 2024) - "Although the newly-developed BLI taniborbactam (TAN) possesses the ability to inhibit MBL hydrolytic activities, all IMP-type enzymes and some variants such as NDM-9 and VIM-83 have been found resistant... Recombinant E. coli strains encoding a series of subclass B1 MBLs (VIM, NDM and IMP variants, together with DIM-1, GIM-1, SIM-1, SPM-1), B2 (PFM-1) or B3 (AIM-1) were constructed and susceptibility testing was performed for meropenem (MER), cefepime (FEP), ceftazidime (CAZ) and their combinations with XER (FEP-XER, CAZ-XER, MER-XER) at a fixed concentration of 4 mg/L...Noteworthy, the IMP-10 variant differing from IMP-1 by a single amino-acid substitution was found resistant to XER... This research revealed that XER exhibited a wider range of activity against B1 MBLs, but an overall weaker inhibitory activity than TAN. Noteworthy, VIM-1-like enzymes were less sensitive to XER and to TAN compared to VIM-2-like enzymes. No inhibition was observed against GIM-1, SIM-1,..."

Relative inhibitory activities of the broad-spectrum β-lactamase inhibitor xeruborbactam in comparison with taniborbactam against metallo-β-lactamases produced in Escherichia coli and Pseudomonas aeruginosa. (PubMed, Antimicrob Agents Chemother) - "As observed with taniborbactam, the combination of xeruborbactam (XER) with β-lactams, namely, ceftazidime, cefepime and meropenem, led to significantly decreased MIC values for a wide range of B1-type MBL-producing E. coli, including most recombinant strains producing NDM, VIM, IMP, GIM-1, and DIM-1 enzymes. The determination of the constant inhibition (Ki) of XER revealed a much higher value against IMP-10 than against NDM-1, VIM-2, and IMP-1. Hence, IMP-10 that differs from IMP-1 by a single amino-acid substitution (Val67Phe) can, therefore, be considered resistant to XER."

Journal

The emerging concern of IMP-10 being resistant to the only IMP-type metallo-ß-lactamase inhibitor, xeruborbactam (ECCMID 2024) - No abstract available

Relative inhibitory activities of the broad-spectrum ß-lactamase inhibitor xeruborbactam against metallo-ß-lactamases (ECCMID 2024) - No abstract available

In vitro potency of ceftibuten combinations with xeruborbactam, ledaborbactam or avibactam against recent European isolates of Enterobacterales (ECCMID 2024) - No abstract available

Preclinical