nacubactam (RG6080) / Roche, Meiji Seika - LARVOL DELTA

Application of Epithelial Lining Fluid Drug Concentrations to MICi-Based PK/PD Modeling of Cefepime/Nacubactam in a Murine Model of CPE Pneumonia. (PubMed, J Infect Chemother) - "These findings support the utility of MICi-based PK/PD analysis for optimizing combination antibiotic therapy in pneumonia."

Journal • PK/PD data • Preclinical • Infectious Disease • Pneumonia • Respiratory Diseases

Pharmacokinetics, safety, and tolerability of nacubactam (OP0595) after intravenous infusion: a randomized, double-blind, placebo-controlled phase I clinical trial in healthy Chinese male subjects. (PubMed, Clin Exp Med) - P1 | "Nacubactam, a novel β-lactamase inhibitor, combined with cefepime or aztreonam, effectively supports CRE infection treatment...Its combination with ceftazidime or aztreonam is promising for treating multidrug-resistant Gram-negative bacterial infections...In this work, we conducted a phase I randomized, double-blind, placebo-controlled trial to clinically evaluate nacubactam for the first time in healthy Chinese male subjects, demonstrating its good safety profile, dose-proportional pharmacokinetics, and mainly renal excretion. These data provide insights into the clinical application of nacubactam.Trial registration This trial was registered on the Chinese Clinical Trial Registration website, registration number ChiCTR2500103582."

Clinical • Journal • P1 data • PK/PD data • Infectious Disease

Integral-2: P3 Study to Assess Efficacy and Safety of Cefepime/Nacubactam and Aztreonam/Nacubactam Versus Best Available Therapy for Adults With Infection Due to Carbapenem Resistant Enterobacterales (clinicaltrials.gov) - P3 | N=126 | Completed | Sponsor: Meiji Seika Pharma Co., Ltd. | Recruiting ➔ Completed

Trial completion • Infectious Disease • Nephrology • Pneumonia • Respiratory Diseases

Classification and applicability of new beta-lactamase inhibitors. (PubMed, Rev Esp Quimioter) - "This non-exhaustive minireview describes the main characteristics of the new beta-lactamase inhibitors (enmetazobactam, avibactam, relebactam, durlobactam, zidebactam, nacubactam, vaborbactam, taniborbactam, and xeruborbactam), their spectrum of inhibition, their activity in combination with different beta-lactams, the main resistance mechanisms that can compromise their activity and the main applications of the different beta-lactam-beta-lactamase inhibitor combinations depending on the type of beta-lactamase/carbapenemase and the microorganism involved."

Journal • Review

The Rapid CarbaLux Combination Test to Uncover Bacterial Resistance and Heteroresistance Prior to Antibiotic Treatment. (PubMed, Diagnostics (Basel)) - "It was expected that a specific inhibitor that protects imipenem or meropenem from enzymatic deactivation during antibacterial therapy would perform the same in vitro with fluorescent carbapenem and preserve its fluorescence. The new additional CarbaLux combination test is used if the classic test is positive for carbapenemases: a classic test tube pre-dosed with fluorescent carbapenem is spiked with cloxacillin; with recently launched carbapenemase inhibitors, e.g., avibactam, relebactam, zidebactam, nacubactam, or vaborbactam; or with picolinic acid...They are simpler, broader in scope, and more cost-effective; they can also detect antimicrobial heteroresistance or AmpC beta-lactamase hyperproduction, which is normally undetected when performing automated antibiotic susceptibility testing. The new tests are suitable for clinical diagnosis, public health purposes, and infection control."

Journal • Infectious Disease

Evaluation of in vitro efficacy of aztreonam-nacubactam and cefepime-nacubactam against clinical isolates of Stenotrophomonas maltophilia. (PubMed, Antimicrob Agents Chemother) - "While ATM-NAC showed more significant MIC reduction, FEP-NAC also remarkably decreased MICs, despite cefepime being a substrate for L1 β-lactamase. These findings suggest the potential of β-lactam-NAC combinations as promising alternatives, warranting further in vivo studies to confirm clinical applicability."

Journal • Preclinical

Electrostatic interactions influence diazabicyclooctane inhibitor potency against OXA-48-like β-lactamases. (PubMed, RSC Med Chem) - "Diazabicyclooctane (DBO) inhibitors, including avibactam and nacubactam, act on a wide range of enzymes to overcome β-lactamase-mediated resistance...Crystallographic and mass spectrometry data demonstrate that all three enzymes support desulfation of the bound DBOs. The results indicate that interactions with Arg214 affect DBO potency, suggesting that sequence variation in OXA-48-like β-lactamases affects reactivity towards inhibitors as well as β-lactam substrates."

Journal

Nacubactam (OP0595): a Novel Triple-Action Diazabicyclooctane in Combination with Cefepime or Aztreonam (IDWeek 2025) - No abstract available

Combination therapy • Infectious Disease

Clinical efficacy, safety and pharmacokinetics of novel β-lactam/β-lactamase inhibitor combinations: a systematic review. (PubMed, JAC Antimicrob Resist) - "A total of 191 articles addressing clinical research regarding the efficacy, safety, tolerability, and PK of new BL/BLI combinations with avibactam, durlobactam, enmetazobactam, nacubactam, relebactam, taniborbactam, tazobactam, vaborbactam and zidebactam were included...In spite of that, the development of new BLI effective for class B metallo-β-lactamases (MBL) is still challenging, being aztreonam/avibactam the only approved combination active against MBL-producing bacteria. Although there has been extensive research to develop new BLI and BL/BLI combinations, only a few have reached the market. More evidence of its usefulness in the real world is still needed."

Journal • PK/PD data • Review • Infectious Disease • Nephrology • Pneumonia • Respiratory Diseases

Rapid emergence of resistance to broad-spectrum direct antimicrobial activity of avibactam. (PubMed, Microbiol Spectr) - "Avibactam (AVI) is a diazabicyclooctane (DBO) β-lactamase inhibitor used clinically in combination with ceftazidime...This activity has some mechanistic similarities to that of more potent novel DBOs (zidebactam and nacubactam) in late clinical development...We also found that bacteria with impairments in the stringent response could still develop resistance to AVI through different mutations. Our findings indicate the importance of studying how resistance will emerge to newer, more potent DBOs in development and early clinical use."

Journal • Infectious Disease

A randomized, double-blind, placebo-controlled Phase 1 study to evaluate the pharmacokinetic profile, safety and tolerability of Nacubactam administered by single and multiple intravenous infusions in healthy Chinese male subjects (ChiCTR) - P1 | N=20 | Completed | Sponsor: The Third Xiangya Hospital of Central South University; Meiji Seika Pharma Co., Ltd.

New P1 trial • Infectious Disease

Integral-2: P3 Study to Assess Efficacy and Safety of Cefepime/Nacubactam and Aztreonam/Nacubactam Versus Best Available Therapy for Adults With Infection Due to Carbapenem Resistant Enterobacterales (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Meiji Seika Pharma Co., Ltd. | Trial completion date: Feb 2025 ➔ Sep 2025 | Trial primary completion date: Feb 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Infectious Disease • Nephrology • Pneumonia • Respiratory Diseases

In vitro microbiological activity of aztreonam, cefepime and cefiderocol combined with nacubactam against NDM-harbouring Escherichia coli and Klebsiella pneumoniae clinical isolates (ESCMID Global 2025) - No abstract available

Late-breaking abstract • Preclinical • Infectious Disease • Pneumonia

Activity of the novel combination therapies cefepime/nacubactam against 12,613 clinical isolates of Enterobacterales collected worldwide during 2021-2023 (ESCMID Global 2025) - No abstract available

Clinical • Combination therapy

Genomic approach to evaluate the intrinsic antibacterial activity of novel diazabicyclooctanes (zidebactam and nacubactam) against clinical Escherichia coli isolates from diverse clonal lineages in the United Arab Emirates. (PubMed, J Infect Public Health) - "This study provides compelling evidence for the potential of DBOs, particularly zidebactam, as novel antibacterial agents. Their unique characteristics and broad-spectrum activity position them as promising candidates for future antibiotic development. While the inclusion of DBO therapies in the antibiotic arsenal could significantly impact MDR pathogen treatment, realizing their full potential requires further research, clinical evaluation, and vigilant monitoring of resistance mechanisms through integrated genomic approaches."

Journal

Susceptibility of a worldwide collection of 12,613 Enterobacterales isolated during 2021-2023 to the novel combination therapy aztreonam/nacubactam (ESCMID Global 2025) - No abstract available

Combination therapy

In vitro activities of aztreonam/nacubactam and cefepime/nacubactam against carbapenemase-producing Enterobacterales collected as part of a global surveillance study in 2021-2022 (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

The combined dual β-lactams and diazabicyclooctane β-lactamase inhibitor is highly effective against Mycobacterium abscessus species in vitro. (PubMed, J Glob Antimicrob Resist) - "The combination of cefazolin, cefotiam, cefoxitin, or cefuroxime with imipenem and nacubactam was highly effective against MABS. Without nacubactam, the combination of cefoxitin and imipenem was effective."

Journal • Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases

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

Integral-1: Efficacy and Safety of Cefepime/Nacubactam or Aztreonam/Nacubactam Compared to Imipenem/Cilastatin in Subjects With Complicated Urinary Tract Infections or Acute Uncomplicated Pyelonephritis (clinicaltrials.gov) - P3 | N=614 | Completed | Sponsor: Meiji Seika Pharma Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Nephrology

In vitro antimicrobial activity of six novel β-lactam and β-lactamase inhibitor combinations and cefiderocol against NDM-producing Enterobacterales in China. (PubMed, Int J Antimicrob Agents) - "Aztreonam/avibactam and aztreonam/nacubactam showed the highest activity against NPE. The potential resistance mechanisms of novel antimicrobial agents against NPE should be under active surveillance."

Journal • Preclinical • Infectious Disease • Pneumonia

Simulated achievement rate of β-lactams/nacubactam treatment in humans using instantaneous MIC-based PK/PD analysis. (PubMed, J Antimicrob Chemother) - "AZT/NAC and CFPM/NAC are bactericidal against CPE at practically achievable dosages."

Journal • PK/PD data • Infectious Disease

Integral-1: Efficacy and Safety of Cefepime/Nacubactam or Aztreonam/Nacubactam Compared to Imipenem/Cilastatin in Subjects With Complicated Urinary Tract Infections or Acute Uncomplicated Pyelonephritis (clinicaltrials.gov) - P3 | N=614 | Active, not recruiting | Sponsor: Meiji Seika Pharma Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Nephrology