relebactam (MK-7655) / Merck (MSD) - LARVOL DELTA

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

Structural insights into the activity of carbapenemases: understanding the mechanism of action of current inhibitors and informing the design of new carbapenem adjuvants. (PubMed, RSC Med Chem) - "β-Lactamase inhibitors currently available on the market include clavulanic acid, sulbactam, tazobactam, avibactam, relebactam and vaborbactam but, while they are active against serine β-lactamases, they are inactive against the zinc-containing metallo-β-lactamases. This review aims to discuss the distinctive structural qualities of β-lactamase enzymes and to summarise the efficacy of clinically approved and emerging β-lactamase inhibitors against clinically significant carbapenemases."

Journal • Review

Adverse Event Signals Associated with Beta-Lactamase Inhibitors: Disproportionality Analysis of USFDA Adverse Event Reporting System. (PubMed, J Xenobiot) - "This analysis highlights a spectrum of AE signals with BLIs, including unexpected associations warranting further investigation. While some events may reflect comorbidities or concomitant therapies, these findings underscore the importance of continued pharmacovigilance and targeted clinical studies to clarify causality and ensure the safe use of BLIs in practice."

Adverse events • Journal • Agranulocytosis • Cardiovascular • CNS Disorders • Epilepsy • Granulocytopenia • Hematological Disorders • Immunology • Infectious Disease • Respiratory Diseases • Septic Shock

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

An Unusual Citrobacter Sedlakii Isolate Yielding a False Positive ECIM Result (ASM Microbe 2025) - "Carbapenems such as meropenem (MEM) and imipenem (IPM) are broad-spectrum β-lactams used in severe infections with multi-drug resistant Gram-negative bacteria...Conversely, we confirmed the presence of a SBL using the SBL inhibitor relebactam, which completely prevented the breakdown of IPM, suggesting for the first time that SED-1 possesses appreciable carbapenemase activity. Ultimately, we attributed the false-positive eCIM test to the combined antibacterial activity of MEM and EDTA against C. sedlakii, not an MBL. Our report exemplifies challenges in CPO testing, namely the discrepancies between susceptibility testing and other phenotypic methods due to inoculum effects and weakly active carbapenemases."

Infectious Disease

Resistance to the combination of ?-lactams and ?-lactamase inhibitors in Mycobacterium abscessus (ECFS 2025) - "We have previously shown that second-generation -lactamase inhibitors belonging to the diazabicyclooctanes (DBOs) family, avibactam (AVI) and relebactam, improve -lactams activity. Recently, we identified a synergistic effect in vitro, in vivo, and intracellularly between two -lactams, IMI and amoxicillin (AMOX), in the presence of DBOs against M. abscessus... In vitro resistance to the triple combination is not associated with mutations in -lactam targets but appears to be due to mutations in efflux pumps or mutations affecting the mycomembrane permeability. The next objective will be to evaluate the risk of the emergence of resistance associated with the administration of the triple combination in a murine model of infection."

Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Respiratory Diseases

Breaking Through Resistance: A Comparative Review of New Beta-Lactamase Inhibitors (Avibactam, Vaborbactam, Relebactam) Against Multidrug-Resistant Superbugs. (PubMed, Antibiotics (Basel)) - "The introduction of new β-lactam-β-lactamase inhibitors (BLBLIs), such as ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/cilastatin/relebactam, expands our therapeutic options against carbapenem-resistant Gram-negative bacteria, including those pathogens for which therapeutic options are limited...The recent introduction of aztreonam/avibactam marks a significant advancement in our therapeutic armamentarium against metallo-β-lactamase-producing pathogens...The present review aims to provide clinicians with a detailed understanding of each BLBLI treatment option to guide the optimal use of these new agents for the effective treatment of difficult infections caused by carbapenemase-producing Enterobacterales infections. This review is based on literature retrieved from PubMed, Scopus, Web of Science, and the Cochrane Library."

Journal • Review • Infectious Disease

REL/DPA/AVI method: a novel approach for rapid detection of carbapenemase-producing Enterobacterales directly from positive blood cultures based on optical density. (PubMed, J Clin Microbiol) - "The relebactam, dipicolinic acid, and avibactam sodium (REL/DPA/AVI) method is a novel phenotypic test for carbapenemase targeting to address these challenges...Although numerous advanced technologies such as mNGS, Filmarray, Verigene, and NG-Test CARBA 5 DetecTool have been developed for carbapenemase typing of CPE in positive blood cultures, our method is distinguished by a significant economic advantage, with a cost of less than $1 USD per test. This substantial cost-effectiveness underscores the immense potential for widespread clinical applications."

Journal • Infectious Disease

Impact of the double deletion ΔG242-T243 in KPC-2 in the effectiveness of ceftazidime-avibactam and imipenem-relebactam. (PubMed, Antimicrob Agents Chemother) - "Expansion of the substrate profile of KPC-14 toward ceftazidime is associated with a trade-off for carbapenems, other penicillins, and cephalosporins, as well as a higher inhibition by clavulanic acid compared to KPC-2. This study provides a better understanding of how deletions in the 237-243 loop affect the effectiveness of novel DBO-combinations and supports the hypothesis that these mutations result in CZA resistance by other different biochemical mechanisms than mutations in the Ω-loop."

Journal • Infectious Disease • Pneumonia

Comparative evaluation of five β-Lactamase inhibitors in combination with β-Lactams against multidrug-resistant Mycobacterium tuberculosis in vitro. (PubMed, BMC Infect Dis) - "the combination of tebipenem and relebactam shows the most potent activity against MDR-TB isolates. In addition, the Ser111Arg and Asn213Thr substitution of BlaC may be associated with increased susceptibility of MDR-TB isolates to meropenem in thepresence of clavulanate and sulbactam."

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

Phenotypic and kinetic characterisation of PER-14: a novel beta-lactamase variant resistant to avibactam and relebactam (ESCMID Global 2025) - No abstract available

Standardising aztreonam/relebactam disk diffusion susceptibility testing in Enterobacterales: a step towards reliable clinical application (ESCMID Global 2025) - No abstract available

Clinical

SY105 - Novel beta-lactams and beta-lactamase inhibitors: a diagnostic and therapeutic approach (ESCMID Global 2025) - "Organised by EUCAST Steering Committee Novel beta-lactams (e.g., cefiderocol) or beta-lactamase inhibitors (e.g., avibactam, relebactam) are promising agents in the era of global spread of carbapenemase-producing bacteria. Unfortunately, resistance to those novel drugs has been described immediately after their introduction into the market even though in a nai?ve population. This session combines laboratory and clinical aspects of the novel antibiotics in routine practice."

In Vitro Activity of Aztreonam in Combination with Relebactam against Gram-Negative Pathogens Producing Various Serine and Metallo-β-Lactamases. (PubMed, J Glob Antimicrob Resist) - "The addition of relebactam has a potential to restore the activity of aztreonam against strains that produce metallo-β-lactamase and serine-β-lactamase. The combination may have a role in the treatment of infections due to these strains in countries without access to ceftazidime-avibactam."

Journal • Preclinical • Infectious Disease • Pneumonia

Restoring ceftolozane susceptibility: a role for diazabicyclooctane β-lactamase inhibitors? (PubMed, Antimicrob Agents Chemother) - "Median MIC fold-increase from baseline was 32-, 24-, 16-, and 6-fold for ceftolozane-tazobactam, ceftolozane-avibactam (AVI), ceftolozane-relebactam (REL), and ceftolozane-durlobactam (DUR), respectively. Enhanced ceftolozane-durlobactam activity was evident in specific ampC mutations."

Journal • 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

FL058, a novel β-lactamase inhibitor, increases the anti-Mycobacterium abscessus activity of imipenem. (PubMed, Int J Antimicrob Agents) - "The elevated anti-MABC activity exhibited by imipenem combined with FL058 suggests a potential new approach to treating MABC infections."

Journal • Infectious Disease

Efficiency of combination therapy versus monotherapy for the treatment of infections due to carbapenem-resistant Gram-negative bacteria: a systematic review and meta-analysis. (PubMed, Syst Rev) - "Monotherapy or combination therapy is controversial. The systematic review and meta-analysis suggested that monotherapy is associated with higher mortality, lower clinical success, and lower microbiological eradication for treating infection caused by CRGNB. The available evidence suggests that treatment should be selected based on the specific bacteria and antibiotic used. Monotherapy for CRE infections may lead to adverse outcomes. For CRAB infections, no significant differences were found between combination therapy and monotherapy."

Clinical • Gram negative • Journal • Monotherapy • Retrospective data • Review • Infectious Disease

Eco-Friendly Synchronous Spectrofluorimetric Determination of Imipenem, Cilastatin, and Relebactam; Application to Market Formulations and Biological Fluids; Greenness Assessment. (PubMed, J Fluoresc) - "Fourier Self-Deconvolution was subsequently applied to the spectrum to estimate relebactam and imipenem at 430 nm and 470 nm, respectively after detection of cilastatin at 360 nm ensuring no cross-interference. The proposed method was rigorously validated according to ICH guidelines. Furthermore, the method's environmental impact was assessed using Eco-scale and Green Analytical Procedure Index (GAPI) techniques."

Journal

In-vitro activity of newly-developed β-lactamase inhibitors avibactam, relebactam and vaborbactam in combination with anti-pseudomonal β-lactam antibiotics against AmpC-overproducing clinical Pseudomonas aeruginosa isolates. (PubMed, Eur J Clin Microbiol Infect Dis) - "Our results showed that all combinations including relebactam led to higher "non-resistance" rates against AmpC-overproducing P. aeruginosa clinical isolates. The best activity was achieved by combining ceftolozane and relebactam, that might therefore be considered as an excellent clinical alternative against AmpC overproducers."

Combination therapy • Journal • Preclinical

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

Multicenter evaluation of activity of aztreonam in combination with avibactam, relebactam, and vaborbactam against metallo-β-lactamase-producing carbapenem-resistant gram-negative bacilli. (PubMed, Antimicrob Agents Chemother) - "AVI restored ATM activity for MBL-producing CREs (ATM: 9.8% vs ATM-AVI: 78.0%) and S. maltophilia (ATM: 0% vs ATM-AVI: 93.3%). The combination of ATM with ceftazidime-AVI (CAZ-AVI) demonstrated maximum activity against CREs. Although ATM-CAZ-AVI is the most potent regimen available for CREs and S. maltophilia, ATM-IMI-REL might be a reasonable alternative."

Clinical • Combination therapy • Gram negative • Journal • Infectious Disease

Outcomes of inadequate empiric therapy and timing of newer antibacterial therapy in hospitalized adults with culture-positive Enterobacterales and Pseudomonas aeruginosa: a multicenter analysis. (PubMed, BMC Infect Dis) - "Overall, IET and delayed use of newer antibacterials are associated with significantly worse hospital outcomes. More rapid identification of high-risk patients can facilitate adequate therapy and timely use of newer antibacterials developed for resistant Gram-negative pathogens."

Journal • Infectious Disease

New tricks for old drugs: Novel monobactam antibiotics to battle antimicrobial resistance (ACS-Fall 2024) - "To combat this issue, we aimed to discover a novel monobactam antibiotic to be used in combination with our class A/C β-lactamase inhibitor, relebactam...Addressing these challenges in drug discovery could be beneficial to the medicinal chemistry community as a whole. Coverage sepctrum of Gram-negative antibiotics"

Infectious Disease