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

Rapid ESBL-Carba Combo PN test for simultaneous detection of ESBL and carbapenemase activity in Enterobacterales. (PubMed, Microbiol Spectr) - "By incorporating relebactam as a selective class A inhibitor, the assay improves phenotypic discrimination between class A and class D carbapenemases while preserving reliable ESBL detection. The rapid ESBL-Carba Combo PN test provides 1 h of phenotypic information on the most clinically relevant β-lactam resistance mechanisms and represents a useful tool to guide early antibiotic treatment."

Journal • Infectious Disease

Phenotypic and biochemical characterization of the class C β-lactamase, PAC-1. (PubMed, J Antimicrob Chemother) - "PAC-1 is not inhibited by avibactam and hydrolyses a broad range of β-lactams including the novel cephalosporin cefiderocol. The combination cefiderocol/zidebactam was the most active against PAC-1. Transposon-mediated dissemination across distinct lineages warrants continued epidemiological surveillance of PAC-type β-lactamases."

Journal

Imipenem and relebactam pharmacokinetics in peritoneal fluid: microdialysis reveals infection-independent penetration. (PubMed, Antimicrob Agents Chemother) - "Subsequent pharmacodynamic target attainment (PTA) analysis showed that under the latest EUCAST PK/PD criteria, PTA values dropped markedly to an MIC of 1 mg/L, indicating a substantially reduced probability of achieving adequate peritoneal exposure. These results highlight the need for dosing strategies to ensure sufficient peritoneal drug concentration to maintain antimicrobial efficacy."

Journal • PK/PD data • Infectious Disease

Relebactam enhances the activity of imipenem against Burkholderia cepacia complex isolates. (PubMed, J Glob Antimicrob Resist) - "Imipenem/relebactam effectively inhibited the growth of BCC isolates in vitro and reduced bacterial burden of BCC isolates in vivo. There are no interpretive susceptibility criteria for imipenem/relebactam against BCC; however, these results warrant further investigation in clinical studies."

Journal • Infectious Disease • Pulmonary Disease

PER-14, a β-lactamase variant with reduced sensitivity to avibactam and relebactam. (PubMed, Antimicrob Agents Chemother) - "PER-1-producing Pseudomonas and Acinetobacter and PER-2-producing Enterobacterales, respectively, are increasingly difficult to treat due to combined resistance to antibiotics like ceftazidime, cefiderocol, and ceftazidime/aztreonam-avibactam, among others. PER-14 differs from PER-2 by an S130T substitution. Through combined functional and in silico analyses, we demonstrated that PER-14 is resistant to avibactam and relebactam inhibition while retaining an extended-spectrum activity and the ability to hydrolyze cefiderocol, as the S130T substitution affects the proper binding of the DBOs."

Journal • PER1

LOCAL/2024/CR-03: Defining Antibiotic Levels in Intensive care patients (DALI-2) protocol (clinicaltrialsregister.eu) - P4 | N=200 | Recruiting | Sponsor: Centre Hospitalier Universitaire De Nimes | Not yet recruiting ➔ Recruiting

Enrollment open • Trial initiation date • Critical care • Infectious Disease

AmpC β-Lactamases in SPICE (Serratia, Pseudomonas, Indole-Positive Proteus, Citrobacter, Enterobacter) Organisms: A Rising Threat to Antimicrobial Therapy. (PubMed, Cureus) - "However, newer non-β-lactam β-lactamase inhibitors, including avibactam and relebactam, demonstrate activity against many AmpC-producing organisms, thereby complicating treatment strategies. This review highlights the molecular mechanisms, epidemiological patterns, clinical implications, detection methods, and emerging therapeutic options for AmpC β-lactamases in SPICE organisms. The review underscores the urgent need for enhanced surveillance, rapid diagnostics, and antimicrobial stewardship to manage infections caused by these resistant pathogens."

Journal • Review • Infectious Disease

In vitro activity of β-lactamase inhibitors avibactam, relebactam and vaborbactam in combination with aztreonam against metallo-β-lactamase producing Escherichia coli clinical isolates. (PubMed, Eur J Clin Microbiol Infect Dis) - "Among ATM-AVI-resistant isolates, none of the combinations restored aztreonam susceptibility. CMY-type enzymes seem to play a pivotal role in the failure of both relebactam and vaborbactam to restore aztreonam susceptibility in our collection of isolates."

Journal • Preclinical • Infectious Disease

An update on beta-lactam-beta-lactamase inhibitor combinations for the treatment of carbapenem-resistant gram-negative pathogens. (PubMed, Expert Opin Drug Metab Toxicol) - "This expert review summarizes the pharmacology, clinical efficacy, and safety of approved and emerging BLBLIs, including ceftolozane - tazobactam, cefepime - enmetazobactam, ceftazidime - avibactam, meropenem - vaborbactam, imipenem - relebactam, aztreonam - avibactam, and sulbactam - durlobactam. However, their impact is threatened by the rising prevalence of metallo-β-lactamases and the persistent therapeutic gap in carbapenem-resistant A. baumannii. Future success will depend on next-generation inhibitors with broader enzyme coverage, optimized dosing strategies guided by PK/PD principles, and robust antimicrobial stewardship to preserve long-term efficacy."

Journal • Review • Infectious Disease

Data-driven design and screening of novel Klebsiella pneumoniae carbapenemase-2 β-lactamase inhibitors using a generative CLM. (PubMed, RSC Adv) - "Stability metrics, including RMSD, RMSF, R g, PCA and FEL were benchmarked against the clinically approved inhibitor of KPC-2, relebactam...These findings establish a robust and scalable computational framework for the discovery of novel KPC-2 inhibitors, demonstrate the potential of CLMs as powerful tools for accelerating antibiotic discovery in the fight against antimicrobial resistance, and provide a generalizable strategy for targeting other critical resistance determinants. The CLM used in this study is publicly available at https://github.com/sumayya-tariq/Chemical-Language-Model-CLM-."

Journal • Infectious Disease • Pain • Pneumonia

In vitro and in vivo antibacterial activity of oral tebipenem in combination with novel β-lactamase inhibitors (avibactam, relebactam, vaborbactam) against KPC-producing Enterobacterales. (PubMed, Eur J Clin Microbiol Infect Dis) - "The combinations of oral TEB and novel β-lactamase inhibitors exhibit a potent antibacterial activity against KPC-producing Enterobacterales isolates in vitro and in vivo. Their potency is comparable to that of CAZ-AVI, and they even demonstrate potential efficacy against CAZ-AVI-resistant isolates. These findings provide a theoretical basis for the clinical management of CRE infections. Additionally, this combination serves as a viable step-down therapeutic option potentially facilitating earlier hospital discharge."

Journal • Preclinical • Infectious Disease

Development of a novel LC-MS/MS method for concurrent determination of imipenem, relebactam, and cilastatin in human serum, urine and peritoneal drainage fluid. (PubMed, BMC Chem) - "All intra-day and inter-day coefficients of variation (CVs) were < 15%, the recovery rates ranged from 89.7% to 103.2%, and the matrix effects were acceptable (87.7%-110.8%). In conclusion, this LC-MS/MS method is simple to operate, exhibits high sensitivity and accuracy, and meets the requirements for the TDM of 'Imipenem, Cilastatin Sodium and Relebactam for Injection', providing support for individualized treatment and reducing the risk of adverse reactions."

Journal • Infectious Disease

Role of Ambler Position 104 in Defining Substrate Specificity in the KPC Family of β-Lactamases. (PubMed, ACS Infect Dis) - "The E. coli containing the P104K and P104R variants exhibited markedly increased resistance to ceftazidime, ceftazidime/avibactam, ceftazidime/relebactam, and cefiderocol, while carbapenem susceptibility remained largely unchanged. Molecular dynamics simulations and deep-learning analyses revealed that substitutions at position 104 alter W105 orientation, expand active-site volume, and increase hinge-loop flexibility, enabling accommodation of bulky substrates. These findings highlight the critical role of residue 104 in shaping substrate specificity and inhibitor susceptibility in KPC enzymes, with implications for antimicrobial therapy and resistance evolution."

Journal • Infectious Disease • Pneumonia

In vivo evolution of resistance to contemporary β-lactam/β-lactamase inhibitor combinations during treatment of a KPC-producing Serratia marcescens infection. (PubMed, Antimicrob Agents Chemother) - "Ceftazidime-avibactam (CZA), a BL/BLI combination in which the cephalosporin ceftazidime is protected from KPC-mediated hydrolysis, demonstrated improved outcomes in early clinical use...Notably, the evolution of blaKPC-44 not only conferred resistance to CZA but also marked cross-resistance to meropenem-vaborbactam and imipenem-relebactam while remaining susceptible to cefiderocol...pneumoniae Enterobacterales species. Ultimately, the evolved strain persisted despite therapy throughout a fatal clinical course, underscoring the potential for CZA selective pressure to drive treatment-emergent resistance to multiple contemporary BL/BLI agents."

Journal • Preclinical • Infectious Disease • Pneumonia

Optimal Duration of Antibiotic Therapy in Drained Pyogenic Liver Abscess: 3 weeks versus 6 weeks, a non-inferiority trial (clinicaltrialsregister.eu) - P4 | N=456 | Not yet recruiting | Sponsor: Assistance Publique Hopitaux De Paris

Head-to-Head • New P4 trial • Hepatology

cirA Promoter Disruption and SHV-12 Production Contribute to Cefiderocol Resistance in Carbapenem-Resistant Klebsiella pneumoniae. (PubMed, Int J Antimicrob Agents) - "This study identifies a novel CFDC resistance mechanism and underscores the importance of assessing regulatory regions when evaluating resistance determinants. It also supports the potential use of relebactam as an effective adjunct to CFDC against SHV-12-producing, CFDC-resistant CRKP."

Journal • Infectious Disease • Pneumonia

Disarming carbapenemase-producing Acinetobacter baumannii: high potency of the novel therapeutic combination of meropenem and the innovative diazabicyclooctane β-lactamase inhibitor pilabactam (formerly ANT3310). (PubMed, Antimicrob Agents Chemother) - "Pilabactam (formerly ANT3310) is a novel diazabicyclooctane (DBO) β-lactamase inhibitor featuring a fluorine substituent that extends its activity spectrum, relative to approved DBOs like avibactam and relebactam, to include CHDLs. Molecular dynamics simulations revealed the critical role of the fluorine substituent in forming stabilizing hydrogen-bonding and CH-F interactions within the tunnel-like OXA-23 active site. These findings identify pilabactam as a potent novel DBO supporting its development with meropenem for treating CRAB infections."

Journal • Infectious Disease

Imipenem/cilastatin/relebactam dosing regimen justification using exposure-efficacy analyses in participants with hospital-acquired bacterial pneumonia or ventilator-associated bacterial pneumonia in the RESTORE-IMI 2 phase 3 study. (PubMed, Antimicrob Agents Chemother) - P3 | "There were no apparent trends in ACM rates by imipenem or relebactam exposure distributions overall or by individual key pathogens, suggesting an exposure-efficacy plateau. These results further support the recommended and currently approved IMI/REL 500/500/250 mg dosing regimen for patients with HABP/VABP."

Journal • P3 data • Infectious Disease • Pneumonia • Respiratory Diseases

Impact of Sampling Window Variability on Pharmacokinetic Parameters Estimated by Non-Compartmental Analysis: Case Studies of Various Types of Drugs. (PubMed, Clin Pharmacol Drug Dev) - "As a result, we were able to quantitatively evaluate how changes in sampling window length affect NCA-based PK parameters. Based on these findings, we provide recommendations for appropriate sampling windows."

Journal • PK/PD data

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