imipenem/relebactam / Merck (MSD) - LARVOL DELTA

Emergence of KPC-producing Pseudomonas aeruginosa in Spain: insights into an outbreak and resistance to the novel carbapenem/β-lactamase inhibitor combinations imipenem/relebactam and meropenem/vaborbactam. (PubMed, Antimicrob Agents Chemother) - "Functional assays demonstrated synergy between KPC-2 production and porin loss on resistance to carbapenem/β-lactamase inhibitors. The findings highlight the clinical threat posed by KPC-producing P. aeruginosa."

Journal

Novel Insights into Carbapenem Resistance: Mechanisms, Diagnostics, and Future Directions. (PubMed, Antibiotics (Basel)) - "Newly introduced β-lactam/β-lactamase inhibitor combinations exert distinct selective pressures: ceftazidime-avibactam favors KPC Ω-loop variants and permeability defects, often restoring carbapenem susceptibility, whereas meropenem-vaborbactam and imipenem-relebactam resistance is driven mainly by porin loss and β-lactamase gene amplification. Cefiderocol resistance is multifactorial, frequently involving impaired siderophore uptake and heteroresistance, while sulbactam-durlobactam remains active against OXA-producing A. baumannii but is compromised by metallo-β-lactamases and PBP3 alterations...While high-level randomized evidence remains limited for some resistance mechanisms, emerging mechanistic, microbiological, and clinical data support the need for mechanism-aware diagnostics, repeated susceptibility assessment during therapy, and stewardship strategies informed by resistance biology. Integrating molecular context into routine practice will be critical to..."

Journal • Review • Infectious Disease

In Vitro Activity of Cefiderocol, Eravacycline, and Imipenem-Relebactam Against Multidrug-Resistant Acinetobacter baumannii Clinical Isolates. (PubMed, Antibiotics (Basel)) - " All isolates were resistant to imipenem and meropenem. Cefiderocol and eravacycline demonstrated promising in vitro activity against MDR A. baumannii, including colistin-resistant isolates, whereas imipenem-relebactam showed no activity. These findings support the potential role of cefiderocol and eravacycline as alternative treatment options for CRAB infections and highlight the multifactorial nature of cefiderocol resistance beyond OXA-type carbapenemase production."

Journal • Preclinical • Infectious Disease

Real-World Evidence and Multidrug Resistant Infections: How Can We Leverage RWE to Improve Patient Outcome with the Novel Beta-Lactam and Beta-Lactam/Beta-Lactamase Inhibitor Combinations. (PubMed, Infect Drug Resist) - "A comprehensive literature search was performed on PubMed-MEDLINE from January 2015 to September 2025 for identifying pivotal trials and real-world evidence concerning the use of cefiderocol and of novel beta-lactam/beta-lactamase inhibitor combination (BL/BLIc) including those of tomorrow (ie, ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefepime-enmetazobactam, cefepime-taniborbactam, cefepime-zidebactam, sulbactam-durlobactam, aztreonam-avibactam). Real-world evidence concerning both well-designed observational studies and PK/PD models may represent a mandatory tool for overcoming issues associated with pivotal trials evaluating novel BL/BLIc. The implementation of dedicated well-designed real-world studies would be warranted for ensuring a constant update of proposed therapeutic algorithms."

HEOR • Journal • Real-world evidence • Review • Infectious Disease

SY160 - Emerging resistance to new antibiotics: are we already losing the newest tools? (ESCMID Global 2026) - "This session explores the troubling rise of resistance to recently approved antibiotics, including cefiderocol, ceftazidime-avibactam, imipenem/relebactam, cefepime-taniborbactam, aztreonam-avibactam, etc. Although these drugs were introduced as critical last-resort options against multidrug-resistant infections, reports of resistance have emerged within just a few years of clinical use. The panel will address the urgent need for improved stewardship, faster diagnostics, and equitable access to new antibiotics to preserve their effectiveness. Participants will gain insights into how resistance spreads, how policies impact antimicrobial use, and what strategies might still help us stay ahead in the race against resistant pathogens."

Infectious Disease

Comparative effectiveness of ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/relebactam for multidrug-resistant Gram-negative bloodstream infections: a retrospective cohort study (ESCMID Global 2026) - No abstract available

Gram negative • HEOR • Retrospective data • Infectious Disease

Emergence of KPC-producing Pseudomonas aeruginosa in Spain: insights into an outbreak and resistance to the novel carbapenem/β-lactamase inhibitor combinations imipenem/relebactam and meropenem/vaborbactam (ESCMID Global 2026) - No abstract available

Deciphering resistance development under in vitro meropenem/vaborbactam or imipenem/relebactam exposure in KPC-producing Klebsiella pneumoniae ST307 high-risk clone (ESCMID Global 2026) - No abstract available

Preclinical • Infectious Disease • Pneumonia

In vitro activity of imipenem/relebactam against Enterobacterales and Pseudomonas aeruginosa collected in Taiwan: SMART 2020-2024 (ESCMID Global 2026) - No abstract available

Preclinical

Imipenem/relebactam activity against Gram-negative pathogens collected in South Africa: SMART 2020-2024 (ESCMID Global 2026) - No abstract available

Gram negative • Infectious Disease

Activity of ceftolozane/tazobactam, imipenem/relebactam and comparators against clinical Gram-negative isolates collected from patients with respiratory tract infections in the Americas: SMART 2021-2024 (ESCMID Global 2026) - No abstract available

Clinical • Gram negative • Infectious Disease • Respiratory Diseases

Synergistic effects of ceftazidime/avibactam, imipenem/relebactam, meropenem/varbobactam with aztreonam, colistin or fosfomycin on metallo-β-lactamase–producing Klebsiella pneumoniae strains (ESCMID Global 2026) - No abstract available

Infectious Disease • Pneumonia

Targeting carbapenem-resistant and hypervirulent Klebsiella pneumoniae: in vitro evaluation of cefepime/zidebactam, aztreonam/avibactam, imipenem/relebactam, and meropenem/vaborbactam. (PubMed, BMC Infect Dis) - "Cefepime/zidebactam and aztreonam/avibactam hold great promise for the treatment of CR-hvKP infections. Our findings will not only effectively address the challenge of CR-hvKP resistance, but also provide evidence to support the optimization of clinical therapeutic strategies and further promote the development and application of novel antimicrobial drugs."

Journal • Preclinical • Infectious Disease • Pneumonia

New Delhi Metallo-β-Lactamase Carbapenem-Resistant Klebsiella pneumoniae in Neonates: A Genome-Based Surveillance Study. (PubMed, J Infect Dis) - "This study suggests clonal dissemination of CRKP in neonates and documents a shift in the predominant ST from ST789 to ST35. ST35 strains displayed distinct resistance phenotypes and siderophore-linked virulence genes. Given that CRKP represented 73 of 310 (23.5%) neonatal K. pneumoniae isolates during 2018-2024, these data underscore the need for sustained surveillance and strengthened infection control measures in neonatal care units."

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

Exploring the Effectiveness of Imipenem/Relebactam in Patients with Antimicrobial-Resistant Hospital-Acquired Infections: Findings from Systematic Literature Reviews. (PubMed, Antibiotics (Basel)) - "Imipenem/cilastatin + relebactam (I/R) is used against multidrug-resistant infections providing an alternative option which may support patients where traditional treatments are no longer effective... Two systematic literature reviews were conducted to include randomized controlled trials which aligned with the inclusion criteria reporting on the efficacy of I/R against placebo or other comparators such as piperacillin/tazobactam or colistin... These findings support the efficacy of I/R for key Gram-negative infections, particularly within vulnerable patient populations. Despite the favorable outcomes reported, there is a need for further real-world evidence generation to support the efficacy of I/R to aid in standardizing treatment guidelines and reducing the clinical and economic burden associated with multidrug-resistant bacterial infections."

Journal • Review • Infectious Disease • Nephrology • Pneumonia • Renal Disease • Respiratory Diseases

Suboptimal ceftazidime-avibactam exposure drives sequential blaKPC mutations and intra-host coexistence of Klebsiella pneumoniae harboring distinct variants leading to persistent infection. (PubMed, Microbiol Spectr) - "Meropenem-vaborbactam, imipenem-relebactam, and aztreonam-avibactam showed in vitro activity against both KPC- and KPC variant-producing isolates. Moreover, insufficient ceftazidime-avibactam and carbapenems fail to eradicate the bacteria, allowing the coexistence of K. pneumoniae subpopulations carrying distinct blaKPC variants within a single patient. The findings highlight the need for individualized treatment regimens and optimized dosing and combination strategies to limit the emergence and persistence of KPC variant-producing K. pneumoniae during therapy."

Journal • Infectious Disease • Pneumonia • Renal Disease

Optimizing target inactivation to treat multidrug-resistant Escherichia coli with NDM and PBP3 mutations: "going the extra mile". (PubMed, Antimicrob Agents Chemother) - "After surgery, ceftazidime-avibactam/aztreonam was administered. Due to poor clinical response, he was switched to imipenem-relebactam/aztreonam, resulting in a successful outcome. Whole-genome sequencing detected blaNDM-5 and blaCMY-148 β-lactamases, PBP3 YRIN insertion, and mutated cirA gene. This case illustrates the importance of considering different mechanisms of resistance when choosing combination therapy."

Journal

Emerging resistance to imipenem-relebactam among enterobacterales and non-fermenting gram-negative bacilli: a systematic review and meta-analysis. (PubMed, Infection) - "IMI/REL remains largely effective against Enterobacterales, including ESBL and MDR strains, but resistance is increasing in high-risk subgroups and non-fermenting bacteria. These findings underscore the need for local susceptibility testing, cautious empiric therapy, and robust antimicrobial stewardship to preserve the efficacy of IMI/REL."

Journal • Retrospective data • Review • Infectious Disease

Comparative activity of established versus new-generation β-lactams against AmpC-hyperproducing clinical isolates of Enterobacter cloacae complex and Klebsiella aerogenes: a multicentre study. (PubMed, J Antimicrob Chemother) - "Our findings underscore the need to take this phenotype into account in clinical practice and confirm the limited activity of conventional β-lactams against AmpC-hyperproducing E. cloacae complex and K. aerogenes, and support the use of newer agents as effective alternatives."

Clinical • Journal

Insights into Klebsiella pneumoniae carbapenem resistance-a two-year retrospective study from a Romanian tertiary care hospital. (PubMed, Front Microbiol) - "All carbapenem-non-susceptible Klebsiella pneumoniae strains (meropenem minimum inhibitory concentration > 0.125 μg/mL) further underwent extended-spectrum beta-lactamase (ESBL) and carbapenemase production testing via phenotypical methods...In terms of antimicrobial resistance, more than > 90% of the strains exhibited resistance to fluoroquinolones, third generation cephalosporins, penicillins and monobactams, > 75% resistance to aminoglycosides and novel beta-lactam/beta-lactamase inhibitor combinations and > 70% resistance to colistin and imipenem-relebactam. Overall cefiderocol resistance was 32.05%...Moreover, 54.17% (n = 104) of XDR isolates were only susceptible to one antimicrobial drug. Rates of resistance remain concerningly high amongst CRKP isolates, with double carbapenemase producers and XDR/PDR isolates dominating the landscape, implying the foreseeable need for updated means of approaching antimicrobial resistance, as last-resort..."

Journal • Retrospective data • Infectious Disease • Pneumonia

Achromobacter xylosoxidans isolates exhibit genome diversity, variable virulence, high levels of antibiotic resistance, and potential intrahost evolution. (PubMed, mSphere) - "Our data show that imipenem/relebactam is as effective against A. xylosoxidans as imipenem alone, indicating that relebactam does not inhibit β-lactamase activity in Achromobacter...This work showed that A. xylosoxidans is resistant to relebactam when combined with imipenem, a combination effective in other bacteria. These findings emphasize the urgent need for targeted therapeutic strategies to combat this opportunistic pathogen."

Journal • Cardiovascular • CNS Disorders • Infectious Disease • Pertussis • Pneumonia • Respiratory Diseases

In vitro activity of cefiderocol against carbapenem-resistant Gram-negative pathogens in Japan. (PubMed, J Infect Chemother) - "Cefiderocol showed potent in vitro activity against CRGNB in Japan, including MBL producers. Disk diffusion correlated well with BMD results; however, confirmatory BMD testing should be considered when resistance is clinically suspected."

Journal • Preclinical • Infectious Disease

Multidrug-resistant gram-negative bacteria in Spanish ICU patients: clinical and microbiological characterization (MURAN-UCI Project). (PubMed, Microbiol Spectr) - "The antibiotics with the greatest activity against Enterobacterales (n = 26) were colistin, cefiderocol, and meropenem-vaborbactam (100%); while in CR P. aeruginosa (n = 20), they were colistin, cefiderocol, and imipenem-relebactam (95%-100%). We believe that monitoring resistance epidemiology at the ICU level-especially through molecular surveillance of resistance mechanisms and clonal dissemination-is essential for optimizing antimicrobial use and guiding stewardship and infection control programs. Notably, carbapenem-resistant Pseudomonas aeruginosa was the most frequently identified organism in both colonization (first/second week) and infection cases, highlighting the need for its inclusion in routine hospital colonization screening."

Journal • Critical care • Infectious Disease • Pneumonia

Global trends in carbapenem-resistant gram-negative bacteria research (2020-2025): a bibliometric analysis and systematic review. (PubMed, Front Cell Infect Microbiol) - "Randomized controlled trials indicated promising outcomes for several new antimicrobial agents, such as cefiderocol, sulbactam-durlobactam, and imipenem-relebactam. CRGNB research is increasingly directed toward elucidating resistance mechanisms, improving diagnostic tools, and exploring non-antibiotic therapeutic options. Strengthening international collaboration and fostering multidisciplinary approaches are imperative to advance high-quality research and address this growing threat."

Journal • Review • Infectious Disease • Pneumonia