imipenem/relebactam / Merck (MSD) - LARVOL DELTA

Phenotypic screening for metallo-β-lactamases and extended-spectrum β-lactamases in Pseudomonas aeruginosa using the VITEK-2 AST-N443 and Phoenix NMIC-486 cards. (PubMed, Microbiol Spectr) - "However, these groups exhibit distinct susceptibility patterns to novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations, including ceftolozane/tazobactam (C/T), ceftazidime/avibactam (C/A), imipenem/relebactam (I/R), and meropenem/vaborbactam (M/V)...Antimicrobial susceptibility testing was performed using the VITEK-2 AST-N443 and Phoenix NMIC-486 cards on 135 whole-genome-sequenced international CRPA isolates resistant by disc diffusion to ceftazidime, cefepime, imipenem, and/or meropenem...Our study identifies reliable screening cut-offs for MBL- and ESBL-production in CRPA using standard VITEK 2 and Phoenix automated AST panels. This readily available approach may accelerate detection, support routine laboratory workflows, reduce unnecessary confirmatory testing, and facilitate earlier targeted therapy and infection-control interventions in laboratories using these systems worldwide without requiring additional specialized testing or infrastructure."

Journal • Infectious Disease

Activity of High-Dose Imipenem/Relebactam (i/R) Plus Aztreonam (ATM) Against MBL-Producing Pseudomonas aeruginosa (PSA) in a Hollow Fiber Infection Model (HFIM) (IDWeek 2026) - No abstract available

Infectious Disease

In vitro susceptibility of aztreonam combined with imipenem-relebactam and ceftazidime-avibactam in metallo-beta-lactamase producing Enterobacteriaceae (IDWeek 2026) - No abstract available

Preclinical • Infectious Disease

Aztreonam-avibactam Activity against Enterobacterales from Asia Pacific and Latin American Medical Centres: Summary of 5 years of Surveillance prior to Clinical Use (2020-2024). (PubMed, Int J Antimicrob Agents) - "The results of this investigation provide a baseline for monitoring the activity of aztreonam-avibactam in APAC and LATAM and emphasize the importance of surveillance programs to monitor the emergence of resistance markers."

Journal • Infectious Disease • Pneumonia

In vitro potency of novel ertapenem/zidebactam combination (WCK 6777) against carbapenemase-producing Enterobacterales collected across India. (PubMed, JAC Antimicrob Resist) - "MICs of ertapenem/zidebactam and comparator agents (carbapenems, imipenem/relebactam, ceftazidime/avibactam and aztreonam/avibactam) were determined by broth microdilution method. The enhanced activity of ertapenem/zidebactam is attributed to zidebactam's dual mechanism, β-lactamase inhibition and high-affinity PBP2 binding, enabling effective coverage despite complex resistance mechanisms. Its once-daily dosing supports its potential as an OPAT-enabling therapeutic option and warrant further clinical development."

Journal • Preclinical • Infectious Disease • Pneumonia

Carbapenem-resistant Gram-negative pathogens: molecular epidemiology, diagnostic advances, and emerging therapeutic strategies. (PubMed, Front Microbiol) - "At the same time, new drugs have been developed, such as ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol and combinations of aztreonam, offering increased treatment options, but with emerging resistance an issue. This mini review covers the molecular epidemiology of CR-GNPs, the latest developments and challenges in diagnosing these infections, new therapeutic options, and future perspectives on genomic surveillance, antimicrobial stewardship, and precision medicine strategies to address the increasing threat of carbapenem resistance."

Journal • Review • Infectious Disease • Pneumonia

A Ten-Year Trend of Antimicrobial Resistance in Pseudomonas aeruginosa From United States Medical Centers: Results From the INFORM Surveillance Program (2015-2024). (PubMed, Open Forum Infect Dis) - "Ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-relebactam were active against 97.0%-97.9% of isolates overall. Piperacillin-tazobactam and ceftazidime activities decreased slightly during the study period, whereas the activities of meropenem, levofloxacin, and tobramycin improved since 2017."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Antibiotic Treatment of Severe Infections with Multiresistant Bacteria. (PubMed, Dtsch Arztebl Int) - "The treatment should be tailored in consideration of the site of infection, the antibiotic sensitivity profile, the resistance mechanism, and the clinical situation. New reserve antibiotics should be used selectively and in the framework of antimicrobial stewardship."

Clinical guideline • Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Real-world use of novel β-lactams in immunologically vulnerable patients: insights from an Italian retrospective cohort. (PubMed, JAC Antimicrob Resist) - "Adult patients receiving NBLs (cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/relebactam or meropenem/vaborbactam) were included. In a real-world Italian cohort spanning 5 years, NBLs were widely used in immunologically vulnerable patients, a population often underrepresented in pivotal antibiotic trials, with K. pneumoniae carbapenemase-producing K. pneumoniae and P. aeruginosa as predominant pathogens. Unadjusted comparisons showed similar clinical outcomes despite greater baseline severity among non-vulnerable patients, a hypothesis-generating finding warranting confirmation in adjusted, prospective studies."

Journal • Real-world evidence • Retrospective data • Hematological Disorders • Human Immunodeficiency Virus • Immunology • Infectious Disease • Pneumonia • Rheumatology • Solid Organ Transplantation • Transplantation

TAILOR: Targeted Versus Standard Peri-operative Antibiotic Prophylaxis in Patients Colonized With Carbapenemase Producing Enterobacterales Undergoing Liver Transplantation (clinicaltrials.gov) - P3 | N=168 | Not yet recruiting | Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

New P3 trial • Transplantation

In vitro activity of cefiderocol against highly resistant Gram-negative pathogens collected in the SENTRY Surveillance Program between 2020 and 2024. (PubMed, J Glob Antimicrob Resist) - "Cefiderocol showed potent in vitro activity against contemporary isolates of Gram-negative bacteria displaying challenging resistance phenotypes."

Journal • Preclinical • Infectious Disease

Prevalence, mortality, risk factors, and treatment of carbapenem-resistant hypervirulent Klebsiella pneumoniae: an evidence map. (PubMed, Infection) - "CR-hvKP remains a formidable public health threat due to its substantial prevalence, elevated mortality, and multidrug resistance. Current therapeutic strategies lack standardization, and widely applied combination therapy has inconsistent efficacy. Further research is urgently needed to optimize treatment regimens. Early detection, precise antimicrobial stewardship, and stringent infection control measures are crucial to mitigate the spread and impact of CR-hvKP."

Journal • Review • Diabetes • Infectious Disease • Metabolic Disorders • Pneumonia

Epidemiology of KPC-producing Enterobacterales isolated from 2019 to 2023 in France. (PubMed, J Antimicrob Chemother) - "KPC-producing K. pneumoniae referred to the French NRC show marked clonal diversification. The emergence of resistant isolates and convergent resistance-virulence profiles underscore the need for sustained genomic surveillance."

Journal • Infectious Disease • Pneumonia

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

Comparative evaluation of the activity of novel β-lactam antibiotics against difficult-to-treat Pseudomonas aeruginosa clinical isolates. (PubMed, JAC Antimicrob Resist) - "Among the 502 isolates, cefepime-zidebactam exhibited the highest in vitro activity (100% susceptibility), followed by cefiderocol-xeruborbactam (98%), cefiderocol (95%), ceftolozane-tazobactam (90%), cefepime-taniborbactam (86%), ceftazidime-avibactam (85%), and imipenem-relebactam (41%). While currently approved β-lactam agents retained activity against many DTR P. aeruginosa isolates, their performance was markedly compromised in the presence of carbapenemases, with the notable exceptions of cefepime-zidebactam and cefiderocol. Investigational β-lactam/β-lactamase inhibitor combinations exhibited consistently robust activity across resistance phenotypes, including carbapenemase-producing isolates, representing promising options for DTR P. aeruginosa infections."

Journal • Infectious Disease

Performance evaluation of antimicrobial susceptibility testing methods for ceftazidime-avibactam and imipenem-relebactam against Klebsiella pneumoniae and Pseudomonas aeruginosa. (PubMed, Eur J Clin Microbiol Infect Dis) - "CAZ-AVI and IMI-REL retain potent in vitro activity against contemporary CR-KP and CR-PA isolates. Gradient diffusion is a reliable alternative to BMD for ceftazidime-avibactam, whereas its accuracy is limited for imipenem-relebactam. K-B disk diffusion for IMI-REL is associated with unacceptably high error rates; reference method confirmation is recommended for isolates yielding non-susceptible results by this method."

Journal • Infectious Disease • Pneumonia

Addressing therapeutic options for KPC-3-producing ST307-Klebsiella pneumoniae: insights from in vitro evolution and mutant prevention strategies. (PubMed, Antimicrob Agents Chemother) - "Imipenem-relebactam exerted stronger collateral effects than meropenem-vaborbactam, extending cross-resistance to aztreonam-avibactam and cefepime-taniborbactam, while cefiderocol activity remained largely preserved. Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam impose distinct evolutionary pressures on KPC-ST307-Kp, resulting in divergent resistance pathways and collateral resistance profiles. CZA + MER may offer a more sustainable strategy by preventing resistance emergence and limiting cross-resistance to last-line agents."

Journal • Preclinical • Infectious Disease • Pneumonia

Genomic characterization of ceftazidime/avibactam-resistant KPC-producing Klebsiella pneumoniae in bloodstream infections indicates OmpK35 and OmpK36 as pivotal key players in resistance mechanisms. (PubMed, Front Microbiol) - "AST revealed resistance to last-line agents: imipenem/relebactam (4/16), meropenem/vaborbactam (2/16) and colistin (3/16), alongside reduced susceptibility to cefiderocol (11/16), thereby limiting effective treatment strategies. Given the heterogeneity of the KPC variants found in the isolates, and the consistent loss of porin function, the OmpK35/36 impairment may represent the pivotal driver of the MDR phenotype in these strains. Our findings indicate that the synergy between multiple KPC variants and porin structural alterations may represent a critical determinant underlying the clinical challenge posed by CAZ/AVI resistance in invasive infections."

Journal • Infectious Disease • Pneumonia

Ceftazidime-Avibactam/Colistin Combination Against Carbapenem-Resistant Pseudomonas aeruginosa: In Vitro Synergy Indicating a Possible Therapeutic Approach. (PubMed, Microb Drug Resist) - "CZA-COL combination may offer partial synergy, especially in CZA-resistant CRPA strains; however, broader in vivo and prospective studies are needed to support clinical use."

Journal • Preclinical

In Vitro Activity of Cefiderocol Against Clinically Relevant Gram-Negative Bacilli Collected in China in 2023. (PubMed, J Glob Antimicrob Resist) - "Cefiderocol showed potent in vitro activity against most Gram-negative species collected in China; however, continuous surveillance of resistance patterns, particularly for E. cloacae, is essential to ensure its long-term effectiveness."

Journal • Preclinical • Infectious Disease • Pneumonia

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

Distinct effects of GES variants on ceftazidime-avibactam and imipenem-relebactam resistance in carbapenem-resistant Pseudomonas aeruginosa: a ten-year retrospective study. (PubMed, Emerg Microbes Infect) - "Analysis of publicly available genomes further indicated that blaGES-positive isolates were mainly associated with the high-risk clone ST235, were distributed across multiple Gram-negative species with P. aeruginosa as the predominant host and exhibited an expanding cross-species distribution. In summary, these findings demonstrate that subtype-specific variation in GES enzymes is likely to shape the activity of β-lactam/β-lactamase inhibitor combinations within a conserved ST235 background."

Journal • Retrospective data • Infectious Disease

Carbapenem-resistant Enterobacterales across the UK: a nationwide study of carbapenemase testing and novel antimicrobial activity. (PubMed, Int J Antimicrob Agents) - "Whilst most UK CRE are tested for carbapenemases, coverage gaps persist. The community burden of CRE is increasing. Cefiderocol resistance is concerningly high, particularly among metallo-β-lactamase-producers."

Journal • Infectious Disease • Pneumonia

Update on the comparative in vitro activity of cefiderocol and four β-lactam-β-lactamase-inhibitor combinations against clinically important Gram-negative pathogens. (PubMed, JAC Antimicrob Resist) - "The aim of this study was to investigate the in vitro activity of the siderophore cephalosporin cefiderocol (FDC) and four comparator beta-lactam-beta-lactamase-inhibitor combinations (ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/relebactam and meropenem/vaborbactam) against 401 clinical isolates of Gram-negative pathogens collected in Germany between 2019 and 2020. MICs produced by ComASP test kits were comparable to the results of broth microdilution in E. coli, K. pneumoniae, P. aeruginosa and S. maltophilia (categorical agreement > 95%; essential agreement > 91%). Overall, cefiderocol activity against P. aeruginosa, A. baumannii and S. maltophilia was higher compared to the other agents tested."

Journal • Preclinical • Infectious Disease • Pneumonia

In vitro activity of the novel β-lactamase inhibitor nacubactam against a nationwide collection of carbapenem-resistant Enterobacterales in Japan. (PubMed, JAC Antimicrob Resist) - "Cefepime-nacubactam and aztreonam-nacubactam demonstrated potent activity against CPE, with MIC50/90 of 2/4 and 0.5/2 mg/L, respectively, which were lower than those for ceftazidime-avibactam (64/>64 mg/L) and imipenem-relebactam (2/16 mg/L). Both combinations exhibited potent antibacterial activity against non-carbapenemase-producing carbapenem-resistant Enterobacterales (non-CP-CRE), with MIC50/90 of 0.25/4 and 0.5/4 mg/L, respectively. Cefepime-nacubactam and aztreonam-nacubactam have excellent antibacterial activities against CPE and non-CP-CRE, supporting their potential as therapeutic options for CRE infections."

Journal • Preclinical • Infectious Disease • Pneumonia