imipenem/relebactam / Merck (MSD) - LARVOL DELTA

In vitro efficacy of sulbactam/durlobactam combined with β-lactam antibiotics in Australian Mycobacterium abscessus isolates. (PubMed, J Antimicrob Chemother) - "Sulbactam/durlobactam significantly increased susceptibility to oral and intravenous β-lactam antibiotics in the form of cefuroxime, cefuroxime/amoxicillin and meropenem against clinical isolates of M. abscessus. This study also found significant differences in susceptibility to β-lactam antibiotics dependent on the culture media used, highlighting that the optimal culture methods for determining MIC in M. abscessus remains uncertain. Future in vivo studies are required to determine whether the in vitro efficacy of the β-lactam combinations studied could result in clinical efficacy for M. abscessus disease."

Journal • Preclinical

Current Management Strategies of Difficult-to-Treat Resistant Pseudomonas aeruginosa Infections. (PubMed, Infect Dis Clin North Am) - "Although new active therapeutic options such as ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam and cefiderocol are currently available, lack of randomized control trials, drug access limitations, and emerging resistance have a negative impact on the management of these infections. This review discusses the mechanisms of resistance, molecular epidemiology, clinical management, and current and future therapeutic strategies for DTR P aeruginosa infections."

Journal • Review • Infectious Disease

Deciphering the emergence of mutations in Pseudomonas aeruginosa after ceftolozane/tazobactam treatment and evaluating therapeutic alternatives. (PubMed, BMC Microbiol) - "Ceftolozane/tazobactam resistance development was associated mainly with chromosomal mutations in the ampC gene but also with mutations in its regulatory genes. Knowledge about these mutations and gene polymorphisms is essential for interpreting resistance phenotypes from genomic data."

Journal

One-year surveillance of last-resort antimicrobial resistance patterns in carbapenemase-producing Klebsiella pneumoniae strains isolated in a Romanian tertiary care hospital: a prospective study. (PubMed, Germs) - "Strains presenting a minimum inhibitory concentration to meropenem of >0.125 μg/mL underwent phenotypic enzyme production testing, followed by synergistic testing to identify antimicrobial salvage therapy options...Forty-six strains were resistant to cefiderocol (35.7%), 108 (83.7%) to ceftazidime/avibactam, 127 (98.4%) to ceftolozane/tazobactam, 116 (90.0%) to imipenem/relebactam and 127 (98.4%) to aztreonam. The association of aztreonam with ceftazidime/avibactam demonstrated a synergistic effect in 127 (98.5%) strains, while aztreonam with imipenem/relebactam was efficient in vitro against 103 (79.8%) strains. Antimicrobial resistance remains a concerning phenomenon among Enterobacterales, especially when considering the increasing resistance rates even against salvage therapy antimicrobials."

Journal • Infectious Disease • Pneumonia

Phenotypic profile and molecular mechanism of resistance in carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa isolates from Brazilian hospitals: implications for the introduction of imipenem-relebactam. (PubMed, Front Microbiol) - "This study highlights the emergence of significant resistance to imipenem-relebactam in Brazil, driven by both enzymatic and non-enzymatic mechanisms. Ongoing molecular surveillance and tailored treatment strategies are essential to address the evolving threat of multidrug-resistant Gram-negative infections in endemic regions."

Clinical • Journal • Infectious Disease • Pneumonia

Antimicrobial Activity of Aztreonam-Avibactam and Other β-Lactamase Inhibitor Combinations Tested Against Enterobacterales Isolates from Pediatric Patients from United States Medical Centers (2019-2023). (PubMed, Antibiotics (Basel)) - "Susceptibility to imipenem-relebactam varied from 97.1% (ceftriaxone-nonsusceptible) to 100.0% (ESBL producers). Ceftolozane-tazobactam showed good activity against ESBL producers (91.8% susceptible), but limited activity against ceftriaxone-nonsusceptible (75.8% susceptible) and MDR isolates (80.9% susceptible)...ESBL-producing Enterobacterales, mainly CTX-M, remain an important cause of infection in children. Aztreonam-avibactam, ceftazidime-avibactam, and meropenem-vaborbactam were highly active against isolates from both pediatric and adult population."

Journal • Infectious Disease • Nephrology • Pediatrics • Pneumonia • Respiratory Diseases

Treatment Options for Critically Ill Patients with Infections Caused by Metallo-Beta-Lactamase-Producing Klebsiella pneumoniae. (PubMed, Antibiotics (Basel)) - "The emergence of metallo-beta-lactamases (MBLs) has contributed to the protection of pathogens against all current beta-lactam/beta-lactamase inhibitors (BL/BLIs), including the newer ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam, and imipenem-relebactam...In vitro and clinical data suggest that combinations of CAZ-AVI with aztreonam (ATM) and the use of two different carbapenems (double carbapenem therapy, DCT) may be an option for MBL-producing pathogens... Treatment with CAZ-AVI + ATM or DCT presented similar efficacy with appropriate antibiotic therapy for infections caused by MBL-producing K. pneumoniae strains. Larger studies are required to confirm the findings."

Journal • Critical care • Infectious Disease • Pneumonia

β-Lactam/β-Lactamase Inhibitor Combinations in Sepsis-Associated Acute Kidney Injury and Renal Replacement Therapy. (PubMed, Antibiotics (Basel)) - "This review summarizes PK/PD features, extracorporeal clearance, and practical dosing considerations about ceftolozane-tazobactam, ceftazidime-avibactam, aztreonam-avibactam, cefiderocol, meropenem-vaborbactam, imipenem-relebactam, and newer agents including sulbactam-durlobactam, cefepime-enmetazobactam, and cefepime-taniborbactam. Full-dose initiation during the first 24-48 h, followed by careful adjustment, appears prudent. Therapeutic drug monitoring should be used when available, and institution-specific protocols should be integrated into stewardship programs to improve efficacy and minimize resistance."

Journal • Review • Acute Kidney Injury • Infectious Disease • Nephrology • Pediatrics • Renal Disease • Septic Shock

New Drugs, Old Problems: A Narrative Review of Antibiotic Stewardship Program in the era of novel Gram-negative antibiotics. (PubMed, Clin Microbiol Infect) - "Effective stewardship of new Gram-negative antibiotics requires combining enablement, personalized pharmacology, and selective restriction within multidisciplinary ASPs. Strengthening real-world evidence, digital infrastructure, and standardized outcome measures is essential to guide equitable and sustainable implementation."

Journal • Review • Infectious Disease

First report of treatment-emergent resistance to cefepime-zidebactam in Pseudomonas aeruginosa. (PubMed, Clin Infect Dis) - "During treatment cefepime-zidebactam MICs increased from 8/8 to 32/32mg/L. Whole-genome sequence analysis showed new mutations in the MexAB-OprM efflux operon that were associated with cross-resistance to ceftazidime-avibactam and imipenem-relebactam."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Evaluation of phenotypic and genotypic susceptibility testing methods for newer β-lactam/β-lactamase inhibitor combinations in multidrug resistant Pseudomonas aeruginosa. (PubMed, J Infect Dis) - "The Sensititre panel met standard acceptance criteria while the Phoenix panel had low CA for all tested BL/BLIs compared to BMD. Acquired β-lactamases were a rare cause of BL/BLI resistance. Further understanding of resistance mechanisms is required before phenotypic BL/BLI resistance can be reliably predicted from genotype, especially in settings where prevalence of acquired β-lactamases is low."

Journal

Effectiveness of imipenem-relebactam for multidrug-resistant Pseudomonas aeruginosa in pneumonia and bloodstream infections in the United States (MIRAGE). (PubMed, Antimicrob Agents Chemother) - "Forty percent of index isolates that were tested displayed non-susceptibility to both ceftolozane-tazobactam and ceftazidime-avibactam. Clinical outcomes following imipenem-relebactam for treatment of MDR P. aeruginosa were comparable to those reported in real-world studies for other novel β-lactam agents. Our data suggests that imipenem-relebactam has a role in the treatment of patients infected with MDR P. aeruginosa."

Journal • Critical care • Infectious Disease • Pneumonia • Respiratory Diseases

In vivo evolution of resistance to novel β-lactam/β-lactamase inhibitor combinations through overproduction of the horizontally acquired extended-spectrum AmpC β-lactamase FOX-14 and porin disruption in Serratia marcescens. (PubMed, Eur J Clin Microbiol Infect Dis) - "We tested the susceptibility of the isolates to ceftazidime/avibactam, aztreonam/avibactam, imipenem/relebactam and meropenem/vaborbactam. Purified FOX-14 displayed marked cephalosporinase activity against ceftazidime and cefepime, with low Km values, while negligible turnover for aztreonam and ertapenem and a low avibactam IC50. In S. marcescens, in vivo resistance in clinical isolates emerged from FOX-14 overproduction combined with reduced outer-membrane permeability, predominantly due to OmpF disruption. These findings elucidate resistance to newer β-lactam/β-lactamase inhibitor combinations and warrant close monitoring of antimicrobial activity during carbapenem-based therapy for S. marcescens infections."

Journal • Preclinical • Infectious Disease

First nationwide survey on Pseudomonas aeruginosa in Bolivia: susceptibility profiles, resistome, and genomic epidemiology. (PubMed, Antimicrob Agents Chemother) - "The most active antipseudomonal agents were colistin (98.2% intermediate, MIC50/90=1/2 mg/L) and cefiderocol (92.7% susceptible, MIC50/90=0.25/4 mg/L) according to the Clinical and Laboratory Standards Institute (CLSI). High resistance rates to ceftazidime/avibactam (79.3%), ceftolozane/tazobactam (82.9%), and imipenem/relebactam (71.2%) were documented...The high resistance rates for novel beta-lactams linked to an alarming spread of high-risk clones ST277 and ST235 and the very high prevalence of MBLs and ESBLs raise significant concern. This underscores the urgent need for establishing epidemiological surveillance and infection control strategies."

Journal • Infectious Disease • PER1

Emergence of co-resistance to imipenem/relebactam and ceftazidime/avibactam in clinical Klebsiella pneumoniae ST11 clone due to KPC-2 N132S and CTX-M-65 S130G/P167S substitutions. (PubMed, Antimicrob Agents Chemother) - "Plasmid-borne blaKPC-157 (KPC-2 N132S substitution) and blaCTX-M-249 (CTX-M-65 S130G/P167S substitutions) conferred resistance to imipenem/relebactam and ceftazidime/avibactam, respectively. The emergence of these novel resistance determinants in the high-risk clone underscores the need for enhanced surveillance."

Journal • Infectious Disease • Pneumonia

An update on antimicrobial selection and duration for intra-abdominal infections. (PubMed, Expert Rev Anti Infect Ther) - "Novel antibiotics such as ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, eravacycline, and cefiderocol have broadened treatment options for MDR pathogens. Shorter antibiotic courses, guided by source control and biomarkers, have shown to be as effective as traditional longer regimens. Future research should focus on understanding of global resistance patterns, expanding real-world evidence for novel antibiotics, refining biomarker-guided strategies, enhancing rapid diagnostics, and applying artificial intelligence for more personalized and precise management of IAIs."

Journal • Review • Infectious Disease

In vitro efficacy of sulbactam-durlobactam combined with β-lactam antibiotics in Australian Mycobacterium abscessus isolates (WBC 2025) - " Sulbactam-durlobactam significantly lowered the MICs of M. abscessus to meropenem, cefuroxime, and cefuroxime-amoxicillin to MICs comparable to those of imipenem and imipenem-relebactam. Sulbactam-durlobactam significantly increased susceptibility to oral and intravenous β-lactam antibiotics in the form of cefuroxime, amoxicillin and meropenem against clinical isolates of M. abscessus . Further research is required to determine if the in vitro data correlates with clinical efficacy with the optimal culture methods for determining MIC in M. abscessus remaining uncertain."

Preclinical

Imipenem/Relebactam Plus Aztreonam: First Reported Use in MDR Klebsiella pneumoniae Sternal Infection Complicated by Bacteremia. (PubMed, Antibiotics (Basel)) - "Sternal swab and mediastinal liquid culture results highlighted CRKP harboring blaNDM and blaKPC genes, while the blood isolate showed blaCTX and blaKPC, indicating phenotypic resistance to ceftazidime-avibactam. All the strains exhibited phenotypic susceptibility to meropenem-vaborbactam (MEV), despite having a high minimum inhibitory concentration. Following clinical failure of MEV-based therapy, combination treatment with aztreonam (ATM) and imipenem/cilastatin/relebactam (IMI/REL), plus gentamicin, was initiated...The patient completed 49 days of ATM and IMI/REL without relapse over a 3-month follow-up period. This is, to the best of our knowledge, the first reported case of IMI/REL being used in combination with ATM."

Journal • Infectious Disease • Pneumonia

Therapeutic challenges in treating ESBL- and/or AmpC-producing non-carbapenemase-producing Enterobacterales: an in vitro evaluation of novel β-lactam/β-lactamase inhibitor combinations and cefiderocol. (PubMed, J Antimicrob Chemother) - "CR non-CPE exhibit heterogeneous resistance profiles, especially in ESBL/AmpC co-producers and CTX-M-33-producing isolates. While cefepime-zidebactam, imipenem-relebactam, and cefiderocol were the most active agents, susceptibility testing remains essential to guide therapy in this emerging and neglected bacterial group."

Journal • Preclinical

The Emerging Resistance Index: tracking early resistance to new antibiotics. (PubMed, Lancet Infect Dis) - "Our analysis revealed rapid resistance development to all new Gram-negative-targeting antibiotics, with particularly high ERI values for imipenem-relebactam and cefiderocol. The ERI could offer a quantitative and dynamic tool for monitoring resistance trends. Also, the ERI could support more timely surveillance efforts, inform antibiotic policy decisions, and aid in prioritising antibiotic research and development."

Journal • Review • Infectious Disease

Loss of MexEF-OprN function increases virulence of clinical Pseudomonas aeruginosa isolates (NACFC 2025) - "Recently, we and others have shown that inactivating mutations in the MexEF-OprN efflux pump arise during chronic exposure of PAO1 to aztreonam, cefiderocol and imipenemrelebactam (1–3) and deletion of the efflux pump increased virulence of the Pa lab strain PAO1 during acute murine infections (4). Inactivating mutations in the MexEF-OprN efflux pump enhance the virulence of Pa clinical isolates. These mutations are also enriched in Pa CF isolates indicating that the CF host environment or chronic antibiotic exposure may select for these virulence enhancing mutations."

Clinical • Infectious Disease • Respiratory Diseases • ELANE

In vitro activity of essential antimicrobial agents, including ceftazidime/avibactam, imipenem/relebactam, and cefiderocol, against carbapenem-resistant Gram-negative bacteria primarily harboring the IMP-type carbapenemase gene in the Kinki region of Japan. (PubMed, Diagn Microbiol Infect Dis) - "The MIC distributions for colistin, tigecycline, and cefiderocol were narrow across resistant strains, indicating consistent activity. Furthermore, the MIC distributions of CAZ/AVI and IPM/REL exhibited a narrow range of concentrations against non-CP-CRE and non-CP-CRPA, respectively. In contrast, CTLZ/TAZ exhibited a similarly narrow distribution against non-CP-CRPA. These findings suggest that these antimicrobials effectively treat infections caused by MRGNB."

Journal • Preclinical • Infectious Disease

Antimicrobial resistance profiles in multidrug-resistant Pseudomonas aeruginosa isolates in a university hospital in Argentina. Activity of new antibiotic combinations. (PubMed, Rev Argent Microbiol) - "Resistance rates to ceftazidime/avibactam, aztreonam/avibactam, ceftolozane/tazobactam and imipenem/relebactam were 40%, 88%, 3%, and 20%, respectively. Ceftazidime/avibactam reverted ceftazidime resistance in 25% of the isolates, whereas imipenem/relebactam did so in 77% of the imipenem-resistant isolates. The analysis of the resistance patterns observed suggests a high contribution of non-enzymatic mechanisms such as efflux pumps and porin alterations."

Journal

Effectiveness of iMIpenem-Relebactam for multidrug-resistant Pseudomonas AeruGinosa in pnEumonia and bloodstream infections in the United States (MIRAGE) (IDWeek 2025) - No abstract available

Infectious Disease

Effect of Starting Inoculum and β-lactamase Retention on the Activity of Imipenem/Relebactam (I/R) and Aztreonam (ATM) plus I/R in Hollow Fiber Infection (HFIM) Studies of P. aeruginosa (PSA) (IDWeek 2025) - No abstract available

Infectious Disease