cefepime/taniborbactam (cefepime/VNRX-5133) / VenatoRx, Everest Medicines - LARVOL DELTA

Escherichia coli with penicillin-binding protein 3 insertions: implications for newer β-lactam/β-lactamase inhibitor combinations. (PubMed, Antimicrob Agents Chemother) - "Newer β-lactam/β-lactamase inhibitor combinations (ceftazidime/avibactam, aztreonam/avibactam, and cefepime/taniborbactam) and cefiderocol with affinities for PBP3 show reduced activity against E. coli with YRIN and YRIK insertions...In contrast, agents targeting PBP2, such as cefepime/zidebactam and cefiderocol-xeruborbactam, retain potent in vitro activity and will likely be important for future treatment strategies...There is an urgent need for enhanced global surveillance, along with rapid diagnostic tools capable of identifying PBP3 insertions and associated high-risk clones among carbapenemase-producing E. coli. Future strategies should prioritize agents with activities against multiple essential PBPs to preserve β-lactam efficacy."

Journal • Review

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

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

Overview of novel cefepime-based β-Lactam/β-lactamase inhibitor combinations. (PubMed, Expert Rev Anti Infect Ther) - "This review summarizes approved and investigational cefepime-based BL/BLI combinations, including cefepime/enmetazobactam (FEP/EMT), cefepime/taniborbactam (FTB), cefepime/zidebactam (FPZ), and cefepime/nacubactam (FEP/NAC)...FPZ combines β-lactamase inhibition and β-lactam - enhancer activity, retaining activity against XDR Enterobacterales and P. aeruginosa, including cefiderocol- or aztreonam/avibactam (ATM/AVI)-resistant strains. FEP/NAC shows promise against carbapenem- and MBL-producing strains, though clinical data remain limited. Optimal use relies on rapid molecular diagnostics, susceptibility testing, and antimicrobial stewardship to maximize efficacy and limit the emergence of resistance."

Journal • Review • Infectious Disease

Cefepime Combined with Late-Generation β-Lactamase Inhibitors: Mechanisms of Action, In Vitro Activity, PK/PD Characteristics, Clinical Evidence and Resistance Mechanisms. (PubMed, Antibiotics (Basel)) - "Cefepime combined with late-generation β-lactamase inhibitors-enmetazobactam, zidebactam, and taniborbactam-represents a promising strategy to treat multidrug-resistant Gram-negative infections...It also highlights future directions, including the establishment of clinical breakpoints, evaluation in severe infections, and exploration of combination strategies to counteract complex resistance. Overall, these agents exemplify a strategic evolution in β-lactam therapy, offering versatile options to reduce carbapenem reliance while maintaining high efficacy against multidrug-resistant Gram-negative pathogens."

Journal • PK/PD data • Preclinical • Review • Infectious Disease • Nephrology

Comparative in vitro efficacy of aztreonam-avibactam and other alternatives (cefepime-taniborbactam, cefepime-zidebactam, and cefiderocol) against metallo-β-lactamase-producing Enterobacterales isolated in 2024 in France. (PubMed, Antimicrob Agents Chemother) - "Cefepime-taniborbactam and cefiderocol showed reduced overall activity (76.4% and 74.9% susceptibility, respectively), with reduced efficacy mainly observed among NDM-producing isolates. Comparison with 1,465 isolates from 2023 showed no increase in aztreonam-avibactam resistance."

Journal • Preclinical

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

Activity of cefiderocol/xeruborbactam against NDM-producing Escherichia coli isolates with PBP3 insertions and decreased susceptibility or resistance to aztreonam/avibactam, cefiderocol, and cefepime/taniborbactam (ESCMID Global 2026) - No abstract available

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

Cefepime/taniborbactam: an unmet expectation for NDM-1-producing Pseudomonas aeruginosa? (ESCMID Global 2026) - No abstract available

Activity of cefiderocol/xeruborbactam against NDM-producing Escherichia coli isolates with PBP3 insertions and decreased susceptibility or resistance to aztreonam/avibactam, cefiderocol, and cefepime/taniborbactam (ESCMID Global 2026) - No abstract available

Comparative activity of cefepime/taniborbactam and cefiderocol/xeruborbactam against producers of KPC variants conferring resistance to ceftazidime/avibactam and cefiderocol (ESCMID Global 2026) - No abstract available

Reduced Susceptibility to Cefepime-Taniborbactam in Carbapenem-Resistant Klebsiella pneumoniae Attributed to Penicillin-Binding Protein 3 Modifications. (PubMed, J Infect Dis) - "Although PBP3-mediated FEP-TAN resistance entails measurable fitness costs, especially under nutrient-limited conditions, PBP3 polymorphism surveillance should be incorporated into resistance monitoring."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Cefepime and New Cefepime/Beta-Lactamase Inhibitor Combination for the Treatment of Gram-Negative Bacteria: Chemical Structure and Mechanism of Action, Microbiological Target, Clinical Use and PK/PD Characteristics. (PubMed, Pharmaceuticals (Basel)) - "This review examines preclinical and clinical studies on cefepime-based BL/BLI combinations, specifically cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, and cefepime/nacubactam, as found in the PubMed database. Cefepime-based BL/BLI combinations are emerging as promising carbapenem-sparing agents, offering broad-spectrum activity, dual mechanisms of action, and encouraging clinical outcomes. These findings support their inclusion in antimicrobial stewardship strategies aimed at mitigating resistance."

Journal • PK/PD 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

Activity of novel antibiotics against dual metallo-Beta-lactamase producing Enterobacter hormaechei clinical isolates. (PubMed, JAC Antimicrob Resist) - "Our findings indicate that E. hormaechei clinical isolates co-producing NDM and VIM metallo-carbapenemases exhibited susceptibility to all tested novel BL/BLIs, including aztreonam/avibactam, cefepime/taniborbactam and cefepime/zidebactam. The combination of cefiderocol and xeruborbactam restored the activity of cefiderocol."

Journal • Infectious Disease

Pharmacodynamic studies of taniborbactam (VNRX-5133) combined with cefepime against β-lactamase-producing Gram-negative bacteria in a neutropenic murine thigh infection model. (PubMed, J Antimicrob Chemother) - "Taniborbactam restored cefepime's activity against resistant Gram-negative bacteria in a time- and concentration-dependent manner at low and higher cefepime exposures, respectively."

Journal • PK/PD data • Preclinical • Infectious Disease • Pneumonia

In vitro susceptibility of cefepime-enmetazobactam, cefepime-taniborbactam and cefepime-zidebactam towards carbapenemase-producing Enterobacterales. (PubMed, J Antimicrob Chemother) - "This study support the use of cefepime-enmetazobactam against ESBL/OXA-48-like co-producers. Cefepime-taniborbactam may be use against KPC and VIM producers and could represent a second-line option for NDM. Cefepime-zidebactam shows the most promising activity against MBLs, although already emerging resistance calls for caution."

Journal • Preclinical • Infectious Disease • Pneumonia

Activity of aztreonam-avibactam, cefiderocol, and cefepime-taniborbactam against a global collection of genetically characterized metallo-β-lactamase-producing Enterobacterales. (PubMed, Antimicrob Agents Chemother) - "Tigecycline and colistin inhibited 94.1% and 76.6% of the isolates (FDA and EUCAST breakpoints, respectively). MBL-producing organisms are still considered an unmet medical need. Aztreonam-avibactam was active against this large collection of MBL-producing isolates that had elevated MIC values for many comparator agents."

Journal

Susceptibilities of cefiderocol, meropenem-xeruborbactam, cefepime-taniborbactam, aztreonam-avibactam, and sulbactam-durlobactam against imipenem-non-susceptible Gram-negative bacilli in Taiwan. (PubMed, Int J Infect Dis) - " Cefiderocol was highly effective, whereas novel β-lactam/β-lactamase inhibitors activity varied by species and carbapenemase types. PBP3 alterations reduced FTB and AZA activity in INS-EC."

Journal • 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

Revitalizing cephalosporins: The promise of β-lactamase inhibitor combinations. (PubMed, GMS Hyg Infect Control) - "It examines β-lactam resistance mechanisms, established combinations (e.g., ticarcillin/clavulanic acid, piperacillin/tazobactam), and the clinical efficacy of newer therapies like ceftazidime/avibactam (CAZ-AVI) for carbapenem-resistant Klebsiella pneumoniae (CRKP) and ceftolozane/tazobactam (TOL-TAZ) for MDR Pseudomonas aeruginosa. Additionally, novel combinations (e.g., cefepime-enmetazobactam, cefepime-taniborbactam) are discussed for tackling extensively drug-resistant (XDR) bacteria. Through comparative analyses, this review provides key insights into efficacy, resistance, pharmacokinetics, and safety, guiding researchers in optimizing antimicrobial strategies and clinicians in managing MDR infections, while supporting antibiotic management and future research."

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

Evaluating Antibacterial Efficacy of Cefiderocol and Cefepime/Taniborbactam Against OXA-48-Like and NDM-Expressing Enterobacterales: An In-Vitro and In-Silico Approach. (PubMed, Curr Microbiol) - "Recently, a triple combination of ceftazidime/avibactam and aztreonam has been utilized to combat these infections. Computational studies confirmed better binding affinity for both OXA-48-like and NDM. However, in-vitro studies demonstrated that cefepime/taniborbactam and cefiderocol represent viable alternative options, specifically for OXA-48-like producers, as their effectiveness is significantly compromised in the presence of NDM."

Journal • Preclinical • Infectious Disease • Pneumonia

Investigating cefepime/taniborbactam for the treatment of complicated urinary tract infections. (PubMed, Expert Opin Pharmacother) - "Cefepime/taniborbactam demonstrates promising in vitro activity against a broad range of β-lactamase-producing bacteria, such as carbapenemase-producing Enterobacterales, including those producing metallo-β-lactamases, and difficult-to-treat Pseudomonas aeruginosa. Its efficacy and safety profile in complicated urinary tract infections suggest it could represent a valuable therapeutic option, particularly in settings with high prevalence of difficult-to-treat pathogens."

Journal • Review • Infectious Disease • Nephrology