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

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

How I manage patients with New Delhi metallo-beta-lactamase and OXA-48-producing Enterobacterales infections: a practical approach. (PubMed, Curr Opin Infect Dis) - "Optimal management of NDM- and OXA-48-producing Enterobacterales requires individualized approach guided by pathogen type, resistance profile, and patient characteristics. Improved diagnostics and surveillance are essential to guide early treatment, while novel agents may enhance therapeutic options in the near future."

Journal • Infectious Disease

Novel beta-lactamase inhibitors with cefepime: where do they fit in clinical practice? (PubMed, Expert Opin Pharmacother) - "We performed a literature review of articles written in English using MEDLINE, PUBMED, and EMBASE, using the search terms 'Cefepime-enmetazobactam,' 'cefepime-taniborbactam,' and 'Cefepime-zidebactam' between January of 2015 and May 2025. On balance, the in vitro activity of cefepime-zidebactam fills critical gaps for the most challenging Gram-negative pathogens, including those that harbor metallo-β-lactamases with or without mutations in penicillin-binding proteins. For each of these agents, clinical data and real-world evidence generation are needed to better define their therapeutic niche, potential for resistance selection, and potential benefits compared to currently available antibiotics."

Journal • Review • Infectious Disease

Burkholderia pseudomallei PenI β-lactamase and variants are potently inhibited by taniborbactam. (PubMed, Antimicrob Agents Chemother) - "Isogenic Escherichia coli strains producing PenI and its ceftazidime-resistance-conferring variants (C69Y and P167S) showed ceftazidime minimum inhibitory concentration (MIC) of 64 mg/L for the strain producing PenI and 1,024 mg/L for the strains producing the variants, whereas cefepime MIC was 128-256 mg/L for these three strains. Lastly, co-crystallography and molecular dynamics simulations showed that taniborbactam induced the formation of a disulfide bond between Cys77 and Cys123, which destabilizes the deacylation water and strengthens the taniborbactam-PenI complex. These results support the development of cefepime-taniborbactam as a promising agent for the treatment of infections by B. pseudomallei."

Journal • Infectious Disease

In Vitro Antimicrobial Activity of Cefepime-Taniborbactam Against Molecularly Characterized Enterobacterales and P. aeruginosa Collected Worldwide from 2018-2023 (IDWeek 2025) - No abstract available

Preclinical • Infectious Disease

In Vitro Antimicrobial Activity of Cefepime in Combination with Taniborbactam Against Resistant Clinical Gram-negative Isolates from a Global Collection, 2018-2023 (IDWeek 2025) - No abstract available

Combination therapy • Gram negative • Preclinical • Infectious Disease

ICU environment as a reservoir of KPC-ST307-Klebsiella pneumoniae high-risk clone resistant to ceftazidime-avibactam. (PubMed, Sci Rep) - "Regardless of the origin (patients or sinks), KPC-92-, KPC-150 and KPC-62-Kp isolates combining altered porin proteins also exhibited increased/resistant MIC values to cefiderocol, cefepime-taniborbactam, aztreonam-avibactam, meropenem-vaborbactam and/or imipenem-relebactam. A variant calling analysis and plasmid characterization showed possible transmission between patients and sinks. Our results suggest that the patient care environment likely contributed to persistence and spread of last-line antibiotics-resistant KPC-Kp within the ICU during the COVID-19 pandemic."

Journal • Infectious Disease • Novel Coronavirus Disease • Pneumonia

Establishing the reference broth microdilution MIC method for cefepime-taniborbactam. (PubMed, J Clin Microbiol) - P3 | "It also held up well under different testing conditions, showing that it is a dependable tool for guiding treatment decisions. This is an important step in meeting the challenge of antibiotic-resistant infections since it will help clinicians evaluate cefepime-taniborbactam as a potential treatment option as they strive to improve the care of patients suffering from serious infections."

Journal • Infectious Disease

Assessment of human exposures of cefepime-taniborbactam against cefepime-resistant Enterobacterales and Pseudomonas aeruginosa in a 7-day hollow fiber infection model. (PubMed, Antimicrob Agents Chemother) - "Therefore, human cefepime-taniborbactam exposures demonstrated sustained bactericidal activity and suppressed the emergence of resistance in a 7-day HFIM among serine and metallo-β-lactamase-positive Enterobacterales and P. aeruginosa strains. These observations support the clinical development of cefepime-taniborbactam and inform understanding of its potential role in treating serine and/or metallo-β-lactamase-positive Gram-negative bacterial infections."

Journal • Infectious Disease • Pneumonia

Amphiphilic nebramine analogs synergize with β-lactam/β-lactamase inhibitor combinations, including cefepime-taniborbactam and meropenem-xeruborbactam against metallo-β-lactamase-carrying Pseudomonas aeruginosa. (PubMed, RSC Med Chem) - "Cefepime-taniborbactam (FEP-TAN) and meropenem-xeruborbactam (MEM-XER) are β-lactam-β-lactamase inhibitor (BL-BLI) combinations currently in development and both projected to treat metallo-β-lactamase (MBL)-producing Gram-negative pathogens. Compound 4 was found to be less toxic than both polymyxin B and its corresponding amphiphilic tobramycin counterpart (compound 7) in human renal cell lines, RPTEC and HK-2. Overall, our study suggests that addition of compound 4 alongside next-generation BL-BLIs such as FEP-TAN, MEM-XER as well as the recently approved ATM-AVI combination can overcome intrinsic and acquired in vitro P. aeruginosa resistance determinants that confer high-level resistance to β-lactam antibiotics."

Journal • Infectious Disease

Broad spectrum of β-lactamase coverage and potent antimicrobial activity of xeruborbactam in combination with meropenem against carbapenemase-producing Enterobacterales, including strains resistant to new β-lactam/β-lactamase inhibitor combinations. (PubMed, Antimicrob Agents Chemother) - "The MICs of meropenem, meropenem/xeruborbactam, meropenem/vaborbactam, imipenem, imipenem/relebactam, cefepime, cefepime/taniborbactam, ceftazidime, ceftazidime/avibactam, aztreonam, and aztreonam/avibactam were determined by reference broth microdilution and interpreted following the European Committee on Antimicrobial Susceptibility Testing guidelines, using the breakpoint of the β-lactam alone for not yet approved combinations. Xeruborbactam restored meropenem activity against the strains carrying resistance mechanisms to β-lactam/β-lactamase inhibitor combinations, including strains producing KPC variants or MBLs in combination with additional chromosomal alterations (MIC range: ≤0.06-0.25 and ≤0.06-4 mg/L, respectively). Our findings highlight the potential of xeruborbactam in combination with meropenem as a promising treatment against carbapenemase-producing Enterobacterales, including strains with emerging resistance to other β-lactam/β-lactamase inhibitor..."

Journal

Cefepime-zidebactam therapy for extensively drug-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae infection as a bridge to liver transplantation. (PubMed, JAC Antimicrob Resist) - "Serial clinical isolates recovered from biliary fluid and ascitic fluid were tested for susceptibility to cefiderocol, aztreonam-avibactam, cefepime-taniborbactam, cefepime-zidebactam, and cefiderocol-xeruborbactam by broth microdilution...The patient was treated with a regimen of cefiderocol and eravacycline, with persistent fever and development of hepatic microabscesses on imaging...Antimicrobial therapy with cefepime-zidebactam along with source control allowed successful liver transplantation in a patient with cefiderocol-resistant K. pneumoniae and P. aeruginosa. Cefepime-zidebactam may be a therapeutic option for extensively drug-resistant Gram-negative organisms."

Journal • Infectious Disease • Pneumonia • Transplantation

Rapid detection of cefepime-taniborbactam susceptibility/resistance in Enterobacterales. (PubMed, Int J Antimicrob Agents) - "All results were obtained within a three-hour incubation period at 35°C ± 2°C, representing a significant reduction in time compared to current antimicrobial susceptibility testing methods. The results of this study demonstrated that the Rapid Cefepime-Taniborbactam NP test is a highly accurate and time-efficient technique for the detection of bacterial resistance."

Journal • Infectious Disease

Cefepime-taniborbactam: Ushering in the era of metallo-β-lactamase inhibition. (PubMed, Pharmacotherapy) - "The clinical efficacy of FTB was demonstrated in the phase III Cefepime Rescue with Taniborbactam in Complicated Urinary Tract Infection (CERTAIN-1) trial, where it demonstrated both non-inferiority and superiority (prespecified analysis) to meropenem in the composite of clinical and microbiologic success at the test of cure for the treatment of complicated urinary tract infection. Thirteen percent of patients experienced a treatment-related adverse drug event in the phase III clinical trial, with 3% of patients requiring discontinuation of the study agent. Cefepime-taniborbactam appears to be a promising addition to the antibiotic arsenal, particularly as the prevalence of infections caused by MBL-producing organisms continues to rise."

Journal • Review • Infectious Disease • Nephrology • Renal Disease

Structure and mechanism of taniborbactam inhibition of the cefepime-hydrolyzing, partial R2-loop deletion Pseudomonas-derived cephalosporinase variant PDC-88. (PubMed, Antimicrob Agents Chemother) - "Structurally, taniborbactam positioned very similarly in the PDC-3 and PDC-88 active sites, interacting with many nearby residues. Based upon these data, cefepime-taniborbactam may represent an important alternative to ceftazidime-avibactam and ceftolozane-tazobactam for P. aeruginosa infections."

Journal • Infectious Disease

Plasma and intrapulmonary pharmacokinetics of cefepime and taniborbactam in healthy adult participants. (PubMed, Antimicrob Agents Chemother) - P1 | "The highest and lowest values of AUC0-8 values for ELF and DPRELF/plasma for cefepime and taniborbactam were observed with aspirate 1 and aspirate 4, respectively. These results support further consideration of cefepime-taniborbactam as a potential treatment for bacterial pneumonia caused by susceptible MDR Gram-negative pathogens.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04951505."

Journal • PK/PD data • Infectious Disease • Pneumonia • Respiratory Diseases

Cefepime-Taniborbactam-a Novel Combination Therapy for Multidrug-Resistant Pathogens. (PubMed, J Infect Dis) - "In this review, we discuss the advances in medicinal chemistry that led to the development of cefepime-taniborbactam, the pharmacokinetics and pharmacodynamics, the antimicrobial spectrum of activity, potential uses in the clinic, and mechanisms of resistance. We propose future clinical scenarios to better explore the precise niche of this novel inhibitor combination."

Journal • Infectious Disease • Pneumonia

Ex vivo assessment and simulation to guide cefepime-taniborbactam dosing recommendations for patients receiving continuous renal replacement therapy. (PubMed, Antimicrob Agents Chemother) - "For ER ≥3.5 L/h, the optimum regimen was cefepime and taniborbactam 2 g-0.5 g q8h as a 4 h infusion. When incorporated into a population pharmacokinetic model, these CLTM data were used to propose dosing recommendations for cefepime and taniborbactam as a function of ER in patients undergoing CRRT."

Journal • Preclinical • Infectious Disease • Pneumonia • Renal Disease • Respiratory Diseases

Critical reappraisal of current issues for improving the proper clinical use of the incoming beta-lactam/beta-lactamase inhibitor combinations of tomorrow. (PubMed, Expert Rev Anti Infect Ther) - "A literature search was performed on PubMed-MEDLINE (until December 2024) for retrieving available studies on cefepime-enmetazobactam, sulbactam-durlobactam, and cefepime-taniborbactam. Overall, old habits die hard and issues retrieved with licensed beta-lactams emerged also with novel BL/BLIc of tomorrow, potentially affecting their efficacy when used in real-world practice. Adopting appropriate corrective measures for overcoming these issues might increase the likelihood of preserving their efficacy in the future by minimizing the propensity risk of resistance development."

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