Xacduro (sulbactam-durlobactam) / ZAI Lab, Innoviva - LARVOL DELTA

Carbapenem Resistance in Acinetobacter baumannii: Mechanisms, Therapeutics, and Innovations. (PubMed, Microorganisms) - "Emerging treatment strategies are discussed, such as the use of new beta-lactam-beta-lactamase inhibitor combinations (e.g., sulbactam-durlobactam), siderophore cephalosporins, next-generation polymyxins, as well as novel agents like zosurabalpin and rifabutin (BV100). Together, these innovations represent a multifaceted strategy to overcome CRAB infections, yet their successful implementation requires further clinical validation and coordinated surveillance efforts. This analysis highlights the urgent need for continued investment in innovative treatments and effective resistance monitoring to limit the spread of CRAB and protect the effectiveness of last-line antibiotics."

Journal • Review • Critical care • Infectious Disease

The global epidemiology of carbapenem-resistant Acinetobacter baumannii. (PubMed, JAC Antimicrob Resist) - "The novel agent sulbactam-durlobactam holds promise for improved patient outcomes, but ongoing therapeutic development, infection prevention, and antimicrobial stewardship are critical to combat this formidable pathogen. Here, we review the emergence and dissemination of CRAb, its molecular epidemiology and resistance mechanisms, summarize contemporary global clinical epidemiology and patient outcomes, and briefly describe existing and future therapeutics."

Journal • Review • Gene Therapies • Infectious Disease

Nephrotoxicity of New Antibiotics: A Systematic Review. (PubMed, Toxics) - "The agents assessed included aztreonam/avibactam, cefepime/enmetazobactam, cefiderocol, ceftobiprole, contezolid, gepotidacin, imipenem/cilastatin/relebactam, lascufloxacin, lefamulin, levonadifloxacin, plazomicin, and sulbactam/durlobactam. There is a need for post-marketing studies to better characterize renal safety. Clinicians should remain vigilant and continue to monitor for and report renal-related adverse events."

Journal • Review

Sulbactam-durlobactam in combination with aztreonam and carbapenems against carbapenem-resistant Acinetobacter baumannii: an assessment using the MIC-based broth disk elution. (PubMed, J Clin Microbiol) - No abstract available

Journal

In vitro efficacy of sulbactam-durlobactam combined with β-lactam antibiotics in Australian Mycobacterium abscessus isolates (WBC 2025) - No abstract available

Preclinical

Non-KPC Attributes of the Newer β-lactam/β-lactamase Inhibitors, Part 2: Burkholderia cepacia complex, Stenotrophomonas maltophilia, and Acinetobacter baumannii. (PubMed, Clin Infect Dis) - "The BL/BLI combination drugs, ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/relebactam, have proven especially useful for treating carbapenemase producing, carbapenem resistant organisms (CRO), specifically Klebsiella pneumoniae carbapenemases (KPCs)...These newer BL/BLIs, including sulbactam/durlobactam, have an array of activity against mechanisms of carbapenem resistance beyond KPC and therefore play an important role in the treatment of non-KPC CRO. This review, the second in a two-part series, lays out the non-KPC attributes of the newer BL/BLIs with a focus on clinical utility against Burkholderia cepacia complex, Stenotrophomonas maltophilia, Acinetobacter baumannii and other rare pathogens."

Journal • Infectious Disease • Pneumonia

Pharmacokinetics of Sulbactam/Durlobactam in a Patient With Acute Renal Failure, Severe Obesity, and Carbapenem-Resistant Acinetobacter baumannii Bacteremia: A Case Report. (PubMed, Pharmacotherapy) - "Carbapenem-resistant Acinetobacter baumannii (CRAB) are difficult-to-treat pathogens that primarily cause health care-associated infections. Susceptibility testing using the broth disk elution test did not show synergy between SUL/DUR and meropenem. No adverse effects were observed, and the patient achieved clinical cure without recurrence of A. baumannii infection."

Journal • PK/PD data • Acute Kidney Injury • Genetic Disorders • Infectious Disease • Obesity • Renal Disease

Activity of ampicillin-sulbactam, sulbactam-durlobactam, and comparators against Acinetobacter baumannii-calcoaceticus complex strains isolated from respiratory and bloodstream sources: results from ACNBio study. (PubMed, Antimicrob Agents Chemother) - "Minocycline susceptibility was <50%, while tigecycline and eravacycline MIC50/90 were 1/2 and 0.5/1 µg/mL, respectively. Susceptibility rates of clinically utilized antimicrobials against a US collection of ABC isolates ranged from 23% to 97%, with meropenem displaying the lowest rate and sulbactam-durlobactam demonstrating the highest overall rate. Sulbactam-durlobactam activity was preserved against sulbactam, carbapenem, and cefiderocol non-susceptible isolates among respiratory tract and bloodstream isolates."

Journal • Critical care • Infectious Disease

Critical Care Management of Pan-Resistant Acinetobacter Osteomyelitis Requiring Novel Antibiotic Therapy (ASA 2025) - "Due to the high cost, IV-only administration, and Q6H dosing of sulbactam-durlobactam, discharge planning was complex, necessitating LTACH placement. This case highlights challenges in perioperative management, antimicrobial stewardship, and post-ICU transitions for patients requiring emerging antimicrobials."

CNS Disorders • Critical care • Diabetes • Infectious Disease • Inflammation • Metabolic Disorders • Septic Shock

Acinetobacter baumannii treatment strategies: a review of therapeutic challenges and considerations. (PubMed, Antimicrob Agents Chemother) - "Consistent with the 2024 Infectious Diseases of America (IDSA) update, sulbactam-durlobactam, in combination with background carbapenem therapy, remains the combination with the greatest reduction in mortality for pulmonary infections and has promising outcomes in bloodstream infections with CRAB...Certain agents have been highlighted in the literature for suboptimal outcomes, primarily pulmonary infections treated with cefiderocol, tigecycline, and eravacycline. Studies including non-pulmonary infections, specifically bacteremia and central nervous system (CNS) infections, are overall limited to case series and subgroup analyses. Important areas for further research include breakpoint evaluations for eravacycline and minocycline as well as subclinical resistance in cefiderocol."

Journal • Review • Infectious Disease • Respiratory Diseases

Comparative in vitro activity of sulbactam with avibactam or durlobactam against carbapenem-resistant Acinetobacter baumannii. (PubMed, JAC Antimicrob Resist) - "Standardized susceptibility testing by broth microdilution was performed to determine MICs for imipenem, meropenem and sulbactam alone, and for combinations including sulbactam/avibactam, sulbactam/durlobactam, sulbactam/avibactam/meropenem, sulbactam/avibactam/imipenem, sulbactam/durlobactacm/meropenem and sulbactam/durlobactam/imipenem. Carbapenem combinations were more active than combinations without a carbapenem against isolates with PBP3 mutations. These data show that imipenem potentiates sulbactam-based combinations to a greater extent than meropenem; however, future studies are needed to define how these data should be applied in clinical practice."

Journal • Preclinical

Development of a Sulbactam-Durlobactam AST Verification Panel of 30 A. baumannii and Comparison of Reference Broth Microdilution to Gradient Strip Mic and to Disk Results (ASM Microbe 2025) - "The availability of a curated verification panel of A. baumannii is a valuable resource for laboratories. Overall, Etest and MTS results were comparable to the modal rBMD results for these strains."

Infectious Disease • Pneumonia • Respiratory Diseases

Critical Antimicrobial Susceptibility Testing Results for Critical Patients: A 2025 Perspective (ASM Microbe 2025) - "The use of new generation therapeutics like sulbactam/durlobactam and MIC results for determining optimal treatment are critical in the face of growing antibiotic resistance. The availability of accurate broth microdilution-based MICs for new antibiotics can help improve patient outcomes and reduce the lengths-of-stay, therapeutic dosages and duration, adverse reactions, and costs.??Actions taken by the antimicrobial stewardship team to enforce the judicious use of antimicrobials are most effective when supported by timely diagnostic information from and collaboration with microbiology laboratory personnel. Effective collaborations among microbiologists, clinicians, the antimicrobial stewardship team, and policy makers can help improve patient care and meet the challenges of increased antibiotic resistance in a post-Covid world."

Clinical • Infectious Disease • Novel Coronavirus Disease

Verification of Sulbactam-Durlobactam Gradient Diffusion Test for Acinetobacter baumannii: A Multi-Site Study (ASM Microbe 2025) - "The data from this multi-site study show that FDA-cleared GD test strips and a commercially available verification isolate panel can be used to implement sulbactam-durlobactam susceptibility testing in clinical laboratories."

Infectious Disease • Pneumonia • Respiratory Diseases

Sensitizing NDM-1-Producing Acinetobacter baumannii to Sulbactam/Durlobactam with Low Levels of Polymyxin B (ASM Microbe 2025) - "PMB at low concentrations sensitized NDM-1-producing A. baumannii isolates to SUD. Cell morphology changes suggest the mechanism to be direct antibacterial activity by both SUL and DUR, likely facilitated by increased entry into cells following outer membrane damage by PMB. Next steps include assessment of bactericidal activity and preclinical studies."

Infectious Disease

Susceptibility toward cefiderocol and sulbactam-durlobactam in extensively drug-resistant Acinetobacter baumannii detected from ICU admission screening in Hanoi, Vietnam, 2023. (PubMed, Microbiol Spectr) - "All isolates were resistant to ciprofloxacin, levofloxacin, imipenem, and meropenem, with high resistance rates to amikacin (96.8%) and trimethoprim/sulfamethoxazole (96.8%). Alarmingly, some bacteria were resistant to cefiderocol and sulbactam-durlobactam even in patients who had never received these drugs, suggesting that resistance is spreading quietly. This highlights the urgent need for ongoing surveillance, early detection, and careful use of antibiotics to prevent the spread of untreatable infections."

Journal • Critical care • Infectious Disease

A Study to Assess the Safety and Risk of Hypersensitivity Reactions of Sulbactam-durlobactam in Adults With Acinetobacter Baumannii-calcoaceticus (ABC) Complex Infection (clinicaltrials.gov) - P=N/A | N=100 | Recruiting | Sponsor: Innoviva Specialty Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Infectious Disease

New β-Lactam/β-Lactamase Inhibitor Combination Antibiotics. (PubMed, Pathogens) - "During the last 2 years from the writing of this article, cefepime/enmetazobactam, aztreonam/avibactam, and sulbactam/durlobactam were approved for use in clinical practice. Aztreonam/avibactam is indicated for the treatment of adult patients who suffer from complicated intra-abdominal infections, complicated urinary tract infections including pyelonephritis, hospital-acquired pneumonia, and ventilator-associated pneumonia due to aerobic Gram-negative infections with limited therapeutic options. Sulbactam/durlobactam, a combination of 2 β-lactamase inhibitors, is indicated for the treatment of adult patients with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia due to the Acinetobacter baumannii-calcoaceticus complex [including carbapenem-resistant Acinetobacter baumannii (CRAB) infections]."

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

Quantification of sulbactam and durlobactam in saline and human plasma via ultra-performance liquid chromatography tandem mass spectrometry. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "The standard curves for each drug were linear over the range 0.5 to 50 μg/mL and use the isotopic analogs sulbactam-d5 and [13C2, 15N2]-durlobactam as internal standards for their respective analytes. This simple, reproducible method for the determination of sulbactam and durlobactam concentrations was developed with the intent to conduct future pharmacokinetic analyses and to guide clinical laboratories in the development of a therapeutic drug monitoring assay."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Pharmacokinetic and pharmacodynamic evaluation of sulbactam-durlobactam in a critically ill patient on continuous venovenous hemofiltration infected with carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex. (PubMed, Pharmacotherapy) - "Sulbactam-durlobactam monotherapy dosed at 2 g every 4 h (3-h infusion) in CVVH achieved PD targets for this CRAB isolate with a MIC of 4/4 mcg/ml. Although sulbactam-durlobactam monotherapy resulted in initial microbiological clearance for the CRAB bacteremia, recurrence occurred, and the patient ultimately died."

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

Evolution of an extensively antibiotic resistant sublineage of lineage 1 of GC1 Acinetobacter baumannii. (PubMed, NPJ Antimicrob Resist) - "The blaNDM and blaPER genes contribute to reduced susceptibility to cefiderocol and/or sulbactam/durlobactam. The phylogeny indicated that separation of the sublineage into KL1 and KL17 groups coincided with the KL switch and Aci-IE1 was acquired later."

Journal

Successful Combination Therapy with Cefiderocol and Sulbactam-Durlobactam for Donor-Derived Carbapenem-Resistant Acinetobacter baumannii in a Kidney Transplant Recipient. (PubMed, Transpl Infect Dis) - No abstract available

Journal • Solid Organ Transplantation • Transplantation

Genomic characterization of Carbapenem-Resistant Acinetobacter baumannii clinical strains resistant to Sulbactam/Durlobactam from Italy. (PubMed, Eur J Clin Microbiol Infect Dis) - No abstract available

Journal

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

Sulbactam for carbapenem-resistant Acinetobacter baumannii infections: a literature review. (PubMed, JAC Antimicrob Resist) - "The aim of this review is to analyse primary and secondary research studies that compare sulbactam-based with other regimens, such as polymyxin-containing regimens, tigecycline-containing regimens and other antimicrobial combinations against CRAB infections, especially ventilator-associated pneumonia (VAP), hospital-acquired pneumonia (HAP) and bacteraemia...The auspicious novel β-lactam/β-lactamase inhibitor combination sulbactam/durlobactam is also discussed, although real-world clinical data regarding its efficacy in CRAB infections are still scarce. More randomized controlled trials comparing sulbactam-based with other regimens are warranted to determine the most effective antimicrobial combination against CRAB infections. Nevertheless, current data suggest that sulbactam could play a major role in this combination treatment."

Journal • Review • Infectious Disease • Pneumonia • Respiratory Diseases