"Durlobactam"

Sulbactam, durlobactam (Xacduro) - To treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia Skip to main contentSkip to FDA SearchSkip to footer links An official website of the United States government Here's how you know U.S. Food and Drug Administration  Search   MenuSearch FDASubmit search Home Drugs Drug Approvals and Databases Drugs@FDADrug Approval

A microbiological and structural analysis of the interplay between sulbactam/durlobactam and imipenem against penicillin-binding proteins (PBPs) of Acinetobacter spp. In the ATTACK Phase 3 trial examining the efficacy of sulbactam (SUL)/durlobactam (DUR) to treat primarily complex (ABC) infections, imipenem (IPM)/cilastatin was added as a common therapy to both the SUL/DUR and the comparator

Successful Treatment of Carbapenem-Resistant Acinetobacter baumannii Meningitis with Sulbactam-Durlobactam. The treatment of carbapenem-resistant Acinetobacter baumannii/calcoaceticus complex (CRAB) presents significant treatment challenges. We report the case of a 42-year-old woman with CRAB meningitis who experienced persistently positive cerebrospinal fluid (CSF) cultures for 13 days despite treatment with high-dose ampicillin-sulbactam and cefiderocol. On day 13, she was transitioned to sulbactam-durlobactam and meropenem; four subsequent CSF cultures remained negative. After 14 days of sulbactam-durlobactam, she was cured of infection. Whole genome sequencing investigations identified putative mechanisms that contributed to reduced cefiderocol susceptibility observed during cefiderocol

The growing threat of NDM-producing E. coli with penicillin-binding protein 3 mutations in the United States - is there a potential role for durlobactam? We report identification of 5 patients with infections caused by NDM-5-producing E. coli harboring PBP3 mutations that showed reduced susceptibility to aztreonam-avibactam and cefiderocol. Durlobactam, a novel diazabicyclooctane β-lactamase

In vitro activity of sulbactam-durlobactam against colistin-resistant and/or cefiderocol-non-susceptible, carbapenem-resistant Acinetobacter baumannii collected in U.S. hospitals. The activity of a novel β-lactamase inhibitor combination, sulbactam-durlobactam (SUL-DUR), was tested against 87 colistin-resistant and/or cefiderocol-non-susceptible carbapenem-resistant clinical isolates collected

Clinical Outcomes for Patients With Monomicrobial vs Polymicrobial Acinetobacter baumannii-calcoaceticus Complex Infections Treated With Sulbactam-Durlobactam or Colistin: A Subset Analysis From a Phase 3 Clinical Trial. In a previous study, the efficacy and safety of sulbactam-durlobactam vs colistin for the treatment of patients with carbapenem-resistant complex (CRABC) infections were and polymicrobial CRABC infections. Minimal inhibitory concentrations of antibiotics against baseline isolates were determined by broth microdilution according to Clinical and Laboratory Standards Institute methodology. Clinical cure, 28-day all-cause mortality, and microbiological outcomes were similar for patients in the sulbactam-durlobactam treatment arm with monomicrobial or polymicrobial infections

Characterization of Acinetobacter baumannii-calcoaceticus complex isolates and microbiological outcome for patients treated with sulbactam-durlobactam in a phase 3 trial (ATTACK). s complex (ABC) causes severe, difficult-to-treat infections that are frequently antibiotic resistant. Sulbactam-durlobactam (SUL-DUR) is a targeted β-lactam/β-lactamase inhibitor combination antibiotic designed

The role of sulbactam-durlobactam in treating carbapenem-resistant Acinetobacter infections. Infections caused by multidrug-resistant Acinetobacter baumannii present a significant global health challenge. Available treatment options are limited and frequently constrained by unfavourable safety and pharmacokinetic profiles. Sulbactam-durlobactam is a novel β-lactamase inhibitors combination specifically developed to target A. baumannii , including carbapenem-resistant strains. The purpose of this review is to assess the current evidence supporting the role of sulbactam-durlobactam in the management of A. baumannii infections. We summarize the available evidence regarding the pharmacokinetic and pharmacodynamic profiles of sulbactam-durlobactam from key in-vitro and in-vivo studies. Additionally

Population pharmacokinetic analyses for sulbactam-durlobactam using Phase 1, 2, and 3 data. Sulbactam-durlobactam is a β-lactam/β-lactamase inhibitor combination approved in the United States for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible isolates of in adults. A population pharmacokinetic (PK) model of sulbactam-durlobactam in plasma HD was started 1 hour after the end of the infusion. Assuming protein binding estimates of 10% and 38% for durlobactam and sulbactam, respectively, ELF penetration ratios were found to be 41.3% for durlobactam and 86.0% for sulbactam. Of the statistically significant covariates of PK identified, which included body weight, body mass index, infection type, and region of origin, renal function

Durlobactam to boost the clinical utility of standard of care β-lactams against Mycobacterium abscessus lung disease. β-Lactams present several desirable pharmacodynamic features leading to the rapid eradication of many bacterial pathogens. Imipenem (IPM) and cefoxitin (FOX) are injectable β-lactams recommended during the intensive treatment phase of pulmonary infections caused by (Mab). However , their potency against Mab is many-fold lower than against Gram-positive and Gram-negative pathogens for which they were optimized, putting into question their clinical utility. Here, we show that adding the recently approved durlobactam-sulbactam (DUR-SUL) pair to either IPM or FOX achieves growth inhibition, bactericidal, and cytolytic activity at concentrations that are within those achieved in patients

Ex vivo assessment of sulbactam-durlobactam clearance during continuous renal replacement therapy to guide dosing recommendations. Sulbactam-durlobactam is approved for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible isolates of complex. Patients with serious infections may require support with continuous renal replacement therapy (CRRT ), which presents challenges for optimal dosing of antibiotics. Sulbactam-durlobactam dosing regimens were derived for this population using an CRRT model and Monte Carlo simulation (MCS). Transmembrane clearance (CL) was determined in hemofiltration (CVVH) and hemodialysis (CVVHD) modes using the Prismaflex M100 and HF1400 hemofilter sets and with effluent rates of 1, 2, and 3 L/h. Pre-filter, post

Durlobactam in combination with β-lactams to combat Mycobacterium abscessus. () presents significant clinical challenges. This study evaluated the synergistic effects of a β-lactam and β-lactamase inhibitor combination against and explored the underlying mechanisms. Synergy was assessed through MIC tests and time-kill studies, and binding affinities of nine β-lactams and BLIs to eight target , sulopenem, tebipenem, and amoxicillin exhibited moderate to low binding affinity. Durlobactam inactivated Bla and LDT/PBPs more potently than avibactam. The s of durlobactam for PBP B, PBP-lipo, and LDT2 were below clinically achievable unbound concentrations, while avibactam's for LDT/PBPs exceeded the clinical concentrations. Single β-lactam treatments resulted in minimal killing (~1 log reduction

The Pharmacokinetics/Pharmacodynamic Relationship of Durlobactam in Combination With Sulbactam in In Vitro and In Vivo Infection Model Systems Versus Acinetobacter baumannii-calcoaceticus Complex. Sulbactam-durlobactam is a β-lactam/β-lactamase inhibitor combination currently in development for the treatment of infections caused by Acinetobacter, including multidrug-resistant (MDR) isolates of sulbactam in the treatment of this pathogen. Durlobactam is a rationally designed β-lactamase inhibitor within the diazabicyclooctane (DBO) class. The compound demonstrates a broad spectrum of inhibition of serine β-lactamase activity with particularly potent activity against class D enzymes, an attribute which differentiates it from other DBO inhibitors. When combined with sulbactam, durlobactam

Durlobactam, a Broad-Spectrum Serine β-lactamase Inhibitor, Restores Sulbactam Activity Against Acinetobacter Species. Sulbactam-durlobactam is a pathogen-targeted β-lactam/β-lactamase inhibitor combination in late-stage development for the treatment of Acinetobacter infections, including those caused by multidrug-resistant strains. Durlobactam is a member of the diazabicyclooctane class of β decades due to its susceptibility to cleavage by numerous β-lactamases present in this species. However, when combined with durlobactam, the activity of sulbactam is restored against this problematic pathogen. The following summary describes what is known about the molecular drivers of activity and resistance as well as results from surveillance and in vivo efficacy studies for this novel combination.

Sulbactam-durlobactam: A Step Forward in Treating Carbapenem-Resistant Acinetobacter baumannii (CRAB) Infections. Antimicrobial resistance in gram-negative pathogens, such as Acinetobacter baumannii, is a serious threat to human health. Sulbactam-durlobactam, a unique β-lactam and a β-lactamase inhibitor combination, is a novel agent targeted against carbapenem-resistant A. baumannii

Sulbactam-durlobactam: A Novel β-lactam-β-lactamase Inhibitor Combination Targeting Carbapenem-Resistant Acinetobacter baumannii Infections. Carbapenem-resistant Acinetobacter baumannii (CRAB), is a difficult-to-treat nosocomial pathogen responsible for significant morbidity and mortality. Sulbactam-durlobactam (SUL-DUR), formerly ETX2514SUL, is a novel β-lactam-β-lactamase inhibitor designed

Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical tr An urgent need exists for antibiotics to treat infections caused by carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (ABC ). Sulbactam-durlobactam is a β-lactam-β-lactamase inhibitor combination with activity against Acinetobacter, including multidrug-resistant strains. In a phase 3, pathogen-specific, randomised controlled trial, we compared the efficacy and safety of sulbactam-durlobactam versus colistin, both in combination with imipenem-cilastatin as background therapy, in patients with serious infections caused

In vivo dose response and efficacy of the β-lactamase inhibitor, durlobactam, in combination with sulbactam against the Acinetobacter baumannii-calcoaceticus complex. Multi-drug resistant (MDR) is emerging as a pathogen of increasing prevalence and concern. Infections associated with this Gram-negative pathogen are often associated with increased morbidity and mortality and few therapeutic therapies. Durlobactam is a non-β-lactam β-lactamase inhibitor that demonstrates broad β-lactamase inhibition including class D enzymes produced by and has shown potent activity against MDR , particularly carbapenem-resistant isolates in susceptibility and pharmacodynamic model systems. The objective of this study is to evaluate the exposure-response relationship of sulbactam and durlobactam

In vitro pharmacokinetics/pharmacodynamics of the β-lactamase inhibitor, durlobactam, in combination with sulbactam against Acinetobacter baumannii-calcoaceticus complex. Infections caused by are increasingly multidrug resistant and associated with high rates of morbidity and mortality. Sulbactam is a β-lactamase inhibitor with intrinsic antibacterial activity against . Durlobactam is a non-β -lactam β-lactamase inhibitor with an extended spectrum of activity compared to other inhibitors of its class. pharmacodynamic infection models were undertaken to establish the pharmacokinetic/pharmacodynamic (PK/PD) index and magnitudes associated with sulbactam and durlobactam efficacy and to simulate epithelial lining fluid (ELF) exposures at clinical doses to understand sulbactam-durlobactam

Molecular drivers of resistance to sulbactam-durlobactam in contemporary clinical isolates of Acinetobacter baumannii. - complex (ABC) causes severe infections that are difficult to treat due to pre-existing antibiotic resistance. Sulbactam-durlobactam (SUL-DUR) is a targeted β-lactam/β-lactamase inhibitor combination antibiotic designed to treat serious infections caused by , including , this study shows that certain common PBP3 variants, such as A515V, are insufficient to confer sulbactam resistance and that the efflux of durlobactam by AdeIJK is likely to play a role in a subset of strains.