relebactam
PharmacologyA Single- and Multiple-Dose Study To Characterize the Pharmacokinetics, Safety, and Tolerability of Imipenem and Relebactam in Healthy Chinese ParticipantsRelebactam/imipenem/cilastatin is approved in the United States to treat complicated urinary tract and intra-abdominal infections in patients who have limited or no alternative treatment options and hospital-acquired bacterial pneumonia (HABP)/ventilator-associated bacterial pneumonia (VABP). Initial pharmacokinetic, safety, and tolerability studies of relebactam with and without imipenem/cilastatin included mostly Caucasian...
Mechanisms of ResistanceStructural Investigations of the Inhibition of Escherichia coli AmpC β-Lactamase by Diazabicyclooctanesβ-Lactam antibiotics are presently the most important treatments for infections by pathogenic Escherichia coli, but their use is increasingly compromised by β-lactamases, including the chromosomally encoded class C AmpC serine-β-lactamases (SBLs). The diazabicyclooctane (DBO) avibactam is a potent AmpC inhibitor; the clinical success of avibactam combined with...
Experimental TherapeuticsActivity of Aztreonam in Combination with Avibactam, Clavulanate, Relebactam, and Vaborbactam against Multidrug-Resistant Stenotrophomonas maltophiliaThe intrinsic L1 metallo- and L2 serine-β-lactamases in Stenotrophomonas maltophilia make it naturally multidrug resistant and difficult to treat. There is a need to identify novel treatment strategies for this pathogen, especially against isolates resistant to first-line agents. Aztreonam in combination with avibactam has demonstrated potential, although data on...
Mechanisms of ResistanceMolecular Basis of Class A β-Lactamase Inhibition by Relebactamβ-Lactamase production is the major β-lactam resistance mechanism in Gram-negative bacteria. β-Lactamase inhibitors (BLIs) efficacious against serine β-lactamase (SBL) producers, especially strains carrying the widely disseminated class A enzymes, are required. Relebactam, a diazabicyclooctane (DBO) BLI, is in phase 3 clinical trials in combination with imipenem for the treatment of infections by multidrug-resistant...
SusceptibilityIn Vitro Activity of the New β-Lactamase Inhibitors Relebactam and Vaborbactam in Combination with β-Lactams against Mycobacterium abscessus Complex Clinical IsolatesPulmonary disease due to infection with Mycobacterium abscessus complex (MABC) is notoriously difficult to treat, in large part due to the intrinsic resistance of MABC strains to most antibiotics, including β-lactams. MABC organisms express a broad-spectrum β-lactamase that is resistant to traditional β-lactam-based β-lactamase inhibitors but inhibited by a newer non-...
- PharmacologyPharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of Relebactam, a β-Lactamase Inhibitor, in Combination with Imipenem and Cilastatin in Healthy Participants
Relebactam is a novel class A and C β-lactamase inhibitor that is being developed in combination with imipenem-cilastatin for the treatment of serious infections with Gram-negative bacteria. Here we report on two phase 1 randomized, double-blind, placebo-controlled pharmacokinetics, safety, and tolerability studies of relebactam administered with or without imipenem-cilastatin to healthy participants: (i) a single-dose (25 to 1,150 mg)...
- Experimental TherapeuticsIn Vivo Efficacy of Relebactam (MK-7655) in Combination with Imipenem-Cilastatin in Murine Infection Models
The World Health Organization has identified antimicrobial resistance as a global public health threat since the prevalence and spread of antibiotic resistance among bacterial pathogens worldwide are staggering. Carbapenems, such as imipenem and meropenem, have been used to treat multidrug-resistant bacteria; however, since the development of resistance to carbapenems, β-lactam antibiotics in combination with β-lactamase inhibitors (BLI...
- Mechanisms of ResistanceInactivation of the Pseudomonas-Derived Cephalosporinase-3 (PDC-3) by Relebactam