is a frequent cause of difficult-to-treat healthcare-associated infections. The use of a novel beta-lactamase inhibitor, durlobactam, has been proposed against multidrug-resistant . A systematic review of studies assessing the efficacy and safety of durlobactam in the treatment of multidrug-resistant infections was carried out. The study protocol was pre-registered on PROSPERO (CRD42022311723). Published articles on durlobactam were identified through computerized literature searches with the search terms "durlobactam" and "ETX2514" using PubMed. PubMed was searched until 15 February 2022. Articles providing data on the main characteristics of durlobactam and on the efficacy and safety of durlobactam in the treatment of infections were included in this systematic review. Attempt was made to obtain information about unpublished studies. English language restriction was applied. The risk of bias in the included studies was not assessed. Both quantitative and qualitative information were summarized by means of textual descriptions. Thirty studies on durlobactam were identified, published from June 2017 to November 2020. Sixteen studies met the inclusion criteria. Durlobactam is effective against when used in combination with sulbactam. Future clinical trials are needed to confirm the possibility to treat infections caused by multidrug-resistant with this combination.
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http://dx.doi.org/10.3390/jcm11123258 | DOI Listing |
Antimicrob Agents Chemother
January 2025
Microbiology department, A Coruna University Hospital (CHUAC), Institute of Biomedical Research of A Coruna (INIBIC), A Coruna, Spain.
Carbapenemase OXA-48 and its variants pose a serious threat to the development of effective treatments for bacterial infections. OXA-48-producing Enterobacterales are the most prevalent carbapenemase-producing bacteria in large parts of the world. Although these bacteria exhibit low-level carbapenem resistance , the infections they cause are challenging to treat with conventional therapies, owing to their spread and complex detection in clinical settings.
View Article and Find Full Text PDFAntimicrob Agents Chemother
December 2024
Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA.
() 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 receptors (L,D-transpeptidases [LDT] 1-5, D,D-carboxypeptidase, penicillin-binding protein [PBP] B, and PBP-lipo) were assessed using mass spectrometry and kinetic studies.
View Article and Find Full Text PDFAntimicrob Agents Chemother
December 2024
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
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).
View Article and Find Full Text PDFExpert Rev Anti Infect Ther
December 2024
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.
Introduction: Carbapenem-resistant (CRAB) is a critical priority pathogen posing a substantial threat to our public health due to its virulence and resistance to broad-spectrum antimicrobials. Sulbactam-durlobactam (Xacduro) is a newly approved β-lactam-β-lactamase inhibitor combination agent with potent and activity against CRAB. The phase III randomized trial (ATTACK) demonstrated the safety and efficacy of sulbactam-durlobactam in combination with imipenem-cilastatin as background therapy in treating adult patients with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by CRAB.
View Article and Find Full Text PDFDrugs
November 2024
Center for Innovative Antimicrobial Therapy, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Carbapenem-resistant Acinetobacter baumannii has been associated with over three hundred thousand annual deaths globally. It is resistant to most available antibiotics and associated with high morbidity and mortality. No global consensus currently exists for treatment strategies that balance safety and efficacy because of heterogeneity of treatment regimens in current clinical practice and scarcity of large-scale controlled studies arising from difficulties in establishing robust clinical outcomes.
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