Durlobactam in the Treatment of Multidrug-Resistant Acinetobacter baumannii Infections: A Systematic Review

Abstract

A. baumannii 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. baumannii. A systematic review of studies assessing the efficacy and safety of durlobactam in the treatment of multidrug-resistant A. baumannii 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 A. baumannii 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 Attempt was made to obtain information about unpublished studies.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 A. baumannii when used in combination with sulbactam. Future clinical trials are needed to confirm the possibility to treat infections caused by multidrug-resistant A. baumannii with this combination.

Genomic Determinants of Pathogenicity and Antimicrobial Resistance of Nosocomial Acinetobacter baumannii Clinical Isolates of Hospitalized Patients (2019–2021) from a Sentinel Hospital in Hangzhou, China

“…Many nosocomial infections were treatable with medicines; however, the increase in AMR rate has resulted in favoring the use of wide-spectrum antimicrobials in clinical practices, which in turn could lead to antimicrobial selection effects, conversely, this made it challenging to treat AB-infected patients. 46 , 47 …”

“…Many nosocomial infections were treatable with medicines; however, the increase in AMR rate has resulted in favoring the use of wide-spectrum antimicrobials in clinical practices, which in turn could lead to antimicrobial selection effects, conversely, this made it challenging to treat AB-infected patients. 46,47 The results of phenotypic AMR profiling showed that the resistance rate of MDR-AB to cephalosporins and carbapenems was higher than aminoglycosides, fluoroquinolones, tigecycline, and cefoperazone-sulbactam sodium. 48 The analysis of clinical diagnosis and antibiotics used in the infected patients revealed that the most used antimicrobial drug in clinical practice was the enzyme-inhibitor complex (cefoperazone-sulbactam sodium or piperacillin-sulbactam), followed by the combined application of two or more antimicrobial drugs.…”

In Vitro Activity of Sulbactam–Durlobactam against Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates: A Multicentre Report from Italy

“…However, in the eleven SUL–DUR-resistant A. baumannii we found Q488K and Y528H mutations in PBP3. To date, reports of SUL–DUR resistance have been rare and resistance is usually attributed to the presence of metallo-β-lactamases, which DUR does not inhibit, or to mutations near the active site of PBP3, the target of sulbactam [ 24 , 25 , 26 ]. Few therapeutic choices are available to treat CR Ab isolates [ 14 , 16 , 53 ].…”

“…Durlobactam (DUR), previously called ETX2514, is a non-β-lactam diazabicyclooctane (DBO) inhibitor with activity against Ambler class A, C and D β-lactamases [ 22 , 23 ]. Recently, some studies have shown that sulbactam in combination with durlobactam is active against MDR A. baumannii [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. Sulbactam (SUL) is one of the first β-lactamase inhibitors used in combination with ampicillin for the treatment of class A β-lactamase-producing pathogens.…”

How to treat severe Acinetobacter baumannii infections

“…SUL/DUR was approved in May 2023 for adult patients with hospital-acquired bacterial pneumonia and ventilator-associated pneumonia caused by susceptible AB isolates, following the ATTACK trial [108 ▪ ,109 ▪▪ ]. The ATTACK trial showed that SUL/DUR was more effective than Colistin, with a lower mortality rate and less nephrotoxicity.…”