In vitro activity of sulbactam/durlobactam against extensively drug-resistant Acinetobacter baumannii isolates belonging to South American major clones

Nodari, Carolina Silva; Santos, Fernanda dos; Kurihara, Mariana Neri Lucas; Valiatti, Tiago Barcelos; Cayô, Rodrigo; Gales, Ana Cristina

doi:10.1016/j.jgar.2021.05.001

Cited by 14 publications

(14 citation statements)

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“…Compared to other studies on the activity of SD, our collection of isolates presented higher resistance rates and MICs for the comparators, as well as for SD. In particular, both the SD MIC 50 and MIC 90 of the strains in the present study exceeded by one to three-fold the respective values of those reported in international studies ( McLeod et al., 2020 ; Seifert et al., 2020 ; Yang et al, 2020 ; Nodari et al, 2021 ), indicating the presence of less susceptible strains in Greek hospitals. COL MICs were also considerably lower in three of those studies (MIC 90 1 μg/ml in references Higgins et al, 2004 ; Pournaras et al, 2017 ; Seifert 2020 ), with only one study from China reporting COL MIC 90 128 μg/ml ( Durand-Réville et al, 2017 ).…”

Section: Discussioncontrasting

confidence: 62%

“…A promising new therapeutic option for CRAB is the combination of sulbactam with durlobactam (SD), a new member of the diazabicyclooctane class of β-lactamase inhibitors, with broad spectrum activity against Ambler class A, C and D serine β-lactamases, resulting in the restoration of the susceptibility of CRAB isolates to β-lactams ( Durand-Réville et al., 2017 ). Durlobactam (DUR) restores SUL susceptibility of A. baumannii strains overexpressing individual β-lactamases ( Seifert et al., 2020 ; Shapiro et al., 2021 ) as well as diverse clinical isolates, in international, contemporary surveillance studies ( McLeod et al., 2020 ; Yang et al 2020 ; Nodari et al 2021 ). SD is currently in late-stage development for the treatment of infections caused by Acinetobacter spp.…”

Section: Introductionmentioning

confidence: 99%

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Activity of Sulbactam-Durlobactam and Comparators Against a National Collection of Carbapenem-Resistant Acinetobacter baumannii Isolates From Greece

Petropoulou

Siopi

Vourli

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundAcinetobacter baumannii is a leading cause of healthcare-associated infections worldwide, due to both its persistence in the hospital setting and ability to acquire high levels of antibiotic resistance. Carbapenem-resistant A. baumannii isolates (CRAB) limit the activity of current antimicrobial regimens and new alternatives or adjuncts to traditional antibiotics are urgently needed. Durlobactam is a novel broad-spectrum inhibitor of serine-type β-lactamases that restores sulbactam (SUL) activity against A. baumannii. The sulbactam-durlobactam (SD) combination has recently completed Phase 3 testing in the global ATTACK trial.ObjectivesThe aim of this study is to evaluate the in vitro activity of SD versus comparators against a representative nationwide collection of CRAB isolates.MethodsOne hundred ninety CRAB isolates were collected from clinical samples of patients hospitalized in 11 hospitals throughout Greece during 2015. In vitro activities of SD and comparators (SUL alone, amikacin, minocycline, imipenem, meropenem, colistin, SD and imipenem combined with SD) were determined by broth microdilution.ResultsDurlobactam restored sulbactam activity against the majority of the strains tested, with SD exhibiting the lowest MIC90 (8 μg/ml) relative to the other single comparators tested; 87.9% of the isolates had SD MICs ≤4/4 µg/ml. The most active comparator was colistin (MIC90 = 16 μg/ml). The addition of imipenem further lowered the MIC90 of SD by one two-fold dilution.ConclusionsThis study demonstrated the potential utility of SD for the treatment of infections caused by A. baumannii. If its clinical efficacy is confirmed, SD may be an important therapeutic option for CRAB infections.

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Section: Discussioncontrasting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Activity of Sulbactam-Durlobactam and Comparators Against a National Collection of Carbapenem-Resistant Acinetobacter baumannii Isolates From Greece

Petropoulou

Siopi

Vourli

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Among the 29, five studies that represented review articles, four studies that did not report data on durlobactam, one study representing a “correction article”, one representing an “expert opinion article”, and two representing case reports were excluded. Of the 16 studies included in this systematic review ( Figure 1 ) [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ], six were clinical trials: four phase I trials [ 16 , 17 , 19 , 27 ], one phase II clinical trial [ 18 ] and one ongoing phase III clinical trial [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

“…However, the sole durlobactam has minimal antibacterial activity against A. baumannii , mainly due to its ability to bind penicillin-binding proteins (PBP) 2 [ 13 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

Section: Resultsmentioning

confidence: 99%

“…Durlobactam showed a synergistic bactericidal activity in combination with beta-lactam antibiotics [ 14 , 20 , 21 , 22 , 23 , 24 , 25 ]. Durlobactam improves the activity of several beta-lactam partners tested against A. baumannii , but the most potent combination has been observed with another beta-lactamase inhibitor, sulbactam [ 14 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

Section: Resultsmentioning

confidence: 99%

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

Granata

Taglietti

Schiavone

et al. 2022

JCM

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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.

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Sulbactam‐durlobactam: A novel β‐lactam‐β‐lactamase inhibitor combination targeting carbapenem‐resistant Acinetobacter baumannii infections

et al. 2023

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Multi-drug-resistant (MDR) Acinetobacter baumannii is identified by the Center for Disease Control and Prevention (CDC) as an urgent threat to public health, requiring the development of novel treatment options. 1,2 A. baumannii is a significant contributor to serious nosocomial infections including hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP), bloodstream infections (BSI), complicated urinary tract infections (cUTI), and wound infections.Mortality rates due to MDR A. baumannii have been estimated between 40% and 60%, with some studies showing rates of up to 75% in critically ill patients. 3 From 2019 to 2020, the CDC reported a 35% increase in carbapenem-resistant Acinetobacter spp. overall and a 78% increase in hospital-associated carbapenem-resistant Acinetobacter baumannii (CRAB) infections, which may be a consequence of increased intensive care unit (ICU) admission and length of stay (LOS) attributed to the COVID-19 pandemic. 4 Antimicrobial resistance, including resistance to all standard-ofcare antibiotics, is a feature of A. baumannii secondary to the acquisition of both intrinsic and acquired resistance phenotypes. 3,5 In

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In vitro activity of sulbactam/durlobactam against extensively drug-resistant Acinetobacter baumannii isolates belonging to South American major clones

Cited by 14 publications

References 5 publications

Activity of Sulbactam-Durlobactam and Comparators Against a National Collection of Carbapenem-Resistant Acinetobacter baumannii Isolates From Greece

Activity of Sulbactam-Durlobactam and Comparators Against a National Collection of Carbapenem-Resistant Acinetobacter baumannii Isolates From Greece

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

Sulbactam‐durlobactam: A novel β‐lactam‐β‐lactamase inhibitor combination targeting carbapenem‐resistant Acinetobacter baumannii infections

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