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 trial (ATTACK)

Kaye, Keith S.; Shorr, Andrew F.; Wunderink, Richard G.; Du, Bin; Poirier, Gabrielle; Rana, Khurram; Miller, Alita A.; Lewis, Drew; O’Donnell, John P.; Cui, Lan; Reinhart, Harald H.; Srinivasan, Subasree; Isaacs, Robin; Altarac, David

doi:10.1016/s1473-3099(23)00184-6

Cited by 88 publications

(74 citation statements)

References 23 publications

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“…Sulbactam-durlobactam met the noninferiority endpoint of 28-day all-cause mortality (19% vs. 32%in sulbactam-durlobactam and colistin arm, respectively, difference of –13·2%, 95% CI –30.0 to 3.5). Furthermore, nephrotoxicity was significantly lower in sulbactam-durlobactam arm (13% vs. 38%, P < 0.001) [49 ▪▪ ].…”

Section: Future Antibiotics For Treating Nonfermenting Gram-negative ...mentioning

confidence: 85%

“…Sulbactam-durlobactam was evaluated clinically in a phase 3 noninferiority trial (ATTACK – Acinetobacter Treatment Trial Against Colistin) which randomized 181 patients with serious infections from carbapenem-resistant A.baumanii to receive either sulbactam-durlobactam or colistin [49 ▪▪ ].…”

Section: Future Antibiotics For Treating Nonfermenting Gram-negative ...mentioning

confidence: 99%

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Antibiotic therapy for nonfermenting Gram-negative bacilli infections: future perspectives

Bassetti,

Castaldo,

Fantin

et al. 2023

Current Opinion in Infectious Diseases

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Purpose of review Serious infections caused by nonfermenting Gram-negative bacteria (NF-GNB) pose a significant challenge for clinicians due to the limited treatment options available, which are frequently associated with issues of toxicity and unfavourable pharmacokinetic profiles. The aim of this review is to provide a brief overview of the existing data concerning the ongoing development of antiinfective agents targeting NF-GNB. Recent findings Several agents exhibiting efficacy against NF-GNB are under clinical investigation. Durlobactam-sulbactam and cefepime-taniborbactam emerge as promising therapeutic avenues against carbapenem-resistant Acinetobacter baumanii. Cefepime-zidebactam may serve as a suitable treatment option for urinary tract infections caused by a wide range of NF-GNB. Cefepime-enmetazobactam demonstrates potent in vitro activity against various NF-GNB strains; however, its role as an anti-Pseudomonal agent is inadequately substantiated by available data. Xeruborbactam is a wide β-lactamase inhibitor that can be associated with a range of agents, enhancing in-vitro activity of these against many NF-GNB, including those resistant to newer, broader spectrum options. Lastly, murepavadin appears to be a potential pathogen-specific solution for severe Pseudomonas infections; however, additional investigation is necessary to establish the safety profile of this compound. Summary Each of the novel molecules reviewed possesses an interesting range of in-vitro activity against NF-GNB. In addition, some of them have already been proved effective in vivo, underscoring their potential as future treatment options.

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Section: Future Antibiotics For Treating Nonfermenting Gram-negative ...mentioning

confidence: 85%

Section: Future Antibiotics For Treating Nonfermenting Gram-negative ...mentioning

confidence: 99%

Antibiotic therapy for nonfermenting Gram-negative bacilli infections: future perspectives

Bassetti,

Castaldo,

Fantin

et al. 2023

Current Opinion in Infectious Diseases

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“…Similarly, Gu, S et al reported a study of CR-AB infected patients treated with Cefoperazone/Sulbactam, demonstrating a signi cantly lower mortality rate in the Cefoperazone/Sulbactam group (25.4% vs 53.4%, P = 0.005) 19 . In recent years, more and more research has been done on sulbactam-durlobactam 20 , Keith et al had conducted a phase 3, non-inferiority clinical trial involving 181 patients randomly assigned to sulbactam-durlobactam or colistin due to carbapenemresistant Acinetobacter baumannii-calcoaceticus complex (ABC) infection. This study demonstrated a lower 28-day all-cause mortality in patients receiving sulbactam-durlobactam compared to colistin group (19% vs 32%).…”

Section: Discussionmentioning

confidence: 99%

A retrospective study of the efficacy of sulbactam in the treatment of patients with extensively drug-resistant Acinetobacter baumannii infections

Yu,

Zhang,

Yang

et al. 2024

Preprint

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Purpose Sulbactam (SBT) is one of the most significant treatments for patients with extensively drug-resistant Acinetobacter baumannii (XDR-AB). However, the efficacy and safety of SBT and its high dose regimen has not been well documented. This retrospective study aimed to assess the efficacy and safety of SBT-based treatment, particularly at high-dose (≥ 6g/day), for XDR-AB infection. Method A total of 52 XDR-AB infected patients treated with intravenous SBT at Peking Union Medical College Hospital were included. The primary outcome was 28-day all-cause mortality, while the secondary outcome was 14-day clinical response and the time of response. Results Among the patients, the 28-day all-cause mortality rate was 36.5% (19/52), and the favorable 14-day clinical response rate was 59.6% (31/52). The 28-day mortality was independently associated coinfection with gram-positive bacteria (GPB) and a shorter duration of therapy. Patients with intracranial infection might have a longer survival time. A favorable 14-day clinical response was associated with high dose SBT, and a longer treatment duration. However, the higher creatinine clearance (CrCl) associated with a worse clincal response. In addition, a higher SBT dosage was significantly correlated with a quicker clinical response. No adverse effects related were reported. Conclusion The single-agent formulation of SBT emerges as a promising alternative for the treatment of XDR-AB infection, such as intracranial infection, particularly at high doses (≥ 6g/day). Besides, longer duration of treatment correlates with higher survival rate and better favorable clinical response. Higher CrCl negatively correlates with favorable clinical response.

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“…Data from the Phase 3 ATTACK trial comparing sulbactam/durlobactam plus imipenem/cilastatin versus colistin plus imipenem/cilastatin in patients with BSI and VAP by CRAB showed non-inferiority in 28 day all-cause mortality and overall trends favouring sulbactam/durlobactam (higher clinical cure rates and microbiologically favourable response). 22 …”

Section: Discussionmentioning

confidence: 99%

Salvage therapy with sulbactam/durlobactam against cefiderocol-resistant Acinetobacter baumannii in a critically ill burn patient: clinical challenges and molecular characterization

Tiseo

Giordano

Leonildi

et al. 2023

JAC-Antimicrobial Resistance

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Background Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are associated with high mortality rates. The optimal treatment regimen for CRAB has not been defined. Cefiderocol has been recently introduced in the armamentarium against CRAB but there is concern about treatment-emergent resistance. Since mortality rates in CRAB infections remain high, further antibiotic options are needed. Methods We report a case of severe infection by CRAB resistant to both colistin and cefiderocol treated with sulbactam/durlobactam and describe the molecular features of the strain. Susceptibility to cefiderocol was detected by disc diffusion according to EUCAST breakpoints. Susceptibility to sulbactam/durlobactam was determined by Etest according to preliminary breakpoints provided by Entasis Therapeutics. Whole Genome Sequencing (WGS) of the CRAB isolate was performed. Results A burn patient with ventilator-associated pneumonia by CRAB resistant to colistin and cefiderocol received sulbactam/durlobactam as compassionate use. She was alive after 30 days from the end of therapy. Complete microbiological eradication of CRAB was achieved. The isolate harboured blaADC-30, blaOXA-23 and blaOXA-66. A missense mutation in PBP3 was detected. The isolate harboured a mutation in the TonB-dependent siderophore receptor gene piuA that showed a frameshift mutation causing a premature stop codon (K384fs). Moreover, the fepA gene, which is orthologous to pirA, was interrupted by a transposon insertion P635-ISAba125 (IS30 family). Conclusions Further treatment options for severe infections by CRAB resistant to all available antibiotics are urgently needed. Sulbactam/durlobactam may be a future option against MDR A. baumannii.

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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 trial (ATTACK)

Cited by 88 publications

References 23 publications

Antibiotic therapy for nonfermenting Gram-negative bacilli infections: future perspectives

Antibiotic therapy for nonfermenting Gram-negative bacilli infections: future perspectives

A retrospective study of the efficacy of sulbactam in the treatment of patients with extensively drug-resistant Acinetobacter baumannii infections

Salvage therapy with sulbactam/durlobactam against cefiderocol-resistant Acinetobacter baumannii in a critically ill burn patient: clinical challenges and molecular characterization

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