Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates

Cedano, José; Baez, Michelle; Pasterán, Fernando; Montaña, Sabrina; Ra, Grace; Fua, Venjaminne; Corso, Alejandra; Tolmasky, Marcelo E.; Ramírez, María Soledad

doi:10.3389/fcimb.2022.918868

Cited by 5 publications

(1 citation statement)

References 25 publications

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“…Zidebactam is a β-lactamase inhibitor classified as a bicyclo-acyl hydrazide [ 34 , 36 ]. Currently, WCK5222, a combination of zidebactam and cefepime, is undergoing phase 1 clinical trials investigating whether it could be used to treat severe infections caused by Gram-negative multidrug-resistant microorganisms [ 37 ].…”

Section: Treatmentmentioning

confidence: 99%

Strategies to combat Gram-negative bacterial resistance to conventional antibacterial drugs: a review

Bhowmik,

Modi,

Roy

et al. 2023

PHRP

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The emergence of antimicrobial resistance raises the fear of untreatable diseases. Antimicrobial resistance is a multifaceted and dynamic phenomenon that is the cumulative result of different factors. While Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus and Clostridium difficile, were previously the most concerning issues in the field of public health, Gram-negative pathogens are now of prime importance. The World Health Organization’s priority list of pathogens mostly includes multidrug-resistant Gram-negative organisms particularly carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa, and extensively drug-resistant Acinetobacter baumannii. The spread of Gram-negative bacterial resistance is a global issue, involving a variety of mechanisms. Several strategies have been proposed to control resistant Gram-negative bacteria, such as the development of antimicrobial auxiliary agents and research into chemical compounds with new modes of action. Another emerging trend is the development of naturally derived antibacterial compounds that aim for targets novel areas, including engineered bacteriophages, probiotics, metal-based antibacterial agents, odilorhabdins, quorum sensing inhibitors, and microbiome-modifying agents. This review focuses on the current status of alternative treatment regimens against multidrug-resistant Gram-negative bacteria, aiming to provide a snapshot of the situation and some information on the broader context.

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Section: Treatmentmentioning

confidence: 99%

Strategies to combat Gram-negative bacterial resistance to conventional antibacterial drugs: a review

Bhowmik,

Modi,

Roy

et al. 2023

PHRP

View full text Add to dashboard Cite

show abstract

Strategic re-engineering of antibiotics

Homer,

Johnson,

Koelln

et al. 2024

Nat Rev Bioeng

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Defining optimal sulbactam regimens for treatment of Acinetobacter baumannii pneumonia and impact of blaOXA-23 on efficacy

Abouelhassan,

Nicolau,

Abdelraouf

2024

Journal of Antimicrobial Chemotherapy

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Objectives We evaluated the efficacies of human-simulated regimens (HSRs) of two clinically utilized sulbactam regimens: 1 g q6h 0.5 h infusion (maximum FDA-approved dosage) and 3 g q8h 4 h infusion (high-dose, prolonged-infusion regimen), against Acinetobacter baumannii in a translational murine model. Methods Thirty-two clinical A. baumannii isolates were investigated, of which 16 were sulbactam resistant (MIC ≥ 16 mg/L), 6 were sulbactam intermediate (MIC = 8 mg/L) and 10 were sulbactam susceptible (MIC ≤ 4 mg/L). Efficacies of the two sulbactam HSRs were assessed in the neutropenic murine pneumonia model. Changes in log10 cfu/lungs at 24 h compared with 0 h controls were measured, and efficacy was defined as achieving 1 log kill relative to baseline. WGS of the isolates and bioinformatics analysis were performed to explore potential associations between the genomic backgrounds and the in vivo responses. Results Eleven isolates harboured blaOXA-23, of which 10 were sulbactam resistant, 1 was sulbactam intermediate while none was sulbactam susceptible. Both sulbactam HSRs achieved >1 log kill against sulbactam-susceptible isolates. Against sulbactam-intermediate and sulbactam-resistant isolates, lack of efficacy correlated with the presence of the blaOXA-23 gene; sulbactam 1 g HSR and 3 g HSR did not show efficacy against 11/11 and 9/11 blaOXA-23-positive isolates, respectively, while efficacy was observed against all 11 blaOXA-23-negative sulbactam-intermediate and sulbactam-resistant isolates (i.e. harbouring other resistance genes). Conclusions A sulbactam high-dose prolonged-infusion regimen provides comparable activity to the standard dose against isolates currently considered sulbactam susceptible. However, the activity against isolates with intermediate and resistant susceptibility could be predicted by the detection of blaOXA-23. Enhancing detection capabilities of common diagnostic modalities to include OXA-23 can improve patient outcome.

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Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates

Cited by 5 publications

References 25 publications

Strategies to combat Gram-negative bacterial resistance to conventional antibacterial drugs: a review

Strategies to combat Gram-negative bacterial resistance to conventional antibacterial drugs: a review

Strategic re-engineering of antibiotics

Defining optimal sulbactam regimens for treatment of Acinetobacter baumannii pneumonia and impact of blaOXA-23 on efficacy

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