In vitro activity of the siderophore monosulfactam BAL30072 against contemporary Gram-negative pathogens from New York City, including multidrug-resistant isolates

Landman, David; Singh, Manisha; El-Imad, Badiaa; Miller, Ezra; Win, Thida; Quale, John

doi:10.1016/j.ijantimicag.2014.02.017

Cited by 18 publications

(10 citation statements)

References 20 publications

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“…To overcome the threat of KPC-producing CREs, novel ␤-lactamase inhibitors such as avibactam and RPX7009, broad-spectrum inhibitors for class A, C, and D ␤-lactamases, have been strategically selected for clinical development as combination therapy with ␤-lactam agents; however, these ␤-lactam/␤-lactamase inhibitors do not have antimicrobial activity against strains producing class B ␤-lactamases such as NDM-1 (28). BAL30072, a siderophore-conjugated monosulfactam, displays antimicrobial activity against class B ␤-lactamase-producing strains, including P. aeruginosa, but BAL30072 shows weak antimicrobial activity against KPC-producing K. pneumoniae (29). Importantly, S-649266 showed potent antimicrobial activity against various types of carbapenemase-producing strains without the addition of a ␤-lactamase inhibitor.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Antimicrobial Activity of a Siderophore Cephalosporin, S-649266, against Enterobacteriaceae Clinical Isolates, Including Carbapenem-Resistant Strains

Kohira

West

Ito

et al. 2016

Antimicrob Agents Chemother

209

181

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Enterobacter cloacae isolates were all <1 g/ml, and there were only 8 isolates (1.3%) among these 617 clinical isolates with MIC values of >8 g/ml. In the second set, the MIC values of S-649266 were <4 g/ml against 109 strains among 116 KPC-producing and class B (metallo) carbapenemase-producing strains. In addition, S-649266 showed MIC values of <2 g/ml against each of the 13 strains that produced other types of carbapenemases such as SME, NMC, and OXA-48. The mechanisms of the decreased susceptibility of 7 class B carbapenemase-producing strains with MIC values of >16 g/ml are uncertain. This is the first report to demonstrate that S-649266, a novel siderophore cephalosporin, has significant antimicrobial activity against Enterobacteriaceae, including strains that produce carbapenemases such as KPC and NDM-1.

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Section: Discussionmentioning

confidence: 99%

In Vitro Antimicrobial Activity of a Siderophore Cephalosporin, S-649266, against Enterobacteriaceae Clinical Isolates, Including Carbapenem-Resistant Strains

Kohira

West

Ito

et al. 2016

Antimicrob Agents Chemother

209

181

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“…255,263 BAL30072 (42) was found to be effective against a series of clinical isolates from New York City hospitals. 267 LCB01-0371 (44) 268 is another new oxazolidinone, with a cyclic amidrazone substituent, belonging to LegoChem Biosciences, Inc. (Daejeon, South Korea). Purported to be more safe than linezolid or tedizolid, it has completed three phase-I trials (NCT01554995, NCT01842516 and NCT02540460) and has recently completed a phase-II trial (NCT01554995).…”

Section: Compounds Undergoing Clinical Evaluationmentioning

confidence: 99%

Antibiotics in the clinical pipeline at the end of 2015

2016

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There is growing global recognition that the continued emergence of multidrug-resistant bacteria poses a serious threat to human health. Action plans released by the World Health Organization and governments of the UK and USA in particular recognize that discovering new antibiotics, particularly those with new modes of action, is one essential element required to avert future catastrophic pandemics. This review lists the 30 antibiotics and two β-lactamase/β-lactam combinations first launched since 2000, and analyzes in depth seven new antibiotics and two new β-lactam/β-lactamase inhibitor combinations launched since 2013. The development status, mode of action, spectra of activity and genesis (natural product, natural product-derived, synthetic or protein/mammalian peptide) of the 37 compounds and six β-lactamase/β-lactam combinations being evaluated in clinical trials between 2013 and 2015 are discussed. Compounds discontinued from clinical development since 2013 and new antibacterial pharmacophores are also reviewed.

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“…A recent siderophore sulfactam conjugate BAL20072 developed by Basilea Pharmaceutic has shown significant promise against multidrug-resistant Gram-negative isolates including P. aeruginosa and Bcc spp. (Page et al, 2010;Hofer et al, 2013;Landman et al, 2014), and is currently in phase 1 clinical trials. Another promising conjugate in development is S-649266 from Shionigi, which is a catechol-substituted siderophore conjugated to cephalosporin with significant activity against multidrug-resistant Gram-negatives including P. aeruginosa.…”

Section: Novel Therapeutic Strategies Targeting Iron Acquisition In Cmentioning

confidence: 99%

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Tyrrell¹,

Callaghan²

2016

Microbiology

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Iron acquisition is vital to microbial survival and is implicated in the virulence of many of the pathogens that reside in the cystic fibrosis (CF) lung. The multifaceted nature of iron acquisition by both bacterial and fungal pathogens encompasses a range of conserved and speciesspecific mechanisms, including secretion of iron-binding siderophores, utilization of siderophores from other species, release of iron from host iron-binding proteins and haemoproteins, and ferrous iron uptake. Pathogens adapt and deploy specific systems depending on iron availability, bioavailability of the iron pool, stage of infection and presence of competing pathogens. Understanding the dynamics of pathogen iron acquisition has the potential to unveil new avenues for therapeutic intervention to treat both acute and chronic CF infections. Here, we examine the range of strategies utilized by the primary CF pathogens to acquire iron and discuss the different approaches to targeting iron acquisition systems as an antimicrobial strategy.

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In vitro activity of the siderophore monosulfactam BAL30072 against contemporary Gram-negative pathogens from New York City, including multidrug-resistant isolates

Cited by 18 publications

References 20 publications

In Vitro Antimicrobial Activity of a Siderophore Cephalosporin, S-649266, against Enterobacteriaceae Clinical Isolates, Including Carbapenem-Resistant Strains

In Vitro Antimicrobial Activity of a Siderophore Cephalosporin, S-649266, against Enterobacteriaceae Clinical Isolates, Including Carbapenem-Resistant Strains

Antibiotics in the clinical pipeline at the end of 2015

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

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