BAL30072 / Basilea - LARVOL DELTA

Discovery and Development of Antibacterial Agents: Fortuitous and Designed. (PubMed, Mini Rev Med Chem) - "These include solithromycin, plazomicin, lefamulin, omadacycline, eravacycline, delafloxacin, zabofloxacin, finafloxacin, nemonoxacin, gepotidacin, zoliflodacin, cefiderocol, BAL30072, avycaz, zerbaxa, vabomere, relebactam, tedizolid, cadazolid, sutezolid, triclosan and afabiacin. This article aims to review the investigational and recently approved antibacterials with a focus on their structure, mechanisms of action/resistance, and spectrum of activity. Delving deep, their success or otherwise in various phases of clinical trials is also discussed while attributing the same to various causal factors."

Journal

[VIRTUAL] Effects of Exogenous Pyoverdine on the Anti-pseudomonal Activity of Cefiderocol (WMF 2021) - "Susceptibility of P. aeruginosa to FDC and MB-1, SMC-3176, BAL30072 was comparable between pvdS mutants and iron transporter PiuA- and PirA-deficient mutants (Table A). We found that MIC increase in pvdS mutant strains was mainly due to reduced expression of iron transporters probably due to increased intracellular iron level and that exogenous pyoverdine at physiological levels does not lead to MIC increase, suggesting that FDC had an iron binding capacity similar to pyoverdine not to cause competition. These mutations had smaller impact on MIC increase for FDC than for other siderophore β-lactams."

Infectious Disease

Complexes formed by the siderophore-based monosulfactam antibiotic BAL30072 and their interaction with the outer membrane receptor PiuA of P. aeruginosa. (PubMed, Biometals) - "By using one of the sulfate oxygen atoms as a third donor in addition to the bidentate pyridinone moiety, BAL30072 can form a LM complex, which was predicted to be the one with the best binding affinity to PiuA. The example of BAL30072 strongly suggests that a lower stoichiometry might be the one recognized by the receptor, so that to focus only on the highest stoichiometry might be misleading for siderophores with less than six donors."

Journal

The TonB-receptor repertoire offor the uptake of siderophore-drug conjugates. (PubMed, Antimicrob Agents Chemother) - "PiuD has a similar crystal structure as PiuA and is involved in the transport of the siderophore-drug conjugates BAL30072, MC-1, and cefiderocol in strain LESB58. To screen for additional siderophore-drug uptake systems, we overexpressed 28 of the 34 TBDRs of strain PAO1 and identified PfuA, OptE, OptJ and the pyochelin receptor FptA as novel TBDRs conferring increased susceptibility to siderophore-drug conjugates. The existence of a TBDR repertoire in, able to transport siderophore-drug molecules, potentially decreases the likelihood of resistance emergence during therapy."

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Prediction of Safety Margin and Optimization of Dosing Protocol for a Novel Antibiotic using Quantitative Systems Pharmacology Modeling. (PubMed, Clin Transl Sci) - "DILIsym was then used to recommend potential modifications to this dosing scheme; weight-adjusted dosing and a requirement to assay plasma alanine aminotransferase (ALT) daily and stop dosing as soon as ALT increases were observed improved the predicted safety margin of BAL30072 and decreased the predicted likelihood of severe injury. This research demonstrates a potential application for QSP modeling in improving the safety profile of candidate drugs."

Clinical • Journal