title: In vitro activity of the siderophore monosulfactam BAL30072 against contemporary Gram-negative pathogens from New York City, including multidrug-resistant isolates.
abstract: The in vitro activity of BAL30072 was assessed against clinical isolates from NYC hospitals, including isolates from a citywide surveillance study and a collection of isolates with well-characterised resistance mechanisms. BAL30072 was the most active β-lactam against Pseudomonas aeruginosa (MIC50/90, 0.25/1 μg/mL), Acinetobacter baumannii (MIC50/90, 4/>64 μg/mL) and KPC-possessing Klebsiella pneumoniae (MIC50/90, 4/>64 μg/mL). Combining BAL30072 with meropenem resulted in a ≥ 4-fold decrease in the BAL30072 MIC90 both for A. baumannii and K. pneumoniae. For isolates with a BAL30072 MIC>4 μg/mL, addition of a sub-MIC concentration of colistin resulted in a four-fold decrease in the BAL30072 MIC in 44% of P. aeruginosa, 82% of A. baumannii and 23% of K. pneumoniae. Using sub-MIC concentrations, BAL30072 plus colistin was bactericidal against 4 of 11 isolates in time-kill studies. BAL30072 MICs were frequently lower for P. aeruginosa and K. pneumoniae when tested using Mueller-Hinton agar versus Iso-Sensitest agar or Mueller-Hinton broth. Against the well-characterised isolates, reduced susceptibility to BAL30072 correlated with mexA and mexX expression (P. aeruginosa), adeB expression (A. baumannii) and presence of SHV-type ESBLs (A. baumannii and K. pneumoniae). BAL30072 shows promising activity against contemporary Gram-negatives, including MDR P. aeruginosa, A. baumannii and K. pneumoniae. Enhanced activity was often present when BAL30072 was combined with meropenem or colistin. BAL30072 MICs were influenced by the testing method, particularly for P. aeruginosa and K. pneumoniae. Further in vivo studies are warranted to determine the potential clinical utility of BAL30072 alone and combined with other agents.
authors.affiliation: Department of Medicine, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA. Electronic address: dlandman@downstate.edu.
authors.forename: David
authors.initials: D
authors.lastname: Landman
authors.affiliation: Department of Medicine, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
authors.forename: Manisha
authors.initials: M
authors.lastname: Singh
authors.affiliation: Department of Medicine, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
authors.forename: Badiaa
authors.initials: B
authors.lastname: El-Imad
authors.affiliation: Department of Medicine, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
authors.forename: Ezra
authors.initials: E
authors.lastname: Miller
authors.affiliation: Department of Medicine, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
authors.forename: Thida
authors.initials: T
authors.lastname: Win
authors.affiliation: Department of Medicine, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
authors.forename: John
authors.initials: J
authors.lastname: Quale
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology*; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D008997:Monobactams / Q000494:pharmacology*; D009519:New York City; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; C552042:BAL 30072; D008997:Monobactams; D013844:Thiazoles
keywords: Acinetobacter baumannii; Klebsiella pneumoniae; Multidrug-resistant; Pseudomonas aeruginosa