title: In vitro activity of the novel monosulfactam BAL30072 alone and in combination with meropenem versus a diverse collection of important Gram-negative pathogens.
abstract: The problem of antimicrobial resistance is exemplified by multidrug-resistant (MDR) isolates of Gram-negative species. Of particular concern are expanded-spectrum cephalosporin-resistant isolates of Enterobacteriaceae, epidemic lineages of Acinetobacter baumannii producing OXA-type carbapenemases, and MDR Pseudomonas aeruginosa. In this study, the in vitro activity of the novel monosulfactam BAL30072 was investigated both alone and in combination with meropenem against a diverse collection of commonly encountered Gram-negative pathogens. Thirty-one isolates were studied, including type strains and clinical isolates with defined mechanisms conferring resistance to various antimicrobial agents including to carbapenems, colistin and tigecycline. BAL30072 minimum inhibitory concentrations (MICs) were determined in the presence and absence of meropenem (1:1, w/w) by agar dilution. Potential synergy or antagonism between BAL30072 and meropenem was investigated using standard chequerboard assays. Versus MDR A. baumannii strains producing class D oxacillinases, BAL30072 MICs were all ≤4 mg/L with the exception of the isolate belonging to the UK 'Burn' lineage. BAL30072 exhibited MIC values of 0.5 mg/L to >64 mg/L towards the five P. aeruginosa strains. Against three meropenem-susceptible Escherichia coli, including the CTX-M-15 extended-spectrum β-lactamase-producer, BAL30072 exhibited MICs of 0.25-2 mg/L; higher MICs were recorded against some of the Enterobacteriaceae isolates tested. The in vitro data suggest that BAL30072 has a potential role in the treatment of infections due to Gram-negative pathogens, including those with important resistances to other agents. In addition, BAL30072 shows powerful synergistic activity in combination with meropenem, potentially expanding its coverage for the treatment of infections caused by problematic species.
authors.affiliation: Antimicrobial Research Group, Centre for Immunology and Infectious Disease, Blizard Institute, Barts & The London School of Medicine and Dentistry, Queen Mary University London, 4 Newark Street, London E1 2AT, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Hornsey
authors.forename: Lynette
authors.initials: L
authors.lastname: Phee
authors.forename: William
authors.initials: W
authors.lastname: Stubbings
authors.forename: David W
authors.initials: DW
authors.lastname: Wareham
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004357:Drug Synergism; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology; D006801:Humans; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008997:Monobactams / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D013845:Thienamycins / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; C552042:BAL 30072; D008997:Monobactams; D013844:Thiazoles; D013845:Thienamycins; D000077731:Meropenem
keywords: Carbapenems; Enterobacteriaceae; Non-fermenters; Siderophore β-lactams