title: Activity of polymyxin B and the novel polymyxin analogue CB-182,804 against contemporary Gram-negative pathogens in New York City.
abstract: Multidrug-resistant Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa have become common in many regions, often requiring therapy with colistin or polymyxin B. An increase in resistance to these agents would render many infections untreatable. We tested the activity of polymyxin B and the novel polymyxin analogue CB-182,804 against over 5,000 recent Gram-negative clinical isolates from New York City, a region with a high prevalence of multiresistant strains. Over 96% of Escherichia coli, K. pneumoniae, A. baumannii, and P. aeruginosa were susceptible to polymyxin B; only 76% of Enterobacter spp. was susceptible. The MICs of CB-182,804 were generally two-fold higher than polymyxin B and cross-resistance was observed. The addition of rifampin resulted in synergistic inhibition and bactericidal activity in time kill studies, and restored activity against all polymyxin-resistant strains. The synergistic effect of the combination with rifampin was most pronounced against A. baumannii strains, and was slightly greater with CB-182,804 than with polymyxin B against K. pneumoniae and Enterobacter spp. Despite considerable usage of polymyxin B and colistin in this region, polymyxin B retains excellent activity against most Gram-negative isolates. CB-182,804 shows similar activity, particularly when combined with rifampin. The clinical utility of CB-182,804 remains to be determined.
authors.affiliation: Department of Medicine, SUNY Downstate Medical Center, Brooklyn, New York 11203, USA.
authors.forename: John
authors.initials: J
authors.lastname: Quale
authors.forename: Neha
authors.initials: N
authors.lastname: Shah
authors.forename: Paul
authors.initials: P
authors.lastname: Kelly
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Babu
authors.forename: Martin
authors.initials: M
authors.lastname: Backer
authors.forename: Gabriella
authors.initials: G
authors.lastname: Rosas-Garcia
authors.forename: Julius
authors.initials: J
authors.lastname: Salamera
authors.forename: Avrille
authors.initials: A
authors.lastname: George
authors.forename: Simona
authors.initials: S
authors.lastname: Bratu
authors.forename: David
authors.initials: D
authors.lastname: Landman
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D009519:New York City; D011112:Polymyxin B / Q000494:pharmacology*; D011113:Polymyxins / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D011113:Polymyxins; D011112:Polymyxin B; D012293:Rifampin