Journal Article

Activity of Polymyxin B and the Novel Polymyxin Analogue CB-182,804 Against Contemporary Gram-Negative Pathogens in New York City

Bratu, Simona, George, Avrille, Shah, Neha, Rosas-Garcia, Gabriella, Landman, David, Kelly, Paul, Quale, John, Babu, Elizabeth, Salamera, Julius, Backer, Martin

2012

Overview

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.

• Publisher: Mary Ann Liebert, Inc,SAGE Publications
• Subject: Acinetobacter baumannii / Anti-Bacterial Agents - pharmacology / Antimicrobial agents / Bactericidal activity / Clinical isolates / Colistin / Cross-resistance / Drug resistance / Drug Resistance, Multiple, Bacterial / Drug Synergism / E coli / Enterobacter / Epidemiology / Escherichia coli / Gram-negative bacteria / Gram-Negative Bacteria - drug effects / Gram-Negative Bacteria - isolation & purification / Gram-Negative Bacterial Infections - microbiology / Humans / Infection / Klebsiella pneumoniae / Microbial Sensitivity Tests / Minimum inhibitory concentration / New York City / Pathogens / polymyxin B / Polymyxin B - pharmacology / Polymyxins / Polymyxins - analogs & derivatives / Polymyxins - pharmacology / Pseudomonas aeruginosa / Rifampin / Rifampin - pharmacology / Synergistic effect