Citywide emergence of Pseudomonas aeruginosa strains with reduced susceptibility to polymyxin B

Objectives: To determine the prevalence of Pseudomonas aeruginosa isolates with reduced susceptibility to polymyxin B, and to assess the in vitro activity of antibiotic combinations. Methods: All unique patient isolates of P. aeruginosa were collected from 11 Brooklyn, NY hospitals during a three month period in 2003. Isolates with reduced susceptibility to polymyxin B (MIC > 2 mg/L) underwent ribotyping. The activity of polymyxin B combined with rifampicin, azithromycin and/or imipenem was tested by the chequerboard and time-kill methods against a subset of isolates. Results: Of 527 isolates, only 61% were susceptible to imipenem. Twenty-five isolates (5%), from 8/11 hospitals, had reduced susceptibility to polymyxin B (MICs 4-8mg/L), compared with 0/691 isolates collected in 2001. Ten of 25 were resistant to multiple other antibiotic classes. Ribotyping of the isolates revealed 19 unique types. Chequerboard testing of the 10 multiresistant isolates demonstrated synergy for the combinations of polymyxin B with azithromycin, imipenem and rifampicin in 6, 2, and 1 isolates, respectively. Time-kill studies revealed bactericidal activity for the following antibiotics when combined with polymyxin B: imipenem plus rifampicin against all 10 isolates, rifampicin in 9/10 isolates, imipenem in 8/10 isolates and azithromycin in 4/10 isolates. MICs of bacteria surviving incubation in polymyxin B alone rose for 4/9 isolates (MIC range 12-48 mg/L). Conclusions: A aeruginosa with reduced susceptibility to polymyxin B have emerged in multiple strains in Brooklyn, NY. Combinations of polymyxin B with rifampicin and/or imipenem are bactericidal. The clinical utility of these combinations remains to be determined.