In vitro activity of ceftolozane/tazobactam against clinical isolates of Pseudomonas aeruginosa in the planktonic and biofilm states

Pseudomonas aeruginosa causes a variety of life-threatening infections, some of which are associated with planktonic and others with biofilm states. Herein, we tested the combination of the novel cephalosporin, ceftolozane, with the β-lactamase inhibitor, tazobactam, against planktonic and biofilm forms of 54 clinical isolates of P. aeruginosa, using cefepime as a comparator. MIC values were determined following Clinical and Laboratory Standards Institute (CLSI) guidelines. Minimum biofilm inhibitory concentration (MBIC) values were determined using biofilm-laden pegged lids incubated in antimicrobial challenge plates containing varying concentrations of ceftolozane/tazobactam. Pegged lids were then incubated in growth recovery plates containing cation-adjusted Mueller-Hinton broth to determine the minimum biofilm bactericidal concentration (MBBC). Ceftolozane/tazobactam was highly active against planktonic P. aeruginosa, with all 54 isolates studied testing susceptible (MIC ≤4/4 μg/mL). On the other hand, 51/54 biofilm P. aeruginosa had MBICs ≥16/4 μg/mL, and all 54 isolates had MBBCs >32 μg/mL. Of the 54 isolates, 45 (83.3%) tested susceptible to cefepime, with the MIC50/MIC90 being 4/16 μg/mL, respectively, and the MBIC90 and MBBC90 both being >256 μg/mL. Although ceftolozane/tazobactam is a promising antimicrobial agent for the treatment of P. aeruginosa infections, it is not highly active against P. aeruginosa biofilms.