Does the piperacillin minimum inhibitory concentration for Pseudomonas aeruginosa influence clinical outcomes of children with pseudomonal bacteremia?

BACKGROUND The Clinical and Laboratory Standards Institute (CLSI) recently elected to adjust the previous piperacillin susceptibility breakpoint of ≤64 µg/mL against Pseudomonas aeruginosa to ≤16 µg/mL, based largely on pharmacokinetic-pharmacodynamic (PK-PD) modeling studies. Data on whether PK-PD modeling correlates with clinical outcomes in children are needed before resorting to broader classes of antibiotics to treat P. aeruginosa. METHODS We performed a retrospective cohort study of children with P. aeruginosa bacteremia between 2001 and 2010 who were prescribed piperacillin. Baseline characteristics and clinical outcomes of children with piperacillin minimum inhibitory concentrations (MICs) of ≤16 µg/mL and of 32-64 µg/mL were compared. The primary outcome was 30-day mortality. RESULTS There were 170 children with P. aeruginosa bacteremia receiving piperacillin therapy who met inclusion criteria. One hundred twenty-four (72%) children had piperacillin MICs of ≤16 µg/mL and 46 (28%) children had piperacillin MICs of 32-64 µg/mL. There was no significant difference in baseline characteristics between the 2 groups. Thirty-day mortality was 9% and 24% in children with a piperacillin MIC of ≤16 µg/mL and of 32-64 µg/mL, respectively. Using multivariable logistic regression, children with elevated MICs had increased odds of mortality compared with children with lower MICs (odds ratio, 3.21; 95% confidence interval, 1.26-8.16). CONCLUSIONS Our finding that elevated piperacillin MICs are associated with higher mortality in children supports the recent CLSI recommendation to lower the breakpoint of piperacillin against P. aeruginosa to ≤16 µg/mL. Alternate therapeutic choices should be considered when piperacillin MICs against P. aeruginosa are ≥32 µg/mL.