Objectives: To conduct a retrospective study of antibiotic pharmacodynamics in the treatment of Pseudomonas aeruginosa bacteraemia, and to identify pharmacodynamic indices associated with clinical cure.
Methods: Cases of P. aeruginosa bacteraemia were identified, and information related to patient demographics, clinical status, antibiotic treatment and clinical outcome were documented. Anti-pseudomonal therapy was assessed, and concentration versus time profiles were constructed using measured levels for aminoglycosides, or population pharmacokinetic models for other antibiotics. P. aeruginosa isolates from all patients were retrieved and MICs for the anti-pseudomonal agents used to treat the episode of bacteraemia were determined. Patient- and treatment-related factors were tested for associations with clinical outcome using univariate and multivariate analyses.
Results: Fifty cases of P. aeruginosa bacteraemia were identified and 38 cases were included in the pharmacodynamic analysis. Eighty-seven percent of patients received an aminoglycoside or ciprofloxacin and 79% received piperacillin or ceftazidime. A majority of patients, 71%, were administered a combination of antibiotics. Treatment outcomes were documented as persistent infection in 21%, death within 2-30 days in 21% and clinical cure in 58% of cases. Peak/MIC (P=0.001) and AUC24/MIC (P=0.002) for aminoglycosides and ciprofloxacin were significant factors in univariate tests. Only peak/MIC was associated independently with treatment outcome (P=0.017) in logistic regression analysis. The predicted probability of cure was > or =90% when peak/MIC was at least 8.
Conclusion: Pharmacodynamic considerations including aggressive dosing with targeted peak/MICs for aminoglycosides and ciprofloxacin are strongly associated with clinical outcome and essential to the appropriate management of P. aeruginosa bacteraemia.