JAC Advance Access published online on September 1, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg403
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Faculties of Pharmacy
and Medicine, University
of Manitoba, and Pharmacy, St Boniface General Hospital,
Winnipeg, MB, Canada
* Corresponding author. E-mail: zelenits{at}ms.umanitoba.ca.
Received 10 March 2003
; revised 3 June 2003
; accepted 6 July 2003
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 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.
Keywords: pseudomonal, bloodstream infections, peak/MIC,
AUC/MIC
Treatment and outcome of Pseudomonas
aeruginosa bacteraemia:
an antibiotic pharmacodynamic analysis
2 Faculties of Medicine, University
of Manitoba, and Microbiology
Laboratory and Infectious Diseases, St Boniface General Hospital,
Winnipeg, MB, Canada
3 Faculty of Pharmacy, University of Manitoba
4 Faculty of Pharmacy, St Boniface General Hospital,
Winnipeg, MB, Canada
90% when
peak/MIC was at least 8. 
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