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JAC Advance Access published online on October 27, 2009
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkp384
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Combination testing of multidrug-resistant cystic fibrosis isolates of Pseudomonas aeruginosa: use of a new parameter, the susceptible breakpoint index

K. E. N. Milne* and I. M. Gould

Medical Microbiology Department, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB25 2ZN, UK

Received 7 July 2009; returned 28 August 2009; revised 2 October 2009; accepted 2 October 2009

* Corresponding author. Tel: +44-1224-554954; Fax: +44-1224-550632; E-mail: kate.milne{at}nhs.net

Objectives: The microbiology laboratory at Aberdeen Royal Infirmary operates an extended susceptibility testing service for multidrug-resistant Gram-negative non-fermenting isolates from the sputum of Scottish cystic fibrosis patients. The service aims to provide clinicians with useful treatment options and developed the use of a novel parameter—the susceptible breakpoint index (SBPI), which allows easy ranking of the antimicrobial combinations in order of their possible in vivo effectiveness.

Methods: Three hundred and fifteen isolates of Pseudomonas aeruginosa were submitted for testing. MICs of 14 antimicrobials were determined using the Etest and the results categorized using CLSI guidelines. Usually, six antimicrobial pairs were tested in combination also using the Etest. The results were assessed using the fractional inhibitory concentration index (FICI) and also by a novel parameter, the SBPI.

Results: Some 4173 MICs and 1663 combination pairs were performed. The most active individual antimicrobials were colistin, tobramycin and amikacin, with 84%, 69% and 32% of isolates susceptible, respectively. Twenty-eight of 44 antimicrobial combinations were tested >10 times. Of the combinations, 3.6% were synergistic (FICI ≤ 0.5) and 0.1% were antagonistic (FICI > 4.0). Amikacin + ceftazidime (17%), ciprofloxacin + ceftazidime (12.9%) and ciprofloxacin + piperacillin/tazobactam (12%) were the most synergistic combinations. By median SBPI, the most effective combinations in vitro were colistin + ticarcillin/clavulanate, colistin + piperacillin/tazobactam and colistin + meropenem.

Conclusions: The Etest is a useful tool for determining MICs and testing antimicrobial combinations. The SBPI is more discriminatory than the FICI, allowing easy ranking of the combinations, and is likely to have clinical relevance.

Key Words: Etest , MIC , synergy


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