In vitro assessment of colistin's antipseudomonal antimicrobial interactions with other antibiotics

Authors

  • Alasdair P. MacGowan,

    Corresponding author
    1. Bristol Centre for Antimicrobial Research and Evaluation, Southmead Health Services NHS Trust and University of Bristol, Department of Medical Microbiology, Southmead Hospital. Bristol, UK
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  • Caroline Rynn,

    1. Bristol Centre for Antimicrobial Research and Evaluation, Southmead Health Services NHS Trust and University of Bristol, Department of Medical Microbiology, Southmead Hospital. Bristol, UK
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  • Mandy Wootton,

    1. Bristol Centre for Antimicrobial Research and Evaluation, Southmead Health Services NHS Trust and University of Bristol, Department of Medical Microbiology, Southmead Hospital. Bristol, UK
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  • Karen E. Bowker,

    1. Bristol Centre for Antimicrobial Research and Evaluation, Southmead Health Services NHS Trust and University of Bristol, Department of Medical Microbiology, Southmead Hospital. Bristol, UK
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  • H. Alan Holt,

    1. Bristol Centre for Antimicrobial Research and Evaluation, Southmead Health Services NHS Trust and University of Bristol, Department of Medical Microbiology, Southmead Hospital. Bristol, UK
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  • David S. Reeves

    1. Bristol Centre for Antimicrobial Research and Evaluation, Southmead Health Services NHS Trust and University of Bristol, Department of Medical Microbiology, Southmead Hospital. Bristol, UK
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Corresponding author and reprint requests: Alasdair P. MacGowan, Bristol Centre for Antimicrobial Research and Evaluation, Southmead Health Services NHS Trust and University of Bristol, Department of Medical Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK, Tel: +44 117 9595654 Fax: +44 117 9593154 E-mail:

Abstract

Objective: To study the interactions of colistin (MIC 2 mg/L) at concentrations of 0.5 and 5 mg/L with ceftazidime (1 and 75 mg/L, MIC 0.5 mg/L), aztreonam (1 and 30 mg/L, MIC 0.12 mg/L), meropenem (1 and 25 mg/L, MIC 0.03 mg/L), gentamicin (1 and 10 mg/L, MIC 2 mg/L), piperacillin (5 and 100 mg/L, MIC 4 mg/L) and ciprofloxacin (0.25 and 4 mg/L, MIC 1 mg/L) using a representative strain of Pseudomonas aeruginosa isolated from a cystic fibrosis patient.

Methods: The method used was a bacterial time kill curve with single agents and combinations. Using inocula of 106 CFU/mL, multiple sampling was performed over 6 h and in triplicate. The AUBKC of the time versus viable count curve, with single agents and combinations of agents, was taken as the endpoint for comparison.

Results: For colistin plus ceftazidime, colistin plus aztreonam, colistin plus meropenem and colistin plus ciprofloxacin, the pattern was for all the combinations (high or low concentrations) to produce smaller AUBKCs than single agents. In experiments using a bacteriostatic agent such as ceftazidime, the AUBKCs (log CFU/μL per h) for colistin 0.5 mg/L or 5 mg/L alone were 32.3±0.8 or 12.7±0.5, and for ceftazidime 1 mg/L or 75 mg/L alone they were 24.3±1.5 or 20.9±2.7. Combinations of colistin 0.5 mg/L plus either ceftazidime 1 mg/L or 75 mg/L produced AUBKCs of 23.8±1.8 or 16.1 mg/L. Combinations of colistin 5 mg/L plus ceftazidime 1 mg/L or 75 mg/L produced AUBKCs of 12.2±0.8 or 8.7±1.0. The AUBKCs for colistin 5 mg/L plus 75 mg/L are significantly smaller than those for the single agents, indicating synergy. In experiments using the bactericidal agent ciprofloxacin, the AUBKCs (log CFU/mL per h) for colistin 0.5 mg/L or 5 mg/L alone were 33.6±1.9 or 11.2±2.4, and for ciprofloxacin 0.25 mg/L or 4 mg/L alone they were 32.8±1.3 or 5.0±0.7. Combinations of colistin 0.5 mg/L plus either ciprofloxacin 0.25 mg/L or 4 mg/L produced AUBKCs of 32.2±0.9 or 4.3±1.4. Combinations of colistin 5 mg/L plus ciprofloxacin 0.25 mg/L or 4 mg/L produced AUBKCs of 10.7±1.5 or 4.2±0.6. Although combination AUBKCs were smaller than those for single agents, in no case did this reach statistical significance (p < 0.05).

Conclusions: These studies indicate that addition of colistin to other antipseudomonal drugs tends to produce smaller AUBKCs and hence greater killing of Pseudomonas aeruginosa than monotherapy.

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