Abstract
The need for synergy testing is driven by the necessity to extend the antimicrobial spectrum, reducing drug dosage/toxicity and the development of resistance. Despite the abundance of synergy testing methods, there is the absence of a gold standard and a lack of synergy correlation among methods. The most popular method (checkerboard) is labor-intensive and is not practical for clinical use. Most clinical laboratories use several gradient synergy methods which are quicker/easier to use. This study sought to evaluate three gradient synergy methods (direct overlay, cross, MIC:MIC ratio) with the checkerboard, and compare two interpretative criteria (the fractional inhibitory concentration index (FICI) and susceptibility breakpoint index (SBPI)) regarding these methods. We tested 70 multidrug-resistant Pseudomonas aeruginosa, using a tobramycin and ceftazidime combination. The agreement between the checkerboard and gradient methods was 60 to 77% for FICI, while agreements for SBPI that ranged between 67 and 82.86% were statistically significant (p ≤ 0.001). High kappa agreements were observed using SBPI (Ƙ > 0.356) compared to FICI (Ƙ < 0.291) criteria, and the MIC:MIC method demonstrated the highest, albeit moderate, intraclass correlation coefficient (ICC = 0.542) estimate. Isolate resistance profiles suggest methoddependent synergism for isolates, with ceftazidime susceptibility after increased exposure. Theresults show that when interpretative criteria are considered, gradient diffusion (especiallyMIC:MIC) is a valuable and practical method that can inform the treatment of cystic fibrosis patients who are chronically infected with P. aeruginosa
Original language | English |
---|---|
Article number | 967 |
Number of pages | 12 |
Journal | Antibiotics |
Volume | 10 |
Issue number | 8 |
Early online date | 12 Aug 2021 |
DOIs | |
Publication status | Published - 12 Aug 2021 |
Bibliographical note
Funding: This research was funded by the NHS Grampian Endowment fund, grant number EA9431, and the NHS Grampian Clinical Microbiology Fund (NHS Grampian Endowment Funds, Registered Charity Number SC017296).Acknowledgments: The authors would like to thank the laboratories and clinicians who use the Cystic Fibrosis Susceptibility Testing Service. CFASS is an adult patient-testing facility, funded by the National Services Division of the Common Services Agency of the Scottish Executive.
Keywords
- antimicrobials
- ceftazidime
- combination antimicrobial susceptibility testing
- gradient diffusion
- Pseudomonas aeruginosa
- synergy testing
- tobramycin