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Broth microdilution and E-test for determining fluoroquinolone activity against Streptococcus pneumoniae
Michael B Kays1, Melissa A Graff
1School of Pharmacy and Pharmacal Sciences, Purdue University, Indianapolis, IN 46202-2879, USA. mkays@iupui.edu
The Annals of Pharmacotherapy
|March 16, 2002
Summary
Broth microdilution and E-test methods yield different minimum inhibitory concentrations (MICs) for fluoroquinolones against Streptococcus pneumoniae. This variation significantly impacts calculated AUC0-24/MIC ratios, affecting antimicrobial susceptibility interpretation.
Area of Science:
- Microbiology
- Pharmacology
- Clinical Diagnostics
Background:
- Accurate determination of antimicrobial susceptibility is crucial for effective treatment of bacterial infections.
- Fluoroquinolones are important antibiotics used against Streptococcus pneumoniae, a common respiratory pathogen.
- In vitro susceptibility testing methods can influence antimicrobial activity and pharmacokinetic/pharmacodynamic (PK/PD) parameter calculations.
Purpose of the Study:
- To compare minimum inhibitory concentrations (MICs) of four fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin) against Streptococcus pneumoniae using broth microdilution and E-test methods.
- To evaluate the impact of these different MIC testing methodologies on the calculation of AUC0-24/MIC ratios, a key PK/PD index.
Main Methods:
- MICs of four fluoroquinolones were determined for 100 clinical isolates of S. pneumoniae using broth microdilution (air incubation) and E-test (CO2 incubation).
- Simulations of steady-state serum concentration-time profiles were performed for standard oral dosing regimens.
- AUC0-24/MIC ratios were calculated using MIC data from both methods after adjusting for protein binding.
Main Results:
- Broth microdilution and E-test MICs showed high agreement for levofloxacin (94%) and gatifloxacin (93%), but lower agreement for moxifloxacin (61%) and gemifloxacin (35%).
- Broth microdilution yielded significantly lower MICs than E-test for all four fluoroquinolones (p < 0.001).
- AUC0-24/MIC ratios were significantly higher when MICs were determined by broth microdilution compared to E-test (p < 0.001).
Conclusions:
- Significant differences exist in fluoroquinolone activity against S. pneumoniae depending on whether broth microdilution or E-test is used.
- The choice of MIC testing methodology substantially influences the calculated AUC0-24/MIC ratios.
- Clinicians must consider the MIC testing method's impact when interpreting fluoroquinolone activity and PK/PD parameters for S. pneumoniae infections.