Killing of Streptococcus pneumoniae by azithromycin, clarithromycin, telithromycin and gemifloxacin using the minimum inhibitory and mutant prevention drug concentrations

Abstract number: 1134_02_411

Blondeau J., Borsos S.

Objective:

SP continues to be a significant respiratory pathogen & increasing antimicrobial resistance has compromised the use of beta-lactam & macrolide compounds. Bacterial eradication impacts on clinical outcome & as bacterial load at the site of infection exceeds the inoculum used in standardized susceptibility testing, elimination of higher organism numbers is necessary for successful therapy. We determined the killing of macrolide & quinolone susceptible SP by Az, CL, TL & GM against a range of bacterial inoculums using the MIC & MPC drug concentrations.

Method:

The MICs were determined by microbroth dilution in accordance with NCCLS guidelines. For MPC testing, >=1 billion organisms were inoculated to agar plates containing drug & incubated & read at 24 & 48 hours. The MIC & MPC were recorded as the lowest concentration showing no growth. For kill experiments, 1million–1billion colony forming units (cfu/ml) were exposed to drug & sampled at 0, 30 min, 1, 2, 3, 4, 6, 12 & 24 hours following drug exposure & log10 reduction & % reduction in viable cells recorded.

Results:

The MIC/MPC (mg/ml) values for Az, CL, TL & GM were 0.063/0.5, 0.031/0.5, 0.008/0.016 & 0.031/0.25 respectively. Exposure of 1 million–1 billion cfu/ml to the MIC drug concentration resulted in +0.38 to ­0.65 log10 reduction by 6 hours with Az as compared to +0.12 to ­1.11 for CL, +0.43 to ­0.74 for TL & +0.07 to ­4.64 for GM (biggest decrease over 6 hours). Significant log10 reductions occurred by 12 & 24 hours for all drugs. Following exposure of 1 million–1 billion cfu/ml to MPC drug concentration resulted in the following log10 reduction by 6 hours of drug exposure: Az ­0.10 to ­3.72; CL ­0.02 to ­3.77; TL +0.36 to ­0.89; GM ­0.30 to ­5.03 (biggest decrease over 6 hours). A >=3 log10 reduction in viable cells was seen for all drugs following 12–24 hours of drug exposure.

Conclusion:

Bacterial load at the site of infection may range from 1 million–1 billion organisms & kill experiments utilizing higher bacterial inoculums provided a more accurate measure of antibiotic performance in high biomass situations. It has been previously established that a 3 log10 reduction in viable cells is indicative of bactericidal activity. All agents tested achieved >=3 log reduction by 12–24 hours & kill was greater & fastest with MPC versus MIC drug concentrations. This data suggests that dosing to achieve MPC drug concentration results is more rapid & thorough killing.