Reassessment of cefaclor breakpoints for Haemophilus influenzae

Area of Science:

• Microbiology
• Infectious Diseases
• Pharmacology

Background:

• Standard methods for determining antibiotic susceptibility, such as NCCLS broth microdilution, may overestimate minimum inhibitory concentrations (MICs) for certain drugs.
• In vitro chemical instability of cefaclor has been previously shown to affect MICs for Streptococcus pneumoniae.

Purpose of the Study:

• To evaluate the accuracy of standard methods in determining cefaclor MICs for Haemophilus influenzae.
• To compare cefaclor's efficacy against H. influenzae with cefuroxime using kill curve analysis.

Main Methods:

• Determined standard NCCLS broth microdilution and E-Test MICs for eight H. influenzae isolates.
• Utilized kill curves to define bacteriostatic MICs, accounting for cefaclor's chemical instability over six hours.

Main Results:

• Standard NCCLS methods overestimated cefaclor MICs for H. influenzae due to in vitro chemical instability over 18-24 hours.
• The mean cefaclor MIC by NCCLS was 3.0 mg/L, compared to 0.8 mg/L for cefuroxime.
• Bacteriostatic MICs determined by kill curves were not significantly different between cefaclor and cefuroxime.

Conclusions:

• Standard susceptibility testing methods can overestimate cefaclor MICs against H. influenzae.
• Accurate cefaclor MICs, when accounting for instability, are comparable to cefuroxime, suggesting potential for effective treatment.
• Kill curve analysis provides a more reliable assessment of cefaclor's bacteriostatic activity against H. influenzae.