JAC Advance Access published online on March 6, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm015
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Are ß-lactam breakpoints adequate to define non-susceptibility for all Haemophilus influenzae resistance phenotypes from a pharmacodynamic point of view?
1 Microbiology Department, School of Medicine, Universidad Complutense, Avda. Complutense s/n, 28040 Madrid, Spain 2 Scientific Department, Tedec-Meiji Farma SA, Ctra. M-300, Km. 30 500, 28802 Alcalá de Henares, Madrid, Spain
Received 26 September 2006; returned 21 November 2006; revised 24 November 2006; accepted 16 January 2007
* Corresponding author. Tel/Fax: +34-91-3941511; E-mail: laguilar{at}med.ucm.es
Objectives: To investigate the bactericidal activity, against Haemophilus influenzae strains exhibiting different resistance phenotypes, of simulated serum concentrations obtained in humans after administration of 400 mg of cefditoren twice daily, 500 mg of cefuroxime twice daily, 875/125 mg of co-amoxiclav twice daily or 875/125 mg of co-amoxiclav three times daily.
Methods: An in vitro computerized pharmacodynamic simulation was carried out and colony counts determined over 24 h. Four H. influenzae strains were used, one ampicillin-susceptible strain (Strain 1) and three ampicillin-resistant strains following CLSI and BSAC breakpoints: one ß-lactamase-positive strain with an MIC of co-amoxiclav of 0.5 mg/L (Strain 2), one ß-lactamase-negative ampicillin-resistant strain (BLNAR; ampicillin MIC = 16 mg/L) (Strain 3) and one ß-lactamase-positive strain with an MIC of co-amoxiclav of 4 mg/L (Strain 4). All strains were susceptible to cefuroxime and co-amoxiclav according to current CLSI breakpoints, but Strains 3 and 4 were resistant according to BSAC breakpoints. All strains exhibited cefditoren MIC 
0.12 mg/L.
Results: Bacterial counts of Strains 1 and 2 were 
6 log10 reduced with all antibiotics tested at 12 and 24 h. Against Strains 3 and 4, log10 reductions at 12 and 24 h were significantly higher for cefditoren versus cefuroxime (P < 0.01) (although both exhibited bactericidal activity, i.e. 3 log10 reduction) and versus the two co-amoxiclav regimens (P < 0.001) (that exhibited negligible initial inocula reductions).
Conclusions: Cefditoren exhibited the highest bactericidal activity maintained over time against ampicillin-resistant H. influenzae, regardless of ß-lactamase production and/or BLNAR phenotype. From the pharmacodynamic perspective, BSAC breakpoints seem more adequate to define or detect BLNAR strains.
Key Words: cefditoren , co-amoxiclav , H. influenzae
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