Levofloxacin vs. Azithromycin Pharmacodynamic Activity Against S. pneumoniae and H. influenzae with Decreased Susceptibility to Amoxicillin/Clavulanic Acid

Abstract

Resistant clones/phenotypes are putting into question the activity of commonly used β-lactams, thus prompting the need for alternative options. A 500 mg levofloxacin vs. azithromycin once daily pharmacodynamic simulation was performed against 10⁸ cfu/ml of four Streptococcus pneumoniae strains (exhibiting higher amoxicillin than penicillin MIC) and four Haemophilus influenzae strains: β-lactamase producing, BLNAR (β-lactamase-negative ampicillin-resistant) and BLPACR (β- lactamase-positive amoxicillin/clavulanate-resistant). High levofloxacin AUC/MIC values for H. influenzae, and values of 50-100 for S. pneumoniae produced a >5 log₁₀ reduction at 24h for all strains. Azithromycin AUC/MIC values of ≍10 were needed to obtain a 2-3 log₁₀ reduction of S. pneumoniae initial inocula, but lower AUC/MIC values (of ≍6) obtained ≥3 log₁₀ reduction against all strains of H. influenzae. While in vitro simulated serum concentrations of levofloxacin were bactericidal at the end of the dosing interval against all S. pneumoniae strains and azithromycin against the susceptible ones, both antimicrobials achieved this endpoint against the BLNAR and BLPACR strains.

Keywords:

• Levofloxacin
• azithromycin
• pharmacodynamic simulation
• BLNAR
• H. influenzae
• S. pneumoniae