Influence of different resistance traits on the competitive growth of : an in vitro pharmacodynamic approachHaemophilus influenzae: an in vitro pharmacodynamic approach in antibiotic-free medium and selection of resistant populations by different β-lactams: an in vitro pharmacodynamic approach

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Abstract

Objectives

The aim was to study the pharmacodynamics of cefditoren, amoxicillin/clavulanic acid and cefuroxime against mixed Haemophilus influenzae strains.

Methods

Isolates [MICs (mg/L) of cefditoren, cefuroxime and amoxicillin/clavulanic acid] used were: one β-lactamase-negative (β−; 0.015, 1 and 1), one β-lactamase-positive (β+; 0.03, 4 and 8) and two strains exhibiting ftsI gene mutations [one β− ampicillin-resistant (BLNAR; 0.015, 8 and 4) and one β+ amoxicillin/clavulanic acid-resistant (BLPACR; 0.03, 8 and 4)]. A computerized pharmacodynamic model simulating free antibiotic concentrations (calculated considering reported percentages of protein binding) of 400 mg twice-daily cefditoren, 500 mg twice-daily cefuroxime and 875/125 mg three times daily amoxicillin/clavulanic acid was used to explore antibacterial activity against initial mixed inocula with 25% of each strain. Areas under bacterial curves (AUBCs) from 0 to 24 h (log cfu·h/mL) were calculated and differences between values in antibiotic-free (AUBCK) and in antibiotic simulations determined (ABBC0–24 = AUBCK0–24−AUBC0–24).

Results

In antibiotic-free medium, total population increased by 1.7 log10 cfu/mL from 0 to 24 h: final composition ≈90% β−, ≈6.5% β+, ≈2.5% BLNAR and ≈1% BLPACR. At the end of antibiotic simulations, the predominant population was BLPACR followed by β+ after amoxicillin/clavulanic acid or BLNAR after cefuroxime exposures. ABBC0–24 was higher (P < 0.01) for cefditoren compared with cefuroxime or amoxicillin/clavulanic acid whether considering total population (70.4 versus ≈33), β+ (77.8 versus ≈52), BLNAR (66.1 versus 18.6–30.4) or BLPACR (40.8 versus ≈0).

Conclusions

Cefditoren offered higher antibacterial effect than cefuroxime and amoxicillin/clavulanic acid against a mixed population of H. influenzae strains due to its higher activity against β-lactamase-producing strains and those carrying ftsI gene mutations.

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