González Hidalgo, NataliaAguilar, LorenzoAlou Cervera, LuisGimenez, María JoséSevillano Fernández, DavidTorrico, MarthaCafini, FabioCoronel, PilarPrieto Prieto, José2024-07-242024-07-242009-03-22Natalia González, Lorenzo Aguilar, Luis Alou, Maria-Jose Giménez, David Sevillano, Martha Torrico, Fabio Cafini, Pilar Coronel, Jose Prieto, Influence of different resistance traits on the competitive growth of Haemophilus influenzae in antibiotic-free medium and selection of resistant populations by different β-lactams: an in vitro pharmacodynamic approach, Journal of Antimicrobial Chemotherapy, Volume 63, Issue 6, June 2009, Pages 1215–1222, https://doi.org/10.1093/jac/dkp0970305-745310.1093/jac/dkp097https://hdl.handle.net/20.500.14352/107103Objectives: 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 beta-lactamase-negative (beta(-); 0.015, 1 and 1), one beta-lactamase-positive (beta(+); 0.03, 4 and 8) and two strains exhibiting ftsI gene mutations [one beta(-) ampicillin-resistant (BLNAR; 0.015, 8 and 4) and one beta(+) 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 (AUBC(K)) and in antibiotic simulations determined (ABBC(0-24) = AUBC(K0-24)-AUBC(0-24)). Results: In antibiotic-free medium, total population increased by 1.7 log(10) cfu/mL from 0 to 24 h: final composition approximately 90% beta(-), approximately 6.5% beta(+), approximately 2.5% BLNAR and approximately 1% BLPACR. At the end of antibiotic simulations, the predominant population was BLPACR followed by beta(+) after amoxicillin/clavulanic acid or BLNAR after cefuroxime exposures. ABBC(0-24) was higher (P < 0.01) for cefditoren compared with cefuroxime or amoxicillin/clavulanic acid whether considering total population (70.4 versus approximately 33), beta(+) (77.8 versus approximately 52), BLNAR (66.1 versus 18.6-30.4) or BLPACR (40.8 versus approximately 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 beta-lactamase-producing strains and those carrying ftsI gene mutations.engjournal article1460-2091https://doi.org/10.1093/jac/dkp097https://academic.oup.com/jac/article/63/6/1215/747321restricted access611.02amoxicillin/clavulanic acidin vitro simulationcefditorenMicrobiología médica2414 Microbiología