González Hidalgo, NataliaAguilar, LorenzoSevillano Fernández, DavidGiménez, María JoséAlou Cervera, LuisCafini, FabioTorrico, MarthaLópez, Ana MaríaCoronel, PilarPrieto Prieto, José2024-07-162024-07-162011-06González N, Aguilar L, Sevillano D, Giménez MJ, Alou L, Cafini F, Torrico M, López AM, Coronel P, Prieto J. Efficacy of simulated cefditoren versus amoxicillin-clavulanate free concentrations in countering intrastrain ftsI gene diffusion in Haemophilus influenzae. Antimicrob Agents Chemother. 2011 Jun;55(6):2788-94.0066-480410.1128/aac.01719-10https://hdl.handle.net/20.500.14352/106729This study explores the effects of cefditoren (CDN) versus amoxicillin-clavulanic acid (AMC) on the evolution (within a single strain) of total and recombined populations derived from intrastrain ftsI gene diffusion in β-lactamase-positive (BL+) and β-lactamase-negative (BL−) Haemophilus influenzae. DNA from β-lactamase-negative, ampicillin-resistant (BLNAR) isolates (DNABLNAR) and from β-lactamase-positive, amoxicillin-clavulanate-resistant (BLPACR) (DNABLPACR) isolates was extracted and added to a 107-CFU/ml suspension of one BL+ strain (CDN MIC, 0.007 μg/ml; AMC MIC, 1 μg/ml) or one BL− strain (CDN MIC, 0.015 μg/ml; AMC MIC, 0.5 μg/ml) in Haemophilus Test Medium (HTM). The mixture was incubated for 3 h and was then inoculated into a two-compartment computerized device simulating free concentrations of CDN (400 mg twice a day [b.i.d.]) or AMC (875 and 125 mg three times a day [t.i.d.]) in serum over 24 h. Controls were antibiotic-free simulations. Colony counts were performed; the total population and the recombined population were differentiated; and postsimulation MICs were determined. At time zero, the recombined population was 0.00095% of the total population. In controls, the BL− and BL+ total populations and the BL− recombined population increased (from ≈3 log10 to 4.5 to 5 log10), while the BL+ recombined population was maintained in simulations with DNABLPACR and was decreased by ≈2 log10 with DNABLNAR. CDN was bactericidal (percentage of the dosing interval for which experimental antibiotic concentrations exceeded the MIC [ft>MIC], >88%), and no recombined populations were detected from 4 h on. AMC was bactericidal against BL− strains (ft>MIC, 74.0%) in DNABLNAR and DNABLPACR simulations, with a small final recombined population (MIC, 4 μg/ml; ft>MIC, 30.7%) in DNABLPACR simulations. When AMC was used against the BL+ strain (in DNABLNAR or DNABLPACR simulations), the bacterial load was reduced ≈2 log10 (ft>MIC, 44.3%), but 6.3% and 32% of the total population corresponded to a recombined population (MIC, 16 μg/ml; ft>MIC, 0%) in DNABLNAR and DNABLPACR simulations, respectively. AMC, but not CDN, unmasked BL+ recombined populations obtained by transformation. ft>MIC values higher than those classically considered for bacteriological response are needed to counter intrastrain ftsI gene diffusion by covering recombined populations.engjournal article1098-6596https://doi.org/10.1128/aac.01719-10https://journals.asm.org/doi/10.1128/aac.01719-10https://pubmed.ncbi.nlm.nih.gov/21464255/restricted access611.02Microbiología médica2414 Microbiología