RT Journal Article
T1 Efficacy of simulated cefditoren versus amoxicillin-clavulanate free concentrations in countering intrastrain ftsI gene diffusion in Haemophilus influenzae
A1 González Hidalgo, Natalia
A1 Aguilar, Lorenzo
A1 Sevillano Fernández, David
A1 Giménez, María José
A1 Alou Cervera, Luis
A1 Cafini, Fabio
A1 Torrico, Martha
A1 López, Ana María
A1 Coronel, Pilar
A1 Prieto Prieto, José
AB This 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.
PB American Society for Microbiology
SN 0066-4804
YR 2011
FD 2011-06
LK https://hdl.handle.net/20.500.14352/106729
UL https://hdl.handle.net/20.500.14352/106729
LA eng
NO González 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.
DS Docta Complutense
RD 15 dic 2025