RT Journal Article
T1 Decrease in Bacterial Load Versus Resistance Selection of Pneumococcal Subpopulations by β-Lactam Physiological Concentrations over Time: An In Vitro Pharmacodynamic Simulation
A1 Cafini, Fabio
A1 Aguilar, Lorenzo
A1 Sevillano Fernández, David
A1 Giménez, María José
A1 Alou Cervera, Luis
A1 Fenoll, Asunción
A1 Echevarría, Olatz
A1 Torrico, Martha
A1 González Hidalgo, Natalia
A1 Coronel, Pilar
A1 Prieto Prieto, José
AB To investigate β-lactam effects on Streptococcus pneumoniae–mixed cultures, a computerized pharmacodynamic model simulating over 24-hr concentrations obtained after several β-lactam regimens was used. Strain 1 (no penicillin binding protein [PBP] mutations) and strain 2 (mutation in pbp1a) were penicillin/amoxicillin susceptible. Strain 3 (mutations in pbp1a, pbp2x, and pbp2b) and strain 4 (mutations in pbp1a, pbp2x, and pbp2b [10 changes]) were penicillin/amoxicillin resistant. Initial inoculum was approximately 6 × 106 CFU (colony forming units)/ml (with a 1:1:1:1 proportion of each strain). Population analysis profile was performed pre- and postsimulations. Strain 1 exhibited the best fitness (growth over 24 hr) in individual cultures, and strain 2 did so in mixed cultures in antibiotic-free simulations. In antibiotic simulations with the mixed inocula, penicillin/amoxicillin-susceptible strains were eradicated with all study drugs (time that concentrations exceed the minimal inhibitory concentration [T > MIC ≥ 43%]). Penicillin-resistant strains showed different evolution depending on the antibiotic: (a) cefditoren produced >2 log10 reduction of initial inocula at 12–24 hr (T>MIC ≥45%), with a remaining population growing in plates with ≥4 mg/L amoxicillin; (b) cefuroxime, cefixime, and cefaclor did not decrease initial inocula at 12–24 hr (T > MIC = 0%), with minor subpopulations growing in plates with 4 mg/L amoxicillin; (c) amoxicillin produced 2.6 log10 decrease of initial inocula at 12 hr (T>MIC = 47.5%), but 1.1 log10 increase of initial inocula at 24 hr, with a significant population growing in plates with 4 mg/L amoxicillin. Antibiotic activity against mixed inocula (susceptible and resistant strains) depends on intrinsic activity (as well as its subsequent pharmacodynamic activity: T > MIC against resistant strains), and on possible selection of intra-strain-resistant subpopulations.
PB Mary Ann Liebert
SN 1076-6294
YR 2008
FD 2008-03
LK https://hdl.handle.net/20.500.14352/107294
UL https://hdl.handle.net/20.500.14352/107294
LA eng
NO Cafini F, Aguilar L, Sevillano D, Giménez MJ, Alou L, Fenoll A, Echevarría O, Torrico M, González N, Coronel P, Prieto J. Decrease in bacterial load versus resistance selection of pneumococcal subpopulations by beta-lactam physiological concentrations over time: an in vitro pharmacodynamic simulation. Microb Drug Resist. 2008 Mar;14(1):13-21
NO Tedec-Meiji Farma S.A.
DS Docta Complutense
RD 15 dic 2025