Cafini, FabioAguilar, LorenzoSevillano Fernández, DavidGiménez, María JoséAlou Cervera, LuisFenoll, AsunciónEchevarría, OlatzTorrico, MarthaGonzález Hidalgo, NataliaCoronel, PilarPrieto Prieto, José2024-07-312024-07-312008-03Cafini 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):13-211076-629410.1089/mdr.2008.0783https://hdl.handle.net/20.500.14352/107294To 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.engjournal article1931-8448https://doi.org/10.1089/mdr.2008.0783https://www.liebertpub.com/doi/10.1089/mdr.2008.0783restricted access611.02Microbiología médica2414 Microbiología