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- Odenholt, Inga, et al.
(författare)
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In vitro studies of the pharmacodynamics of teicoplanin against Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecium
- 2003
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Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1469-0691 .- 1198-743X. ; 9:9, s. 930-937
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the basic pharmacodynamic properties of teicoplanin in vitro for Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecium. Methods The following experiments were performed: (1) bacterial killing by teicoplanin at different concentrations; (2) bacterial killing by teicoplanin at 8 x MIC against the same strains with inocula of 5x10(3), 5x10(5) and 5x10(7) CFU/mL; (3) studies of the postantibiotic effect (PAE) and the postantibiotic sub-MIC effect (PASME) of teicoplanin; (4) studies of the killing by teicoplanin in an in vitro kinetic model following exposure to simulated human serum pharmacokinetic concentrations (6 mg/kg OD at steady state). Results Concentration-dependent killing was noted against S. epidermidis, with a >4 log(10) difference in CFUs between 2 x MIC and 64 x MIC at 24 h. Also, against S. aureus there was slight concentration-dependent killing, which, however, did not reach 2 log(10) CFU/mL. Teicoplanin exerted a similar killing rate at all inocula for S. epidermidis, except for slower initial killing up to 6 h at the highest inoculum. In contrast, overall slower killing at all inocula was seen for S. aureus, where an inoculum effect was noted at the highest inoculum. For E. faecium, only a bacteriostatic effect was noted at all concentrations and inocula. No or very short PAEs were noted for the investigated strains. However, when the strains in the postantibiotic phase were exposed to 0.1, 0.2 and 0.3 x MIC of teicoplanin (PASME), substantial prolongation of the PAEs was seen. Although no significant killing was achieved in our kinetic model for any of the strains, regrowth of S. epidermidis was noted first after 8 h, despite a T>MIC24 of only 5% (1.2 h), illustrating the long post-MIC effect for this strain. For S. aureus, T>MIC was 38%, and regrowth occurred later than for S. epidermidis. Neither killing nor regrowth was seen for E. faecium with a T>MIC24 of 27%. Conclusion Teicoplanin exerted a concentration-dependent bactericidal effect against S. epidermidis, a less notable one against S. aureus, and a bacteriostatic effect against E. faecium. A reduced killing rate with increasing inocula was seen for S. aureus and also for S. epidermidis at the highest inoculum. No or very short PAEs were noted for the investigated strains, but were substantially prolonged with the addition of subinhibitory concentrations. When human pharmacokinetics was simulated (6 mg/kg OD at steady state) in the kinetic model, no net bactericidal effect was noted for any of the strains at 24 h.
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- Odenholt, Inga, et al.
(författare)
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Pharmacodynamics of moxifloxacin against Streptococcus pyogenes in an in vitro kinetic model
- 2002
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Ingår i: Antimicrobial Agents and Chemotherapy. - 1098-6596. ; 46:6, s. 2046-2048
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate the pharmacodynamics of moxifloxacin against strains of Streptococcus pyogenes with different susceptibilities to erythromycin by using an in vitro kinetic model simulating human pharmacokinetics of moxifloxacin at oral doses of 400 and 200 mg, respectively. When the different strains of S. pyogenes were exposed to the higher dose, the number of bacteria was reduced below the detection limit after 12 h and no regrowth was noted during the following 12 h. At the lower dose there was regrowth of the strains with constitutive and inducible erythromycin resistance of the MLSB phenotype. Replication assays of the regrowing bacteria indicated that the failure of moxifloxacin to kill the MLSB strains at the lower dose was likely caused by the emergence of preexisting resistant subpopulations. Thus, the present study indicates that the presently used 400-mg dose seems to have an advantage over the lower dose in that the risk for selection of resistant subpopuIations is minimized.
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- Odenholt, Inga, et al.
(författare)
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Postantibiotic, postantibiotic sub-MIC, and subinhibitory effects of PGE-9509924, ciprofloxacin, and levofloxacin
- 2003
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Ingår i: Antimicrobial Agents and Chemotherapy. - 1098-6596. ; 47:10, s. 3352-3356
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Tidskriftsartikel (refereegranskat)abstract
- Postantibiotic effects (PAEs), postantibiotic sub-MIC effects, and sub-MIC effects of the new nonfluoroquinolone PGE-9509924, ciprofloxacin, and levofloxacin against gram-positive and gram-negative strains were investigated. In comparison to ciprofloxacin and levofloxacin, PGE-9509924 exerted very similar PAEs against all strains except for both strains of Streptococcus pneumoniae, where longer PAEs were found for PGE-9509924. All three investigated quinolones showed no minimal PAEs against Pseudomonas aeruginosa.
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