| 1. |
- Odenholt, Inga, et al.
(author)
-
Pharmacodynamics of moxifloxacin against Streptococcus pyogenes in an in vitro kinetic model
- 2002
-
In: Antimicrobial Agents and Chemotherapy. - 1098-6596. ; 46:6, s. 2046-2048
-
Journal article (peer-reviewed)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.
|
|
| 2. |
- Odenholt, Inga, et al.
(author)
-
Postantibiotic, postantibiotic sub-MIC, and subinhibitory effects of PGE-9509924, ciprofloxacin, and levofloxacin
- 2003
-
In: Antimicrobial Agents and Chemotherapy. - 1098-6596. ; 47:10, s. 3352-3356
-
Journal article (peer-reviewed)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.
|
|
| 3. |
- Odenholt, Inga, et al.
(author)
-
Suboptimal antibiotic dosage as a risk factor for selection of penicillin-resistant Streptococcus pneumoniae: In vitro kinetic model
- 2003
-
In: Antimicrobial Agents and Chemotherapy. - 1098-6596. ; 47:2, s. 518-523
-
Journal article (peer-reviewed)abstract
- Optimizing pharmacokinetic/pharmacodynamic indices of antibiotics to obtain clinical and microbiological efficacy is essential, but dosing regimens must also be tailored to minimize the risk for emergence of resistance. The aim of the present study was to investigate whether certain concentrations of benzylpenicillin are critical for the selection of resistant subpopulations. A mixed culture of Streptococcus pneumoniae containing ca. 90% susceptible (MIC = 0.031 mg/liter), 9% intermediate (MIC = 0.25 mg/liter), and 1% resistant (MIC = 8 mg/liter) was studied in an in vitro kinetic model. The time that concentrations exceeded the MIC (T>MIC) for the three strains in the culture was varied by different initial concentrations of benzylpenicillin. Samples for viable counts were withdrawn at different times during 24 h and seeded on blood agar plates and on selective antibiotic-containing plates. The T>MIC varied from 46 to 100% for the susceptible strain, from 6 to 100% for the intermediate strain, and from 0 to 48% for the resistant strain. Our study, which may mimic the clinical situation with carriage of a mixed population of S. pneumoniae with different antibiotic susceptibilities, has shown that selection of resistant bacteria may easily occur if dosing regimens are only targeted toward fully susceptible strains.
|
|
