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Suboptimal antibiotic dosage as a risk factor for selection of penicillin-resistant Streptococcus pneumoniae: In vitro kinetic model

Odenholt, Inga LU ; Gustafsson, I; Lowdin, E and Cars, O (2003) In Antimicrobial Agents and Chemotherapy 47(2). p.518-523
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... (More)
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 Samples for viable counts were withdrawn at different times during 24 h and seeded on blood agar plates and on selective antibiotic-containing plates.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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Antimicrobial Agents and Chemotherapy
volume
47
issue
2
pages
518 - 523
publisher
American Society for Microbiology
external identifiers
  • pmid:12543652
  • wos:000180646800010
  • scopus:0037311178
ISSN
1098-6596
DOI
10.1128/AAC.47.2.518-523.2003
language
English
LU publication?
yes
id
b6f456f3-fa76-4e46-bf22-124e68abf827 (old id 891326)
alternative location
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=151721&blobtype=pdf
date added to LUP
2008-01-15 09:39:16
date last changed
2018-02-18 04:20:50
@article{b6f456f3-fa76-4e46-bf22-124e68abf827,
  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.},
  author       = {Odenholt, Inga and Gustafsson, I and Lowdin, E and Cars, O},
  issn         = {1098-6596},
  language     = {eng},
  number       = {2},
  pages        = {518--523},
  publisher    = {American Society for Microbiology},
  series       = {Antimicrobial Agents and Chemotherapy},
  title        = {Suboptimal antibiotic dosage as a risk factor for selection of penicillin-resistant Streptococcus pneumoniae: In vitro kinetic model},
  url          = {http://dx.doi.org/10.1128/AAC.47.2.518-523.2003},
  volume       = {47},
  year         = {2003},
}