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Abstract
Purpose
Pneumococcus is one of the most important causes of invasive infection through the childhood period. In January 2008, the Clinical and Laboratory Standards Institute (CLSI) published revised penicillin breakpoints for Streptococcus pneumoniae and penicillin susceptibility rates of S. pneumoniae increased in Korea. This study was performed to determine the probability of oral amoxicillin for the empirical treatment achieving bactericidal exposure against pneumococcus using pharmacodynamics model.
Methods
Twenty-three isolates of pneumococci were subjected to determine minimum inhibitory concentration (MIC) for -lactams and macrolide. For the -lactams, exposure of T >MIC (time that free drug concentrations remain above the β β ƒ MIC) for 50% of the administration interval have determined the probability of target attainment (PTA), and regimens that had a PTA >90% were considered optimal. An analysis was performed by applying MIC of 23 isolates to a 5000-patient Monte Carlo simulation model.
Results
Among 23 isolates from healthy children, 7 (30.4%) isolates were MIC 1.0 g/mL and 19 (82.6%) were MIC 2≤ µ ≤µ≤ µ g/mL for amoxicillin. Amoxicillin 40 mg/kg/day achieved PTA >90% at MIC 1.0 g/mL but PTA decreased to 52% at MIC 2 g/mL, whereas amoxicillin 90 mg/kg/day can predict 97% of PTA at MIC 2 g/mL. Overall, oral amoxicillin 90 mg/µµ kg/day for the empirical treatment against pneumococcus can expect more successful response in Korean children. Conclusion: Considering the resistantce pattern of pneumococci in Korean children, we estimate that oral amoxicillin 90 mg/kg/day will provide a pharmacodynamic advantage for the empirical treatment against pneumococcus. And low dose amoxicillin or macrolide are expected to have higher chance of treatment failure than high dose oral amoxicillin. (Korean J Pediatr Infect Dis 2011;18:109–116)
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Fig. 1.
Probability of target attainment for amoxicillin-based regimens achieving free drug concentrations above the MIC for 50% of the administration interval 19).(50% T >MIC) at increasing MIC dilutions ƒ
Table 1.
The Minimum Inhibitory Concentration at which 50% (MIC50) and 90% (MIC90) of Bacteria are Inhibited and the Percent Susceptibility for 23S. pneumoniae Isolates
| Antibiotics | Susceptible MIC* (g/mL) µ | MIC50(g/mL) µ† | MIC90(g/mL) µ† | Percentage susceptible (%) |
|---|---|---|---|---|
| –lactams (nonmeningitis)β | ||||
| Penicillin parenteral | 2≤ | 0.75 | 3 | 78.3 |
| Penicillin oral | 0.06≤ | 0.75 | 3 | |
| Amoxicillin oral | 2≤ | 1.5 | 6 | 82.6 |
| Cefotaxime parenteral | 1≤ | 0.75 | 1.5 | 82.6 |
| Macrolide | ||||
| Erythromycin | 0.25≤ | >256 | >256 | 4.3 |
Table 2.
Distribution of Minimum Inhibitory Concentration of Amoxicillin among 23S. pneumoniae Carriage Isolates Obtained from Healthy Korean Children
| Amoxicillin MIC* (g/mL) µ | No. of isolates indicated | No. of isolates/Total No. (%) |
|---|---|---|
| 1.0≤ | 7 | 30.4 |
| 1< 2.0≤ | 12 | 52.2 |
| 2< 3.0≤ | 1 | 4.3 |
| 3< 6.0≤ | 3 | 13.0 |
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