Evaluation of Intravenous Fosfomycin Disodium Dosing Regimens in Critically Ill Patients for Treatment of Carbapenem-Resistant Enterobacterales Infections Using Monte Carlo Simulation
Abstract
:1. Introduction
2. Results
2.1. MIC Distributions
2.2. Pharmacokinetic/Pharmacodynamic Simulations
3. Discussion
4. Materials and Methods
4.1. Pharmacokinetic Parameters
4.2. Microbiology
4.3. Pharmacodynamic Parameters
4.4. Intravenous Fosfomycin Disodium Dosing Regimens
4.5. Monte Carlo Simulation
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Carbapenem-Resistant Enterobacterales Isolates | Number of Isolates | Fosfomycin MICs (mg/L) | % of Isolates | |||
---|---|---|---|---|---|---|
CLSI a | EUCAST b | |||||
MIC50 | MIC90 | MICs Range | S/I/R | S/R | ||
Klebsiella pneumoniae | 116 | 64 | >1024 | 0.38 to >1024 | - | 40.52/59.48 |
Escherichia coli | 12 | NA c | NA c | 1 to 16 | 100/0/0 | 100/0 |
Enterobacter cloacae | 1 | NA c | NA c | 12 | - | 100/0 |
All isolates | 129 | 48 | >1024 | 0.38 to >1024 | - | 46.51/53.49 |
CLCr (mL/min) a | Daily Doses Suggestion | Dosage Adjustments | |
---|---|---|---|
CLSI Breakpoints b | EUCAST Breakpoints c | ||
≥80 | 16 g per day (in 2 or 4 divided doses) (1 h or 4 h infusion) | 8 g per day (in 2 divided doses) (1 h or 4 h infusion) | Initial dosage |
50 to <80 | 12 g per day (in 2 to 3 divided doses) (1 h or 4 h infusion) | 6 g per day (in 1 to 3 divided doses) (1 h or 4 h infusion) | Reduce maintenance dosage by 25% |
30 to <50 | 8 g per day (in 2 divided doses) (1 h or 4 h infusion) | 4 g per day (in 1 to 2 divided doses) (1 h or 4 h infusion) | Reduce maintenance dosage by 50% |
15 to <30 | 6 g per day (in 1 to 2 divided doses) (1 h or 4 h infusion) | 3 g per day (in 1 to 2 divided doses) (1 h or 4 h infusion) | Reduce maintenance dosage by 62.5% |
<15 | 4 g per day (in 1 divided doses) (1 h infusion) | 2 g per day (in 1 divided doses) (1 h infusion) | Reduce maintenance dosage by 75% |
Dosing Regimens for Monte Carlo Simulation | CLCr (mL/min) a | |||||
---|---|---|---|---|---|---|
Daily Doses | Dosing Regimens | ≥80 | 50 to <80 | 30 to <50 | 15 to <30 | <15 |
24 g/day | 8 g q8h (1 h infusion) | / b | / c | |||
8 g q8h (4 h infusion) | / c | / c | ||||
18 g/day | 6 g q8h (1 h infusion) | / b | / c | |||
6 g q8h (4 h infusion) | / c | |||||
16 g/day | 8 g q12h (1 h infusion) | / b | / b | |||
8 g q12h (4 h infusion) | / c | / c | ||||
4 g q6h (1 h infusion) | / b | |||||
4 g q6h (4 h infusion) | / c | |||||
12 g/day | 6 g q12h (1 h infusion) | / b | / c | / b | ||
6 g q12h (4 h infusion) | / c | / c | ||||
4 g q8h (1 h infusion) | / b | / c | / b | / b | ||
4 g q8h (4 h infusion) | / c | / c | / c | |||
8 g/day | 4 g q12h (1 h infusion) | / c | / c | / b | / b | |
4 g q12h (4 h infusion) | / c | / c | ||||
6 g/day | 6 g q24h (1 h infusion) | / c | /c | / c | ||
6 g q24h (4 h infusion) | / c | / c | / c | / c | ||
3 g q12h (1 h infusion) | / c | / b | / c | |||
3 g q12h (4 h infusion) | / c | |||||
2 g q8h (1 h infusion) | / c | |||||
2 g q8h (4 h infusion) | / c | |||||
4 g/day | 4 g q24h (1 h infusion) | / c | / b | |||
4 g q24h (4 h infusion) | / c | / c | ||||
2 g q12h (1 h infusion) | / c | |||||
2 g q12h (4 h infusion) | / c | |||||
3 g/day | 3 g q24h (1 h infusion) | / c | / b | |||
3 g q24h (4 h infusion) | / c | |||||
1.5 g q12h (1 h infusion) | / c | |||||
2 g/day | 2 g q24h (1 h infusion) | / c |
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Leelawattanachai, P.; Wattanavijitkul, T.; Paiboonvong, T.; Plongla, R.; Chatsuwan, T.; Usayaporn, S.; Nosoongnoen, W.; Montakantikul, P. Evaluation of Intravenous Fosfomycin Disodium Dosing Regimens in Critically Ill Patients for Treatment of Carbapenem-Resistant Enterobacterales Infections Using Monte Carlo Simulation. Antibiotics 2020, 9, 615. https://doi.org/10.3390/antibiotics9090615
Leelawattanachai P, Wattanavijitkul T, Paiboonvong T, Plongla R, Chatsuwan T, Usayaporn S, Nosoongnoen W, Montakantikul P. Evaluation of Intravenous Fosfomycin Disodium Dosing Regimens in Critically Ill Patients for Treatment of Carbapenem-Resistant Enterobacterales Infections Using Monte Carlo Simulation. Antibiotics. 2020; 9(9):615. https://doi.org/10.3390/antibiotics9090615
Chicago/Turabian StyleLeelawattanachai, Pannee, Thitima Wattanavijitkul, Taniya Paiboonvong, Rongpong Plongla, Tanittha Chatsuwan, Sang Usayaporn, Wichit Nosoongnoen, and Preecha Montakantikul. 2020. "Evaluation of Intravenous Fosfomycin Disodium Dosing Regimens in Critically Ill Patients for Treatment of Carbapenem-Resistant Enterobacterales Infections Using Monte Carlo Simulation" Antibiotics 9, no. 9: 615. https://doi.org/10.3390/antibiotics9090615