MPC-Based Prediction of Anti-Mutant Effectiveness of Antibiotic Combinations: In Vitro Model Study with Daptomycin and Gentamicin against Staphylococcus aureus
Abstract
:1. Introduction
2. Results
2.1. MPCs of Daptomycin and Gentamicin Alone and in Combination
2.2. Antibiotic Pharmacodynamics with Resistant S. aureus Mutants
3. Discussion
4. Materials and Methods
4.1. Antimicrobial Agents, Bacterial Strain and Susceptibility Testing
4.2. MPC Determinations
4.3. Antibiotic Dosing Regimens and Simulated Pharmacokinetic Profiles
4.4. In Vitro Dynamic Model
4.5. Quantitation of the Antimicrobial Effects on the Resistant Subpopulations of S. aureus
4.6. T>MPC Relationships with the Emergence of Resistance
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Antibiotic | Daptomycin-to-Gentamicin AUC Ratio | Regimen | MPC, mg/L |
---|---|---|---|
Daptomycin | - | D30 | 16 |
D100 | 16 | ||
Daptomycin in the presence of gentamicin | 1:2 | D30+G65 | 2 |
1:5 | D30+G160 | 1.2 | |
1.5:1 | D100+G65 | 6 | |
1:1.5 | D100+G160 | 2 | |
Gentamicin | - | G65 | 10 |
G160 | 10 | ||
Gentamicin in the presence of daptomycin | 1:2 | D30+G65 | 4 |
1.5:1 | D100+G65 | 4 | |
1:5 | D30+G160 | 6 | |
1:1.5 | D100+G160 | 3 |
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Golikova, M.V.; Strukova, E.N.; Portnoy, Y.A.; Zinner, S.H.; Firsov, A.A. MPC-Based Prediction of Anti-Mutant Effectiveness of Antibiotic Combinations: In Vitro Model Study with Daptomycin and Gentamicin against Staphylococcus aureus. Antibiotics 2021, 10, 1148. https://doi.org/10.3390/antibiotics10101148
Golikova MV, Strukova EN, Portnoy YA, Zinner SH, Firsov AA. MPC-Based Prediction of Anti-Mutant Effectiveness of Antibiotic Combinations: In Vitro Model Study with Daptomycin and Gentamicin against Staphylococcus aureus. Antibiotics. 2021; 10(10):1148. https://doi.org/10.3390/antibiotics10101148
Chicago/Turabian StyleGolikova, Maria V., Elena N. Strukova, Yury A. Portnoy, Stephen H. Zinner, and Alexander A. Firsov. 2021. "MPC-Based Prediction of Anti-Mutant Effectiveness of Antibiotic Combinations: In Vitro Model Study with Daptomycin and Gentamicin against Staphylococcus aureus" Antibiotics 10, no. 10: 1148. https://doi.org/10.3390/antibiotics10101148