Pharmacodynamics of Ceftibuten: An Assessment of an Oral Cephalosporin against Enterobacterales in a Neutropenic Murine Thigh Model
Abstract
:1. Introduction
2. Results
2.1. Murine Pharmacokinetic Studies
2.2. Pharmacodynamic Studies
3. Discussion
4. Materials and Methods
4.1. Antimicrobial Test Agents
4.2. Isolates
4.3. Animals
4.4. Neutropenic Thigh Infection Model
4.5. Murine Pharmacokinetic Studies
4.6. Pharmacodynamic Studies
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Single Dose Regimen | λ1/2 (h) | fCmax | fAUC0–8 | R2 |
---|---|---|---|---|
0.5 mg/kg | 1.0 | 1.0 | 2.3 | 0.90 |
1.5 mg/kg | 1.2 | 5.1 | 6.8 | 0.92 |
6 mg/kg | 1.5 | 12.8 | 37.0 | 0.98 |
20 mg/kg | 1.8 | 40.4 | 119.3 | 0.99 |
45 mg/kg | 1.4 | 95.6 | 191.0 | 0.97 |
Dosing Regimen | %fT > MIC (mg/L) | fAUC0–24 | Cmax | |||||||
---|---|---|---|---|---|---|---|---|---|---|
0.03 | 0.06 | 0.125 | 0.25 | 0.5 | 1 | 2 | 4 | |||
CTB 300 mg q8 h (human) [15] | 100% | 100% | 100% | 100% | 100% | 91% | 59% | 0% | 56.2 | 3.75 |
CTB 300 mg q8 h HSR (murine) | 100% | 100% | 100% | 100% | 100% | 91% | 50% | 0% | 50.1 | 3.6 |
0.5 mg/kg single dose | 24% | 22% | 17% | 12% | 7% | 0% | 0% | 0% | 2.1 | 0.97 |
3 mg/kg single dose | 37% | 35% | 30% | 25% | 20% | 15% | 10% | 4% | 12.8 | 5.8 |
0.5 mg/kg q8 h | 71% | 66% | 51% | 36% | 21% | 0% | 0% | 0% | 6.4 | 0.98 |
1 mg/kg q6 h | 100% | 100% | 90% | 70% | 48% | 28% | 1% | 0% | 16.89 | 2.02 |
6 mg/kg q8 h | 100% | 100% | 100% | 91% | 76% | 61% | 45% | 30% | 76.4 | 11.8 |
20 mg/kg q6 h | 100% | 100% | 100% | 100% | 100% | 100% | 96% | 76% | 337.8 | 40.3 |
20 mg/kg q4 h | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 500.7 | 43.8 |
45 mg/kg q3 h | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 1487.6 | 108.7 |
Isolate (MIC (mg/L)) | Ceftibuten %fT > MIC Required to Achieve | R2 | |
---|---|---|---|
Stasis | 1-log Reduction | ||
KP 956 (0.03) | 46 | 68 | 0.90 |
EC 756 (0.125) | 17 | 35 | 0.72 |
KP 957 (0.125) | NA | NA | 0.74 |
EC 551 (0.25) | 35 | NA | 0.85 |
KP 958 (0.25) | 40 | 59 | 0.92 |
EC 25922 (0.5) | 26 | 56 | 0.78 |
EC 761 (1) | 17 | 31 | 0.9 |
KP 700603 (1) | 44 | NA | 0.89 |
EC 643 (4) | 11 | 69 | 0.39 |
Median 1 | 31 | 58 | - |
IQR 1 | 17–41 | 40–66 | 0.74–0.9 |
Organism | CAIRD ID | Strain | Known Resistance Mechanism(s) | Ceftibuten MIC (mg/L) |
---|---|---|---|---|
Klebsiella pneumoniae | 956 | ARLG 1112 | SHV | 0.03 |
Escherichia coli | 756 | ARLG 1023 | None | 0.12 |
Klebsiella pneumoniae | 957 | ARLG 1118 | None | 0.12 |
Escherichia coli | 551 | CDC 0077 | None | 0.25 |
Klebsiella pneumoniae | 958 | ARLG 1120 | None | 0.25 |
Escherichia coli | 25922 | ATCC 25922 | None | 0.5 |
Escherichia coli | 761 | ARLG 1050 | None | 1 |
Klebsiella pneumoniae | 700603 * | ATCC 700603 | SHV-18, OXA-2, OKP-B-6 | 1 |
Escherichia coli | 643 * | SI-LP377 | CTX-M2 | 4 |
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Lasko, M.J.; Asempa, T.E.; Nicolau, D.P. Pharmacodynamics of Ceftibuten: An Assessment of an Oral Cephalosporin against Enterobacterales in a Neutropenic Murine Thigh Model. Antibiotics 2021, 10, 201. https://doi.org/10.3390/antibiotics10020201
Lasko MJ, Asempa TE, Nicolau DP. Pharmacodynamics of Ceftibuten: An Assessment of an Oral Cephalosporin against Enterobacterales in a Neutropenic Murine Thigh Model. Antibiotics. 2021; 10(2):201. https://doi.org/10.3390/antibiotics10020201
Chicago/Turabian StyleLasko, Maxwell J., Tomefa E. Asempa, and David P. Nicolau. 2021. "Pharmacodynamics of Ceftibuten: An Assessment of an Oral Cephalosporin against Enterobacterales in a Neutropenic Murine Thigh Model" Antibiotics 10, no. 2: 201. https://doi.org/10.3390/antibiotics10020201