Do Critically Ill Patients Undergoing Continuous Renal Replacement Therapy Require Ceftaroline Dosage Adjustments? Ceftaroline PopPK Model and Dosage Simulations with the Probability of Target Attainment Analysis Based on Retrospective Data †
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Pharmacokinetic Model Building
2.3. Monte Carlo Simulations
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Pharmacokinetic Analysis
4.3. Simulations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AKI | Acute kidney injury |
ARC | Augmented renal clearance |
BICc | corrected Bayesian Information Criteria |
CRRT | Continuous renal replacement therapy |
Cl | Climination clearance |
ClCr | Creatinine clearance |
COSSAC | COnditional Sampling use for the Stepwise Approach |
CVVHD | Continuous venovenous hemodialysis |
CVVHDF | Continuous venovenous hemodiafiltration |
EUCAST | The European Committee on Antimicrobial Susceptibility Testing |
GOF | Goodness of fit |
ICU | Intensive care unit |
IIV | Inter-individual variability |
IOV | Inter-occasion variability |
MIC | Minimum inhibitory concentration |
MRSA | Methicillin-resistant Staphylococcus aureus |
OFV | Objective function value |
pcVPC | Prediction-corrected visual predictive check |
PK | Pharmacokinetic |
PK/PD | pharmacokinetic/pharmacodynamic |
PopPK | Population pharmacokinetic |
PTA | Probability of target attainment |
SAEM | Stochastic approximation expectation-maximization |
SmPC | Summary of product characteristics |
Q | Inter-compartmental clearance |
Qb | Blood flow rate |
Qeff | Effluent flow rate |
VCentral | Volume of the central compartment |
VPeripheral | Volume of the peripheral compartment |
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Characteristics | Median [Range] or Number (%) |
---|---|
Gender | |
Female | 12 (36%) |
Male | 21 (64%) |
Age (years) | 51 [21–77] |
Weight (kg) | 75.5 [49–111.8] |
ClCr (mL/min/1.73 m2) | 159 [42–309] |
CRRT | |
Yes | 4 (12%) |
No | 29 (88%) |
CRRT modality | |
CVVHD | 2 (50%) |
CVVHDF | 2 (50%) |
Qb (mL/min) | 250 [250–300] |
Qeff (mL/h) | 3200 [2700–3660] |
Parameters | Mean Estimate (RSE%) | |
---|---|---|
Base Model | Final Model | |
Cl (L/h) | 10.27 (7.0) | 11.23 (5.7) |
ClCr on Cl | – | 0.68 (16.1) |
IOV on Cl (%CV) | 48.12 (10.6) | 34.96 (12.3) |
VCentral (L) | 21.26 (13.2) | 20.04 (4.1) |
CVVHD on VCentral | – | 0.47 (18.2) |
CVVHDF on VCentral | – | −0.42 (21.3) |
IIV on VCentral (%CV) | 24.44 (44.3) | 3.70 (57.8) |
Q (L/h) | 8.51 (25.9) | 8.80 (20.7) |
CRRT on Q | – | 0.99 (26.6) |
IIV on Q (%CV) | 50.69 (38.3) | 16.40 (58.5) |
VPeripheral (L) | 16.72 (11.2) | 16.85 (10.5) |
CRRT on VPeripheral | – | 0.99 (30.5) |
IIV on VPeripheral (%CV) | 38.92 (29.0) | 38.60 (20.8) |
VCRRT (L) | 2.18 (14.9) | 2.69 (42.3) |
VEffluent (L) | 0.44 (17.4) | 0.60 (6.1) |
VPost-filter (L) | 1.29 (4.23) | 1.15 (3.5) |
bPre | 0.29 (5.0) | 0.29 (5.0) |
bPost | 0.18 (20.6) | 0.16 (21.0) |
bEff | 0.17 (17.3) | 0.13 (16.9) |
Streptococcus pneumoniae (MIC = 0.25 mg/L) | Methicillin-Resistant Staphylococcus aureus (MIC = 1 mg/L) | |||
---|---|---|---|---|
100%ƒT>MIC | 100%ƒT>4xMIC | 100%ƒT>MIC | 100%ƒT>4xMIC | |
With CRRT | ||||
CVVHD | ||||
Qeff = 2.5 L/h | 200 mg q12 h Tinf 1 h | 200 mg q8 h Tinf 2 h | 200 mg q8 h Tinf 2 h | 800 mg q8 h Tinf 2 h |
Qeff = 3.0 L/h | 200 mg q12 h Tinf 1 h | 300 mg q8 h Tinf 2 h | 300 mg q8 h Tinf 2 h | – |
Qeff = 3.5 L/h | 200 mg q12 h Tinf 1 h | 300 mg q8 h Tinf 2 h | 300 mg q8 h Tinf 2 h | – |
Qeff = 4.0 L/h | 200 mg q12 h Tinf 1 h | 300 mg q8 h Tinf 2 h | 300 mg q8 h Tinf 2 h | – |
CVVHDF | ||||
Qeff = 2.5 L/h | 200 mg q12 h Tinf 1 h | 300 mg q8 h Tinf 2 h | 300 mg q8 h Tinf 2 h | – |
Qeff = 3.0 L/h | 200 mg q12 h Tinf 1 h | 300 mg q8 h Tinf 2 h | 300 mg q8 h Tinf 2 h | – |
Qeff = 3.5 L/h | 200 mg q12 h Tinf 1 h | 300 mg q8 h Tinf 2 h | 300 mg q8 h Tinf 2 h | – |
Qeff = 4.0 L/h | 300 mg q12 h Tinf 1 h | 400 mg q8 h Tinf 2 h | 400 mg q8 h Tinf 2 h | – |
Without CRRT | ||||
ClCr | ||||
80 mL/min/1.73 m2 | 300 mg q12 h Tinf 1 h | 400 mg q8 h Tinf 2 h | 400 mg q8 h Tinf 2 h | – |
130 mL/min/1.73 m2 | 200 mg q8 h Tinf 2 h | 800 mg q8 h Tinf 2 h | 800 mg q8 h Tinf 2 h | – |
210 mL/min/1.73 m2 | 600 mg q8 h Tinf 2 h | – | – | – |
300 mL/min/1.73 m2 | 800 mg q8 h Tinf 2 h | – | – | – |
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Adamiszak, A.; Pietrzkiewicz, K.; Bartkowska-Śniatkowska, A.; Smuszkiewicz, P.; Kusza, K.; Grześkowiak, E.; Bienert, A. Do Critically Ill Patients Undergoing Continuous Renal Replacement Therapy Require Ceftaroline Dosage Adjustments? Ceftaroline PopPK Model and Dosage Simulations with the Probability of Target Attainment Analysis Based on Retrospective Data. Antibiotics 2025, 14, 347. https://doi.org/10.3390/antibiotics14040347
Adamiszak A, Pietrzkiewicz K, Bartkowska-Śniatkowska A, Smuszkiewicz P, Kusza K, Grześkowiak E, Bienert A. Do Critically Ill Patients Undergoing Continuous Renal Replacement Therapy Require Ceftaroline Dosage Adjustments? Ceftaroline PopPK Model and Dosage Simulations with the Probability of Target Attainment Analysis Based on Retrospective Data. Antibiotics. 2025; 14(4):347. https://doi.org/10.3390/antibiotics14040347
Chicago/Turabian StyleAdamiszak, Arkadiusz, Krzysztof Pietrzkiewicz, Alicja Bartkowska-Śniatkowska, Piotr Smuszkiewicz, Krzysztof Kusza, Edmund Grześkowiak, and Agnieszka Bienert. 2025. "Do Critically Ill Patients Undergoing Continuous Renal Replacement Therapy Require Ceftaroline Dosage Adjustments? Ceftaroline PopPK Model and Dosage Simulations with the Probability of Target Attainment Analysis Based on Retrospective Data" Antibiotics 14, no. 4: 347. https://doi.org/10.3390/antibiotics14040347
APA StyleAdamiszak, A., Pietrzkiewicz, K., Bartkowska-Śniatkowska, A., Smuszkiewicz, P., Kusza, K., Grześkowiak, E., & Bienert, A. (2025). Do Critically Ill Patients Undergoing Continuous Renal Replacement Therapy Require Ceftaroline Dosage Adjustments? Ceftaroline PopPK Model and Dosage Simulations with the Probability of Target Attainment Analysis Based on Retrospective Data. Antibiotics, 14(4), 347. https://doi.org/10.3390/antibiotics14040347