Interprofessional Therapeutic Drug Monitoring of Carbapenems Improves ICU Care and Guideline Adherence in Acute-on-Chronic Liver Failure
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Patient Characteristics
2.2. Characteristics of Interprofessional Collaboration and Education
2.3. Application of Meropenem
2.4. Therapeutic Drug Monitoring (TDM) of Meropenem
2.5. Characterization of Patients with Acute-on-Chronic Liver Failure (ACLF)
2.6. Acquisition of Data for Meropenem Consumption at the ICU
2.7. Statistical Analyses and Collection of Primary Data
3. Results
3.1. Patient Cohort
3.2. Initial Continuous Meropenem Dosing
3.3. Results of Initial TDM for Meropenem
3.4. Results of Follow-Up TDM for Meropenem
3.5. Recommendations of the Interprofessional Team concerning the Use of Meropenem in the Context of TDM and Implementation of These Recommendations
3.6. Analysis of Meropenem Consumption at the ICU
4. Discussion
4.1. Cirrhosis-Associated Immune Dysfunction (CAID) and ACLF
4.2. Continuous Administration of Meropenem
4.3. TDM for Meropenem
4.4. Interprofessional Collaboration and Shared Decision-Making
4.5. Impact of TDM of Meropenem on Local Application Density
4.6. Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ABS | Antibiotic stewardship |
ACLF | Acute-on-chronic liver failure |
A-STAR | AusbildungsSTAtion Regensburg = German for “interprofessional training ward Regensburg” |
CAID | Cirrhosis-associated immune dysfunction |
CDI | Clostridioides difficile infection |
CLI | Chronic liver injury |
CLIF-C | Chronic Liver Failure Consortium |
EASL-CLIF | European Association for the Study of the Liver—Chronic Liver Failure |
ESICM | European Society of Intensive Care Medicine |
HPLC | High-performance liquid chromatography |
ICU | Intensive care unit |
I’M A-STAR | IntensivMedizinische AusbildungsSTAtion Regensburg = German for “Intensive care training ward Regensburg” |
MDR | Multidrug-resistant |
MELD | Model for End-Stage Liver Disease |
MIC | Minimum inhibitory concentration |
MSC | Meropenem serum concentrations |
PD | Patient day |
RDD | Recommended daily doses |
SD | Standard deviation |
TDM | Therapeutic drug monitoring |
WHO | World Health Organization |
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Characteristics | Total Study Population (n = 25) |
---|---|
Age [years]: mean ± SD (range) | 55.4 ± 13.90 (20–74) |
Sex: n (%) Female Male | 8 (32.0) 17 (68.0) |
SOFA score [points]: mean ± SD (range) | 15.8 ± 3.6 (9–22) |
Mortality at the ICU: n (%) Deceased patients Survived patients | 15 (60.0) 10 (40.0) |
Liver cirrhosis: n (%) Child A/B/C | 25 (100.0) 1 (4.0)/5 (20.0)/19 (76.0) |
Cause of liver cirrhosis: n (%) Alcohol-related Cryptogenic Secondary sclerosing cholangitis Non-alcoholic fatty liver disease Autoimmune Primary biliary cholangitis Chronic Hepatitis B Genetic | 10 (40.0) 4 (16.0) 3 (12.0) 2 (8.0) 2 (8.0) 2 (8.0) 1 (4.0) 1 (4.0) |
MELD score [points]: mean ± SD (range) | 27.9 ± 8.7 (14–40) |
ACLF: n (%) ACLF Grade 1/2/3 | 25 (100.0) 6 (24.0)/3 (12.0)/16 (64.0) |
Cause of ACLF: n (%) Pneumonia Spontaneous bacterial peritonitis Cholangitis Urinary tract infection Endocarditis Cryptogenic focus of infection Esophageal variceal hemorrhage | 8 (32.0) 5 (20.0) 2 (8.0) 1 (4.0) 1 (4.0) 4 (16.0) 4 (16.0) |
CLIF-C-ACLF score [points]: mean ± SD (range) | 60.0 ± 9.3 (43–76) |
Initial continuous dosing of meropenem [mg/h]: mean ± SD (range) | 109 ± 20.8 (62.5–125) |
Meropenem Serum Concentration (MSC) | Initial TDM (n = 25) | 2nd TDM (n = 12) | 3rd TDM (n = 2) |
---|---|---|---|
MSC [mg/L]: mean ± SD (range) | 20.9 ± 9.6 (8.4–39) | 15.2 ± 5.7 (9–24.6) | 11.9 ± 2.3 (10.2–13.5) |
No. of MSCs inside target range (%) | 4 (16.0) | 5 (41.7) | 1 (50.0) |
No. of MSCs above target range (%) | 21 (84.0) | 7 (58.3) | 1 (50.0) |
No. of MSCs below target range (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Recommendations of the Interprofessional Team | Initial TDM (n = 25) | 2nd TDM (n = 12) | 3rd TDM (n = 2) |
---|---|---|---|
No change in meropenem dosage (%) | 10 (40.0) | 7 (58.3) | 2 (100.0) |
Decrease in meropenem dosage (%) | 10 (40.0) | 1 (8.3) | 0 (0.0) |
Increase in meropenem dosage (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Change to another antibiotic (%) | 5 (20.0) | 3 (25.0) | 0 (0.0) |
Stopping of antibiotic therapy (%) | 0 (0.0) | 1 (8.3) | 0 (0.0) |
Implementation (%) | 100 | 100 | 100 |
Meropenem Application Density (RDD/100 PD) | Q4 | Q1 | Q2 |
---|---|---|---|
Control period (Q4/2021–Q2/2022) | 49.9 | 39.4 | 37.7 |
Intervention period (Q4/2022–Q2/2023) | 46.0 | 33.1 | 34.5 |
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Schmid, S.; Koch, C.; Zimmermann, K.; Buttenschoen, J.; Mehrl, A.; Pavel, V.; Schlosser-Hupf, S.; Fleischmann, D.; Krohn, A.; Schilling, T.; et al. Interprofessional Therapeutic Drug Monitoring of Carbapenems Improves ICU Care and Guideline Adherence in Acute-on-Chronic Liver Failure. Antibiotics 2023, 12, 1730. https://doi.org/10.3390/antibiotics12121730
Schmid S, Koch C, Zimmermann K, Buttenschoen J, Mehrl A, Pavel V, Schlosser-Hupf S, Fleischmann D, Krohn A, Schilling T, et al. Interprofessional Therapeutic Drug Monitoring of Carbapenems Improves ICU Care and Guideline Adherence in Acute-on-Chronic Liver Failure. Antibiotics. 2023; 12(12):1730. https://doi.org/10.3390/antibiotics12121730
Chicago/Turabian StyleSchmid, Stephan, Chiara Koch, Katharina Zimmermann, Jonas Buttenschoen, Alexander Mehrl, Vlad Pavel, Sophie Schlosser-Hupf, Daniel Fleischmann, Alexander Krohn, Tobias Schilling, and et al. 2023. "Interprofessional Therapeutic Drug Monitoring of Carbapenems Improves ICU Care and Guideline Adherence in Acute-on-Chronic Liver Failure" Antibiotics 12, no. 12: 1730. https://doi.org/10.3390/antibiotics12121730
APA StyleSchmid, S., Koch, C., Zimmermann, K., Buttenschoen, J., Mehrl, A., Pavel, V., Schlosser-Hupf, S., Fleischmann, D., Krohn, A., Schilling, T., Müller, M., & Kratzer, A. (2023). Interprofessional Therapeutic Drug Monitoring of Carbapenems Improves ICU Care and Guideline Adherence in Acute-on-Chronic Liver Failure. Antibiotics, 12(12), 1730. https://doi.org/10.3390/antibiotics12121730