Target Attainment of TDM-guided Infusion of Piperacillin/Tazobactam and Cefepim in Critically Ill Patients

Study Overview
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Brief Summary
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Although alternative dosing strategies can improve antimicrobial exposure in critically ill patients, the high PK variability in this population means that some may still receive sub-optimal antibiotic exposure leading to unfavourable clinical outcomes. Therapeutic drug management (TDM) guided dosing is the only safe and effective way to ensure that all critically ill patients achieve therapeutic antimicrobial exposures and to minimise the likelihood of toxicity. For experts, TDM should be a standard of care, in particular for β-lactams. Nevertheless, because of the assay method for β-lactams and the need for bioanalytical experts, delays in obtaining results frequently occurred. These barriers, combined with difficulties in the interpretation of TDM results, need to be addressed in order to increase its routine utilization. Consequently, study aiming at identify which subgroup of patients or infection are more likely to benefit from TDM are urgently warranted This prospective observational study aimed at evaluating target attainment of piperacillin/tazobactam (PIP/TAZ) and cefepim (CEF) with the use of a Therapeutic Drug Monitoring (TDM) in critically patients during the routine care

Official Title
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Target Attainment of TDM-guided Continuous Infusion of Piperacillin/Tazobactam and Cefepim in Critically Ill Patients: a Prospective Observational Study

Conditions
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Critical Illness, Antibiotic Toxicity, Sepsis, Septic Shock

Intervention / Treatment
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* Other: dosage of concentration of piperacillin and cefepim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Minimun age limits 18 years Critically ill patient receiving piperacillin or cefepim administered continuously Exclusion Criteria: Beta lactam allergy Pregnancy Age less than 18 years

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| critically ill patients<br>Critically ill patients receiving continuous infusion of piperacillin/tazbactam or cefepim and dosage of plasma concentration of the B lactam administered | Other: dosage of concentration of piperacillin and cefepim<br>* Dosage of total plasma concentration of piperacillin and cefepim at different timepoints<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to determine the percentage of patients who met the PK/PD targets at 24 hours | PK/PD target was defined as follows: Concentration of piperacillin or cefepim between a lower and a upper limit: The lower limit was defined as estimated free concentration above 4 times the epidemiological cut-off value of suspected bacteria The upper limit was based on known limit of neurotoxicity, namely 35 and 160 mg/L for cefepim and piperacillin, respectively Consequently : for piperacillin : the PK/PD target is considered to be reach if the free concentration of PIPERACILLIN/TAZOBACTAM is between 32 and 160 mg/l for cefepim : the PK/PD target is considered to be reach if the free concentration of CEFEPIM is between 4 and 35 mg/l | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to determine the percentage of patients who met the PK/PD targets exposure at 24 hours | PK/PD target exposure take into account only the the lower limit was defined as estimated free concentration above 4 times the epidemiological cut-off value of suspected bacteria Consequently : for piperacillin : the PK/PD target is considered to be reach if the free concentration of PIPERACILLIN/TAZOBACTAM is above 32 mg/l for cefepim : the PK/PD target is considered to be reach if the free concentration of CEFEPIM is above 4 mg/l | Day 1 | 
| factors associated with target attainment at day 1 | effect of age on antibiotic concentration | Statistical analysis after 2 years of inclusion | 
| factors associated with target attainment at day 1 | effect of renal clearance on antibiotic concentration | Statistical analysis after 2 years of inclusion | 
| factors associated with target attainment at day 1 | effect of presence of septic shock on antibiotic concentration | Statistical analysis after 2 years of inclusion | 
| factors associated with dose changing | effect of presence of septic shock on number of dose changing after analyse of antibiotic concentration | Statistical analysis after 2 years of inclusion | 
| factors associated with dose changing | effect of renal clearance on number of dose changing after analyse of antibiotic concentration | Statistical analysis after 2 years of inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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therapeutic drug monitoring